Ultrasound manifestation of hepatocellular carcinoma

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Hwang, M S; Yoo, H S; Park, C Y; Choi, H J; Moon, Y M; Lee, S I [Yonsei University College of Medicine, Seoul (Korea, Republic of)

1982-06-15

With the advent of gray scale ultrasonographic equipment, the parenchymal disease of liver is more easily evaluated. Ultrasonography is a non-invasive technique, different from angiography, and performed without discomfort to patient. And also ultrasonography can be used in assessing the liver in cases showing equivocal scintigraphy and in differentiation of solid and cystic masses, first detected on scintigrams. Therefore, the complementary use of ultrasonography, Tc-99m-sulfur colloid scan and angiography provides better diagnostic accuracy for the detection of hepatocellular carcinoma, and moreover, sequential ultrasonographic studies in the same patient are valuable of following the course of hepatocellular carcinoma and monitoring the effectiveness of therapy for hepatocellular carcinoma. In thirty patients with histologically proven hepatocellular carcinoma, an analysis of ultrasound manifestation is made and the results are as follows; 1. Ultrasound manifestation of hepatocellular carcinoma by gray scale showed four different sonographic patterns including discrete echo free, discrete echogenic, ill defined echogenic and mixed patterns. 2. The size of hepatocellular carcinoma by ultrasonographic measurement was larger than 5 cm in diameter in 28 cases. 3. In 7 cases performed with angiography, all echogenicities of hepatocellualr carcinoma were correlated with the findings of vascularity of angiography. 4. In cases combined with liver cirrhosis, the sonographic pattern of hepatocellular carcinoma appeared to be discrete or ill defined echogenic patterns.

Liver cirrhosis and primary carcinoma of the liver among atomic bomb survivors. Study of autopsy cases

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Hamada, T [Hiroshima Atomic Bomb Hospital (Japan)

1980-11-01

Liver cirrhosis and primary carcinoma of the liver were investigated in 1699 autopsies of atomic bomb survivors carried out in Hiroshima from 1956 to 1980. Liver cirrhosis, hepatocellular carcinoma and intrahepatic biliary carcinoma were observed in 116, 111, and 17 cases respectively, the ratios of man to woman and were 2.3, 3.9, and 1.8 with a mean age of 56, 60, and 67 years respectively. There was no evidence that exposure to a-bomb increased the risk of these diseases significantly. About 90% of the hepatocellular carcinomas was combined with liver cirrhosis. Weight of liver and spleen, amount of ascites, hemorrhage from the digestive canals, esophageal varix, combination with other diseases, and histologic correlation with the activities of HBs antigen and ..cap alpha..-fetoprotein were discussed with the relation to the exposure.

Imaging features of microvascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy in HCV-related cirrhosis

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Renzulli, Matteo; Brocchi, Stefano; Golfieri, Rita [Sant' Orsola-Malpighi Hospital, Department of Diagnostic Medicine and Prevention, Bologna (Italy); Buonfiglioli, Federica; Conti, Fabio; Verucchi, Gabriella; Andreone, Pietro [University of Bologna, Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences DIMEC, Bologna (Italy); Serio, Ilaria [Sant' Orsola-Malpighi Hospital, Department of Digestive Diseases, Bologna (Italy); Foschi, Francesco Giuseppe [Ospedale di Faenza, Division of Internal Medicine, Faenza (Italy); Caraceni, Paolo; Mazzella, Giuseppe [University of Bologna, Department of Medical and Surgical Sciences (DIMEC), Bologna (Italy); Brillanti, Stefano [University of Bologna, Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences DIMEC, Bologna (Italy); U.O. di Gastroenterologia, Bologna (Italy)

2018-02-15

To evaluate imaging features of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) developed after direct-acting antiviral (DAA) therapy in HCV-related cirrhosis. Retrospective cohort study on 344 consecutive patients with HCV-related cirrhosis treated with DAA and followed for 48-74 weeks. Using established imaging criteria for MVI, HCC features were analysed and compared with those in nodules not occurring after DAA. After DAA, HCC developed in 29 patients (single nodule, 18 and multinodular, 11). Median interval between therapy end and HCC diagnosis was 82 days (0-318). Forty-one HCC nodules were detected (14 de novo, 27 recurrent): maximum diameter was 10-20 mm in 27, 20-50 mm in 13, and > 50 mm in 1. Imaging features of MVI were present in 29/41 nodules (70.7%, CI: 54-84), even in 17/29 nodules with 10-20 mm diameter (58.6%, CI: 39-76). MVI was present in only 17/51 HCC nodules that occurred before DAA treatment (33.3%, CI: 22-47) (p= 0.0007). MVI did not correlate with history of previous HCC. HCC occurs rapidly after DAA therapy, and aggressive features of MVI characterise most neoplastic nodules. Close imaging evaluations are needed after DAA in cirrhotic patients. (orig.)

Acute Exacerbation of Hepatitis in Liver Cirrhosis with Very High Levels of alpha-Fetoprotein But No Occurrence of Hepatocellular Carcinoma

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Park, Sang Jong; Park, Kwang Bo; Paik, So Ya; Ryu, Jin Kyung; Choi, Chang Kyu; Hwang, Tae Joon

2005-01-01

Aminotransferase levels do not always increase during acute hepatitis or during an acute flare-up of chronic hepatitis. Persistently increased levels of serum alpha-Fetoprotein in an adult with liver disease suggest not only the presence or progression of hepatocellular carcinoma or its recurrence after hepatic resection or after other therapeutic approaches such as chemotherapy or chemoembolization, but also it suggests that there is an acute exacerbation of hepatitis or liver cirrhosis. We report here on two unusual cases of HBV- & HCV-related liver cirrhosis with acute exacerbation of hepatitis in which there was an insignificant elevation of the aminotransferase levels, but there were markedly increased alpha-Fetoprotein levels observed. The levels of alpha-Fetoprotein decreased gradually in both cases since the beginning of antiviral therapy, which implies that the increased levels were due to aggravation of the accompanying hepatitis. These cases also emphasize that using only the measurement of alpha-Fetoprotein is not sufficient for the diagnosis of hepatocellular carcinoma, and that this diagnosis also requires a more specific measurement such as AFP L3 along with the standard imaging studies. PMID:15906959

Prediction of posthepatectomy liver failure using transient elastography in patients with hepatitis B related hepatocellular carcinoma.

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Lei, Jie-Wen; Ji, Xiao-Yu; Hong, Jun-Feng; Li, Wan-Bin; Chen, Yan; Pan, Yan; Guo, Jia

2017-12-29

It is essential to accurately predict Postoperative liver failure (PHLF) which is a life-threatening complication. Liver hardness measurement (LSM) is widely used in non-invasive assessment of liver fibrosis. The aims of this study were to explore the application of preoperative liver stiffness measurements (LSM) by transient elastography in predicting postoperative liver failure (PHLF) in patients with hepatitis B related hepatocellular carcinoma. The study included 247 consecutive patients with hepatitis B related hepatocellular carcinoma who underwent hepatectomy between May 2015 and September 2015. Detailed preoperative examinations including LSM were performed before hepatectomy. The endpoint was the development of PHLF. All of the patients had chronic hepatitis B defined as the presence of hepatitis B surface antigen (HBsAg) for more than 6 months and 76 (30.8%) had cirrhosis. PHLF occurred in 37 (14.98%) patients. Preoperative LSM (odds ratio, OR, 1.21; 95% confidence interval, 95% CI: 1.13-1.29; P hepatocellular carcinoma.

How to detect hepatocellular carcinoma in cirrhosis

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Ward, Janice; Robinson, Philip J. [Department of Clinical Radiology, St. James' s University Hospital, Beckett Street, Leeds LS9 7TF (United Kingdom)

2002-09-01

Cirrhosis predisposes to hepatocellular carcinoma (HCC) which develops by sequential steps of de-differentiation of hepatocytes from regenerative nodules via borderline (dysplastic) nodules to frankly malignant HCC. Effective treatment depends on early recognition of HCC, so the key tasks for imaging are firstly recognising the presence of a suspicious lesion, and secondly differentiating between benign, borderline and malignant nodules. Screening of high-risk cirrhotic patients with sonography and measurement of alpha fetoprotein (AFP) is helpful but will not reliably differentiate small HCC from benign or dysplastic nodules. Large HCCs can usually be recognised by their characteristic morphology on imaging, but the appearances of smaller benign and malignant nodules show considerable overlap on unenhanced sonography, CT and MRI. Increasing degrees of histological malignancy are associated with increasing arterialisation and loss of portal blood supply, so the recognition of HCC requires the use of dynamic imaging with contrast-enhanced CT or T1-weighted MRI with gadolinium enhancement. Sonography with microbubble contrast media now offers another method for detecting arterialised nodules; however, some non-malignant nodules show arterial hypervascularity and a minority of HCCs are hypovascular, so the assessment of perfusion does not conclusively distinguish benign from malignant lesions. Kupffer cell function is another attribute of liver tissue which can be explored using MRI with superparamagnetic iron oxide particles (SPIO). Experience thus far suggests that uptake of SPIO is an effective discriminator between benign and malignant nodules. The combination of SPIO with gadolinium-enhanced MRI offers the opportunity for imaging characterisation of cirrhotic nodules by cellular function as well as by blood supply, and this approach is now proposed as the examination of choice for detecting HCC in cirrhosis. (orig.)

Hepatocellular carcinoma in Danish patients

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Stefansdottir, Jenna; Christensen, Erik; Schiødt, Frank Vinholt

2017-01-01

OBJECTIVE: Hepatocellular carcinoma (HCC) is a common cause of cancer, and most HCC patients have underlying cirrhosis. Retrospectively, we aimed to characterize patients with newly diagnosed HCC at a Danish hospital and to investigate survival and identify predictive factors for survival. METHODS...

Computed tomographic findings of hepatocellular carcinoma

International Nuclear Information System (INIS)

Jo, In Su; Jong, Woo Yung; Lee, Jong Yul; Choi, Han Yong; Kim, Bong Ki

1987-01-01

With Development of Computed Tomography, detection of the Hepatocellular Carcinoma are easily performed and frequently used in the world. During 15 months, from December 1985 to February 1987, 59 patients with hepatocellular carcinoma were evaluated with computed tomography in department of radiology at Wallace Memorial Baptist Hospital. The results were as follow: 1. The most prevalent age group was 5th to 7th decades, male to female ratio was 4.9:1. 2. Classification with incidence of computed tomographic appearance of the hepatocellular carcinoma were solitary type 28 cases (48%), multinodular type 24 cases (40%), and diffuse type 7 cases (12%), Association with liver cirrhosis was noted in 22 cases (38%). 3. Inhomogenous internal consistency of hepatocellular carcinoma due to central necrosis were 35 cases (60%). Portal vein invasion by hepatocellular carcinoma was noted in 15 cases (25%), and particularly most common in diffuse type 4 cases (55%). 4. On precontrast scan, all hepatocellular carcinoma were seen as area of low density except for 3 cases(0.5%) of near isodensity which turned out to be remarkable low density on postcontrast scan. 5. In solitary type, posterior segment of right lobe was most common site of involvement 12 cases (43%). In diffuse type, bilobar involvement was most common, 6 cases (85%)

IP-10, p53, and Foxp3 Expression in Hepatocytes of Chronic Hepatitis B Patients with Cirrhosis and Hepatocellular Carcinoma.

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Shahera, Umme; Munshi, Saifullah; Jahan, Munira; Nessa, Afzalun; Alam, Shahinul; Tabassum, Shahina

2016-01-01

Elucidating differences in gene expression may be useful in understanding the molecular pathogenesis and for developing specific markers for the outcome of hepatitis B virus (HBV) infection. In the present study, expressions of host gene interferon gamma-inducible protein (IP-10), p53, and Foxp3 were studied in hepatocytes of patients with chronic HBV infection to determine a possible link between selected host gene expression and the outcome of HBV infection. The study was conducted in 60 patients with chronic HBV infection and they were divided into four groups: HBV-positive cirrhosis (n = 15), HBV-negative cirrhosis (n = 15), HBV-positive hepatocellular carcinoma (HCC) (n = 15) and HBV-negative HCC (n = 15). Total messenger ribonucleic acid (mRNA) extraction was done followed by complementary deoxyribonucleic acid (cDNA) synthesis, and finally gene expression was performed using real-time polymerase chain reaction (PCR) technique. IP-10 and p53 gene expressions were lower in HBV-positive cirrhosis, and Foxp3 gene expression was upregulated in HBV-positive cirrhosis in comparison to HBV-negative cirrhosis. The expressions of all the three genes were upregulated among HBV-positive HCC in comparison to HBV-negative HCC. The expression of IP-10, p53, and Foxp3 genes was upregulated in HBV-positive HCC in comparison to HBV-positive cirrhosis. This study indicates that there are variations in the expression of the selected genes among cirrhosis and HCC patients with or without HBV. All the three selected genes were more or less upregulated in HBV-positive HCC patients, but only Foxp3 expression was upregulated in HBV-positive cirrhosis. These three particular genes may have a role in the molecular pathogenesis and clinical outcome of HBV-positive cirrhosis and HCC patients. These aspects need further evaluation by studies with larger numbers of cirrhosis and HCC patients. Shahera U, Munshi S, Jahan M, Nessa A, Alam S, Tabassum S. IP-10, p53, and Foxp3 Expression in

A Phase-1b study of tivantinib (ARQ 197) in adult patients with hepatocellular carcinoma and cirrhosis

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Santoro, A; Simonelli, M; Rodriguez-Lope, C; Zucali, P; Camacho, L H; Granito, A; Senzer, N; Rimassa, L; Abbadessa, G; Schwartz, B; Lamar, M; Savage, R E; Bruix, J

2013-01-01

Background: The mesenchymal-epithelial transition factor (MET) receptor is dysregulated in hepatocellular carcinoma (HCC), and tivantinib (ARQ 197) is an oral, selective, MET inhibitor. Methods: This Phase-1b study assessed tivantinib safety as primary objective in patients with previously treated HCC and Child-Pugh A or B liver cirrhosis. Patients received oral tivantinib 360 mg twice daily until disease progression or unacceptable toxicity. Results: Among 21 HCC patients, common drug-related adverse events (AEs) were neutropaenia, anaemia, asthenia, leucopaenia, anorexia, diarrhoea, and fatigue. No drug-related worsening of liver function or performance status occurred, but one Child-Pugh B patient experienced drug-related bilirubin increase. Four patients had drug-related serious AEs, including one neutropaenia-related death. Haematologic toxicities were more frequent than in previous tivantinib studies but were manageable with prompt therapy. Best response was stable disease (median, 5.3 months) in 9 of 16 evaluable patients (56%). Median time to progression was 3.3 months. Conclusion: Tivantinib demonstrated a manageable safety profile and preliminary antitumour activity in patients with HCC and Child-Pugh A or B cirrhosis. PMID:23287988

Effectiveness of interferon alfa on incidence of hepatocellular carcinoma and decompensation in cirrhosis type C. European Concerted Action on Viral Hepatitis (EUROHEP)

DEFF Research Database (Denmark)

Fattovich, G; Giustina, G; Degos, F

1997-01-01

The role of interferon alfa treatment in improving morbidity endpoints in patients with chronic hepatitis C infection is currently under debate. The aim of this study was to evaluate the effectiveness of interferon in preventing hepatocellular carcinoma and decompensation in cirrhosis type C....

Usefulness of Pure Laparoscopic Hepatectomy for Hepatocellular Carcinoma in a Severely Cirrhotic Patient

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Isamu Hosokawa

2013-07-01

Full Text Available The number of patients undergoing laparoscopic hepatectomy has rapidly increased in recent years, and indications for this procedure are gradually expanding. Pure laparoscopic hepatectomy is reportedly useful in cases with severe liver cirrhosis. A 55-year-old woman under observation for liver cirrhosis was found to have hepatocellular carcinoma in liver segment III and was referred to our hospital for surgery. The tumor was located in the edge of liver segment III, where percutaneous ablation therapy was unsuitable. Since her hepatic functional reserve was poor, pure laparoscopic partial hepatectomy was performed. The postoperative course was favorable, with no ascites retention, edema or weight gain. The greatest advantage of pure laparoscopic hepatectomy for hepatocellular carcinoma with concomitant liver cirrhosis is that postoperative ascites retention is minimal, meaning that there is little risk of water-electrolyte imbalance associated with ascites retention or hypoproteinemia. This is believed to be because the abdominal incision is small and mobilization of the liver is minimized, reducing the destruction of the routes of collateral lymph flow and blood flow generated in patients with liver cirrhosis. Pure laparoscopic hepatectomy may be a treatment choice for patients with hepatocellular carcinoma and concomitant severe liver cirrhosis.

Hepatocellular Carcinoma in the Absence of Cirrhosis in US Veterans is Associated with Non-Alcoholic Fatty Liver Disease

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Mittal, Sahil; El-Serag, Hashem B.; Sada, Yvonne H.; Kanwal, Fasiha; Duan, Zhigang; Temple, Sarah; May, Sarah B.; Kramer, Jennifer R.; Richardson, Peter A.; Davila, Jessica A.

2015-01-01

Background & Aims Hepatocellular carcinoma (HCC) can develop in individuals without cirrhosis. We investigated risk factors for development of HCC in the absence of cirrhosis in a US population. Methods We identified a national cohort of 1500 patients with verified HCC during 2005–2010 in the US Veterans Administration (VA), and reviewed their full VA medical records for evidence of cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to categories of level 1 evidence for no cirrhosis (very high probability) or level 2 evidence for no cirrhosis (high probability), based on findings from histologic analyses, laboratory test results, markers of fibrosis from non-invasive tests, and imaging features. Results A total of 43 (2.9%) of the 1500 patients with HCC had level 1 evidence for no cirrhosis and 151 (10.1%) had level 2 evidence for no cirrhosis; the remaining 1203 patients (80.1%) had confirmed cirrhosis. Compared to patients with HCC in presence of cirrhosis, greater proportions of patients with HCC without evidence of cirrhosis had metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), or no identifiable risk factors. Patients with HCC without evidence of cirrhosis were less likely to have abused alcohol or have HCV infection than patients with cirrhosis. Patients with HCC and NAFLD (unadjusted odds ratio, 5.4; 95% confidence interval, 3.4–8.5) or metabolic syndrome (unadjusted odds ratio, 5.0; 95% confidence interval, 3.1–7.8) had more than a 5-fold risk of having HCC in the absence of cirrhosis, compared to patients with HCV-related HCC. Conclusions Approximately 13% of patients with HCC in the VA system do not appear to have cirrhosis. NAFLD and metabolic syndrome are the main risk factors HCC in the absence of cirrhosis. PMID:26196445

Serological diagnosis of hepatocellular carcinoma: challenges and opportunities

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LU Fengmin

2017-07-01

Full Text Available Serological markers have the features of noninvasiveness and simple operation and thus have become a research hotspot in the diagnosis of hepatocellular carcinoma. This article briefly introduces the role of the conventional serological marker alpha-fetoprotein (AFP in assisting the diagnosis and predicting the prognosis of HBV-related liver cancer, as well as the clinical value of new markers such as alpha-fetoprotein-L3 and abnormal prothrombin/des-γ-carboxy prothrombin. Based on literature review, the possibility of serum Golgi protein 73 used for laboratory auxiliary diagnosis of hepatocellular carcinoma has been denied. The results of the author′s experiment suggest that serum GP73 measurement can be used as a laboratory diagnostic index for progressive liver fibrosis and liver cirrhosis.

[Expression and clinical significance of KIAA1199 in primary hepatocellular carcinoma].

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Gu, C J; Ni, Q C; Ni, K; Zhang, S; Qian, H X

2018-05-29

Objective: To investigate the expression and clinical significance of KIAA1199 in primary hepatocellular carcinoma. Methods: A total of 136 cases of primary hepatocellular carcinoma tissues and paired adjacent tissues were collected. Immunohistochemistry and Western blot were used to detect the expression of KIAA1199 in primary hepatocellular carcinoma tissues and paired adjacent tissues. The relationship between KIAA1199 and clinicopathological parameter of primary hepatocellular carcinoma was analyzed. Results: The positive rate of KIAA1199 in primary hepatocellular carcinoma was 82.3% (112/136), which was higher than that in paired para-cancerous tissues (14.7%, 20/136). High expression of KIAA1199 was significantly correlated with age, cirrhosis history, tumor size, tumor number, degree of differentiation, TNM staging and microvenous invasion (MVI) ( P 0.05). The Kaplan-Meier survival curves indicated that high KIAA1199 expression was associated with poor survival ( P hepatocellular carcinoma, which is significantly correlated with the clinicopathological features and prognosis, high expression of KIAA1199 increased the risk of death in patients with primary hepatocellular carcinoma.

Quantitative proteome analysis of plasma microparticles for the characterization of HCV-induced hepatic cirrhosis and hepatocellular carcinoma.

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Taleb, Raghda Saad Zaghloul; Moez, Pacint; Younan, Doreen; Eisenacher, Martin; Tenbusch, Matthias; Sitek, Barbara; Bracht, Thilo

2017-12-01

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and a leading cause of cancer-related deaths worldwide. Cirrhosis induced by hepatitis-C virus (HCV) infection is the most critical risk factor for HCC. However, the mechanism of HCV-induced carcinogenesis is not fully understood. Plasma microparticles (PMP) contribute to numerous physiological and pathological processes and contain proteins whose composition correlates to the respective pathophysiological conditions. We analyzed PMP from 22 HCV-induced cirrhosis patients, 16 HCV-positive HCC patients with underlying cirrhosis and 18 healthy controls. PMP were isolated using ultracentrifugation and analyzed via label-free LC-MS/MS. We identified 840 protein groups and quantified 507 proteins. 159 proteins were found differentially abundant between the three experimental groups. PMP in both disease entities displayed remarkable differences in the proteome composition compared to healthy controls. Conversely, the proteome difference between both diseases was minimal. GO analysis revealed that PMP isolated from both diseases were significantly enriched in proteins involved in complement activation, while endopeptidase activity was downregulated exclusively in HCC patients. This study reports for the first time a quantitative proteome analysis for PMP from patients with HCV-induced cirrhosis and HCC. Data are available via ProteomeXchange with identifier PXD005777. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Resected Hepatocellular Carcinoma in a Patient with Crohn's Disease on Azathioprine

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Heron, Valérie; Fortinsky, Kyle Joshua; Spiegle, Gillian; Hilzenrat, Nir; Szilagyi, Andrew

2016-01-01

Hepatocellular carcinoma rarely occurs in patients without underlying cirrhosis or liver disease. While inflammatory bowel disease has been linked to certain forms of liver disease, hepatocellular carcinoma is exceedingly rare in these patients. We report the twelfth case of hepatocellular carcinoma in a patient with Crohn's disease. The patient is a 61-year-old with longstanding Crohn's disease who was treated with azathioprine and was found to have elevated liver enzymes and a new 3-cm liver mass on ultrasound. A complete workup for underlying liver disease was unremarkable and liver biopsy revealed hepatocellular carcinoma. The patient underwent a hepatic resection, and there is no evidence of recurrence at the 11-month follow-up. The resection specimen showed no evidence of cancer despite the initial biopsy revealing hepatocellular carcinoma. This case represents the third biopsy-proven complete spontaneous regression of hepatocellular carcinoma. Although large studies have failed to show a definite link between azathioprine and hepatocellular carcinoma, the relationship remains concerning given the multiple case reports suggesting a possible association. Clinicians should exercise a high degree of suspicion in patients with Crohn's disease who present with elevated liver enzymes, especially those on azathioprine therapy. PMID:27403102

Hepatitis C Virus and Hepatocellular Carcinoma

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Masao Omata

2013-01-01

Full Text Available Hepatitis C virus (HCV, a hepatotropic virus, is a single stranded-positive RNA virus of ~9,600 nt. length belonging to the Flaviviridae family. HCV infection causes acute hepatitis, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC. It has been reported that HCV-coding proteins interact with host-cell factors that are involved in cell cycle regulation, transcriptional regulation, cell proliferation and apoptosis. Severe inflammation and advanced liver fibrosis in the liver background are also associated with the incidence of HCV-related HCC. In this review, we discuss the mechanism of hepatocarcinogenesis in HCV-related liver diseases.

Resected Hepatocellular Carcinoma in a Patient with Crohn’s Disease on Azathioprine

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Valérie Heron

2016-05-01

Full Text Available Hepatocellular carcinoma rarely occurs in patients without underlying cirrhosis or liver disease. While inflammatory bowel disease has been linked to certain forms of liver disease, hepatocellular carcinoma is exceedingly rare in these patients. We report the twelfth case of hepatocellular carcinoma in a patient with Crohn’s disease. The patient is a 61-year-old with longstanding Crohn’s disease who was treated with azathioprine and was found to have elevated liver enzymes and a new 3-cm liver mass on ultrasound. A complete workup for underlying liver disease was unremarkable and liver biopsy revealed hepatocellular carcinoma. The patient underwent a hepatic resection, and there is no evidence of recurrence at the 11-month follow-up. The resection specimen showed no evidence of cancer despite the initial biopsy revealing hepatocellular carcinoma. This case represents the third biopsy-proven complete spontaneous regression of hepatocellular carcinoma. Although large studies have failed to show a definite link between azathioprine and hepatocellular carcinoma, the relationship remains concerning given the multiple case reports suggesting a possible association. Clinicians should exercise a high degree of suspicion in patients with Crohn’s disease who present with elevated liver enzymes, especially those on azathioprine therapy.

Non-selective beta-blockers may reduce risk of hepatocellular carcinoma

DEFF Research Database (Denmark)

Thiele, Maja; Albillos, Agustín; Abazi, Rozeta

2015-01-01

BACKGROUND & AIMS: Non-selective beta-blockers (NSBB) are used in patients with cirrhosis and oesophageal varices. Experimental data suggest that NSBB inhibit angiogenesis and reduce bacterial translocation, which may prevent hepatocellular carcinoma (HCC). We therefore assessed the effect of NSBB...

Sonographic evolution of hepatocellular carcinoma associated with cirrhosis

International Nuclear Information System (INIS)

Mazzola, G.; Virdone, R.; Orlando, A.; Turri, A.; Caltagirone, M.; Fusco, G.; Parisi, P.; Cottone, M.

1989-01-01

To study the sonographic (US) evolution of hepatocellular carcinoma, 53 tumors in 45 untreated patients were observed regulary with real-time US for a period of 6 to 56 months. At the beginning, 25 tumors were hypoechoic, 18 isoechoic, 4 hyperechoic, and 6 had mixed hypo/hyper echopatterns. At the follow-up, 7 initially hypoechoic tumors had changed to hyperechoic or to mixed echopatterns; 8 hypoechoic tumors had becom isoechoic; 9 of the 25 initially hypoechoic neoplastic lesions had maintained the same echodensity. Ten of the 15 initially isoechoic tumors had changed to mixed echopatterns and 5 had remained unchanged. Three initially isoechoic lesions and a hypoechoic one had turned into diffuse patterns; 2 initially hyperechoic neoplastic lesions had remained unchanged; 1 had switched into hypoechoic, and 1 changed to mixed echopattern; 4 out of 6 tumors with echopattern had remained unchanged, 1 had become hyperechoic and 1 hypoechoic. The current study has proven variou tumors ≤3 cm in diameter to be isoechoic and most tumors >3 in diameter to have mixed hypo/hyper echopatterns. The echogenicity of small hepatocellular carcinomas increases with the tumor growth and remains unchanged when they do not increase in size

Constitutional and functional genetics of human alcohol-related hepatocellular carcinoma.

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Nahon, Pierre; Nault, Jean-Charles

2017-11-01

Exploration of the constitutional genetics of hepatocellular carcinoma (HCC) has identified numerous variants associated with a higher risk of liver cancer in alcoholic cirrhotic patients. Although Genome-Wide Association studies have not been carried out in the field of alcohol-related HCC, common single nucleotide polymorphisms conferring a small increase in the risk of liver cancer risk have been identified and shown to modulate ethanol metabolism, inflammation, oxidative stress, iron or lipid metabolism. Specific patterns of gene mutations including CTNNB1, TERT, ARID1A and SMARCA2 exist in alcohol-related HCC. Moreover, a specific mutational process observed at the nucleotide level by next generation sequencing has revealed cooperation between alcohol and tobacco in the development of HCC. Combining this genetic information with epidemiological and clinical data that might define specific HCC risk classes and refine surveillance strategies needs to be assessed in large prospective cohorts of patients with alcoholic cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hepatocellular carcinoma: a review

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Balogh J

2016-10-01

Full Text Available Julius Balogh,1,2 David Victor III,1,3,4 Emad H Asham,1,2 Sherilyn Gordon Burroughs,1,2 Maha Boktour,1,2 Ashish Saharia,1,2 Xian Li,1,2 R Mark Ghobrial,1,2 Howard P Monsour Jr,1,3,4 1Sherrie and Alan Conover Center for Liver Disease and Transplantation, 2Division of Transplantation, Department of Surgery, 3Department of Gastroenterology and Transplant Hepatology, 4Department of Medicine, Houston Methodist Hospital, Houston, TX, USA Abstract: Hepatocellular carcinoma (HCC is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as α-fetoprotein at 6-month intervals. Multiple treatment modalities exist; however, only orthotopic liver transplantation (OLT or surgical resection is curative. OLT is available for patients who meet or are downstaged into the Milan or University of San Francisco criteria. Additional treatment modalities include transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. Selection of a treatment modality is based on tumor size, location, extrahepatic spread, and underlying liver function. HCC is an

Evaluating hepatocellular carcinoma cell lines for tumour samples using within-sample relative expression orderings of genes.

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Ao, Lu; Guo, You; Song, Xuekun; Guan, Qingzhou; Zheng, Weicheng; Zhang, Jiahui; Huang, Haiyan; Zou, Yi; Guo, Zheng; Wang, Xianlong

2017-11-01

Concerns are raised about the representativeness of cell lines for tumours due to the culture environment and misidentification. Liver is a major metastatic destination of many cancers, which might further confuse the origin of hepatocellular carcinoma cell lines. Therefore, it is of crucial importance to understand how well they can represent hepatocellular carcinoma. The HCC-specific gene pairs with highly stable relative expression orderings in more than 99% of hepatocellular carcinoma but with reversed relative expression orderings in at least 99% of one of the six types of cancer, colorectal carcinoma, breast carcinoma, non-small-cell lung cancer, gastric carcinoma, pancreatic carcinoma and ovarian carcinoma, were identified. With the simple majority rule, the HCC-specific relative expression orderings from comparisons with colorectal carcinoma and breast carcinoma could exactly discriminate primary hepatocellular carcinoma samples from both primary colorectal carcinoma and breast carcinoma samples. Especially, they correctly classified more than 90% of liver metastatic samples from colorectal carcinoma and breast carcinoma to their original tumours. Finally, using these HCC-specific relative expression orderings from comparisons with six cancer types, we identified eight of 24 hepatocellular carcinoma cell lines in the Cancer Cell Line Encyclopedia (Huh-7, Huh-1, HepG2, Hep3B, JHH-5, JHH-7, C3A and Alexander cells) that are highly representative of hepatocellular carcinoma. Evaluated with a REOs-based prognostic signature for hepatocellular carcinoma, all these eight cell lines showed the same metastatic properties of the high-risk metastatic hepatocellular carcinoma tissues. Caution should be taken for using hepatocellular carcinoma cell lines. Our results should be helpful to select proper hepatocellular carcinoma cell lines for biological experiments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Significance of detecting circulating hepatocellular carcinoma cells in peripheral blood of hepatocellular carcinoma patients by nested reverse transcription-polymerase chain reaction and its clinical value: a retrospective study.

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Liu, Yang; Wang, Yue-ru; Wang, Long; Song, Rui-mei; Zhou, Bo; Song, Zhen-shun

2014-01-01

Circulating hepatocellular carcinoma cells may be detected by reverse transcription-polymerase chain reaction. We investigated the relationship between circulating hepatocellular carcinoma cells and hepatoma patient survival after different managements and survival periods. Peripheral vein blood (5 ml) samples were obtained from 113 patients with hepatocellular carcinoma and from 33 control subjects (9 with liver cirrhosis after hepatitis B, 14 with chronic hepatitis B, 10 healthy individuals) between January 1, 2009, and December 31, 2013. To detect circulating hepatocellular carcinoma cells in peripheral blood, alpha-fetoprotein messenger RNA was amplified from total RNA extracted from whole blood by reverse transcription-polymerase chain reaction. Alpha-fetoprotein messenger RNA was detected in 59 blood samples from the hepatocellular carcinoma patients (59/113, 52.2%). In contrast, there were no clinical control subjects whose samples showed detectable alpha-fetoprotein messenger RNA. The presence of alpha-fetoprotein messenger RNA in blood seemed to be correlated with the stage (by TNM classification) of hepatocellular carcinoma, serum alpha-fetoprotein value, and the presence of intrahepatic metastasis, portal vein thrombosis, tumor diameter and/or distant metastasis. In addition, alpha-fetoprotein messenger RNA was detected in the blood of 25 patients showing distant metastasis at extrahepatic organs (100%), in contrast to 32 of 88 cases without metastasis (36.4%). All the patients with hepatocellular carcinoma were followed. Seventeen patients with resection of a T 2 stage hepatocellular carcinoma had a survival of 3.2 years after surgical management, 38 cases with resection of a T3 stage hepatocellular carcinoma had a 1.3-year survival, and only 37 cases with T4 stage disease after different treatments except surgery survived for 0.6 years (P <0.01). The presence of alpha-fetoprotein messenger RNA in peripheral blood may be an indicator of circulating

Current management of hepatocellular carcinoma

Science.gov (United States)

Tabrizian, Parissa; Roayaie, Sasan; Schwartz, Myron E

2014-01-01

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and leading cause of death among patients with cirrhosis. Treatment guidelines are based according to the Barcelona Clinic Liver Cancer staging system. The choice among therapeutic options that include liver resection, liver transplantation, locoregional, and systemic treatments must be individualized for each patient. The aim of this paper is to review the outcomes that can be achieved in the treatment of HCC with the heterogeneous therapeutic options currently available in clinical practice. PMID:25132740

Genetic variations of NTCP are associated with susceptibility to HBV infection and related hepatocellular carcinoma.

Science.gov (United States)

Wang, Peng; Mo, Ruidong; Lai, Rongtao; Xu, Yumin; Lu, Jie; Zhao, Gangde; Liu, Yuhan; Cao, Zhujun; Wang, Xiaolin; Li, Ziqiang; Lin, Lanyi; Zhou, Huijuan; Cai, Wei; Wang, Hui; Bao, Shisan; Xiang, Xiaogang; Xie, Qing

2017-12-01

Sodium taurocholate cotransporting polypeptide (NTCP), encoded by gene SLC10A1, is a receptor for hepatitis B virus (HBV). The aim of the current study was to investigate the role of NTCP polymorphisms in HBV susceptibility, cirrhosis and hepatocarcinogenesis. A total 1221 cases [including 866 chronic hepatitis B (CHB), 238 liver cirrhosis (LC), 117 hepatocellular carcinoma (HCC) patients] and 1232 healthy controls (HCs) were recruited, and 6 single nucleotide polymorphisms (SNPs) were genotyped. Meta-analysis was executed among 14591 CHBs and 12396 HCs to determine the association between NTCP polymorphisms and HBV infection, cirrhosis or hepatocarcinogenesis. The frequency of rs2296651-GA was inversely correlated with CHB, LC or HCC patients [adjusted OR(95%CI)=0.16(0.11-0.23), p HBV infection [OR(95%CI)=0.532(0.287-0.986), p =0.028, codominant] or HBV-related HCC [OR(95%CI)=0.701(0.564-0.872), p =0.001, recessive]. Furthermore, the frequency of rs943277-GA was positively correlated with HBV infection [adjusted OR(95%CI)=2.42(1.05-5.54), p =0.032, codominant]. Our data suggest that NTCP mutants contribute to the susceptibility of HBV infection or HBV-related HCC.

Intraoperative ultrasound for prediction of hepatocellular carcinoma biological behaviour: Prospective comparison with pathology.

Science.gov (United States)

Santambrogio, Roberto; Cigala, Claudia; Barabino, Matteo; Maggioni, Marco; Scifo, Giovanna; Bruno, Savino; Bertolini, Emanuela; Opocher, Enrico; Bulfamante, Gaetano

2018-02-01

Preoperative prediction of both microinvasive hepatocellular carcinoma and histological grade of hepatocellular carcinoma is pivotal to treatment planning and prognostication. The aim of this study was to evaluate whether some intraoperative ultrasound features correlate with both the presence of same histological patterns and differentiation grade of hepatocellular carcinoma on the histological features of the primary resected tumour. All patients with single, small hepatocellular carcinoma that underwent hepatic resection were included in this prospective double-blind study: the intraoperative ultrasound patterns of nodule were registered and compared with similar histological features. A total of 179 patients were enclosed in this study: 97 (54%) patients (34% in HCC ≤2 cm) had a microinvasive hepatocellular carcinoma at ultrasound examination, while 82 (46%) patients (41% in HCC ≤2 cm) at histological evaluation. Statistical analysis showed that diameters ≤2 cm, presence of satellites and microinvasive hepatocellular carcinoma at ultrasound examination were the variables with the strongest association with the histological findings. In the multivariate analysis, the vascular microinfiltration and infiltrative hepatocellular carcinoma aspect were independent predictors for grading. In patients with cirrhosis and hepatocellular carcinoma, the prevalence of microinvasive hepatocellular carcinoma is high, even in cases of HCC ≤2 cm. Intraoperative ultrasound findings strongly correlated with histopathological criteria in detecting microinvasive patterns and are useful to predict neoplastic differentiation. The knowledge of these features prior to treatment are highly desired (this can be obtained by an intraoperative ultrasound examination), as they could help in providing optimal management of patients with hepatocellular carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Expression of Embryonic Liver Development Genes in Hepatitis C Induced Cirrhosis and Hepatocellular Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Behnke, Martha, E-mail: mbehnke@mcvh-vcu.edu [Transplant Program Administration, Virginia Commonwealth University Health System, 1200 E. Broad St., Richmond, VA 23298 (United States); Reimers, Mark [Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, 800 E Leigh St., Richmond, VA 23298 (United States); Fisher, Robert [Department of Surgery, Virginia Commonwealth University, 1200 E. Broad St., Richmond, VA 23298 (United States)

2012-09-18

Hepatocellular carcinoma (HCC) remains a difficult disease to study even after a decade of genomic analysis. Patient and disease heterogeneity, differences in statistical methods and multiple testing issues have resulted in a fragmented understanding of the molecular basis of tumor biology. Some researchers have suggested that HCC appears to share pathways with embryonic development. Therefore we generated targeted hypotheses regarding changes in developmental genes specific to the liver in HCV-cirrhosis and HCV-HCC. We obtained microarray studies from 30 patients with HCV-cirrhosis and 49 patients with HCV-HCC and compared to 12 normal livers. Genes specific to non-liver development have known associations with other cancer types but none were expressed in either adult liver or tumor tissue, while 98 of 179 (55%) genes specific to liver development had differential expression between normal and cirrhotic or HCC samples. We found genes from each developmental stage dysregulated in tumors compared to normal and cirrhotic samples. Although there was no single tumor marker, we identified a set of genes (Bone Morphogenetic Protein inhibitors GPC3, GREM1, FSTL3, and FST) in which at least one gene was over-expressed in 100% of the tumor samples. Only five genes were differentially expressed exclusively in late-stage tumors, indicating that while developmental genes appear to play a profound role in cirrhosis and malignant transformation, they play a limited role in late-stage HCC.

Usefulness of screening ultrasonography for hepatocellular carcinoma detection: chronic hepatitis versus hepatic cirrhosis caused by hepatitis B virus

International Nuclear Information System (INIS)

Chang, Sam Uel; Choi, Don Gil; Lim, Jae Hoon

2004-01-01

To evaluate the usefulness of screening liver ultrasonography (US) for hepatocellular carcinoma (HCC) detection in patients with chronic hepatitis or hepatic cirrhosis caused by hepatitis B virus (HBV). A retrospective study was performed with 1,189 patients with clinical hepatopathy caused by HBV who underwent screening liver US for HCC detection at least twice. All patients were followed up with liver US examinations (mean, 8.3 times), CT, or MR for at least 3 months (range, 3-102 months; mean, 47 months) for the detection of HCC. The study population was divided into two groups: chronic hepatitis (n=492) and hepatic cirrhosis (n=697), which was further divided into two groups with (n=156) or without (n=541) evident shrinkage. The radiologic examinations that had detected HCC for the first time were analyzed and compared between the groups. Among 20 (4.1%) patients with chronic hepatitis and 132 (18.9%) patients with hepatic cirrhosis diagnosed as HCC, screening US was the modality of detection in 17 (85.0%) of 20 patients with chronic hepatitis and 76 (57.6%) of 132 patients with hepatic cirrhosis (p=0.038, Chi-square test). The detection rate of HCC on screening US between the chronic hepatitis and hepatic cirrhosis with evident shrinkage (51.4%, 19/37) showed a significant difference (p=0.027, Chi-square test). For chronic liver disease caused by HBV, screening US for HCC detection is more useful in patients with chronic hepatitis than with hepatic cirrhosis with evident shrinkage

Chronic hepatitis C presenting with a diagnosis of hepatocellular carcinoma

DEFF Research Database (Denmark)

Hallager, Sofie; Weis, Nina

2014-01-01

Chronic hepatitis C (CHC) affects around 16,000 individuals in Denmark of whom about 50% are diagnosed. In the presence of CHC and cirrhosis the annual risk of hepatocellular carcinoma (HCC) is 1-5%. We report on two patients who presented with disseminated HCC at the time of CHC diagnosis...

Clinical evaluation of scintigraphies with sup(99m)Tc-phytate and /sup 67/Ga-citrate as a screening test for hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Ayabe, Y; Oshiumi, Y; Kamoi, I; Ichiya, Y [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine; Murakami, J

1981-02-01

sup(99m)Tc-phytate and /sup 67/Ga-citrate scintigraphies were evaluated clinically in 50 cases of histologically proven hepatocellular carcinoma. Detectability was higher in sup(99m)Tc-phytate scans than in /sup 67/Ga scans, and was influenced by the presence of liver cirrhosis. However, by using both scans, the highest detectability was obtained. /sup 67/Ga scan was useful especially in cases with equivocal sup(99m)Tc-phytate scintigraphy and cases with liver cirrhosis. There was no definite correlation seen between Edmondson's histological gradings and grades of /sup 67/Ga accumulation. No significant difference of /sup 67/Ga accumulation in hepatocellular carcinoma was observed regardless of the presence of liver cirrhosis. We conclude that it is better to use sup(99m)Tc-phytate as the first choice in screening of hepatocellular carcinoma and subsequent /sup 67/Ga scan if indicated.

Fibrolamellar Hepatocellular Carcinoma Presenting as Obstructive Jaundice: Uncommon Presentation of a Rare Entity

International Nuclear Information System (INIS)

Arora, Richa

2015-01-01

Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver tumor, significantly different from generic hepatocellular carcinoma with distinct demographics, risk factors, imaging features, histopathology and prognosis. Unlike conventional hepatocellular carcinoma, it presents in young individuals with no preexisting hepatitis or cirrhosis and does not cause elevation of serum alpha feto proteins in most cases. This paper presents a case report of this rare tumor in a young female with an unusual clinical manifestation of obstructive jaundice (which has not been reported so far) along with a review of its imaging and pathological features, with treatment options. Fibrolamellar HCC is a rare variant of classic HCC with different epidemiology, risk factors, clinical manifestations, radiological, pathological and prognostic features. Therefore, it is important to be familiar with the entity for its early diagnosis and management

Hepatitis C impairs survival following liver transplantation irrespective of concomitant hepatocellular carcinoma

DEFF Research Database (Denmark)

Melum, Espen; Friman, Styrbjörn; Bjøro, Kristian

2007-01-01

BACKGROUND/AIMS: Liver transplantation (LTX) is the only curative treatment for end-stage liver disease caused by hepatitis C (HCV). Hepatocellular carcinoma (HCC) is common in patients with HCV cirrhosis. METHODS: Two hundred and eighty-two HCV patients listed for LTX in the Nordic countries...

Specific diagnosis of hepatocellular carcinoma by delayed hepatobiliary imaging

International Nuclear Information System (INIS)

Hasegawa, Y.; Nakano, S.; Ibuka, K.

1986-01-01

For assessment of the value of delayed hepatobiliary imaging with technetium 99m (/sup 99m/Tc)-(Sn)-N-pyridoxyl-5-methyltryptophan (/sup 99m/Tc-PMT) for specific diagnosis of hepatocellular carcinoma, 88 patients with various malignant and benign liver diseases (49 with hepatocellular carcinoma, 4 with cholangiocellular carcinoma, 10 with metastatic liver carcinoma, 2 with liver cysts, 2 with liver hemangioma, 1 with liver abscess, 2 with intrahepatic lithiasis, 12 with liver cirrhosis, and 6 with chronic hepatitis) were studied. In 20 (41%) of the 49 patients with hepatocellular carcinoma, greater uptake of /sup 99m/Tc-PMT by the tumor than by the surrounding liver tissue was seen in delayed hepatobiliary images, whereas in eight patients (16%), equilibrated uptake was seen. No increased uptake of the radioisotope by hepatic lesions was seen in 21 patients with localized liver diseases other than hepatoma. Moreover, in 18 patients with diffuse liver diseases, no focal accumulation of the radioisotope was seen in delayed /sup 99m/Tc-PMT images. In addition, of 28 patients with hepatocellular carcinoma in whom the serum alpha-fetoprotein level showed little or no increase, 12 showed increased uptake of /sup 99m/Tc-PMT by the tumor. In assessing delayed /sup 99m/Tc-PMT images, however, it was necessary to consider following complications: accumulation of tracer in obstructed and dilated biliary trees; retention of radioactivity in nonneoplastic liver tissues; difficulties in evaluating /sup 99m/Tc-PMT uptake by small hepatic tumors; overlapping of radioactivity in the gut and gallbladder in delayed /sup 99m/Tc-PMT images of tumors. This study indicates that delayed /sup 99m/Tc-PMT images can be useful in the diagnosis of hepatocellular carcinoma

Findings in multidetector computed tomography in the diagnosis of hepatocellular carcinoma in patients with cirrhosis and correlation with pathology of liver explants

International Nuclear Information System (INIS)

Haberman, D.; Castignola, M.; Mela, M.; Paladini, H.; Santilli, J.P.; Gruz, F.; Gondolesi, G.

2013-01-01

Objectives: To describe the imagenological behavior of hepatocellular carcinoma in cirrhotic patients using a dynamic multidetector computed tomography (MDCT) technique, and correlate these findings with histological tumor grades. Materials and methods: A retrospective, descriptive observational study was conducted to evaluate 51 nodules in 32 liver transplant patients diagnosed with liver cirrhosis. The pathology of liver explants was used as a reference. Nodules with hepatocellular carcinoma histopathology were retrospectively analyzed by computed tomography scans performed pre-transplant. Using a dynamic multidetector computed tomography technique, we evaluated the most common imagenological behavior reported in the literature: arterial enhancement, washout, capsule, and intratumoral arterial vessels. Results: Forty-six of 51 (90%) tumors showed arterial enhancement. Of the 46 tumors with arterial enhancement, 39 (85%) had washout in portal-late phase. Five of 51 (10%) were hypovascular. Twenty-two of 51 (43%) had capsule and 12 of 51 (24%) showed intratumoral arterial vessels. The more frequent image combination was the combination of arterial enhancement and washout (39 of 51 tumors or 76%). The most frequent histological grade was II (35 of 51 tumors or 69%). Statistically significant relationships were found between histological grade tumors and imagenological behavior: arterial enhancement and hypovascular. Conclusion: In our population, arterial enhancement with washout in portal-late phases was observed in most of the tumors. Our results are consistent with previously reported studies, demonstrating the high reliability of this imaging pattern for the diagnosis of hepatocellular carcinoma. (authors) [es

Percutaneous laser ablation of hepatocellular carcinoma in patients with liver cirrhosis awaiting liver transplantation

International Nuclear Information System (INIS)

Pompili, Maurizio; Pacella, Claudio Maurizio; Francica, Giampiero; Angelico, Mario; Tisone, Giuseppe; Craboledda, Paolo; Nicolardi, Erica; Rapaccini, Gian Ludovico; Gasbarrini, Giovanni

2010-01-01

Objective: The aim of this study was to determine the effectiveness and safety of percutaneous laser ablation for the treatment of cirrhotic patients with hepatocellular carcinoma awaiting liver transplantation. Materials and methods: The data of 9 male cirrhotic patients (mean age 50 years, range 45-60 years) with 12 biopsy proven nodules of hepatocellular carcinoma (mean diameter 2.0 cm, range 1.0-3.0 cm) treated by laser ablation before liver transplantation between June 2000 and January 2006 were retrospectively reviewed. Laser ablation was carried out by inserting 300 nm optical fibers through 21-Gauge needles (from two to four) positioned under ultrasound guidance into the target lesions. A continuous wave Neodymium:Yttrium Aluminium Garnet laser was used. Transarterial chemoembolization prior to liver transplantation was performed in two incompletely ablated tumors. Results: No procedure-related major complications were recorded. During the waiting time to liver transplantation local tumor progression after ablation occurred in 3 nodules (25%). At histological examination of the explanted livers complete necrosis was found in 8 nodules (66.7%, all treated exclusively with laser ablation), partial necrosis >50% in 3 nodules (25%), and partial necrosis <50% in 1 nodule. Conclusion: In patients with cirrhotic livers awaiting liver transplantation, percutaneous laser ablation is safe and effective for the management of small hepatocellular carcinoma.

Hepatocellular Carcinoma after Sustained Viral Response to Interferon and Ribavirin Therapy in Cirrhosis Secondary to Chronic Hepatitis C

International Nuclear Information System (INIS)

Khokhar, N.; Qureshi, M.U.; Niazi, T.K.

2013-01-01

Objective: To determine the frequency of development of hepatocellular carcinoma in patients with chronic liver disease secondary to hepatitis C who had achieved sustained virological response with Interferon and Ribavirin therapy. Study Design: Retrospective descriptive study. Place and Duration of Study: Shifa International Hospital, Islamabad, Pakistan, from January 2007 to January 2012. Methodology: Hepatitis C related chronic liver disease patients who were treated with interferon and ribavirin, after they achieved sustained virological response, they were followed for a mean of 42 A+- 17 months. During this time, development of hepatocellular carcinoma was ascertained. All underwent surveillance with alpha-feto-protein and ultrasonography every 6 months. Results: Out of the 58 patients who had achieved sustained virological response, 3 developed hepatocellular carcinoma after a mean follow-up of 38 A+- 14 months. It was multifocal in 2 cases and was single lesion in the 3rd. Two patients ultimately died, one with upper GI bleeding and the other with hepatic encephalopathy, while 3rd patient with single lesion is still surviving. Conclusion: Three out of 58 patients of hepatitis C related chronic liver disease developed hepatocellular carcinoma during follow-up in patients who had achieved sustained virological response. These patients need closer follow-up, for development of complications, even if they have achieved sustained viral response. (author)

Incidence, Mortality, and Predictive Factors of Hepatocellular Carcinoma in Primary Biliary Cirrhosis

Directory of Open Access Journals (Sweden)

Kenichi Hosonuma

2013-01-01

Full Text Available Background. The study aims to analyze in detail the incidence, mortality using the standardized incidence ratio (SIR, and standardized mortality ratio (SMR of hepatocellular carcinoma (HCC in primary biliary cirrhosis (PBC, because no large case studies have focused on the detailed statistical analysis of them in Asia. Methods. The study cohorts were consecutively diagnosed at Gunma University and its affiliated hospitals. Age- or sex-specific annual cancer incidence and deaths were obtained from Japanese Cancer Registry and Death Registry as a reference for the comparison of SIR or SMR of HCC. Moreover, univariate analyses and multivariate analyses were performed to clarify predictive factors for the incidence of HCC. Results. The overall 179 patients were followed up for a median of 97 months. HCC had developed in 13 cases. SIR for HCC was 11.6 (95% confidence interval (CI, 6.2–19.8 and SMR for HCC was 11.2 (95% CI, 5.4–20.6 in overall patients. The serum albumin levels were a predictive factor for the incidence of HCC in overall patients. Conclusions. The incidence and mortality of HCC in PBC patients were significantly higher than those in Japanese general population. PBC patients with low serum albumin levels were populations at high risk for HCC.

Radiological imagings of small hepatocellular carcinomas

Energy Technology Data Exchange (ETDEWEB)

Miyake, Hidetoshi; Hayashi, Kuniaki; Futagawa, Sakae; Matsunaga, Naofumi; Maeda, Tohru [Nagasaki Univ. (Japan). School of Medicine

1984-08-01

Forty three cases of small hepatocellular carcinoma (measuring less than 3 cm in diameter on imaging modalities) were detected during a period of four years and two months. There were two cases in which hepatoma measured 1 cm in diameter, twenty four cases between 1 and 2 cm, and seventeen cases between 2 and 3 cm. The relative role of each modality and AFP value in the detection of these tumors was evaluated. The detection rate of small hepatocellular carcinoma by liver scintigraphy, ultrasonography (US), computed tomography (CT) and angiography was 8%, 74%, 70% and 95%, respectively. The sensitivity of serum AFP value was 67% (either measuring more than 200ng/ml or showing a tendency of steady rising even if below the level of 200ng/ml). Most hepatomas less than 2 cm in size were hypoechoic on US, and those above 2 cm in size were hyperechoic with peripheral sonolucency (halo). Almost all cases were described as low density area on both plain and enhancement CT. Angiography was the best method for detecting small hepatomas. It may be recommended to perform angiography on every patient with liver cirrhosis at the time of diagnosis of this disease. Periodic examinations by AFP, US and CT should be done if the angiography was negative. Evaluation by US in every three months and by CT in every twelve months may be appropriate.

Clinical utility of imaging for evaluation of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Murakami T

2014-07-01

Full Text Available Takamichi Murakami,1 Masakatsu Tsurusaki,1 Tomoko Hyodo,1 Yasuharu Imai2 1Department of Radiology, Kinki University Faculty of Medicine, 2Department of Hepatology and Gastroenterology, Ikeda Municipal Hospital, Osaka, Japan Abstract: The hemodynamics of a hepatocellular nodule is the most important imaging parameter used to characterize various hepatocellular nodules in liver cirrhosis, because sequential changes occur in the feeding vessels and hemodynamic status during hepatocarcinogenesis. Therefore, the imaging criteria for hepatocellular carcinoma (HCC are also usually based on vascular findings, eg, early arterial uptake followed by washout in the portal venous and equilibrium phases. Contrast-enhanced ultrasonography, dynamic multidetector-row computed tomography (MDCT, and dynamic magnetic resonance (MR imaging with gadopentetate dimeglumine (Gd-DTPA are useful for detecting hypervascular HCC on the basis of vascular criteria but are not as useful for hypovascular HCC. Contrast-enhanced MR imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA, a hepatocyte-specific MR contrast agent, is superior to dynamic MDCT and dynamic MR imaging with Gd-DTPA in detecting both hypervascular and hypovascular HCC. Moreover, Gd-EOB-DTPA-enhanced MR imaging can display each histologically differentiated HCC as hypointense relative to the liver parenchyma. 18F-fluorodeoxyglucose positron emission tomography imaging might not be suitable for the screening and detection of HCC, given its lower diagnostic performance. However, this technique plays an important role in determining whether HCC has spread beyond the liver. Keywords: hepatocellular carcinoma, evaluation, imaging, clinical utility

Liver transplantation for unresectable hepatocellular carcinoma in patients without liver cirrhosis

NARCIS (Netherlands)

Mergental, Hynek; Porte, Robert J.

P>Hepatocellular carcinoma (HCC) arising in noncirrhotic and nonfibrotic liver (NC-HCC) is a rare type of malignancy frequently found in healthy young individuals. Partial liver resection is the treatment of choice with expected 5-year survival rates between 40% and 70%. As a result of absence of

Dose response relationship in local radiotherapy for hepatocellular carcinoma

International Nuclear Information System (INIS)

Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok

2001-01-01

In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was 48.2±7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at 4-8 weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. An objective response was observed in 106 of 158 patients, giving a response rate of 67. 1%. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only 29.2% showed objective response in patients treated with dose less than 40 Gy, while 68.6% and 77.1 % showed major response in patients with 40-50 Gy and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver

Utilization of metabolomics to identify serum biomarkers for hepatocellular carcinoma in patients with liver cirrhosis

International Nuclear Information System (INIS)

Ressom, Habtom W.; Xiao, Jun Feng; Tuli, Leepika; Varghese, Rency S.; Zhou Bin; Tsai, Tsung-Heng; Nezami Ranjbar, Mohammad R.; Zhao Yi; Wang Jinlian; Di Poto, Cristina; Cheema, Amrita K.; Tadesse, Mahlet G.; Goldman, Radoslav; Shetty, Kirti

2012-01-01

Highlights: ► We analyzed sera from HCC and cirrhotic patients by LC–MS in three experiments. ► Metabolites with significant and consistent changes in HCC vs. cirrhosis were selected. ► Verification of the identities of selected metabolites was performed by MS/MS. ► Quantitation of candidate metabolites was conducted using isotope dilution by SRM. - Abstract: Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC) in patients with liver cirrhosis is believed to contribute towards early detection, treatment, and understanding of the molecular mechanisms of HCC. In this study, we compare metabolite levels in sera of 78 HCC cases with 184 cirrhotic controls by using ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC–QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from patients with cirrhosis are selected by parametric and non-parametric statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. Verification of the identities of selected metabolites is conducted by comparing their MS/MS fragmentation patterns and retention time with those from authentic compounds. Quantitation of these metabolites is performed in a subset of the serum samples (10 HCC and 10 cirrhosis) using isotope dilution by selected reaction monitoring (SRM) on triple quadrupole linear ion trap (QqQLIT) and triple quadrupole (QqQ) mass spectrometers. The results of this analysis confirm that metabolites involved in sphingolipid metabolism and phospholipid catabolism such as sphingosine-1-phosphate (S-1-P) and lysophosphatidylcholine (lysoPC 17:0) are up-regulated in sera of HCC vs. those with liver cirrhosis. Down-regulated metabolites include those involved in bile acid biosynthesis (specifically cholesterol metabolism) such as glycochenodeoxycholic acid 3-sulfate (3-sulfo-GCDCA), glycocholic acid

Utilization of metabolomics to identify serum biomarkers for hepatocellular carcinoma in patients with liver cirrhosis

Energy Technology Data Exchange (ETDEWEB)

Ressom, Habtom W., E-mail: hwr@georgetown.edu [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Xiao, Jun Feng; Tuli, Leepika; Varghese, Rency S.; Zhou Bin; Tsai, Tsung-Heng; Nezami Ranjbar, Mohammad R.; Zhao Yi; Wang Jinlian; Di Poto, Cristina; Cheema, Amrita K. [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Tadesse, Mahlet G. [Department of Mathematics and Statistics, Georgetown University, Washington, DC 20057 (United States); Goldman, Radoslav [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Shetty, Kirti [Department of Surgery, Georgetown University Medical Center, Washington, DC 20057 (United States); Georgetown University Hospital, Washington, DC 20057 (United States)

2012-09-19

Highlights: Black-Right-Pointing-Pointer We analyzed sera from HCC and cirrhotic patients by LC-MS in three experiments. Black-Right-Pointing-Pointer Metabolites with significant and consistent changes in HCC vs. cirrhosis were selected. Black-Right-Pointing-Pointer Verification of the identities of selected metabolites was performed by MS/MS. Black-Right-Pointing-Pointer Quantitation of candidate metabolites was conducted using isotope dilution by SRM. - Abstract: Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC) in patients with liver cirrhosis is believed to contribute towards early detection, treatment, and understanding of the molecular mechanisms of HCC. In this study, we compare metabolite levels in sera of 78 HCC cases with 184 cirrhotic controls by using ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from patients with cirrhosis are selected by parametric and non-parametric statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. Verification of the identities of selected metabolites is conducted by comparing their MS/MS fragmentation patterns and retention time with those from authentic compounds. Quantitation of these metabolites is performed in a subset of the serum samples (10 HCC and 10 cirrhosis) using isotope dilution by selected reaction monitoring (SRM) on triple quadrupole linear ion trap (QqQLIT) and triple quadrupole (QqQ) mass spectrometers. The results of this analysis confirm that metabolites involved in sphingolipid metabolism and phospholipid catabolism such as sphingosine-1-phosphate (S-1-P) and lysophosphatidylcholine (lysoPC 17:0) are up-regulated in sera of HCC vs. those with liver cirrhosis. Down-regulated metabolites include those involved in bile acid biosynthesis (specifically

Hepatocellular carcinoma: illustrated guide to systematic radiologic diagnosis and staging according to guidelines of the American Association for the Study of Liver Diseases.

LENUS (Irish Health Repository)

McEvoy, Sinead H

2013-10-01

Hepatocellular carcinoma is a malignancy that predominantly occurs in the setting of cirrhosis. Its incidence is rising worldwide. Hepatocellular carcinoma differs from most malignancies because it is commonly diagnosed on the basis of imaging features alone, without histologic confirmation. The guidelines from the American Association for the Study of Liver Diseases (AASLD) are a leading statement for the diagnosis and staging of hepatocellular carcinoma, and they have recently been updated, incorporating several important changes. AASLD advocates the use of the Barcelona Clinic Liver Cancer (BCLC) staging system, which combines validated imaging and clinical predictors of survival to determine stage and which links staging with treatment options. Each stage of the BCLC system is outlined clearly, with emphasis on case examples. Focal liver lesions identified at ultrasonographic surveillance in patients with cirrhosis require further investigation. Lesions larger than 1 cm should be assessed with multiphasic computed tomography or magnetic resonance imaging. Use of proper equipment and protocols is essential. Lesions larger than 1 cm can be diagnosed as hepatocellular carcinoma from a single study if the characteristic dynamic perfusion pattern of arterial hyperenhancement and venous or delayed phase washout is demonstrated. If the imaging characteristics of hepatocellular carcinoma are not met, the alternate modality should be performed. Biopsy should be used if neither modality is diagnostic of hepatocellular carcinoma. Once the diagnosis has been made, the cancer should be assigned a BCLC stage, which will help determine suitable treatment options. Radiologists require a systematic approach to diagnose and stage hepatocellular carcinoma with appropriate accuracy and precision.

Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Vainshtein, Jeffrey M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Kabarriti, Rafi; Mehta, Keyur J. [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Roy-Chowdhury, Jayanta [Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Department of Genetics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Guha, Chandan, E-mail: cguhamd@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

2014-07-15

Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local disease control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow–derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects, including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the

Medical treatment of hepatocellular carcinoma.

Science.gov (United States)

Granito, Alessandro; Bolondi, Luigi

2009-12-16

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm and the third leading cause of cancer-related deaths worldwide. Cirrhosis, most often due to viral hepatitis, is the predominant risk factors for HCC and geographical differences in both risk factors and incidence are largely due to epidemiological variations in hepatitis B and C infection. Hepatic function is a relevant parameter in selecting therapy in HCC. The current clinical classification of HCC split patients into 5 stages, with a specific treatment schedule for any stage. As patients with early stages can receive curative treatments, such as surgical resection, liver transplantation or local ablation, surveillance program in high-risk populations has become mandatory. Sorafenib, a multikinase inhibitor, has recently shown survival benefits in patients at advanced stage of disease. Hopefully, new molecular targeted therapies and their combination with sorafenib or interventional and surgical procedures, should expand the therapeutic armamentarium against HCC.

Severe Anemia with Hemoperitoneum as a First Presentation for Multinodular Hepatocellular Carcinoma: A Rare Event in Western Countries

Directory of Open Access Journals (Sweden)

Thein Swe

2016-01-01

Full Text Available Hemoperitoneum due to spontaneous rupture of hepatocellular carcinoma is a life-threatening and rare condition in western countries with an incidence of less than 3% because of early detection of cirrhosis and neoplasm. Here, we describe a case of a 66-year-old male patient with altered mental status with hemorrhagic shock. Computed tomography scan of abdomen revealed hemoperitoneum and mass in liver. Patient underwent resection of liver tumor and biopsy revealed multinodular hepatocellular carcinoma. A high degree of suspicion is required where severe anemia and hemoperitoneum can be a first presentation for hepatocellular carcinoma especially in patients with chronic hepatitis C infection. Early diagnosis is crucial since mortality rates remain high for untreated cases.

Radiosensitivity of hepatocellular carcinoma

International Nuclear Information System (INIS)

Hennequin, C.; Quero, L.; Rivera, S.

2011-01-01

The frequency of hepatocellular carcinoma (HCC) is increasing in the western world and the role of radiotherapy is more and more discussed. Classically, hepatocellular carcinoma was considered as a radioresistant tumour: in fact, modern radio-biologic studies, performed on cell lines directly established from patients, showed that hepatocellular carcinoma has the same radiosensitivity than the other epithelial tumours. From clinical studies, its α/β ratio has been estimated to be around 15 Gy. Radiosensitivity of normal hepatic parenchyma is now well evaluated and some accurate NTCP models are available to guide hepatic irradiation. The biology of hepatocellular carcinoma is also better described: the combination of radiotherapy and targeted therapies will be a promising approach in the near future. (authors)

Management of small hepatocellular carcinoma in cirrhosis: Focus on portal hypertension

Science.gov (United States)

Hernandez-Gea, Virginia; Turon, Fanny; Berzigotti, Annalisa; Villanueva, Augusto

2013-01-01

The incidence of hepatocellular carcinoma (HCC) is rising worldwide being currently the fifth most common cancer and third cause of cancer-related mortality. Early detection of HCC through surveillance programs have enabled the identification of small nodules with higher frequency, and nowadays account for 10%-15% of patients diagnosed in the West and almost 30% in Japan. Patients with small HCC can be candidates for potential curative treatments: liver transplantation, surgical resection and percutaneous ablation, depending on the presence of portal hypertension and co-morbidities. This review will analyze recent advancements in the clinical management of these individuals, focusing on issues related to the role of portal hypertension, the debate between resection and ablative therapies and the future impact of molecular technologies. PMID:23482437

Dynamic CT of hepatocellular carcinoma

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Fujita, Nobuyuki; Shirato, Hiroki; Shinohara, Masahiro; Miyasaka, Kazuo; Morita, Yutaka; Irie, Goro

1983-03-01

We performed dynamic CT in 30 cases of hepatocellular carcinoma, and concluded as below. Detecting the stain in the early phase of the dynamic series, it is possible to make a diagnosis of hepatocellular carcinoma. The dynamic CT is effective in a case of small hepatocellular carcinoma in which it is difficult to gain an accurate diagnosis in the routine CT study. The dynamic CT is also effective in the differential diagnosis of hepatic lesions, as other hepatic lesions such as hemangioma and metastatic liver cancer show different patterns compared with hepatocellular carcinoma.

Utilisation of hepatocellular carcinoma screening in Australians at risk of hepatitis B virus-related carcinoma and prescribed anti-viral therapy.

Science.gov (United States)

Sheppard-Law, Suzanne; Zablotska-Manos, Iryna; Kermeen, Melissa; Holdaway, Susan; Lee, Alice; George, Jacob; Zekry, Amany; Maher, Lisa

2018-07-01

To investigate hepatocellular carcinoma screening utilisation and factors associated with utilisation among patients prescribed hepatitis B virus anti-viral therapy and at risk of hepatocellular carcinoma. The incidence of hepatocellular carcinoma has increased in Australia over the past three decades with chronic hepatitis B virus infection a major contributor. hepatocellular carcinoma surveillance programs aim to detect cancers early enabling curative treatment options, longer survival and longer times to recurrence. Multi-site cross-sectional survey. An online study questionnaire was administered to eligible participants attending three Sydney tertiary hospitals. Data were grouped into six mutually exclusive hepatocellular carcinoma risk factor categories as per American Association for the Study of Liver Diseases guidelines. All analyses were undertaken in STATA. Logistic regression was used to assess the associations between covariates and screening utilisation. Multivariate models described were assessed using the Hosmer-Lemeshow goodness of fit. Of the 177 participants, 137 (77.4%) self-reported that US had been performed in the last six months. Awareness that screening should be performed and knowing the correct frequency of US screening were independently associated with screening utilisation. Participants who knew that screening should be undertaken were three times more likely to have had pretreatment education or were prescribed hepatitis B virus anti-viral treatment for >4 years. Participants reporting a family history of hepatocellular carcinoma were less likely to know that screening should be undertaken every 6 months. While utilisation of hepatocellular carcinoma surveillance programs was higher in this study than in previous reports, strategies to further improve surveillance remain necessary. Findings from this research form the basis for proposing strategies to improve utilisation of hepatocellular carcinoma screening, inform hepatitis B virus-related

Results of three-dimensional conformal radiotherapy and thalidomide for advanced hepatocellular carcinoma

International Nuclear Information System (INIS)

Hsu, Wei-Chung; Chung, Na-Na; Wang, Po-Ming; Ying, Kung-Shih; Shin, Jeng-Shiann; Chao, Che-Jen; Lin, Gau-De; Chan, Sue-Ching; Ting, Lai-Lei

2006-01-01

The purpose of this study was to evaluate the effectiveness of three-dimensional conformal radiotherapy and thalidomide in the treatment of advanced hepatocellular carcinoma. Between 1999 and 2003, 121 patients (mean age, 54.4±12.4 years; range, 20-81 years) with advanced hepatocellular carcinoma received three-dimensional conformal radiotherapy and thalidomide. Radiation was delivered in 1.5 Gy fractions twice daily for 5 days a week, for a total dose of 45-75 Gy. Mean treatment volume was 429.52±408.50 cm 3 (range, 26.89-2284.82 cm 3 ). Thalidomide was given concomitantly: 200 mg/day in 109 patients, 300 mg/day in 8 patients and 400 mg/day in 4 patients. Treatment responses, survival rates and factors affecting survival were analyzed. Treatment responses were observed in 61% of the patients. Liver cirrhosis (P=0.001) and tumor size (P=0.001) significantly affected the tumor responses. Overall survival at 6, 12 and 24 months was 84.8, 60.0 and 44.6%, respectively. On univariate analysis, liver cirrhosis (P=0.003), Karnofsky performance status (P=0.007), tumor size (P<0.001), portal vein tumor thrombosis (P<0.001) and alpha-fetoprotein level (P=0.003) were shown to significantly affect survival. On multivariate analysis, only thrombosis (P=0.039) and alpha-fetoprotein level (P=0.006) were shown to be factors affecting survival. Three-dimensional conformal radiotherapy with thalidomide seems to be effective in the treatment of advanced hepatocellular carcinoma. (author)

Imaging of hepatocellular carcinoma; Bildgebung des hepatozellulaeren Karzinoms

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Lincke, Therese; Zech, Christoph [Universitaetsspital Basel (Switzerland). Klinik fuer Radiologie und Nuklearmedizin; Boll, Daniel

2016-12-15

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Besides the improvement in diagnostics and therapy the quantity of new cases and fatalities per year are equal. The main risk factors for HCC developing are liver cirrhosis (causing 90% of HCCs), non-alcoholic fatty liver disease and chronic hepatitis B infection. Therefore, it is recommended to perform an ultrasound screening on patients at risk every 6 month to detect HCC-lesions early. HCC can be definitely diagnosed by imaging techniques using contrast agent such as contrast-enhanced-ultrasound (CEUS), contrast-enhanced-MRI (CE-MRI) and contrast-enhanced-CT (CE-CT). MRI has several advantages compared to the other modalities due to the multi-parametric approach and a higher sensitivity for tumor detection.

Genomic portrait of resectable hepatocellular carcinomas: implications of RB1 and FGF19 aberrations for patient stratification.

Science.gov (United States)

Ahn, Sung-Min; Jang, Se Jin; Shim, Ju Hyun; Kim, Deokhoon; Hong, Seung-Mo; Sung, Chang Ohk; Baek, Daehyun; Haq, Farhan; Ansari, Adnan Ahmad; Lee, Sun Young; Chun, Sung-Min; Choi, Seongmin; Choi, Hyun-Jeung; Kim, Jongkyu; Kim, Sukjun; Hwang, Shin; Lee, Young-Joo; Lee, Jong-Eun; Jung, Wang-Rim; Jang, Hye Yoon; Yang, Eunho; Sung, Wing-Kin; Lee, Nikki P; Mao, Mao; Lee, Charles; Zucman-Rossi, Jessica; Yu, Eunsil; Lee, Han Chu; Kong, Gu

2014-12-01

Hepatic resection is the most curative treatment option for early-stage hepatocellular carcinoma, but is associated with a high recurrence rate, which exceeds 50% at 5 years after surgery. Understanding the genetic basis of hepatocellular carcinoma at surgically curable stages may enable the identification of new molecular biomarkers that accurately identify patients in need of additional early therapeutic interventions. Whole exome sequencing and copy number analysis was performed on 231 hepatocellular carcinomas (72% with hepatitis B viral infection) that were classified as early-stage hepatocellular carcinomas, candidates for surgical resection. Recurrent mutations were validated by Sanger sequencing. Unsupervised genomic analyses identified an association between specific genetic aberrations and postoperative clinical outcomes. Recurrent somatic mutations were identified in nine genes, including TP53, CTNNB1, AXIN1, RPS6KA3, and RB1. Recurrent homozygous deletions in FAM123A, RB1, and CDKN2A, and high-copy amplifications in MYC, RSPO2, CCND1, and FGF19 were detected. Pathway analyses of these genes revealed aberrations in the p53, Wnt, PIK3/Ras, cell cycle, and chromatin remodeling pathways. RB1 mutations were significantly associated with cancer-specific and recurrence-free survival after resection (multivariate P = 0.038 and P = 0.012, respectively). FGF19 amplifications, known to activate Wnt signaling, were mutually exclusive with CTNNB1 and AXIN1 mutations, and significantly associated with cirrhosis (P = 0.017). RB1 mutations can be used as a prognostic molecular biomarker for resectable hepatocellular carcinoma. Further study is required to investigate the potential role of FGF19 amplification in driving hepatocarcinogenesis in patients with liver cirrhosis and to investigate the potential of anti-FGF19 treatment in these patients. © 2014 by the American Association for the Study of Liver Diseases.

Long-term results of percutaneous ethanol injection therapy for hepatocellular carcinoma in cirrhosis: a European experience

International Nuclear Information System (INIS)

Lencioni, R.; Pinto, F.; Armillotta, N.; Bassi, A.M.; Moretti, M.; Di Giulio, M.; Marchi, S.; Uliana, M.; Della Capanna, S.; Lencioni, M.; Bartolozzi, C.

1997-01-01

The objective of our work was to evaluate the long-term results of percutaneous ethanol injection (PEI) for the treatment of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. A total of 184 cirrhotic patients with HCC underwent PEI as the only anticancer treatment over an 8-year period. Patients were followed after therapy by means of clinical examinations, laboratory tests, and US and CT studies performed at regular time intervals. Survival rates were determined according to the Kaplan-Meier method. The overall survival was 67% at 3 years, 41% at 5 years, and 19% at 7 years. The 3-, 5-, and 7-year survival rates of patients with single HCC≤3 cm (78, 54, and 28%, respectively) were significantly higher (p<0.01) than those of patients with single HCC of 3.1-5 cm (61, 32, and 16, respectively) or multiple HCCs (51, 21, and 0%, respectively). Survival of Child-Pugh A patients (79% at 3 years, 53% at 5 years, and 32% at 7 years) was significantly longer (p<0.01) than that of Child-Pugh B patients (50% at 3 years, 28% at 5 years, and 8% at 7 years). A selected group of 70 patients with Child-Pugh A cirrhosis and single HCC≤3 cm had a 7-year survival of 42%. Long-term survival of cirrhotic patients with HCC treated with PEI is comparable to that reported in published series of matched patients submitted to surgical resection. (orig.)

The Multifaceted Role of Podoplanin Expression in Hepatocellular Carcinoma

OpenAIRE

Cioca, Andreea; Ceausu, Amalia R.; Marin, Irina; Raica, Marius; Cimpean, Anca Maria

2017-01-01

The role of podoplanin in hepatocellular carcinoma (HCC) is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD) was increased in patients who had vascular invasion at the time of diagnosis (P=0.018) and in those with associated cirrhosis (P...

Diabetes and Cirrhosis Are Risk Factors for Hepatocellular Carcinoma After Successful Treatment of Chronic Hepatitis C.

Science.gov (United States)

Hedenstierna, Magnus; Nangarhari, Ali; Weiland, Ola; Aleman, Soo

2016-09-15

Successful treatment of hepatitis C virus (HCV) infection reduces the risk for hepatocellular carcinoma (HCC), but a risk remains. Current guidelines recommend continued HCC surveillance after sustained virologic response (SVR) has been achieved. This study aimed to investigate risk factors and incidence rates for HCC after SVR in HCV patients with pretreatment advanced liver disease (Metavir stage F3/F4). All patients with advanced liver disease successfully treated for HCV at Karolinska University Hospital during 1992-2013 (n = 399) were followed up for a median of 7.8 years. Data from national registries were used to minimize loss to follow-up. Incidence rates and hazard ratios (HRs) for development of HCC were calculated by Cox regression analysis. Seventeen patients developed HCC during 3366 person-years (PY) of follow-up. The HCC incidence rate was 0.95 (95% confidence interval [CI], .57-1.6) and 0.15 (95% CI, .05-.49) per 100 PY for patients with pretreatment F4 and F3, respectively. Patients with pretreatment cirrhosis and diabetes had a HR to develop HCC of 6.3, and an incidence rate of 7.9 per 100 PY (95% CI, 3.3-19) during the first 2 years of follow-up. The risk for HCC decreased significantly 2 years after SVR had been achieved. Diabetes mellitus and cirrhosis are strong risk factors for HCC development after SVR has been achieved. The risk to develop HCC diminishes significantly 2 years after SVR. Patients without cirrhosis have a low risk to develop HCC after SVR, and the benefit of HCC surveillance for this group is questionable. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Performance of Alpha Fetoprotein in Combination with Alpha-1-acid Glycoprotein for Diagnosis of Hepatocellular Carcinoma Among Liver Cirrhosis Patients

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Rino A Gani

2016-05-01

Full Text Available Aim: to evaluate the use of alpha-1-acid glycoprotein (AAG for diagnosing hepatocellular carcinoma (HCC, and to combine with alpha fetoprotein (AFP as part of routine examination in liver cirrhosis patients. Methods: this is a diagnostic study using cross-sectional design. A hundred and six patients were included in this study. Baseline data such as age, gender, AFP, AAG, peripheral blood count, AST and ALT were consecutively collected from liver cirrhosis patients with or without HCC. Serum AAG were measured quantitatively using immunoturboditimetric assay and AFP with enzyme immune assay (EIA. Statistical analysis were done using SPSS 13.0. Data comparisons between group were done using Mann-Whitney test. Diagnostic performance for each marker alone was compared to the surrogate use of both markers (combined parallel approach in HCC cases. Results: receiver operating characteristic (ROC analysis showed that area under the curve for AFP AAG combination was 88.1% and higher than AFP only (86.2% or AAG only (76.5% with sensitivity of 83%, 73% and 44%, respectively, at specificity of >80%. Conclusion: our study showed that combination of AFP and AAG is superior than either marker alone in diagnosing HCC in liver cirrhosis patients. Combination of AFP and AAG may be used to prompt early diagnosis screening of HCC. Key words: alpha fetoprotein, alpha-1-acid glycoprotein, biomarker, liver cancer

Cryotherapy for hepatocellular carcinoma

DEFF Research Database (Denmark)

Awad, Tahany; Thorlund, Kristian; Gluud, Christian

2009-01-01

BACKGROUND: Hepatocellular carcinoma is the most common primary malignant cancer of the liver. Evidence for the role of cryotherapy in the treatment of hepatocellular carcinoma is controversial. OBJECTIVES: The aim of this review is to evaluate the potential benefits and harms of cryotherapy...... for the treatment of hepatocellular carcinoma. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS until June 2009. We identified further studies by searching...... of benefit but included for the assessment of harm. Both severe and non-severe adverse events were reported, but the true nature and extent of harm was difficult to asses. AUTHORS' CONCLUSIONS: At present, there is no evidence to recommend or refute cryotherapy for patients with hepatocellular carcinoma...

Dynamic CT of hepatocellular carcinoma

International Nuclear Information System (INIS)

Fujita, Nobuyuki; Shirato, Hiroki; Shinohara, Masahiro; Miyasaka, Kazuo; Morita, Yutaka; Irie, Goro

1983-01-01

We performed dynamic CT in 30 cases of hepatocellular carcinoma, and concluded as below. 1 Decting the stain in the early phase of the dynamic series, it is possible to make a diagnosis of hepatocellular carcinoma. 2 The dinamic CT is effective in a case of small hepatocellular carcinoma in which it is difficult to gain an accurate diagnosis in the routine CT study. 3 The dynamic CT is also effective in the differential diagnosis of hepatic lesions, as other hepatic lesions such as hemangioma and metastatic liver cancer show different patterns compared with hepatocellular carcinoma. (author)

Ultrasonographic finding of hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Ryu, Han Soo; Woo, Seong Ku; Lim, Jae Hoon; Ko, Young Tae; Kim, Ho Kyun; Kim, Soon Yong [Kyung Hee University Hospital, Seoul (Korea, Republic of)

1983-12-15

With the development of gray scale ultrasonography, detection and evaluation of hepatic parenchymal disease including space occupying lesion are easily performed and frequently used in the world. Thrity five cases of histopathologically proven and ultrasonographically suggested hepatocellular carcinoma are retrospectively studied. The results were as follows; 1. Ultrasonographic findings of hepatocellular carcinoma show hyperechoic pattern in 22 cases (63%), hypoechoic pattern in 2 cases (6%), and mixed pattern in 11 cases (31%). 2. The margin of tumor is ill-defined in 19 cases (54%) and well defined in16 cases (46%). 3. The size of tumor by sonographic measurement was large than 5 cm in diameter in 33 cases (94%). 4. The number of tumor is solitary in 19 cases and multiple in 16 cases. The sites of involved lobe were right lobe in 22 cases (63%), left lobe in 2 cases (6%), and both lobes in 11 cases (31%). 5. Associated sonographic findings were hepatomegaly with focal contour change in 25 cases (71%), splenomegaly in 16 cases (46%), cirrhosis of liver in 15 cases (43%), ascites in 11 cases (31%) and tumoral thrombosis in portal vein in 8 cases (23%). 6. The sex ratio is 6 : 1 male predominence and the age ranges from 32 to 76 years with highest incidence in 5th and 6th decades.

Case of minute hepatocellular carcinoma found by CT scan and diagnosed cytology under the ultrasonic aspiration transducer

Energy Technology Data Exchange (ETDEWEB)

Sato, Waichi; Moriai, Norihiko; Komatsu, Kanji [Yuri Kumiai Sogo Hospital, Akita (Japan)

1983-11-01

CT scan detected a suspected minute hepatocellular carcinoma in a case of liver cirrhosis followed up for more than 10 years. A definite diagnosis was established by ultrasonic guided aspiration cytology. The cancer was resected using ultrasonic examination during operation.

Embolization of Cyanoacrylate glue in systemic circulation in a case of hepatocellular carcinoma: an autopsy report

Directory of Open Access Journals (Sweden)

Kochhar Rakesh K

2009-12-01

Full Text Available Abstract We report a case of embolism of the sclerosant dye with subsequent formation of foreign-body giant cell reaction within the veins of pulmonary and portal circulation in an autopsy case of hepatocellular carcinoma developing over an underlying primary biliary cirrhosis.

Detection of an occult hepatocellular carcinoma using ultrasound with liver-specific microbubbles

International Nuclear Information System (INIS)

Harvey, Christopher J.; Lim, Adrian K.P.; Blomley, Martin J.K.; Cosgrove, David O.; Taylor-Robinson, Simon D.; Gedroyc, Wladyslaw M.W.

2002-01-01

The radiological surveillance of cirrhosis to detect the development of hepatocellular carcinoma (HCC) is problematic because no highly sensitive and specific imaging investigation is available. Ultrasound is typically the first modality used but is less accurate than other imaging modalities. We report the first case of a patient with cirrhosis in whom US imaging with liver-specific microbubbles detected an HCC prior to its detection by MR. The use of liver-specific microbubble US contrast agents is an exciting development in the detection of HCC in chronic liver disease and may help to rectify some of the shortcomings of US. (orig.)

Diagnosis of Hepatocellular Carcinoma Complicating Liver Cirrhosis: Utility of Repeat Ultrasound-Guided Biopsy after Unsuccessful First Sampling

International Nuclear Information System (INIS)

Caturelli, Eugenio; Biasini, Elisabetta; Bartolucci, Francesca; Facciorusso, Domenico; Decembrino, Francesco; Attino, Vito; Bisceglia, Michele

2002-01-01

Purpose: To evaluate the utility of a second ultrasound-guided fine-needle biopsy of liver nodules thought to be hepatocellular carcinoma when the original biopsy has failed to provide a reliable diagnosis. Methods: Thirty-seven cirrhotic patients underwent ultrasound-guided fine-needle biopsy of liver nodules that were subsequently diagnosed as hepatocellular carcinoma. Each biopsy involved a single puncture with a 20 G cutting needle, which yielded pathologic material used both for cytologic and histologic studies. In 23 cases (mean diameter of nodules 48 mm) the biopsy furnished exclusively necrotic material (non-diagnostic subgroup); in the other 14 cases (mean diameter 26 mm) the biopsy yielded no neoplastic elements (false-negative subgroup). All 37 nodules were subjected to repeat biopsies performed in the same manner. Results: The repeat biopsies provided a diagnosis of hepatocellular carcinoma in six of the 23 patients from the non-diagnostic subgroup and in seven of the 14 in the false-negative subgroup. Overall, repeat biopsy produced a diagnostic gain of 35.1%. Conclusion: The chance of success with repeat biopsy of hepatocellular carcinoma is limited and may depend to some extent on the characteristics of the lesions (i.e., areas of necrosis in large nodules, well-differentiated cellular populations in small ones)

Preoperative Alpha-Fetoprotein Slope is Predictive of Hepatocellular Carcinoma Recurrence after Liver Transplantation

Directory of Open Access Journals (Sweden)

Kathy Han

2007-01-01

Full Text Available BACKGROUND: Liver transplantation (LT offers a possible cure for patients with hepatocellular carcinoma (HCC and cirrhosis. However, tumour progression while on the waiting list and tumour recurrence after LT are common. The prognostic significance of various pre- and postoperative variables were investigated in regard to tumour recurrence, with an emphasis on the slope of preoperative serum alpha-fetoprotein (AFP levels.

Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma

DEFF Research Database (Denmark)

Ewertsen, Caroline; Henriksen, Birthe Merete; Hansen, Carsten Palnæs

2009-01-01

of synchronous gastric NEC and hepatocellular carcinoma in a patient with several other precancerous lesions is presented. The patient had anaemia, and a gastric tumour and two duodenal polyps were identified on upper endoscopy. A CT scan of the abdomen revealed several lesions in the liver. The lesions were...... invisible on B-mode sonography and real-time sonography fused with CT was used to identify and biopsy one of the lesions. Histology showed hepatocellular carcinoma. A literature search showed that only one case of a hepatocellular carcinoma synchronous with a gastric NEC has been reported previously. TRIAL...

Elevated alpha-fetoprotein: differential diagnosis - hepatocellular carcinoma and other disorders.

Science.gov (United States)

Wong, Robert J; Ahmed, Aijaz; Gish, Robert G

2015-05-01

The incidence of cirrhosis-related hepatocellular carcinoma (HCC) is rising. Curative surgical options are available; outcomes are acceptable with early diagnosis. Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) and des-gamma-carboxy prothrombin (DCP) are HCC risk markers. A high or increasing serum biomarker level can be predictive of the eventual development of HCC, large tumor size, advanced stage, extrahepatic metastases, portal vein thrombosis, and postoperative HCC recurrence. Based on FDA guidelines for HCC risk assessment, clinicians can consider using either the combination of AFP-L3 with DCP, or the combination of AFP-L3 with AFP and DCP. Copyright © 2015 Elsevier Inc. All rights reserved.

Electrochemotherapy as treatment option for hepatocellular carcinoma, a prospective pilot study.

Science.gov (United States)

Djokic, Mihajlo; Cemazar, Maja; Popovic, Peter; Kos, Bor; Dezman, Rok; Bosnjak, Masa; Zakelj, Martina Niksic; Miklavcic, Damijan; Potrc, Stojan; Stabuc, Borut; Tomazic, Ales; Sersa, Gregor; Trotovsek, Blaz

2018-05-01

Electrochemotherapy provides non-thermal ablation of cutaneous as well as deep seated tumors. Based on positive results of the treatment of colorectal liver metastases, we conducted a prospective pilot study on hepatocellular carcinomas with the aim of testing the feasibility, safety and effectiveness of electrochemotherapy. Electrochemotherapy with bleomycin was performed on 17 hepatocellular carcinomas in 10 patients using a previously established protocol. The procedure was performed during open surgery and the patients were followed for median 20.5 months. Electrochemotherapy was feasible for all 17 lesions, and no treatment-related adverse events or major post-operative complications were observed. The median size of the treated lesions was 24 mm (range 8-41 mm), located either centrally, i.e., near the major hepatic vessels, or peripherally. The complete response rate at 3-6 months was 80% per patient and 88% per treated lesion. Electrochemotherapy of hepatocellular carcinoma proved to be a feasible and safe treatment in all 10 patients included in this study. To evaluate the effectiveness of this method, longer observation period is needed; however the results at medium observation time of 20.5 months after treatment are encouraging, in 15 out of 17 lesions complete response was obtained. Electrochemotherapy is predominantly applicable in patients with impaired liver function due to liver cirrhosis and/or with lesions where a high-risk operation is needed to achieve curative intent, given the intra/perioperative risk for high morbidity and mortality. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

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Behl Susanne

2008-03-01

Full Text Available Abstract Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. Methods 44 patients (84 % male, median age 69 years not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Results Median survival was 11.5 months (95% CI 7.9–15.0 with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01, a low score in the Okuda- and CLIP-classification (p Conclusion Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage in addition to response to thymostimulin, while an invasive HCC phenotype had no influence in the multivariate analysis. Thymostimulin could therefore be considered a safe and promising candidate for palliative treatment in a selected target population with advanced hepatocellular carcinoma, in particular as component of a multimodal therapy concept. Trial registration Current Controlled Trials ISRCTN29319366.

Newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with DAAs: A prospective population study.

Science.gov (United States)

Romano, Antonietta; Angeli, Paolo; Piovesan, Sara; Noventa, Franco; Anastassopoulos, Georgios; Chemello, Liliana; Cavalletto, Luisa; Gambato, Martina; Russo, Francesco Paolo; Burra, Patrizia; Vincenzi, Valter; Scotton, Pier Giorgio; Panese, Sandro; Tempesta, Diego; Bertin, Tosca; Carrara, Maurizio; Carlotto, Antonio; Capra, Franco; Carolo, Giada; Scroccaro, Giovanna; Alberti, Alfredo

2018-03-16

Direct-acting antiviral agents (DAAs) are safe and effective in patients with hepatitis C. Conflicting data were reported on the risk of hepatocellular carcinoma (HCC) during/after therapy with DAAs. The aim of this study was to evaluate the incidence of newly diagnosed HCC and associated risk factors in patients with advanced hepatitis C treated with DAAs. The study is based on the NAVIGATORE platform, a prospectively recording database of all patients with hepatitis C receiving DAAs in the Veneto region of Italy. The inclusion criteria were: fibrosis stage ≥F3. The exclusion criteria were: Child-Turcotte-Pugh (CTP)-C, liver transplantation before DAAs, history or presence of HCC, follow-up hepatocarcinoma during the first year is not higher, and might be lower, than that of untreated patients. The risk further declines thereafter. Early hepatocarcinoma appearance may reflect pre-existing, microscopic, undetectable tumors. Hepatocellular carcinoma is one of the complications of hepatitis C related cirrhosis. Treating patients with advanced hepatitis C with the new interferon-free direct-acting antiviral agents has been associated with improvement in liver function and survival, while more conflicting data have been reported regarding the risk of hepatocellular carcinoma. We report the results of a prospective population study on the incidence of newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with direct-acting antiviral agents, clearly indicating that the residual hepatocellular carcinoma risk is reduced and declines progressively with time after a sustained virological response. Development of a liver tumor during/after therapy was associated with known risk factors and with virological failure. Copyright © 2018. Published by Elsevier B.V.

Trends in mortality burden of hepatocellular carcinoma, cirrhosis, and fulminant hepatitis before and after roll-out of the first pilot vaccination program against hepatitis B in Peru: An analysis of death certificate data.

Science.gov (United States)

Ramírez-Soto, Max Carlos; Ortega-Cáceres, Gutia; Cabezas, César

2017-07-05

The first pilot vaccination program against hepatitis B in Peru was implemented in the hyperendemic Abancay province in 1991. To assess the impact of vaccination on mortality rates of hepatitis B-related hepatocellular carcinoma (HCC), cirrhosis, and fulminant hepatitis, we compared mortality trends before (1960-1990) and after (1991-2012) roll-out of the vaccination program, using death certificate data from the Municipalidad Provincial de Abancay. Our results showed that, following program roll-out, the overall mortality rates (per 100,000 population) decreased from 9.20 to 3.30 for HCC (95% CI, 1.28-10.48%; P<0.014), from 16.0 to 6.3 for cirrhosis (95% CI, 3.20-16.10%; P<0.004), and from 34.80 to 1.28 for fulminant hepatitis (95% CI, 16.70-50.30%; P<0.001). The absolute number of deaths attributable to cirrhosis (10 [8.80%] vs. 0.0%; P<0.001) and fulminant hepatitis (83 [40.0%] vs. 5 [19.20%]; P<0.026) decreased in 5-14-year-old children following vaccination. These findings showed reduced mortality rates of hepatitis B-related liver diseases, particularly cirrhosis and fulminant hepatitis in children under 15years, following implementation of the vaccination program against hepatitis B. Copyright © 2017 Elsevier Ltd. All rights reserved.

Circulating microRNA-200 Family as Diagnostic Marker in Hepatocellular Carcinoma.

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Sameer A Dhayat

Full Text Available In this clinical study, we aimed to evaluate the role of circulating microRNA-200 family as a non-invasive tool to identify patients with cirrhosis-associated hepatocellular carcinoma (HCC.Prognosis of HCC remains poor with increasing incidence worldwide, mainly related to liver cirrhosis. So far, no reliable molecular targets exist for early detection of HCC at surgically manageable stages. Recently, we identified members of the microRNA-200 family as potential diagnostic markers of cirrhosis-associated HCC in patient tissue samples. Their value as circulating biomarkers for HCC remained undefined.Blood samples and clinicopathological data of consecutive patients with liver diseases were collected prospectively. Expression of the microRNA-200 family was investigated by qRT-PCR in blood serum samples of 22 HCC patients with and without cirrhosis. Serum samples of patients with non-cancerous chronic liver cirrhosis (n = 22 and of healthy volunteers (n = 15 served as controls.MicroRNA-141 and microRNA-200a were significantly downregulated in blood serum of patients with HCC compared to liver cirrhosis (p<0.007 and healthy controls (p<0.002. MicroRNA-141 and microRNA-200a could well discriminate patients with cirrhosis-associated HCC from healthy volunteers with area under the receiver-operating characteristic curve (AUC values of 0.85 and 0.82, respectively. Additionally, both microRNAs could differentiate between HCC and non-cancerous liver cirrhosis with a fair accuracy.Circulating microRNA-200 family members are significantly deregulated in patients with HCC and liver cirrhosis. Further studies are necessary to confirm the diagnostic value of the microRNA-200 family as accurate serum marker for cirrhosis-associated HCC.

Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma

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Nomura, Fumio, E-mail: fnomura@faculty.chiba-u.jp [Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University and Divisions of Laboratory Medicine, Clinical Genetics and Proteomics, Chiba University Hospital, Chiba (Japan); Sogawa, Kazuyuki; Noda, Kenta; Seimiya, Masanori; Matsushita, Kazuyuki; Miura, Toshihide [Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University and Divisions of Laboratory Medicine, Clinical Genetics and Proteomics, Chiba University Hospital, Chiba (Japan); Tomonaga, Takeshi [Laboratory of Proteome Research, National Institute of Biomedical Innovation, Ibaraki (Japan); Yoshitomi, Hideyuki [Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba (Japan); Imazeki, Fumio [Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba (Japan); Takizawa, Hirotaka [Kashiwado Clinic in Port-Square of the Kashiwado Memorial Foundation, Chiba (Japan); Mogushi, Kaoru [Information Center for Medical Sciences, Tokyo Dental and Medical University, Tokyo (Japan); Miyazaki, Masaru [Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba (Japan); Yokosuka, Osamu [Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba (Japan)

2012-05-18

Highlights: Black-Right-Pointing-Pointer Overexpression of Ku86 in human liver cancer was shown by immunohistochemistry. Black-Right-Pointing-Pointer Serum anti-Ku86 was significantly elevated in early hepatocellular carcinoma. Black-Right-Pointing-Pointer Anti-Ku86 may be more sensitive than the conventional markers for early detection. Black-Right-Pointing-Pointer Serum anti-Ku86 significantly decreased after surgical resection of liver tumors. Black-Right-Pointing-Pointer Elevation of serum anti-Ku86 in other non-liver solid tumors was minimal. -- Abstract: Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is one of the most common cancers worldwide and the third most common cause of cancer-related death. Imaging studies including ultrasound and computed tomography are recommended for early detection of HCC, but they are operator dependent, costly and involve radiation. Therefore, there is a need for simple and sensitive serum markers for the early detection of hepatocellular carcinoma (HCC). In our recent proteomic studies, a number of proteins overexpressed in HCC tissues were identified. We thought if the serum autoantibodies to these overexpressed proteins were detectable in HCC patients. Of these proteins, we focused on Ku86, a nuclear protein involved in multiple biological processes and aimed to assess the diagnostic value of serum anti-Ku86 in the early detection of HCC. Serum samples were obtained prior to treatment from 58 consecutive patients with early or relatively early hepatitis C virus (HCV)-related HCC and 137 patients with HCV-related liver cirrhosis without evidence of HCC. Enzyme immunoassays were used to measure serum levels of autoantibodies. Serum levels of anti-Ku86 antibodies were significantly elevated in HCC patients compared to those in liver cirrhosis patients (0.41 {+-} 0.28 vs. 0.18 {+-} 0.08 Abs at 450 nm, P < 0001). Setting the cut-off level to give 90% specificity, anti-Ku86 was positive in 60.7% of

Systems biology analysis of hepatitis C virus infection reveals the role of copy number increases in regions of chromosome 1q in hepatocellular carcinoma metabolism

DEFF Research Database (Denmark)

Elsemman, Ibrahim; Mardinoglu, Adil; Shoaie, Saeed

2016-01-01

on hepatocellular metabolism. Here, we integrated HCV assembly reactions with a genome-scale hepatocyte metabolic model to identify metabolic targets for HCV assembly and metabolic alterations that occur between different HCV progression states (cirrhosis, dysplastic nodule, and early and advanced hepatocellular...... carcinoma (HCC)) and healthy liver tissue. We found that diacylglycerolipids were essential for HCV assembly. In addition, the metabolism of keratan sulfate and chondroitin sulfate was significantly changed in the cirrhosis stage, whereas the metabolism of acyl-carnitine was significantly changed...

Increased risk of hepatocellular carcinoma in patients with chronic hepatitis C

DEFF Research Database (Denmark)

Hallager, Sofie; Weis, Nina

2014-01-01

Chronic hepatitis C (CHC) frequently leads to cirrhosis with an increased risk of hepatocellular carcinomas (HCC). CHC therapy is currently changing for the better whereas prognosis for HCC remains dismal if not detected early and thus regular screening in cirrhotic CHC patients for HCC...... is recommended. CHC is known to be underdiagnosed in Denmark where it is up to the involved physician to screen for risk factors for CHC and increase the patient's chance of a cure for CHC with therapy....

Prevention of hepatocellular carcinoma: potential targets, experimental models, and clinical challenges

Science.gov (United States)

Hoshida, Yujin; Fuchs, Bryan C.; Tanabe, Kenneth K.

2013-01-01

Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice. PMID:22873223

Branched-Chain Amino Acids Ameliorate Fibrosis and Suppress Tumor Growth in a Rat Model of Hepatocellular Carcinoma with Liver Cirrhosis

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Cha, Jung Hoon; Bae, Si Hyun; Kim, Hye Lim; Park, Na Ri; Choi, Eun Suk; Jung, Eun Sun; Choi, Jong Young; Yoon, Seung Kew

2013-01-01

Purpose Recent studies have revealed that branched-chain amino acids (BCAA) reduce the development of hepatocellular carcinoma (HCC) in patients with obesity and hepatitis C virus infection by improving insulin resistance (IR). The aim of this study was to examine the anti-cancer and anti-fibrotic effects of BCAA on the development of diethylnitrosamine (DEN)-induced HCC and liver cirrhosis in a rat model. Methods Male SD rats received weekly intraperitoneal injections of DEN (50 mg/kg of body weight) for 16 weeks to induce HCC. They were fed a diet containing 3% casein, 3% or 6% BCAA for 13 weeks beginning 6 weeks after DEN administration. DEN was used to induce HCC through stepwise development from cirrhosis to HCC. The effect of BCAA was evaluated in tumor tissues by histopathologic analyses, reverse transcription-polymerase chain reaction, and Western blotting. Results The mean area and number of dysplastic nodules (DNs) and tumors in the casein group tended to be larger than those in the BCAA group 16 weeks after DEN administration. The mean fibrotic area in the BCAA group was smaller than that in the casein group. The BCAA group showed decreased mRNA levels for markers of fibrosis, angiogenesis, and apoptosis inhibition. Compared with the casein group, the BCAA group had lower levels of α-smooth muscle actin, vascular endothelial growth factor, p-β-catenin, p-p38 mitogen-activated protein kinase, proliferating cell nuclear antigen, and caspase-3 protein expression, as well as a higher level of cleaved caspase-3 protein expression. Conclusions BCAA supplementation of the diet ameliorated liver fibrosis and HCC development in a DEN-induced rat model of HCC with liver cirrhosis, but not in the IR model. These results provide a rationale for anti-fibrosis and chemoprevention using BCAA treatment for HCC with liver cirrhosis, as well as decreasing the ammonia level. PMID:24223741

Branched-chain amino acids ameliorate fibrosis and suppress tumor growth in a rat model of hepatocellular carcinoma with liver cirrhosis.

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Jung Hoon Cha

Full Text Available PURPOSE: Recent studies have revealed that branched-chain amino acids (BCAA reduce the development of hepatocellular carcinoma (HCC in patients with obesity and hepatitis C virus infection by improving insulin resistance (IR. The aim of this study was to examine the anti-cancer and anti-fibrotic effects of BCAA on the development of diethylnitrosamine (DEN-induced HCC and liver cirrhosis in a rat model. METHODS: Male SD rats received weekly intraperitoneal injections of DEN (50 mg/kg of body weight for 16 weeks to induce HCC. They were fed a diet containing 3% casein, 3% or 6% BCAA for 13 weeks beginning 6 weeks after DEN administration. DEN was used to induce HCC through stepwise development from cirrhosis to HCC. The effect of BCAA was evaluated in tumor tissues by histopathologic analyses, reverse transcription-polymerase chain reaction, and Western blotting. RESULTS: The mean area and number of dysplastic nodules (DNs and tumors in the casein group tended to be larger than those in the BCAA group 16 weeks after DEN administration. The mean fibrotic area in the BCAA group was smaller than that in the casein group. The BCAA group showed decreased mRNA levels for markers of fibrosis, angiogenesis, and apoptosis inhibition. Compared with the casein group, the BCAA group had lower levels of α-smooth muscle actin, vascular endothelial growth factor, p-β-catenin, p-p38 mitogen-activated protein kinase, proliferating cell nuclear antigen, and caspase-3 protein expression, as well as a higher level of cleaved caspase-3 protein expression. CONCLUSIONS: BCAA supplementation of the diet ameliorated liver fibrosis and HCC development in a DEN-induced rat model of HCC with liver cirrhosis, but not in the IR model. These results provide a rationale for anti-fibrosis and chemoprevention using BCAA treatment for HCC with liver cirrhosis, as well as decreasing the ammonia level.

Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma.

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Mary Ann Comunale

2010-08-01

Full Text Available We previously reported increased levels of protein-linked fucosylation with the development of liver cancer and identified many of the proteins containing the altered glycan structures. One such protein is alpha-1-antitrypsin (A1AT. To advance these studies, we performed N-linked glycan analysis on the five major isoforms of A1AT and completed a comprehensive study of the glycosylation of A1AT found in healthy controls, patients with hepatitis C- (HCV induced liver cirrhosis, and in patients infected with HCV with a diagnosis of hepatocellular carcinoma (HCC.Patients with liver cirrhosis and liver cancer had increased levels of triantennary glycan-containing outer arm (alpha-1,3 fucosylation. Increases in core (alpha-1,6 fucosylation were observed only on A1AT from patients with cancer. We performed a lectin fluorophore-linked immunosorbent assay using Aleuria Aurantia lectin (AAL, specific for core and outer arm fucosylation in over 400 patients with liver disease. AAL-reactive A1AT was able to detect HCC with a sensitivity of 70% and a specificity of 86%, which was greater than that observed with the current marker of HCC, alpha-fetoprotein. Glycosylation analysis of the false positives was performed; results indicated that these patients had increases in outer arm fucosylation but not in core fucosylation, suggesting that core fucosylation is cancer specific.This report details the stepwise change in the glycosylation of A1AT with the progression from liver cirrhosis to cancer and identifies core fucosylation on A1AT as an HCC specific modification.

Viral hepatitis and hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Juei-Low, Sung [ed.; National Taiwan University College of Medicine, Taipei (Republic of China Taiwan). Department of Internal Medicine; Ding-Shinn, Chen [ed.; National Taiwan University College of Medicine, Taipei (Republic of China Taiwan). Hepatitis Research Center National Taiwan University College of Medicine, Taipei (Republic of China Taiwan). Graduate Institute of Clinical Medicine

1990-01-01

Two papers in this volume are in INIS scope, respectively dealing with MRI in the study of viral hepatitis and hepatocellular carcinoma, and The use of {sup 131}I-labeled Lipidol in the diagnosis of hepato-cellular carcinoma. (H.W.). refs.; figs.; tabs.

Viral hepatitis and hepatocellular carcinoma

International Nuclear Information System (INIS)

Sung Juei-Low; Chen Ding-Shinn

1990-01-01

Two papers in this volume are in INIS scope, respectively dealing with MRI in the study of viral hepatitis and hepatocellular carcinoma, and The use of 131 I-labeled Lipidol in the diagnosis of hepato-cellular carcinoma. (H.W.). refs.; figs.; tabs

Squamous Cell Carcinoma Antigen: A Novel Tumor Marker for Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Abdel Messeih, Ph.L.

2009-01-01

Serum Squamous Cell Carcinoma Antigen (SCC-Ag) by ELISA technique and Alpha-fetoprotein (AFP) by IRMA technique were measured in 65 patients with hepatic focal lesion. 49 patients suffered from proved hepatocellular carcinoma and 16 patients were having cirrhosis and 20 normal controls. Median levels of serum AFP and SCC-Ag in HCC patients was significantly higher when compared with both cirrhotic patients and controls. On using receiver operator characteristic curve to improve sensitivity and specificity of AFP and SCC-Ag for detection of HCC, the best chosen cut-off values were 40 IU/mL for AFP and 2.55 ng/L for SCC-Ag, these yielded a sensitivity of 67.2% and 61.2% respectively and specificity 100%. The diagnostic sensitivity of them increased to 87.7% when they was combiendly calculated. It was found that the combined use of AFP and SCC-Ag is useful in screening patients with hepatic focal lesion to increase the chance of early diagnosis of HCC patients.

Direct costs of care for hepatocellular carcinoma in patients with hepatitis C cirrhosis.

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Tapper, Elliot B; Catana, Andreea M; Sethi, Nidhi; Mansuri, Daniel; Sethi, Saurabh; Vong, Annie; Afdhal, Nezam H

2016-03-15

Hepatitis C virus (HCV) is the commonest cause of hepatocellular carcinoma (HCC) in the United States. The benefits of HCV therapy may be measured in part by the prevention of HCC and other complications of cirrhosis. The true cost of care of the HCV patient with HCC is unknown. One hundred patients were randomly selected from a cohort of all HCC patients with HCV at a US transplant center between 2003 and 2013. Patients were categorized by the primary treatment modality, Barcelona class, and ultimate transplant status. Costs included the unit costs of procedures, imaging, hospitalizations, medications, and all subsequent care of the HCC patient until either death or the end of follow-up. Associations with survival and cost were assessed in multivariate regression models. Overall costs included a median of $176,456 (interquartile range [IQR], $84,489-$292,192) per patient or $6279 (IQR, $4043-$9720) per patient-month of observation. The median costs per patient-month were $7492 (IQR, $5137-$11,057) for transplant patients and $4830 for nontransplant patients. The highest median monthly costs were for transplant patients with Barcelona A4 disease ($11,349) and patients who received chemoembolization whether they underwent transplantation ($10,244) or not ($8853). Transarterial chemoembolization and radiofrequency ablation were independently associated with a 28% increase and a 22% decrease in costs, respectively, with adjustments for the severity of liver disease and Barcelona class. These data represent real-world estimates of the cost of HCC care provided at a transplant center and should inform economic studies of HCV therapy. © 2015 American Cancer Society.

Relation of Serum Alkaline Phosphatase to liver scintigram in patients with hepatocellular carcinoma

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Nishimura, H; Harada, T; Nawata, J; Hayakawa, M; Nishioka, M; Takemoto, T; Yokoyama, T; Takahashi, M

1982-12-01

Serum Alkaline Phosphatase (ALP) was studied in relation to liver scintigrams of 54 patients with hepatocellular carcinoma. The ALP activity was higher with larger tumors and in multiple tumors. Within the single tumor group, the activity was higher when the tumor was located in the hilum than in the periphery. The incidence of ALP-1 isoenzyme (bile ALP) roughly paralleled the total ALP activity. These results suggest that the variation of serum ALP seen in each individual patients with hepatocellular carcinoma reflects the volume of cholestatic liver tissue, which is changed by the number, size and localization of the tumor nodules in the liver.

Significance of angio-CT on diagnosis for hepatocellular carcinoma and precancerous lesions

International Nuclear Information System (INIS)

Hatsuse, Kazuo; Aoki, Hideki; Murayama, Michinori; Aihara, Tsukasa; Tsuboi, Kenji; Kakihara, Minoru; Tamakuma, Syoetsu; Irie, Toshiyuki; Terahata, Shintarou

1994-01-01

Fifteen patients with space occupying lesions detected by ultrasonography or computed tomography during angiography (angio-CT). Detectability and diagnostic value of angio-CT for intrahepatic tumor were evaluated in comparison with conventional imaging techniques including digital subtraction angiography (DSA), magnetic resonance imaging (MRI) and lipiodol CT (Lp-CT). Twenty-three lesions detected in 15 patients were as follows: 14 hepatocellular carcinoma (HCC), 3 adenomatous hyperplasia (AH), one early hepatocellular carcinoma (eHCC), one atypical adenomatous hyperplasia (AAH), one regenerative nodule, and 3 miscellaneous lesions. With regard to 8 patients with 2 lesions, there were 2 AHs in one patient and 4 patients with advanced HCC had small HCC, eHCC, AH and AAH, respectively. These findings are suggestive of the presence of multicentric carcinogenesis in cirrhosis. The detection rate for intrahepatic tumors was 86.9% with angio-CT, 56.5% with DSA, 71.4% with MRI and 50% with Lp-CT. The detection rate for eHCC, AH and AAH was 80% with angio-CT, and 20% with DSA, MRI and Lp-CT. Angio-CT visualized AH regarded as a precancerous lesion and eHCC more frequently than other imaging techniques. The above mentioned data suggested that there was such a frequent occurrence of multicentric carcinogenesis that recognition of precancerous lesion by angio-CT was important in surgical intervention for HCC with liver cirrhosis. (author)

Hepatocellular carcinoma: a retrospective analysis of 118 cases

International Nuclear Information System (INIS)

Aman-ur-Rehman; Murad, S.

2002-01-01

Objective: This study aimed at documenting the spectrum of clinico pathological variations in hepatocellular carcinoma (HCC). Design: It was a retrospective study. Place and duration of Study: This study was conducted at the Institute of Nuclear Medicine and Oncology (INMOL) Hospital, Lahore from March 1997 to December 2000. Patients and Methods: The profiles of 118 patients with a biopsy proven hepatocellular carcinoma were analyzed in this period. The data collected was age, sex, clinical presentation and laboratory investigations including liver function tests, alpha fetoprotein and hepatitis profile. Results: Weight loss, jaundice and right upper quadrant abdominal pain were the main presenting symptoms. Out of 118 patients, alpha fetoprotein values were raised in 63(53.38%) patients 106 (89.83%) patients were found to have or have had HBV infections, and 92 (77.96%) patients were anti-HCV positive. Eighty-three (70.33%) patients were cirrhotic. History of alcohol abuse was bound in three patients. Conclusion: The common association of HCC with cirrhosis and hepatitis B and C suggests that vaccination against HBV on nationwide basis can decrease prevalence of this malignancy. There is a need to generate public awareness regarding the transmission of these viruses. Early diagnosis and intervention is also important to the successful management of HCC. (author)

Nonalcoholic fatty liver disease and hepatocellular carcinoma

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LI Liangping

2016-03-01

Full Text Available As the etiology of hepatocellular carcinoma (HCC has been changing, the incidence of HCC related to nonalcoholic fatty liver disease (NAFLD is gradually increasing in developed countries in Europe and America and some countries in Asia. This article introduces the close association between NAFLD and HCC, risk factors, clinicopathological features, and prevention and screening, and points out that although the incidence of NAFLD is not as high as that of hepatitis B- or hepatitis C-related HCC, there are a large absolute number of NAFLD patients, especially the high-risk patients with diabetes and obesity, or liver fibrosis/cirrhosis, due to a huge base number of NAFLD patients. NAFLD-related HCC is commonly seen in the elderly with various comorbidities and a poor prognosis. This article also points out that the prevention should focus on the effective treatment of NAFLD. The strict screening of high-risk population is the strategy for the diagnosis of early-stage HCC. At present, the sensitivity of alpha-fetoprotein is relatively low, and imaging examinations including computed tomography are the main screening methods; however, there are no measures for early warning of NAFLD-related HCC.

Oldenlandia diffusa Promotes Antiproliferative and Apoptotic Effects in a Rat Hepatocellular Carcinoma with Liver Cirrhosis

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Yun-Young Sunwoo

2015-01-01

Full Text Available Oldenlandia diffusa (OD is commonly used with various diseases such as cancer, arthritis, and autoimmune disease. Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC. Here, we show that the therapeutic effect of OD, which was investigated both in vitro and chemically, induced HCC model. OD significantly enhanced apoptosis and antiproliferative activity and reduced migration ability of HCC cells. In vivo, OD was treated twice a day for 28 days after confirmed HCC model through 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG imaging. The survival in OD treated groups was shown to have a greater therapeutic effect than the control group. 28 days after OD treatment, OD treated groups resulted in a significant reduction in tumor number, size, 18F-FDG uptake, and serum levels such as alanine transaminase, aspartate transaminase, and alkaline phosphate compared to the control group. Also, proliferated cells in tumor sites by OD were reduced compared to the control group. Furthermore, several rats in OD treated group survived over 60 days and liver morphology of these rats showed the difference between tumor mass and normal tissue. These results suggest that OD may have antiproliferative activity, inhibition of metastasis, and apoptotic effects in chemically induced HCC model and can have the potential use for clinical application as anticancer drug of the herbal extract.

Detection of hepatocellular carcinoma in gadoxetic acid-enhanced MRI and diffusion-weighted MRI with respect to the severity of liver cirrhosis

International Nuclear Information System (INIS)

Kim, Ah Yeong; Kim, Young Kon; Lee, Min Woo; Park, Min Jung; Hwang, Jiyoung; Lee, Mi Hee; Lee, Jae Won

2012-01-01

Background As gadoxetic acid-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) have been widely used for the evaluation of hepatocellular carcinoma (HCC), it is clinically relevant to determine the diagnostic efficacy of gadoxetic acid-enhanced MRI and DWI for detection of HCCs with respect to the severity of liver cirrhosis. Purpose To compare the diagnostic accuracy and sensitivity of gadoxetic acid-enhanced MRI and DWI for detection of HCCs with respect to the severity of liver cirrhosis. Material and Methods A total of 189 patients with 240 HCCs (≤3.0 cm) (Child-Pugh A, 81 patients with 90 HCCs; Child-Pugh B, 65 patients with 85 HCCs; Child-Pugh C, 43 patients with 65 HCCs) underwent DWI and gadoxetic acid-enhanced MRI at 3.0 T. A gadoxetic acid set (dynamic and hepatobiliary phase plus T2-weighted image) and DWI set (DWI plus unenhanced MRIs) for each Child-Pugh class were analyzed independently by two observers for detecting HCCs using receiver-operating characteristic analysis. The diagnostic accuracy and sensitivity were calculated. Results There was a trend toward decreased diagnostic accuracy for gadoxetic acid and DWI set with respect to the severity of cirrhosis (Child-Pugh A [mean 0.974, 0.961], B [mean 0.904, 0.863], C [mean 0.779, 0.760]). For both observers, the sensitivities of both image sets were highest in Child-Pugh class A (mean 95.6%, 93.9%), followed by class B (mean 83.0%, 77.1%), and class C (mean 60.6%, 60.0%) (P < 0.05). Conclusion In HCC detection, the diagnostic accuracy and sensitivity for gadoxetic acid-enhanced MRI and DWI were highest in Child-Pugh class A, followed by Child-Pugh class B, and Child-Pugh class C, indicating a tendency toward decreased diagnostic capability with the severity of cirrhosis

Diagnostic performance of tumor markers AFP and PIVKA-II in Chinese hepatocellular carcinoma patients.

Science.gov (United States)

Huang, Shujing; Jiang, Feifei; Wang, Ying; Yu, Yanhua; Ren, Siqian; Wang, Xiaowei; Yin, Peng; Lou, Jinli

2017-06-01

Alpha-fetoprotein is an effective biomarker as an aid in hepatocellular carcinoma detection in many countries. However, alpha-fetoprotein has its limitations, especially in early hepatocellular carcinoma diagnosis. Protein induced by vitamin K absence or antagonist-II is another biomarker that is used for hepatocellular carcinoma detection. The aim of this study is to compare the diagnostic performance of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II alone and in combination to explore improving biomarker performance as an aid in early hepatocellular carcinoma detection. In this study a total of 582 serum samples including 132 hepatocellular carcinoma patients, 250 non-hepatocellular carcinoma patients, and 200 healthy volunteers were collected. Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels were measured by both chemiluminescent enzyme immunoassay on LUMIPULSE platform and by chemiluminescent microparticle immunoassay on ARCHITECT platform. Receiver operation characteristic curve analyses were performed for each biomarker and in combination. The results showed that Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in combination have shown higher area under the curve compared to alpha-fetoprotein alone for diagnosis in whole patients (0.906 vs 0.870) in hepatocellular carcinoma early-stage patients (0.809 vs 0.77) and in hepatitis B virus-related hepatocellular carcinoma patients (0.851 vs 0.788) with ARCHITECT platform. Protein induced by vitamin K absence or antagonist-II showed higher area under the curve than alpha-fetoprotein for diagnosis of hepatitis B virus-related hepatocellular carcinoma patients (0.901 vs 0.788).We conclude that Combining alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II may improve the diagnostic value for early detection of hepatocellular carcinoma. Protein induced by vitamin K absence or antagonist-II performs better

CT of hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Nakamura, H; Tanaka, T; Sai, H; Kawamoto, S; Morimoto, K [Osaka Univ. (Japan). Faculty of Medicine

1982-06-01

CT was investigated in 125 cases of hepatocelluar carcinoma and 47 cases of metastatic hepatic neoplasm. The entire contour of each tumor was traced and the average CT value in the tumor was estimated. As a result, the CT value for hepatocellular carcinoma tended to be higher on plain CT and also after contrast enhancement. The CT findings seen frequently were as follows: capsule in 76 cases (60.8%) and septum in 67 cases (53.6%); tumor thrombus in portal vein in 39 cases (31.2%) and that in inferior vena cava in 3 cases (2.4%); localized enlargement of hepatic bile duct in 24 cases (19.2%). These findings were rarely seen in the cases of metastatic hepatic neoplasm. As a relatively outstanding feature of hepatic metastases, a double contour, like concentric circles or contour lines, with a relatively large inner circle or contour line, was found in 21 cases (44.7%). By paying attention to the change of CT value on contrast enhancement and the characteristic image of each case, hepatocellular carcinoma could be differentiated from metastatic hepatic neoplasm with high probability.

Hepatocellular carcinoma complicating cystic fibrosis related liver disease.

LENUS (Irish Health Repository)

O'Donnell, D H

2012-02-01

Early diagnosis and treatment of the respiratory and gastrointestinal complications of cystic fibrosis (CF) have led to improved survival with many patients living beyond the fourth decade. Along with this increased life expectancy is the risk of further disease associated with the chronic manifestations of their condition. We report a patient with documented CF related liver disease for which he was under routine surveillance that presented with histologically proven hepatocellular carcinoma (HCC). It is important that physicians are aware of this association as increased vigilance may lead to earlier diagnosis and perhaps, a better outcome.

Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features.

Science.gov (United States)

Wood, Laura D; Heaphy, Christopher M; Daniel, Hubert Darius-J; Naini, Bita V; Lassman, Charles R; Arroyo, May R; Kamel, Ihab R; Cosgrove, David P; Boitnott, John K; Meeker, Alan K; Torbenson, Michael S

2013-12-01

Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independently screened a cohort of 219 unselected hepatocellular carcinoma resection specimens and divided cases into potential subtypes. One of these promising candidate subtypes was further evaluated using histological and molecular techniques. This subtype was characterized by a unique and consistent set of histological features: smooth chromophobic cytoplasm, abrupt focal nuclear anaplasia (small clusters of tumor cells with marked nuclear anaplasia in a background of tumor cells with bland nuclear cytology), and scattered microscopic pseudocysts--we designate this variant as 'chromophobe hepatocellular carcinoma with abrupt anaplasia'. Thirteen cases were identified (6% of all hepatocellular carcinomas), including 6 men and 7 women with an average age of 61 years. Six cases occurred in cirrhotic livers. Serum AFP was elevated in 6 out of 10 cases. There were a variety of underlying liver diseases, but cases were enrichment for chronic hepatitis B, P=0.006. Interestingly, at the molecular level, this variant was strongly associated with the alternative lengthening of telomere (ALT) phenotype by telomere FISH. ALT is a telomerase-independent mechanism of telomere maintenance and is found in approximately 8% of unselected hepatocellular carcinomas. In contrast, 11/12 (92%) of the cases of chromophobe hepatocellular carcinoma with abrupt anaplasia were ALT-positive. In summary, we propose that chromophobe hepatocellular carcinoma with abrupt anaplasia represents a new subtype of

Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients.

Science.gov (United States)

Yoo, S H; Kwon, J H; Nam, S W; Kim, H Y; Kim, C W; You, C R; Choi, S W; Cho, S H; Han, J-Y; Song, D S; Chang, U I; Yang, J M; Lee, H L; Lee, S W; Han, N I; Kim, S-H; Song, M J; Hwang, S; Sung, P S; Jang, J W; Bae, S H; Choi, J Y; Yoon, S K

2018-04-16

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response. © 2018 John Wiley & Sons Ltd.

Henoch-Schönlein Purpura Complicated by Hepatocellular Carcinoma.

Science.gov (United States)

Akizue, Naoki; Suzuki, Eiichiro; Yokoyama, Masayuki; Inoue, Masanori; Wakamatsu, Toru; Saito, Tomoko; Kusakabe, Yuko; Ogasawara, Sadahisa; Ooka, Yoshihiko; Tawada, Akinobu; Maru, Yugo; Matsue, Hiroyuki; Chiba, Tetsuhiro

2017-11-15

Although Henoch-Schönlein purpura (HSP) is known to be accompanied by malignancies, cases with hepatobiliary cancer are extremely rare. A 62-year-old man with palpable purpura rapidly extending to both lower legs was admitted to our hospital. He was undergoing follow-up for cirrhosis caused by chronic hepatitis B virus infection and hepatocellular carcinoma (HCC). He had renal dysfunction with hematuria and proteinuria and abdominal pain. Based on the clinical presentation and skin biopsy findings, he was diagnosed with HSP. The administration of steroids resulted in the rapid improvement of the patient's symptoms and he was discharged 12 days after admission.

Changes in arginase isoenzymes pattern in human hepatocellular carcinoma

International Nuclear Information System (INIS)

Chrzanowska, Alicja; Krawczyk, Marek; Baranczyk-Kuzma, Anna

2008-01-01

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide affecting preferentially patients with liver cirrhosis. The studies were performed on tissues obtained during surgery from 50 patients with HCC, 40 with liver cirrhosis and 40 control livers. It was found that arginase activity in HCC was nearly 5- and 15-fold lower than in cirrhotic and normal livers, respectively. Isoenzymes AI (so-called liver-type arginase) and AII (extrahepatic arginase) were identified by Western blotting in all studied tissues, however the amount of AI, as well as the expression of AI-mRNA were lower in HCC, in comparison with normal liver, and those of AII were significantly higher. Since HCC is arginine-dependent, and arginine is essential for cells growth, the decrease of AI may preserve this amino acid within tumor cells. Concurrently, the rise of AII can increase the level of polyamines, compounds crucial for cells proliferation. Thus, both arginase isoenzymes seem to participate in liver cancerogenesis.

CT diagnosis of rare histological variant of hepatocellular carcinoma

International Nuclear Information System (INIS)

Li Huaibo; Feng Zhipeng; Duan Shaoyin; Zhaugn Xiangrong

2009-01-01

Objective: To explore and understand the CT findings of 5 rare histological variants of hepatocellular carcinoma. Methods: CT findings of 31 cases of rare histological variants confirmed by surgery and pathology were analyzed retrospectively. Results: 13 cases were clear cell hepatocellular carcinoma. 3 cases of them showed patchy fat density in plain scans. Enhanced CT showed features of 'fast in fast out' which was similar to the common hepatocellular carcinoma. 4 cases belonged to sclerosis hepatocellular carcinoma. They appeared as heterogeneous, slowly enhancement on arterial phase images, and delay enhancement on portal venous phase and delay phase images. 9 cases belonged to mixed hepatocellular carcinoma. 5 cases of them showed inhomogeneous enhancement and 4 without enhancement during arterial phase, 3 cases showed delay enhancement and 4 without during portal venous and delay phase. 3 cases were fibrolamellar hepatocellular carcinoma. All showed obvious and fastly enhancement on arterial phase images, subsided slowly on the portal venous and delay phase images, showing features of 'fast in slow out', no enhancement was seen in the central scar. Shrinkage phenomenon on the surface of liver could be seen on the CT plain scans in sclerosis, mixed and fibrolamellar hepatocellular carcinoma. 2 cases were the type of dense hepatocellular carcinoma. The surrounding part in the 2 cases were slightly enhanced, while the most part of the center were not enhanced similar to necrosis. Conclusion: The CT findings of rate histological variant of hepatocellular carcinoma are characteristic. Analyzing the CT plain and enhancement finding is helpful to the diagnosis of these types of hepatocellular carcinoma. (authors)

Computed tomography diagnosis of hepatocellular carcinoma rupture haemorrhage

International Nuclear Information System (INIS)

Zhi Weike; Jiang Bin; Liu Jinquan; Li Sixia; Zhu Zhichang

2004-01-01

Objective: To evaluate the diagnostic value of hepatocellular carcinoma rupture hemorrhage using Computed Tomography. Methods: Six cases diagnosed hepatocellular carcinoma rupture hemorrhage were analyzed by morphic and histologic method and investigated the key point of scan in diagnosis. Result: The correct rate of hepatocellular carcinoma rupture hemorrhage by Computed Tomography is above 83 percent, it characteristic representation is strip and would high-density shadow after enhancement. Conclusion: The characteristic representation of hepatocellular carcinoma rupture hemorrhage is attain by Computed Tomography, which provides effective operation evidences for clinical operation. (authors)

Laparoscopic RFA with splenectomy for hepatocellular carcinoma.

Science.gov (United States)

Hu, Kunpeng; Lei, Purun; Yao, Zhicheng; Wang, Chenhu; Wang, Qingliang; Xu, Shilei; Xiong, Zhiyong; Huang, He; Xu, Ruiyun; Deng, Meihai; Liu, Bo

2016-07-27

The treatment of hepatocellular carcinoma (HCC) is complicated and challenging because of the frequent presence of cirrhosis. Therefore, we propose a novel surgical approach to minimize the invasiveness and risk in patients with HCC, hypersplenism, and esophagogastric varices. This was a retrospective study carried out in 25 patients with HCC and hypersplenism and who underwent simultaneous laparoscopic-guided radio-frequency ablation and laparoscopic splenectomy with endoscopic variceal ligation. Tumor size was restricted to a single nodule of splenectomy. Laparoscopic-guided radio-frequency ablation with laparoscopic splenectomy and endoscopic variceal ligation could be an available technique for patients with HCC <3 cm, hypersplenism, and esophagogastric varices. This approach may help to minimize the surgical risks and results in a fast increase in platelet counts with an acceptable rate of complications.

Current radiologic interventions in hepatocellular carcinoma

International Nuclear Information System (INIS)

Masoud, I.; Naeem, M.Q.T.; Saeed, F.; Mirza, S.A.M.; Khan, A.; Bhatti, M.A.

2006-01-01

With the rising incidence of chronic liver disease caused by viral hepatitis, hepatocellular carcinoma is showing a corresponding rise worldwide. Surgery remains the mainstay of treatment, but patients unfit for surgery or liver transplantation form the bulk of those presenting with this disease. Palliative treatments are being used to treat those and radiological modalities form the mainstay of the treatment. Radiology plays a major role in the diagnosis, treatment and follow-up of hepatocellular carcinoma. Current radiological treatment modalities include percutaneous ethanol ablation, radiofrequency ablation and trans-arterial chemoembolization. This update highlights the recent advancements in the field and compares their relative merits and demerits. (author)

Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features

OpenAIRE

Wood, Laura D; Heaphy, Christopher M; Daniel, Hubert Darius-J; Naini, Bita V; Lassman, Charles R; Arroyo, May R; Kamel, Ihab R; Cosgrove, David P; Boitnott, John K; Meeker, Alan K; Torbenson, Michael S

2013-01-01

Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independen...

Elevated serum levels of Chromogranin A in hepatocellular carcinoma.

Science.gov (United States)

Biondi, Antonio; Malaguarnera, Giulia; Vacante, Marco; Berretta, Massimiliano; D'Agata, Velia; Malaguarnera, Michele; Basile, Francesco; Drago, Filippo; Bertino, Gaetano

2012-01-01

During the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages. The study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed. The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001). Molecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy.

Hepatocellular carcinoma and impact of aflatoxin difuranocoumarin derivative system: A case report

Directory of Open Access Journals (Sweden)

Ilić Miroslav

2016-01-01

Full Text Available Introduction. Hepatocellular carcinoma (HCC is the most frequent type of liver malignancy. As a carcinogen, aflatoxin B1 (AFB1 causes HCC by inducing deoxyribonucleic acid adducts that lead to genetic changes in liver cells and may be the cause of HCC in up to 30% of cases. The incidence of HCC has been on the rise and is an issue in the countries of the Western Balkans. Case Outline. This paper presents a case of a 37-year-old woman who was diagnosed with HCC, without hepatitis B, hepatitis C, or liver cirrhosis. The patient consumed milk and dairy products in quantities of over two liters per day over the course of 20 years, which indicates the impact of aflatoxin in milk on HCC. A positive signal for the presence of AFB1 was detected by ELISA (enzyme-linked immunosorbent assay in-house using immunoperoxidase screening test. Conclusion. As carcinogenic difuranocoumarin derivative, aflatoxin B1 is the most likely cause of malignant transformation of hepatocytes, which resulted in hepatocellular carcinoma in this patient.

Metastases of Hepatocellular Carcinoma Misdiagnosed as Isolated Hypertrophic Cardiomyopathy.

Science.gov (United States)

Greco, Assunta; De Masi, Roberto; Orlando, Stefania; Metrangolo, Antonio; Zecca, Vittorio; Morciano, Giancarlo; De Donno, Antonella; Bagordo, Francesco; Piccinni, Giancarlo

At present, cardiac metastasis of hepatocellular carcinoma is rarely mentioned in the literature. We report a hepatocellular carcinoma patient with cardiac metastasis misdiagnosed as hypertrophic cardiomyopathy in 2011. Two years later, on presentation of syncope, an abnormal ventricular septal size was recorded by ultrasound scan, and was subsequently shown by magnetic resonance imaging to be a tumour lesion. A myocardial biopsy confirmed infiltration of hepatocellular carcinoma. This observation underlines the risk of hepatocellular carcinoma cardiac metastasis, manifested in its infiltrative form as hypertrophic cardiomyopathy. In conclusion, we suggest that the ultrasound appearance of hypertrophic cardiomyopathy in hepatocellular carcinoma patients should be seen as a "red flag" and recommend the introduction of magnetic resonance imaging assessment of transplant candidates.

Predictors of hospital re-admissions among Hispanics with hepatitis C-related cirrhosis.

Science.gov (United States)

Atla, Pradeep R; Sheikh, Muhammad Y; Gill, Firdose; Kundu, Rabindra; Choudhury, Jayanta

2016-01-01

Hospital re-admissions in decompensated cirrhosis are associated with worse patient outcomes. Hispanics have a disproportionately high prevalence of hepatitis C virus (HCV)-related morbidity and mortality. The goal of this study was to evaluate the factors affecting re-admission rates among Hispanics with HCV-related cirrhosis. A total of 292 consecutive HCV-related cirrhosis admissions (Hispanics 189, non-Hispanics 103) from January 2009 to December 2012 were retrospectively reviewed; 132 were cirrhosis-related re-admissions. The statistical analysis was performed using STATA version 11.1. Chi-square/Fisher's exact and Student's t-tests were used to compare categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to identify predictors for hospital readmissions. Among the 132 cirrhosis-related readmissions, 71% were Hispanics while 29% were non-Hispanics (P=0.035). Hepatic encephalopathy (HE) and esophageal variceal hemorrhage were the most frequent causes of the first and subsequent readmissions. Hispanics with readmissions had a higher Child-Turcotte-Pugh (CTP) class (B and C) and higher model for end-stage liver disease (MELD) scores (≥15), as well as a higher incidence of alcohol use, HE, spontaneous bacterial peritonitis, hepatocellular carcinoma, and varices (P<0.05). The majority of the study patients (81%) had MELD scores <15. Multivariate regression analysis identified alcohol use (OR 2.63; 95%CI 1.1-6.4), HE (OR 5.5; 95%CI 2-15.3), varices (OR 3.2; 95%CI 1.3-8.2), and CTP class (OR 3.3; 95%CI 1.4-8.1) as predictors for readmissions among Hispanics. CTP classes B and C, among other factors, were the major predictors for hospital readmissions in Hispanics with HCV-related cirrhosis. The majority of these readmissions were due to HE and variceal hemorrhage.

Curative salvage liver transplantation in patients with cirrhosis and hepatocellular carcinoma : An intention-to-treat analysis

NARCIS (Netherlands)

de Haas, Robbert J.; Lim, Chetana; Bhangui, Prashant; Salloum, Chady; Compagnon, Philippe; Feray, Cyrille; Calderaro, Julien; Luciani, Alain; Azoulay, Daniel

The salvage liver transplantation (SLT) strategy was conceived for initially resectable and transplantable (R&T) hepatocellular carcinoma (HCC) patients, to try to obviate upfront liver transplantation, with the safety net of SLT in case of postresection recurrence. The SLT strategy is successful or

P0525 : N-Acetylated alpha smooth muscle actin levels are increased in hepatic fibrosis but decreased in hepatocellular carcinoma

DEFF Research Database (Denmark)

Nielsen, M.J.; Nielsen, Signe Holm; Hansen, N.U.B.

2015-01-01

Alpha Smooth Muscle Actin (a-SMA) is upregulated together with extracellular matrix (ECM) during activation of Hepatic Stellate Cells (HSCs) in fibrosis. Histone deacetylase (HDAC) remove acetylations and regulate the expression of genes, which is associated with cancers. There is a close...... relationship between cirrhosis and hepatocellular carcinoma (HCC), and markers enabling identification of patients in risk of developing HCC with cirrhosis is a major unmet clinical need. We developed an ELISA for the assessment of acetylated a-SMA (Aca- SMA) in serum. The objective was to investigate...

SERUM LEPTIN LEVENS AND HEPATOCELLULAR CARCINOMA: REVIEW ARTICLE.

Science.gov (United States)

Andrighetto, Luiza Vitelo; Poziomyck, Aline Kirjner

2016-01-01

Hepatocellular carcinoma is one of the most frequent types of malignant tumors in the world. There is growing evidence of the relationship between it development and obesity. The mechanism that links obesity to cancer is still not fully understood; however, it is essential to the understanding the adipose tissue in metabolic changes related to obesity and hepatocellular carcinoma. To review the influence of serum leptin levels in patients with hepatocelular carcinoma. Systematic review of the literature based on the methodology of the Cochrane Institute. The search for articles was in the database: Science Direct, Scielo, Medline, Lilacs e Pubmed. The key words used were hepatocellular carcinoma, leptin, adipokine. After evaluation of individual studies, were selected seven studies. The results previously studied are still inconsistent and contradictory, and leptin can be effectively involved in the occurrence and development of hepatocellular carcinoma. Therefore, it is necessary to develop prospective, well-designed and conducted focusing on the role and specific mechanisms of this hormone in patients with hepatocellular carcinoma, so that new correlations can be properly supported. O carcinoma hepatocelular é um dos tipos mais frequentes de tumores malignos no mundo. Há crescentes evidências da relação entre o seu desenvolvimento e a obesidade. O mecanismo que os relaciona ainda não é completamente entendido. Entretanto é essencial a compreensão do tecido adiposo nas alterações metabólicas relacionadas à obesidade e ao câncer. Revisar a influência dos níveis séricos de leptina em pacientes com carcinoma hepatocelular. Trata-se de revisão bibliográfica baseada na metodologia do Instituto Cochrane; a busca de dados foi realizada na base de dados Science Direct, Scielo, Medline, Lilacs e Pubmed, empregando as seguintes descritores: hepatocellular carcinoma, leptin, adipokine. Após avaliação individual dos artigos selecionaram-se sete estudos

Diagnostic Approaches to Metastatic Hepatocellular Carcinoma of the Orbit.

Science.gov (United States)

Geske, Michael J; Bloomer, Michele M; Kersten, Robert C; Vagefi, M Reza

Orbital metastasis of hepatocellular carcinoma is exceedingly rare and caries a grave prognosis. Three cases of metastatic orbital hepatocellular carcinoma in which the primary tumor was initially unknown and the diagnostic challenges encountered are presented. With hepatocellular carcinoma, open biopsy and palliative tumor debulking has an increased bleeding risk due to the highly vascular nature of the tumor and coagulopathy associated with chronic liver disease. As an alternative, fine needle aspiration biopsy should be considered for hepatocellular carcinoma with a readily accessible mass and the availability of an experienced cytopathologist.

Morphologic Subtypes of Hepatocellular Carcinoma.

Science.gov (United States)

Torbenson, Michael S

2017-06-01

Hepatocellular carcinomas can be further divided into distinct subtypes that provide important clinical information and biological insights. These subtypes are distinct from growth patterns and are on based on morphologic and molecular findings. There are 12 reasonably well-defined subtypes as well as 6 provisional subtypes, together making up 35% of all hepatocellular carcinomas. These subtypes are discussed, with an emphasis on their definitions and the key morphologic findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Hepatocellular carcinoma: a clinico pathological study

International Nuclear Information System (INIS)

Abbasi, A.; Butt, N.; Bhutto, A.R.; Gulzar, K.; Munir, S.M.

2010-01-01

To describe the clinico-pathological and radiological profile of hepatocellular carcinoma. All consecutive patients suspected of having hepatocellular carcinoma (HCC), were admitted and included in this study. Diagnosis of HCC was established by clinical, biochemical, ultrasonographic and histopathologic findings. Patients with primary carcinoma elsewhere in the body, metastatic in the liver, fibrolamellar carcinoma and benign tumours were excluded from the study. At ultrasonography, the details of tumour size and number, portal vein thrombosis and presence of ascites were recorded. Patients were staged according to Okuda staging system. Results were described in mean and percentage values. There were 82 patients with hepatocellular carcinoma including 58 males and 24 females, with male to female ratio of 2.8:1. The mean age of patients was 56.24 +- 13.65 years. Right hypochondrial pain was the main symptom in 52 (63.4%) patients. The duration of symptoms varied from 1 month to 2 years. Tumour size was larger than 50% of liver size in 42 (51.2%) with portal vein thrombosis in 10 (12.19%). Anti HCV was positive in 44 (53.7%), HBsAg in 26 (31.7%) and both were found positive in 2 (2.44%) patients. Ten patients (12.2/%) found negative both for anti-HCV and HBsAg. According to Okuda staging system 18 patients had stage 1, 50 had stage 2 and 14 had stage 3 hepatocellular carcinoma. The mean age of presentation of hepatocellular carcinoma was younger as compared to western countries with potentially large non-resectable lesions. Chronic hepatitis C and B was found to be the major known factors. Patients with chronic hepatitis C and B should undergo vigorous HCC surveillance to detect early, potentially respectable HCC. (author)

Hook1 inhibits malignancy and epithelial-mesenchymal transition in hepatocellular carcinoma.

Science.gov (United States)

Sun, Xu; Zhang, Qi; Chen, Wei; Hu, Qida; Lou, Yu; Fu, Qi-Han; Zhang, Jing-Ying; Chen, Yi-Wen; Ye, Long-Yun; Wang, Yi; Xie, Shang-Zhi; Hu, Li-Qiang; Liang, Ting-Bo; Bai, Xue-Li

2017-07-01

Hook1 is a member of the hook family of coiled-coil proteins, which is recently found to be associated with malignant tumors. However, its biological function in hepatocellular carcinoma is yet unknown. Here, we evaluated the Hook1 levels in human hepatocellular carcinoma samples and matched peritumoral tissues by real-time polymerase chain reaction. Small interfering RNA knockdown and a transforming growth factor-β-induced epithelial-mesenchymal transition model were employed to investigate the biological effects of Hook1 in hepatocellular carcinoma. Our results indicated that Hook1 levels were significantly lower in hepatocellular carcinoma tissues than in the peritumoral tissues. In addition, Hook1 expression was significantly associated with hepatocellular carcinoma malignancy. Hook1 was downregulated after transforming growth factor-β-induced epithelial-mesenchymal transition. Moreover, Hook1 knockdown promoted epithelial-mesenchymal transition and attenuated the sensitivity of hepatocellular carcinoma cells to doxorubicin. In summary, our results indicate that downregulation of Hook1 plays a pivotal role in hepatocellular carcinoma progression via epithelial-mesenchymal transition. Hook1 may be used as a novel marker and therapeutic molecular target in hepatocellular carcinoma.

CT findings of exophytic hepatocellular carcinoma

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Lee, Sang Jin; Cho, June Sik; Kim, Hyung Lyul; Lee, Chung Keun; Kim, Dae Hong; Rhee, Byung Chull [Chungnam National University College of Medicine, Daejeon (Korea, Republic of)

1993-11-15

We retrospectively evaluated the characteristic computed tomographic(CT) findings in nine patients with exohepatic hepatocellular carcinoma(HCC) pathologically prove by surgery(n=2) or percutaneous needle biopsy(n=7). The CT findings of exphepatic HCC were correlated with clinical findings and compared with those of usual HCC. Lesions were in the left lobe(n=7) and right lobe(n=2) of the liver. All lesions showed a well-marginated hypodense mass with capsular enhancement on enhanced CT scan. The patterns of capsular enhancement were complete in five and partial in four case. The portal vein thrombosis was seen only in one case. There was no difference between exohepatic HCC and usual HCC in clinical findings such as increased {alpha}-fetoprotein({alpha}-FP), positive hepatitis B surface antigen(HBsAg), and underlying liver cirrhosis. In conclusion, the CT findings of exohepatic HCC were a well-defined hyperdense mass with complete or partial capsular enhancement and these findings may be useful in differentiation from the tumors of adjacent organs.

Carcinoma hepatocelular: impacto do tempo em lista e das formas de tratamento pré-operatório na sobrevida do transplante de fígado cadavérico na era pré-MELD em um centro no Brasil Hepatocellular carcinoma: impact of waiting list and pre-operative treatment strategies on survival of cadaveric liver transplantation in pre-MELD era in one center in Brazil

Directory of Open Access Journals (Sweden)

Alexandre Coutinho Teixeira de Freitas

2007-09-01

-Pugh A e com diagnóstico de cirrose por hepatite C. Todos os outros fatores analisados foram iguais entre os 2 grupos. CONCLUSÃO: Os doentes com carcinoma hepatocelular, submetidos a transplante hepático cadavérico, apresentam maior sobrevida em 3 meses e 1 ano do que os não acometidos por esta neoplasia. Essa diferença é possivelmente relacionada à realização do transplante nos pacientes com carcinoma hepatocelular em estádio menos avançado da cirrose.BACKGROUND: Liver transplantation is the main treatment option for hepatocellular carcinoma in patients with cirrhosis. AIM: Three months and 3 years survival were analysed in patients with cirrhosis and hepatocellular carcinoma and in patients with only cirrhosis. METHODS: Charts of patients subjected to cadaveric liver transplantation at the Clinical Hospital of the Federal University of Paraná, Curitiba, PR, Brazil, between January 5th of 2001 and February 17th of 2006 were reviewed. Patients were divided into two groups for 3 months and 1 year survival analysis: cirrhosis and hepatocellular carcinoma and cirrhosis only. The two groups were also compared in relation to donor and recipient sex and age, etiology of cirrhosis, Child-Pugh and MELD scores at the time of the transplantation, warm isquemia time, cold isquemia time, units of red blood cells transfused during the transplantation, intensive care unit stay and total hospital stay. RESULTS: One hundred and forty six liver transplantation patients were analysed: 75 were excluded because of incomplete data and 71 were included. General 3 months and 1 year survivals were 77,4% and 74,6% respectively. Patients with hepatocellular carcinoma (n = 12 presented 3 months and 1 year survivals of 100%. These rates were significantly higher than those of patients without hepatocellular carcinoma (n = 59; 72,8% and 69,4%. Mean MELD score, mean Child-Pugh score and mean number of red blood cells transfused were significantly higher in patients without hepatocellular

Overexpression of Cullin7 is associated with hepatocellular carcinoma progression and pathogenesis.

Science.gov (United States)

An, Jun; Zhang, Zhigang; Liu, Zhiyong; Wang, Ruizhi; Hui, Dayang; Jin, Yi

2017-12-06

Overexpression of Cullin7 is associated with some types of malignancies. However, the part of Cullin7 in hepatocellular carcinoma remains unclear. The aim of this study was to investigate the role of Cullin7 in pathogenesis and the progression of hepatocellular carcinoma. In the present study, the expression of Cullin7 in hepatocellular carcinoma cell lines and five surgical hepatocellular carcinoma specimens was detected with quantitative reverse transcription PCR and western blotting. In addition, the protein expression of Cullin7 was examined in 162 cases of archived hepatocellular carcinoma using immunohistochemistry. We found elevated expression of both mRNA and protein levels of Cullin7 in hepatocellular carcinoma cell lines, and Cullin7 protein was significantly upregulated in hepatocellular carcinoma compared with paired normal hepatic tissues. The immunohistochemistry analysis revealed that overexpression of Cullin7 occurred in 69.1% of hepatocellular carcinoma samples, which was a significantly higher rate than that in adjacent normal hepatic tissue (P hepatocellular carcinoma HepG2 cells, we revealed that Cullin7 could significantly enhance cell proliferation, growth, migration and invasion. Conversely, knocking down Cullin7 expression with short hairpin RNAi in hepatocellular carcinoma HepG2 cells inhibited cell proliferation, growth, migration and invasion. Our studies provide evidence that overexpression of Cullin7 plays an important role in the pathogenesis and progression of hepatocellular carcinoma and may be a valuable marker for hepatocellular carcinoma management.

Hep par-1: a novel immunohistochemical marker for differentiating hepatocellular carcinoma from metastatic carcinoma

International Nuclear Information System (INIS)

Hanif, R.

2014-01-01

To evaluate the diagnostic utility of Hep par-1 in differentiating hepatocellular carcinoma from metastatic carcinoma taking histopathology as a gold standard. Study Design: Comparative cross-sectional study. Place and Duration of Study: Pathology Department, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from April 2007 to February 2008. Methodology: Hep par-1 immunohistochemical stain was performed on 60 cases of liver carcinoma, 30 cases each of metastatic and hepatocellular carcinoma. Information regarding patient age, gender, sign and symptoms, radiographic findings, histological grade of tumour, and expression of Hep par-1 on hepatocellular and metastatic carcinoma were recorded on proforma sheet. Sensitivity, specificity, positive and negative predictive values, and accuracy of Hep par-1 were calculated using the formulas. Results: Hep par-1 expression was noted in 25 out of 30 cases of hepatocellular carcinoma (83%). Out of 30 cases of metastatic carcinoma, only one case expressed staining in < 5% tumour cells and remaining 29 cases showed no reactivity. The age of the patients with hepatocellular carcinoma ranged from 40 to 76 years with a median age of 60.5 years and 40 - 75 years for metastatic carcinomas with a median age of 57.5 years. Conclusion: Hep par-1 is a reliable immunohistochemical marker for cases of hepatocellular carcinoma (HCC). It can be used along with other markers in morphologically difficult cases when differential diagnosis lies between poorly differentiated HCC and metastatic carcinoma of liver. (author)

3 T MRI of hepatocellular carcinomas in patients with cirrhosis: Does T2-weighted imaging provide added value?

International Nuclear Information System (INIS)

Guo, L.; Liang, C.; Yu, T.; Wang, G.; Li, N.; Sun, H.; Gao, F.; Liu, C.

2012-01-01

Aim: To assess whether T2-weighted imaging (T2WI) provides any added value for the detection of hepatocellular carcinoma (HCC) in patients with cirrhosis, especially for lesions smaller than 2 cm. Materials and methods: Sixty-five patients with cirrhosis underwent liver 3 T MRI. Images were qualitatively analysed independently by two observers in two separate sessions, including a dynamic enhanced session and a combination of dynamic and T2WI. The diagnostic accuracy was evaluated using the alternating free-response receiver operating characteristic. Sensitivity and positive predictive values were calculated for all HCCs and for the subgroup of HCCs that were smaller than 2 cm. Additionally, artefacts on T2WI were evaluated by two observers in consensus. Results: Ninety HCCs (>2 cm n = 36; ≤2 cm n = 54) were detected in 46 patients. For all HCCs and for lesions smaller than 2 cm, the sensitivities were significantly higher for the combined session than the dynamic session alone (p < 0.05). Conversely, for the Az and positive predictive values, there was no significant difference between the two sessions. For smaller HCC, 9% (5/54) and 7% (4/54) of the 54 HCCs were correctly interpreted by observers 1 and 2, respectively, only when T2WI was included. Three false-positive lesions (≤2 cm) were correctly diagnosed by one of the observers after combining T2WI. Conspicuity of only one large HCC was severely reduced by the artefacts from massive ascites. Conclusion: At 3 T liver imaging, combining with T2WI can improve the sensitivity of detection of HCC compared with dynamic MRI alone by increasing observer confidence, especially for lesions smaller than 2 cm. Additionally, T2 image quality was not significantly affected by artefacts.

3 T MRI of hepatocellular carcinomas in patients with cirrhosis: Does T2-weighted imaging provide added value?

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Guo, L.; Liang, C.; Yu, T.; Wang, G.; Li, N.; Sun, H.; Gao, F. [Shandong Medical Imaging Research Institute, Shandong University, Jinan (China); Liu, C., E-mail: liucheng1025@163.com [Shandong Medical Imaging Research Institute, Shandong University, Jinan (China)

2012-04-15

Aim: To assess whether T2-weighted imaging (T2WI) provides any added value for the detection of hepatocellular carcinoma (HCC) in patients with cirrhosis, especially for lesions smaller than 2 cm. Materials and methods: Sixty-five patients with cirrhosis underwent liver 3 T MRI. Images were qualitatively analysed independently by two observers in two separate sessions, including a dynamic enhanced session and a combination of dynamic and T2WI. The diagnostic accuracy was evaluated using the alternating free-response receiver operating characteristic. Sensitivity and positive predictive values were calculated for all HCCs and for the subgroup of HCCs that were smaller than 2 cm. Additionally, artefacts on T2WI were evaluated by two observers in consensus. Results: Ninety HCCs (>2 cm n = 36; {<=}2 cm n = 54) were detected in 46 patients. For all HCCs and for lesions smaller than 2 cm, the sensitivities were significantly higher for the combined session than the dynamic session alone (p < 0.05). Conversely, for the Az and positive predictive values, there was no significant difference between the two sessions. For smaller HCC, 9% (5/54) and 7% (4/54) of the 54 HCCs were correctly interpreted by observers 1 and 2, respectively, only when T2WI was included. Three false-positive lesions ({<=}2 cm) were correctly diagnosed by one of the observers after combining T2WI. Conspicuity of only one large HCC was severely reduced by the artefacts from massive ascites. Conclusion: At 3 T liver imaging, combining with T2WI can improve the sensitivity of detection of HCC compared with dynamic MRI alone by increasing observer confidence, especially for lesions smaller than 2 cm. Additionally, T2 image quality was not significantly affected by artefacts.

Small hepatocellular carcinoma versus small cavernous hemangioma

International Nuclear Information System (INIS)

Choi, B.I.; Park, H.W.; Kim, S.H.; Han, M.C.; Kim, C.W.

1989-01-01

To determine the optimal pulse sequence for detection and differential diagnosis of small hepatocellular carcinomas and cavernous hemangiomas less than 5 cm in diameter, the authors have analyzed spin-echo (SE) images of 15 small hepatocellular carcinomas and 31 small cavernous hemangiomas obtained at 2.0 T. Pulse sequences used included repetition times (TRs) of 500 and 2,000 msec and echo times (TEs) of 30,60,90,120,150, and 180 msec. Mean tumor-liver contrast-to-noise ratios on the SE 2,000/60 (TR msec/TE msec) sequence were 23.90 ± 16.33 and 62.10 ± 25.94 for small hepatocellular carcinomas and hemangiomas, respectively, and were significantly greater than for all other pulse sequences. Mean tumor-liver signal intensity ratios on the SE 2,000/150 sequence were 2.34 ± 1.72 and 6.04 ± 2.72 for small hepatocellular carcinomas and hemangiomas, respectively, and were significantly greater than for all other pulse sequences in hemangiomas

Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a case cohort study.

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Carr, Brian I; Buch, Shama C; Kondragunta, Venkateswarlu; Pancoska, Petr; Branch, Robert A

2008-08-01

A total of 967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end-point for all analyses. We found in our overall analysis, that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated alpha-fetoprotein (AFP) or bilirubin or alkaline phosphatases were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient subgroups based on poor liver function and aggressive tumor characteristics. In subgroup analysis based on these subsets, there was clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant, independent but modest risk factors. The results of this large dataset show that amongst nonsurgical HCC patients, there are clear subsets with longer survival than other subsets. This data also supports the concept of heterogeneity of HCC.

Changing incidence patterns of hepatocellular carcinoma among age groups in Taiwan.

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Hung, Giun-Yi; Horng, Jiun-Lin; Yen, Hsiu-Ju; Lee, Chih-Ying; Lin, Li-Yih

2015-12-01

This study examined and compared the incidence patterns of hepatocellular carcinoma among age groups in Taiwan, 30 years after a universal hepatitis B virus immunization program was launched. Data for hepatocellular carcinoma diagnosed in 2003-2011 were collected from the population-based Taiwan Cancer Registry. Age-standardized incidence rates were calculated to analyze and compare the changes in incidence rates and trends. More specific analyses were performed on four age groups separated by sex. A total of 82,856 patients were diagnosed with hepatocellular carcinoma in 2003-2011 in Taiwan, yielding an age-standardized incidence rate of 32.97 per 100,000 person-years. Hepatocellular carcinoma was predominantly diagnosed in middle-aged adults (50.1%) and elderly people (49.1%), in contrast to the low incidences in children (0.04%) and adolescents and young adults (0.8%). Striking variations in trends were found for children (annual percent change: -16.6%, 2003-2010) and adolescents and young adults (annual percent change: -7.9%, 2003-2011). The incidence rate of hepatocellular carcinoma in children decreased to zero in 2011; only a slight decline in trends occurred for the middle-aged group (annual percent change: -2%, 2003-2011), and a slight upward trend was observed for elderly people (1.3%), specifically in women (1.7%). In Taiwan, hepatitis B virus-related hepatocellular carcinoma was nearly eradicated in children in 2011. The findings on age-specific incidence patterns and trends of hepatocellular carcinoma suggest that different control strategies for treating this devastating disease in the future be made according to age. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Pathomorphological characteristics of 102 cases of Thorotrast-related hepatocellular carcinoma, cholangiocarcinoma, and hepatic angiosarcoma

International Nuclear Information System (INIS)

Nakashima, T.; Kojiro, M.; Ito, Y.; Mori, T.; Kido, C.

1987-01-01

We described the pathomorphological characteristics of 102 autopsy cases of Thorotrast (Th) related hepatic malignancies, and compared these to the features of non-Th-related cases. Among the 102 Th-related hepatic malignancies, 44 (43.1%) were cholangiocarcinoma (CHC), 39 (38.3%) were angiosarcoma (AGS), 16 (15.7%) were hepatocellular carcinoma (HCC), and 3 (2.9%) were double cancer. Grossly, the majority (91.7%) of Th-related CHC was located in the middle-peripheral portion of the liver. Th-related AGS was classified into four types: diffuse micronodular, multinodular, massive and mixed multinodular, and massive. Histologically, in CHC and HCC cases, there were no significant differences between Th-related and non-Th-related cases. AGS was characterized by two cell types (spindle-shaped cells and polyhedral cells) and three growth patterns (sinusoidal, carvernous, and solid). In non-cancerous areas, foci of varying degrees of sinusoidal dilatation with hyperplastic changes of sinusoidal lining cells were observed in all AGS cases and in some of the cases of Th-related CHC and HCC cases. In Th-related CHC cases, papillary proliferation of the epithelium of relatively large bile ducts was seen in 11 (29.7%) of the 37 cases, and proliferation of small bile ducts and/or bile ductules was seen in 9 (24.3%) of the 37 cases. However, similar histologic changes were also observed in the non-Th- related CHC cases. In Th-related HCC cases, mixed macro- and micronodular cirrhosis was superimposed on varying degrees of hepatic fibrosis related to Th deposition in 4 cases. (21.1%). (author)

Diagnostic and therapeutic management of hepatocellular carcinoma

Science.gov (United States)

Bellissimo, Francesco; Pinzone, Marilia Rita; Cacopardo, Bruno; Nunnari, Giuseppe

2015-01-01

Hepatocellular carcinoma (HCC) is an increasing health problem, representing the second cause of cancer-related mortality worldwide. The major risk factor for HCC is cirrhosis. In developing countries, viral hepatitis represent the major risk factor, whereas in developed countries, the epidemic of obesity, diabetes and nonalcoholic steatohepatitis contribute to the observed increase in HCC incidence. Cirrhotic patients are recommended to undergo HCC surveillance by abdominal ultrasounds at 6-mo intervals. The current diagnostic algorithms for HCC rely on typical radiological hallmarks in dynamic contrast-enhanced imaging, while the use of α-fetoprotein as an independent tool for HCC surveillance is not recommended by current guidelines due to its low sensitivity and specificity. Early diagnosis is crucial for curative treatments. Surgical resection, radiofrequency ablation and liver transplantation are considered the cornerstones of curative therapy, while for patients with more advanced HCC recommended options include sorafenib and trans-arterial chemo-embolization. A multidisciplinary team, consisting of hepatologists, surgeons, radiologists, oncologists and pathologists, is fundamental for a correct management. In this paper, we review the diagnostic and therapeutic management of HCC, with a focus on the most recent evidences and recommendations from guidelines. PMID:26576088

Peritoneal carcinomatosis: an unusual presentation of fibrolamellar hepatocellular carcinoma

International Nuclear Information System (INIS)

Vicente, R.; Garcia-Gutierrez, J. A.; Fernandez, A.; Santalla, F.

2001-01-01

Fibrolamellar hepatocellular carcinoma is an uncommon malignant tumor with characteristic clinical, radiological and histopathological features that is usually associated with a more favorable natural course and greater survival than more common variants of hepatocellular carcinoma. We describe an atypical case of a fibrolamellar hepatocellular carcinomas sowing aggressive behaviour in a 20-year-old woman. The lesion presented with massive ascites, and imaging studies revealed extensive peritoneal metastatic spread. (Author) 8 refs

Hepatitis virus and hepatocellular carcinoma in Brazil: a report from the State of Espírito Santo

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Patrícia Lofêgo Gonçalves

2014-10-01

Full Text Available Introduction Few studies have examined hepatocellular carcinoma (HCC in Brazil, and the incidence and risk factors for this type of malignancy vary greatly geographically. In this paper, we report several risk factors associated with HCC diagnosed at the University Hospital in Vitória, ES, Brazil. Methods We reviewed 274 cases of HCC (January 1993 to December 2011 in which hepatitis B (HBV and C (HCV virus infection and chronic alcoholism were investigated. A diagnosis of hepatocellular carcinoma was confirmed by histology or by the presence of a characteristic pattern on imaging. Results HCC with associated liver cirrhosis was noted in 85.4% of cases. The mean ages of men and women were 56.6 years and 57.5 years, respectively. The male-to-female ratio was 5.8:1. Associated risk factors included the following: HBV, 37.6% (alone, 23.4%; associated with chronic alcoholism, 14.2%; HCV, 22.6% (alone, 13.5%; associated with chronic alcoholism, 9.1%, chronic alcoholism, 17.1%, non-alcoholic steatohepatitis, 2.6% and cryptogenic, 19.3%. The male-to-female ratio was higher in cases associated with HBV or chronic alcoholism compared with HCV-associated or cryptogenic cases. In 40 cases without associated cirrhosis, the male-to-female ratio and mean age were lower than those in cirrhosis-associated cases. Conclusions These results demonstrate that the main risk factor associated with HCC in the State of Espírito Santo is HBV. Chronic alcoholism is an important etiological factor, alone or in association with HBV or HCV infection.

High Incidence of Hepatitis B Infection-Associated Cirrhosis and Hepatocellular Carcinoma in the Southeast Asian Patients with Portal Vein Thrombosis

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Auewarakul Chirayu U

2011-06-01

Full Text Available Abstract Background Portal vein thrombosis (PVT is a rare condition associated with serious morbidity and mortality. The objective of this study was to determine the frequency, clinical presentations, and risk factors of PVT from the set of data firstly collected among the Southeast Asian population. Methods A retrospective study was undertaken to identify patients diagnosed with thrombosis of the portal system and other abdominal veins. The hospital medical records were retrieved based on the selected ICD-10 codes. Clinical presentations were collected and risk factors determined. Results From 2000-2009, 467 hospital charts with designated ICD-10 codes of I81, I82.2, I82.3, I82.8, I82.9, or K55.0 were identified. PVT (I81 was the most common thrombosis (194 cases, 41.54%. The majority of PVT patients were males (65%, older than 40 years (75%, and presented with abdominal distension/ascites (69%, splenomegaly (54.6%, and abdominal pain (50.5%. Overall, the predominant risk factor was hepatocellular carcinoma (HCC (52.5%, followed by liver cirrhosis without cancer (9.3%, abdominal infection/inflammation (9.3%, cholangiocarcinoma (8.2%, and abdominal intervention (7.7%. In young patients, abdominal interventions including umbilical catheterization (23.1% and hepatectomy (7.7% were the most frequent risks whereas in older cases, primary hepatobiliary cancer and cirrhosis (78% were the major risks. Liver metastases from other organs were infrequently found. Chronic hepatitis B virus (HBV infection was the main etiology associated with cirrhosis/HCC leading to PVT in this cohort. A third of the older PVT patients (age >40 had HBV and very few carried hepatitis C virus (HCV whereas none of the young PVT patients (age Conclusion HBV is the major risk of PVT in the Southeast Asian population. Several risk factors identified in this population have rarely been described and some are remarkably different from those reported in the West. Host and

No increased risk of hepatocellular carcinoma in cirrhosis due to Wilson disease during long-term follow-up

NARCIS (Netherlands)

van Meer, Suzanne; de Man, Robert A.; van den Berg, Aad P.; Houwen, Roderick H. J.; Linn, Francisca H. H.; van Oijen, Martijn G. H.; Siersema, Peter D.; van Erpecum, Karel J.

Background and AimsData on risk of hepatocellular carcinoma (HCC) in patients with Wilson disease are scarce. We determine HCC risk in a well-defined cohort of Wilson patients. MethodsAll patients with a confirmed diagnosis of Wilson disease (Leipzig score4) in three Dutch university referral

radio embolization of yttrium 90 glass microspheres in treatment of hepatocellular carcinoma

International Nuclear Information System (INIS)

El Fouly, A.H.A.

2010-01-01

Hepatocellular carcinoma (HCC) is a common cancer that typically occurs in the setting of cirrhosis and chronic hepatitis virus infections. HCC is considered currently as global problem; its incidence is expected to increase dramatically by the next few decades. More than 90 % of the accidentally diagnosed patients have non resectable tumor. Portal vein thrombosis, diffuse multifocal liver infiltration and large tumor burden are considered to be a great obstacle in front of the modern lines of treatment, even with Child A liver cirrhosis. Transarterial intrahepatic application of Yttrium-90 glass microspheres may allow effective local ablative treatment of patients with intrahepatic advanced hepatocellular carcinoma (HCC) with or without portal vein thrombosis. The aim of this open-label phase II study was to validate evidence on the safety and efficacy of this treatment in an European cohort of patients with locally advanced HCC such as (large tumor burden, multifocal distribution, portal vein thrombosis). And to assess the response rate according to different approved response assessment guidelines (WHO, RECIST and EASL). Patients and Methods Starting from November 2006 till March 2009, one hundred and eight advanced unresectable HCC patients with and without portal vein thrombosis were included in this prospective study. Yttrium-90 microspheres radiotherapy was performed in a lobar fashion through the right or left hepatic artery. In bilobar disease, right and left liver lobe were treated with 4-6 weeks intervals in between. Response rate was assessed according to different international response assessment criteria (WHO, RECIST and EASL) with sequential computed tomography scans till the last clinical visit or death. The safety of this technique was assessed according to the Common Toxicity Criteria version 3

Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma

DEFF Research Database (Denmark)

Oliveri, Roberto S; Wetterslev, Jørn; Gluud, Christian

2011-01-01

Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC.......Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC....

Research progress of vascular change after TACE in hepatocellular carcinoma

International Nuclear Information System (INIS)

Kang Zhen; Xiao Enhua

2013-01-01

Mortality rate of hepatocellular carcinoma is high. The majority of the patients are diagnosed in advanced stage and lose surgical opportunities. Many studies have reported transcatheter arterial chemoembolization (TACE) is an effective treatment for unresectable hepatocellular carcinoma, and recommended TACE as a standard treatment for hepatocellular carcinoma of Barcelona Clinical Liver Cancer staging (BCLC staging) B. However, TACE can hardly fully embolize tumor blood supply, TACE postoperative hemodynamics and angiogenesis can induce tumor recurrence and metastasis. This paper reviewed characteristics of vascular changes, mechanisms, diagnosis and treatment methods, new progress in the field of hepatocellular carcinoma after TACE. (authors)

Autopsy cases of hepatocellular carcinoma in atomic bomb survivors

International Nuclear Information System (INIS)

Fujihara, Megumu; Kurihara, Kanji; Aimitsu, Shiomi; Yukaya, Hirofumi; Hamada, Tadao.

1994-01-01

Since 1956, 388 autopsy cases of hepatocellular carcinoma (HCC) have been obtained at the Hiroshima Red Cross and A-Bomb Survivors Hospital, which consisted of those of proximately exposed 52 A-bomb survivors (mean age, 63.8 years), 105 distally exposed A-bomb survivors (mean age, 64.2 years), and the other 231 non-exposed patients (mean age, 60.6 years). Since 1985, the incidence of HCC tended to be higher in both proximately and distally exposed groups than the non-exposed group. There was no consistent tendency for the incidence of HCC by ages at autopsy and A-bombing. The incidence of liver cirrhosis was approximately 2 times higher in males than females in the non-exposed group, although no gender difference existed after 1981. In the exposed group, the incidence was similar in male and female groups. Approximately 90% of HCC patients had coexistent liver cirrhosis. Liver cirrhosis was associated with HCC in 50-60%. No significant differences in these incidences were observed between the exposed and non-exposed groups. The proportion of liver cirrhosis associated with HCC became constant in patients over the age of 40 in the non-exposed group. In the exposed group, on the other hand, the proportion reached the peak in those in their fifties and sixties. Survival time tended to be longer in the exposed group than the non-exposed group. The patients in the non-exposed group tended to have histologically atypical type and metastases, as compared with those in the exposed group. (N.K.)

Autopsy cases of hepatocellular carcinoma in atomic bomb survivors

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Fujihara, Megumu; Kurihara, Kanji; Aimitsu, Shiomi; Yukaya, Hirofumi [Hiroshima Red Cross Atomic Bomb Hospital (Japan); Hamada, Tadao

1994-12-01

Since 1956, 388 autopsy cases of hepatocellular carcinoma (HCC) have been obtained at the Hiroshima Red Cross and A-Bomb Survivors Hospital, which consisted of those of proximately exposed 52 A-bomb survivors (mean age, 63.8 years), 105 distally exposed A-bomb survivors (mean age, 64.2 years), and the other 231 non-exposed patients (mean age, 60.6 years). Since 1985, the incidence of HCC tended to be higher in both proximately and distally exposed groups than the non-exposed group. There was no consistent tendency for the incidence of HCC by ages at autopsy and A-bombing. The incidence of liver cirrhosis was approximately 2 times higher in males than females in the non-exposed group, although no gender difference existed after 1981. In the exposed group, the incidence was similar in male and female groups. Approximately 90% of HCC patients had coexistent liver cirrhosis. Liver cirrhosis was associated with HCC in 50-60%. No significant differences in these incidences were observed between the exposed and non-exposed groups. The proportion of liver cirrhosis associated with HCC became constant in patients over the age of 40 in the non-exposed group. In the exposed group, on the other hand, the proportion reached the peak in those in their fifties and sixties. Survival time tended to be longer in the exposed group than the non-exposed group. The patients in the non-exposed group tended to have histologically atypical type and metastases, as compared with those in the exposed group. (N.K.).

[Hepatocellular carcinoma originated in the caudate lobe. Surgical strategy for resection. A propos of a case].

Science.gov (United States)

Martínez-Mier, Gustavo; Esquivel-Torres, Sergio; Calzada-Grijalva, José Francisco; Grube-Pagola, Peter

2015-01-01

Hepatocellular carcinoma originating from the caudate lobe has a worse prognosis than other hepatocellular carcinoma in another segment of the liver. An isolated caudate lobe resection of the liver represents a significant technical challenge. Caudate lobe resection can be performed along with a lobectomy or as an isolated liver resection. There are very few reports about isolated caudate lobe liver resection. We report a case of successful isolated resection of hepatocellular carcinoma in the caudate lobe with excellent long-term survival. A 74 years old female with 8cm mass lesion in the caudate lobe without clinical or biochemical evidence of liver cirrhosis, serum alpha-fetoprotein 3.7 U/l, and negative hepatitis serology was evaluated for surgery. Complete resection of the lesion in 270minutes with Pringle maneuver for 13minutes was satisfactorily performed. Patient was discharged ten days after surgery without complications. Patient is currently asymptomatic, without deterioration of liver function and 48 month tumor free survival after the procedure. Isolated caudate lobe resection is an uncommon but technically possible procedure. In order to achieve a successful resection, one must have a detailed knowledge of complete liver anatomy. Tumor free margins must be obtained to provide long survival for these patients who have a malignancy in this anatomic location. Copyright © 2015. Published by Masson Doyma México S.A.

A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

Science.gov (United States)

Faltermeier, Claire; Busuttil, Ronald W.; Zarrinpar, Ali

2015-01-01

Hepatocellular carcinoma (HCC), the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%–30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC. PMID:28943622

A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

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Claire Faltermeier

2015-09-01

Full Text Available Hepatocellular carcinoma (HCC, the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%–30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC.

Hepatocellular carcinoma: Implications for Asia-Pacific Oncology Nurses

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Deborah A Boyle

2017-01-01

Full Text Available Hepatocellular carcinoma (HCC is a prominent malignancy in the Asia-Pacific region. Despite considerable knowledge about it's scope and nature this malignancy remains incurable. This manuscript reviews the epidemiology of this cancer, its pathogenesis, risk factors, potential prevention, surveillance, treatment, and the oncology nurses' role relative to this malignancy. A literature search from the past decade was performed using the PubMed and CINAHL databases using the search terms “hepatocellular carcinoma,” “Asia,” and “nursing issues”. Themes such as etiology, prevention, treatment, and prognosis were included in this synthesis which has particular relevance to oncology nurses within the Asia-Pacific region.

Chronic Hepatitis C-Related Cirrhosis Hospitalization Cost Analysis in Bulgaria

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Maria Dimitrova

2017-08-01

Full Text Available ObjectiveHCV infection is a leading cause of chronic liver disease with long-term complications—extensive fibrosis, cirrhosis, and hepatocellular carcinoma. The objective of this study is to perform cost analysis of therapy of patients with chronic HCV-related cirrhosis hospitalized in the University Hospital “Queen Joanna-ISUL” for 3-year period (2012–2014.MethodsIt is a prospective, real life observational study of 297 patients with chronic HCV infection and cirrhosis monitored in the University Hospital “Queen Joanna-ISUL” for 3-year period. Data on demographic, clinical characteristics, and health-care resources utilization (hospitalizations, highly specialized interventions, and pharmacotherapy were collected. Micro-costing approach was applied to evaluate the total direct medical costs. The points of view are that of the National Health Insurance Fund (NHIF, hospital and the patients. Collected cost data are from the NHIF and hospitals tariffs, patients, and from the positive dug list for medicines prices. Descriptive statistics, chi-squared test, Kruskal–Wallis, and Friedman tests were used for statistical processing.Results76% of patients were male. 93% were diagnosed in grade Child-Pugh A and B. 97% reported complications, and almost all developed esophageal varices. During the 3 years observational period, patients did not change the critical clinical values for Child-Pugh status and therefore the group was considered as homogenous. 847 hospitalizations were recorded for 3 years period with average length of stay 17 days. The mortality rate of 6.90% was extremely high. The total direct medical costs for the observed cohort of patients for 3-year period accounted for 1,290,533 BGN (€659,839 with an average cost per patient 4,577 BGN (€2,340. Statistically significant correlation was observed between the total cost per patient from the different payers’ perspective and the Child-Pugh cirrhosis score.ConclusionHCV-related

Role of microRNA-7 and selenoprotein P in hepatocellular carcinoma.

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Tarek, Marwa; Louka, Manal Louis; Khairy, Eman; Ali-Labib, Randa; Zakaria Zaky, Doaa; Montasser, Iman F

2017-05-01

There is an obvious need to diagnose hepatocellular carcinoma using novel non-invasive and sensitive biomarkers. In this regard, the aim of this study was to evaluate and correlate both relative quantification of microRNA-7 using quantitative real time polymerase chain reaction and quantitative analysis of selenoprotein P using enzyme-linked immunosorbent assay in sera of hepatocellular carcinoma patients, chronic liver disease patients, as well as normal healthy subjects in order to establish a new diagnostic biomarker with a valid non-invasive technique. In addition, this study aimed to investigate whether changes in selenium supply affect microRNA-7 expression and selenoprotein P levels in human hepatocarcinoma cell line (HepG2). The results showed a highly significant decrease in serum microRNA-7 relative quantification values and selenoprotein P levels in malignant group in comparison with benign and control groups. The best cutoff for serum microRNA-7 and selenoprotein P to discriminate hepatocellular carcinoma group from benign and control groups was 0.06 and 4.30 mg/L, respectively. Furthermore, this study showed that changes in selenium supply to HepG2 cell line can alter the microRNA-7 profile and are paralleled by changes in the concentration of its target protein (selenoprotein P). Hence, serum microRNA-7 and selenoprotein P appear to be potential non-invasive diagnostic markers for hepatocellular carcinoma. Moreover, the results suggest that selenium could be used as an anticancer therapy for hepatocellular carcinoma by affecting both microRNA-7 and selenoprotein P.

High MRPS23 expression contributes to hepatocellular carcinoma proliferation and indicates poor survival outcomes.

Science.gov (United States)

Pu, Meng; Wang, Jianlin; Huang, Qike; Zhao, Ge; Xia, Congcong; Shang, Runze; Zhang, Zhuochao; Bian, Zhenyuan; Yang, Xishegn; Tao, Kaishan

2017-07-01

Hepatocellular carcinoma is one of the most prevalent neoplasms and the leading cause of cancer-related mortality worldwide. Mitochondrial ribosomal protein S23 is encoded by a nuclear gene and participates in mitochondrial protein translation. Mitochondrial ribosomal protein S23 overexpression has been found in many types of cancer. In this study, we explored mitochondrial ribosomal protein S23 expression in primary hepatocellular carcinoma tissues compared with matched adjacent non-tumoral liver tissues using mitochondrial ribosomal protein S23 messenger RNA and protein levels collected from public databases and clinical samples. Immunohistochemistry was performed to analyze the relationship between mitochondrial ribosomal protein S23 and various clinicopathological features. The results indicated that mitochondrial ribosomal protein S23 was significantly overexpressed in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 expression was correlated with the tumor size and tumor-metastasis-node stage. Moreover, patients with high mitochondrial ribosomal protein S23 expression levels presented poorer survival rates. Mitochondrial ribosomal protein S23 was an independent prognostic factor for survival, especially at the early stage of hepatocellular carcinoma. In addition, the downregulation of mitochondrial ribosomal protein S23 decreased the proliferation of hepatocellular carcinoma in vitro and in vivo. In conclusion, we verified for the first time that mitochondrial ribosomal protein S23 expression was upregulated in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 levels can predict poor clinical outcomes in hepatocellular carcinoma, and this protein plays a key role in tumor proliferation. Therefore, mitochondrial ribosomal protein S23 may be a potential therapeutic target for hepatocellular carcinoma.

File list: Unc.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

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Dysregulated Expression of MITF in Subsets of Hepatocellular Carcinoma and Cholangiocarcinoma.

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Nooron, Nattakarn; Ohba, Koji; Takeda, Kazuhisa; Shibahara, Shigeki; Chiabchalard, Anchalee

2017-08-01

Cholangiocarcinoma represents the second most common primary liver tumor after hepatocellular carcinoma. Mahanine, a carbazole alkaloid derived from Murraya koenigii (Linn.) Spreng, has been used as folk medicine in Thailand, where the liver fluke-associated cholangiocarcinoma is common. The expression of microphthalmia-associated transcription factor (MITF) is maintained at immunohistochemically undetectable levels in hepatocytes and cholangiocytes. To explore the regulation of MITF expression in the liver, we immunohistochemically analyzed the MITF expression using hepatocellular carcinoma and cholangiocarcinoma specimens of the human liver cancer tissue array. MITF immunoreactivity was detected in subsets of hepatocellular carcinoma (6 out of 38 specimens; 16%) and cholangiocarcinoma (2/7 specimens; 29%). Moreover, immunoreactivity for glioma-associated oncogene 1 (GLI1), a transcription factor of the Hedgehog signaling pathway, was detected in 55% of hepatocellular carcinoma (21/38 specimens) and 86% of cholangiocarcinoma (6/7 specimens). Importantly, MITF was detectable only in the GLI1-positive hepatocellular carcinoma and cholangiocarcinoma, and MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. Subsequently, the effect of mahanine was analyzed in HepG2 human hepatocellular carcinoma and HuCCT1 and KKU-100 human cholangiocarcinoma cells. Mahanine (25 µM) showed the potent cytotoxicity in these hepatic cancer cell lines, which was associated with increased expression levels of MITF, as judged by Western blot analysis. MITF is over-expressed in subsets of hepatocellular carcinoma and cholangiocarcinoma, and detectable MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. MITF expression levels may be determined in hepatic cancer cells by the balance between the Hedgehog signaling and the cellular stress.

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Lifescience Database Archive (English)

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File list: DNS.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Liv.50.AllAg.Carcinoma,_Hepatocellular mm9 DNase-seq Liver Carcinoma, Hepatocel...lular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Liv.50.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: DNS.Liv.20.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Liv.20.AllAg.Carcinoma,_Hepatocellular mm9 DNase-seq Liver Carcinoma, Hepatocel...lular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Liv.20.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: Pol.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Liv.50.AllAg.Carcinoma,_Hepatocellular mm9 RNA polymerase Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Liv.50.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: Pol.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 RNA polymerase Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

The evolutionary scenario of hepatocellular carcinoma in Italy: an update.

Science.gov (United States)

Bucci, Laura; Garuti, Francesca; Lenzi, Barbara; Pecorelli, Anna; Farinati, Fabio; Giannini, Edoardo G; Granito, Alessandro; Ciccarese, Francesca; Rapaccini, Gian Lodovico; Di Marco, Maria; Caturelli, Eugenio; Zoli, Marco; Borzio, Franco; Sacco, Rodolfo; Cammà, Calogero; Virdone, Roberto; Marra, Fabio; Felder, Martina; Morisco, Filomena; Benvegnù, Luisa; Gasbarrini, Antonio; Svegliati-Baroni, Gianluca; Foschi, Francesco Giuseppe; Missale, Gabriele; Masotto, Alberto; Nardone, Gerardo; Colecchia, Antonio; Bernardi, Mauro; Trevisani, Franco

2017-02-01

Epidemiology of hepatocellular carcinoma is changing worldwide. This study aimed at evaluating the changing scenario of aetiology, presentation, management and prognosis of hepatocellular carcinoma in Italy during the last 15 years. Retrospective analysis of the ITA.LI.CA (Italian Liver Cancer) database including 5192 hepatocellular carcinoma patients managed in 24 centres from 2000 to 2014. Patients were divided into three groups according to the date of cancer diagnosis (2000-2004, 2005-2009 and 2010-2014). The main results were as follows: (i) progressive patient aging; (ii) progressive expansion of non-viral cases and, namely, of "metabolic" hepatocellular carcinomas; (iii) increasing proportion of hepatocellular carcinoma diagnosed during a correct (semi-annual) surveillance programme; (iv) favourable cancer stage migration; (v) increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) improved overall survival (adjusted for the lead time in surveyed patients), particularly after 2009, of both viral and non-viral patients presenting with an early- or intermediate-stage hepatocellular carcinoma. During the last 15 years several aetiological and clinical features of hepatocellular carcinoma patients have changed, as their management. The observed improvement of overall survival was owing both to the wider use of semi-annual surveillance, expanding the proportion of tumours that qualified for curative treatments, and to the improved outcome of loco-regional treatments. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Orbital Metastasis of Hepatocellular Carcinoma: A Case Report ...

African Journals Online (AJOL)

Background: Hepatocellular carcinoma is one of the commonest malignancies in Nigeria, however metastasis to the orbit is a rare presentation. Objective: To present a rare case of orbital metastasis of hepatocellular carcinoma. Case Report: A 25-year-old man presented with a 3-month history of pain, progressive swelling ...

File list: Oth.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Liv.50.AllAg.Carcinoma,_Hepatocellular mm9 TFs and others Liver Carcinoma, Hepa...tocellular SRX467209 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.50.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: Oth.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 TFs and others Liver Carcinoma, Hepa...tocellular SRX467209 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: Oth.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Liv.05.AllAg.Carcinoma,_Hepatocellular mm9 TFs and others Liver Carcinoma, Hepa...tocellular SRX467209 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.05.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: Oth.Liv.20.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Liv.20.AllAg.Carcinoma,_Hepatocellular mm9 TFs and others Liver Carcinoma, Hepa...tocellular SRX467209 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.20.AllAg.Carcinoma,_Hepatocellular.bed ...

Synergistic effect of oral corticosteroids use on risk of hepatocellular carcinoma in high risk populations.

Science.gov (United States)

Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu

2018-06-01

Little evidence is available on the relationship between oral corticosteroids use and hepatocellular carcinoma. The objective of this study was to investigate whether oral corticosteroids use correlates with the risk of hepatocellular carcinoma in high risk populations in Taiwan. Using representative claims database established from the Taiwan National Health Insurance Program with a population coverage rate of 99.6%, we identified 102,182 subjects aged 20-84 years with newly diagnosed hepatocellular carcinoma in 2000-2011 as the cases and 102,182 randomly selected subjects aged 20-84 years without hepatocellular carcinoma as the matched controls. In subjects with any one of comorbidities including alcohol-related disease, chronic liver disease, and diabetes mellitus, the adjusted OR of hepatocellular carcinoma was 29.9 (95% CI 28.7, 31.1) for subjects with never use of oral corticosteroids, and the adjusted OR would increase to 33.7 (95% CI 32.3, 35.3) for those with ever use of oral corticosteroids. The adjusted OR of hepatocellular carcinoma was 1.03 for subjects with increasing cumulative duration of oral corticosteroids use for every one year (95% CI 1.01, 1.06), with a duration-dependent effect. The largest OR occurred in subjects with ever use of oral corticosteroids and concurrently comorbid with alcohol-related disease, chronic liver disease, and diabetes mellitus (adjusted OR 122.7, 95% CI 108.5, 138.8). There is a synergistic effect between oral corticosteroids use and the traditional risk factors on the risk of hepatocellular carcinoma. People with risk factors for hepatocellular carcinoma should receive regular ultrasound surveillance, particularly when they currently use oral corticosteroids. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

File list: ALL.Liv.20.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Liv.20.AllAg.Carcinoma,_Hepatocellular mm9 All antigens Liver Carcinoma, Hepato...cellular SRX467209,SRX467208 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Liv.20.AllAg.Carcinoma,_Hepatocellular.bed ...

Radio-embolization for hepatocellular carcinoma

International Nuclear Information System (INIS)

Raoul, J.L.; Edeline, J.; Pracht, M.; Boucher, E.; Rolland, Y.; Garin, E.

2011-01-01

Hepatocellular carcinoma is now a major public health concern. In intermediate stages (one third of hepatocellular carcinoma patients), chemo-embolization is the standard of care despite a poor tolerance and a moderate efficacy. Moreover, despite recent improvements, this technique seems in a dead end. Radio-embolization could be an excellent tool for such patients. Currently 131 I-Lipiodol, 188 Re-Lipiodol, 90 Y-glass or resin microspheres are available. More recent and promising data come from microspheres, but phase II and III studies are needed before drawing any conclusion. In the future, the combination of radio-embolization with systemic chemotherapy or targeted agents (particularly anti-angiogenic drugs) seems very promising. (authors)

Magnetic Resonance Imaging Finding of Metastatic Hepatocellular Carcinoma in Ovary: A Case Report

International Nuclear Information System (INIS)

Kwak, Soon Hyuk; Cho, Bum Sang; Kang, Min Ho; Lee, Seung Young; Han, Gi Seok; Cha, Sang Hoon; Park, Kil Sun; Kim, Sung Jin; Choi, Song Yi

2011-01-01

Hepatocellular carcinoma is the most common primary malignant tumor of liver. Metastasis of hepatocellular carcinoma occurs in various organs, but metastasis to the ovary is extremely rare. We report MRI finding of metastatic hepatocellular carcinoma of the ovary in a 37-year-old woman who was treated hepatocellular carcinoma transarterial chemoembolization and radiofrequency ablation a year ago. Pelvic MRI revealed a mass in pelvic cavity with heterogeneous signal intensity and centripetal enhancement. Surgical excision and pathologic examination confirmed metastatic hepatocellular carcinoma in the ovary.

Metastatic hepatocellular carcinoma on the mandible: a case report

International Nuclear Information System (INIS)

Kim, Jin Soo; Kim, Jae Duk

2005-01-01

Hepatocellular carcinoma is one of the most common cancer worldwide, primarily affecting those in regions with a high prevalence of viral hepatitis. However, the metastasis of hepatocellular carcinoma to the oral cavity is a rare phenomenon. This report presents a case of metastatic hepatocellular carcinoma in the left mandibular angle and ramus region of a 62-year-old man. Panoramic radiograph revealed an ill-defined radiolucent lesion extending from the retained root of the mandibular left second molar into the ascending ramus. The lesion had irregular and ill-defined margins.

Rottlerin upregulates DDX3 expression in hepatocellular carcinoma.

Science.gov (United States)

Wang, Zhong; Shen, Gen-Hai; Xie, Jia-Ming; Li, Bin; Gao, Quan-Gen

2018-01-01

Rottlerin has been reported to exert its anti-tumor activity in various types of human cancers. However, the underlying molecular mechanism has not been fully elucidated. In the current study, we explored whether rottlerin exhibits its tumor suppressive function in hepatocellular carcinoma cells. Our MTT assay results showed that rottlerin inhibited cell growth in hepatocellular carcinoma cells. Moreover, we found that rottlerin induced cell apoptosis and caused cell cycle arrest at G1 phase. Furthermore, our wound healing assay result demonstrated that rottlerin retarded cell migration in hepatocellular carcinoma cells. Additionally, rottlerin suppressed cell migration and invasion. Notably, we found that rottlerin upregulated DDX3 expression and subsequently downregulated Cyclin D1 expression and increased p21 level. Importantly, down-regulation of DDX3 abrogated the rottlerin-mediated tumor suppressive function, whereas overexpression of DDX3 promoted the anti-tumor activity of rottlerin. Our study suggests that rottlerin exhibits its anti-cancer activity partly due to upregulation of DDX3 in hepatocellular carcinoma cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Laparoscopic versus robotic surgery for hepatocellular carcinoma: the first 46 consecutive cases.

Science.gov (United States)

Magistri, Paolo; Tarantino, Giuseppe; Guidetti, Cristiano; Assirati, Giacomo; Olivieri, Tiziana; Ballarin, Roberto; Coratti, Andrea; Di Benedetto, Fabrizio

2017-09-01

Hepatocellular carcinoma has a growing incidence worldwide, and represents a leading cause of death in patients with cirrhosis. Nowadays, minimally invasive approaches are spreading in every field of surgery and in liver surgery as well. We retrospectively reviewed demographics, clinical, and pathologic characteristics and short-term outcomes of patients who had undergone minimally invasive resections for hepatocellular carcinoma at our institution between June 2012 and May 2016. No significant differences in demographics and comorbidities were found between patients in the laparoscopic (n = 24) and robotic (n = 22) groups, except for the rates of cirrhotic patients (91.7% and 68.2%, respectively, P = 0.046). Perioperative data analysis showed that the operative time (mean, 211 and 318 min, respectively, P robotic-assisted resections were related to less Clavien I-II postoperative complications (22 cases versus 13 cases; P = 0.03). As regards resection margins, the two groups were similar with no statistically significant differences in rates of disease-free resection margins. A modern hepatobiliary center should offer both open and minimally invasive approaches to liver disease to provide the best care for each patient, according to the individual comorbidities, risk factors, and personal quality of life expectations. Our results show that the robotic approach is a reliable tool for accurate oncologic surgery, comparable to the laparoscopic approach. Robotic surgery also allows the surgeon to safely approach liver segments that are difficult to resect in laparoscopy, namely segments I-VII-VIII. Copyright © 2017 Elsevier Inc. All rights reserved.

Defining Hepatocellular Carcinoma Subtypes and Treatment Responses in Patient-Derived Tumorgrafts

Science.gov (United States)

2017-10-01

Hepatocellular carcinoma (HCC) is the 6th most common cancer and 3rd leading cause of cancer-related death worldwide. We know that HCC subtypes exist because...italicized descriptions of section contents in your submitted reports. 1. INTRODUCTION: Hepatocellular carcinoma (HCC) is the 6th most common cancer and 3rd...know the results or have not been harvested to assess tumor engraftment in liver. Overall, we have found that there is a good engraftment rate

A serum microRNA panel as potential biomarkers for hepatocellular carcinoma related with hepatitis B virus.

Directory of Open Access Journals (Sweden)

Youwen Tan

Full Text Available The identification of new high-sensitivity and high-specificity markers for HCC are essential. We aimed to identify serum microRNAs (miRNAs as biomarkers to be used in diagnosing hepatitis B virus (HBV -related hepatocellular carcinoma (HCC.We investigated serum miRNA expression in (261 HCC patients, 233 cirrhosis patients, and 173 healthy controls, recruited between August 2010 and June 2013. An initial screening of miRNA expression by Illumina sequencing was performed using serum samples pooled from HCC patients and controls. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR was used to evaluate the expression of selected miRNAs. A logistic regression model was constructed using a training cohort (n = 357 and then validated using an independent cohort (n = 241. The area under the receiver operating characteristic curve (AUC was used to evaluate the accuracy of the use of the biomarkers for disease diagnosis.We identified 8 miRNAs (hsa-miR-206, hsa-miR-141-3p, hsa-miR-433-3p, hsa-miR-1228-5p, hsa-miR-199a-5p, hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-26a-5p and constructed an miRNA set that provided high diagnostic accuracy for HCC (AUC = 0.887 and 0.879 for training and validation sets, respectively. The miRNAs could also be used to differentiate HCC patients from healthy (AUC = 0.893 and cirrhosis (AUC = 0.892 patients.We identified a serum of miRNA panel that has considerable clinical value in HCC diagnosis.

Effect of smoking on survival of patients with hepatocellular carcinoma.

Science.gov (United States)

Kolly, Philippe; Knöpfli, Marina; Dufour, Jean-François

2017-11-01

Lifestyle factors such as smoking, obesity and physical activity have gained interest in the field of hepatocellular carcinoma. These factors play a significant role in the development of hepatocellular carcinoma. Several studies revealed the impact of tobacco consumption on the development of hepatocellular carcinoma and its synergistic effects with viral etiologies (hepatitis B and C). The effects of smoking on survival in patients with a diagnosed hepatocellular carcinoma have not yet been investigated in a Western cohort where hepatitis C infection is a major risk factor. Using data from a prospective cohort of patients with hepatocellular carcinoma who were followed at the University Hospital of Bern, Switzerland, survival was compared by Kaplan-Meier analysis in smokers and nonsmokers, and multivariate Cox regression was applied to control for confounding variables. Of 238 eligible hepatocellular carcinoma patients, 64 were smokers at the time of inclusion and 174 were nonsmokers. Smokers had a significant worse overall survival than nonsmokers (hazard ratio 1.77, 95% confidence interval: 1.22-2.58, P=.003). Analysis of patients according to their underlying liver disease, revealed that smoking, and not nonsmoking, affected survival of hepatitis B virus and C virus-infected patients only. In this subgroup, smoking was an independent predictor for survival (hazard ratio 2.99, 95% confidence interval: 1.7-5.23, Phepatocellular carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience.

Science.gov (United States)

Chen, V L; Yeh, M-L; Le, A K; Jun, M; Saeed, W K; Yang, J D; Huang, C-F; Lee, H Y; Tsai, P-C; Lee, M-H; Giama, N; Kim, N G; Nguyen, P P; Dang, H; Ali, H A; Zhang, N; Huang, J-F; Dai, C-Y; Chuang, W-L; Roberts, L R; Jun, D W; Lim, Y-S; Yu, M-L; Nguyen, M H

2018-07-01

Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed. © 2018 John Wiley & Sons Ltd.

Imaging and embolization of hepatocellular carcinoma supplied by gonadal artery

International Nuclear Information System (INIS)

Wu Hongping; Wang Junjie; Lu Yang; You Kaizhi

2010-01-01

Objective: To evaluate radiology and embolization for hepatocellular carcinoma supplied by gonadal artery. Methods: The medical records of 3 patients with hepatocellular carcinoma supplied by gonadal artery from August 2002 to September 2008 were reviewed. The demography, gonadal artery location, modus operandi, imaging features of liver cancer and prognosis were retrospectively analyzed. Results: Anatomic variation of gonadal artery occurred with the gonadal artery arising from the upper abdominal aorta in 1 patient and from the middle suprarenal artery in 2 patients. The blood supply of the hepatocellular carcinoma derived from the gonadal artery in all 3 patients. No complications occurred in the 6-month follow-up after embolization. Conclusion: Hepatocellular carcinoma may be supplied by gonadal artery with anomalous origin. This anatomic variant can be readily demonstrated by imaging to guide embolization. (authors)

File list: NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 No description Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular mm9 No description Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular.bed ...

Telomere biology and telomerase mutations in cirrhotic patients with hepatocellular carcinoma.

Directory of Open Access Journals (Sweden)

Flávia S Donaires

Full Text Available Telomeres are repetitive DNA sequences at linear chromosome termini, protecting chromosomes against end-to-end fusion and damage, providing chromosomal stability. Telomeres shorten with mitotic cellular division, but are maintained in cells with high proliferative capacity by telomerase. Loss-of-function mutations in telomere-maintenance genes are genetic risk factors for cirrhosis development in humans and murine models. Telomerase deficiency provokes accelerated telomere shortening and dysfunction, facilitating genomic instability and oncogenesis. Here we examined whether telomerase mutations and telomere shortening were associated with hepatocellular carcinoma (HCC secondary to cirrhosis. Telomere length of peripheral blood leukocytes was measured by Southern blot and qPCR in 120 patients with HCC associated with cirrhosis and 261 healthy subjects. HCC patients were screened for telomerase gene variants (in TERT and TERC by Sanger sequencing. Age-adjusted telomere length was comparable between HCC patients and healthy subjects by both Southern blot and qPCR. Four non-synonymous TERT heterozygous variants were identified in four unrelated patients, resulting in a significantly higher mutation carrier frequency (3.3% in patients as compared to controls (p = 0.02. Three of the four variants (T726M, A1062T, and V1090M were previously observed in patients with other telomere diseases (severe aplastic anemia, acute myeloid leukemia, and cirrhosis. A novel TERT variant, A243V, was identified in a 65-year-old male with advanced HCC and cirrhosis secondary to chronic hepatitis C virus (HCV and alcohol ingestion, but direct assay measurements in vitro did not detect modulation of telomerase enzymatic activity or processivity. In summary, constitutional variants resulting in amino acid changes in the telomerase reverse transcriptase were found in a small proportion of patients with cirrhosis-associated HCC.

Ultrasonographic detection of hepatocellular carcinoma: correlation of preoperative ultrasonography and resected liver pathology

International Nuclear Information System (INIS)

Lim, J.H.; Kim, S.H.; Lee, W.J.; Choi, D.; Kim, S.H.; Lim, H.K.

2006-01-01

AIM: The aim of this study was to determine the sensitivity of ultrasonography for detecting hepatocellular carcinoma in patients who underwent surgical liver resection. MATERIALS AND METHODS: The preoperative ultrasonography reports of 103 patients who underwent hepatic resection surgery were retrospectively reviewed. The patients had chronic liver disease with good liver function and a relatively normal liver echotexture. The presence of a mass or masses in the resected part of the liver segments on preoperative ultrasonography was regarded as possible hepatocellular carcinoma, and these results were compared with the surgically resected hepatic lobes or segments. Accuracy for detection was assessed on a lesion-by-lesion basis, on a segment-by-segment basis, and on a patient basis. RESULTS: One hundred and fifty-seven hepatocellular carcinomas were found in 244 hepatic segments of 103 patients. One hundred and one of 157 hepatocellular carcinomas were detected using ultrasonography in 97 patients resulting in a sensitivity of 64%. In six patients, a solitary hepatocellular carcinoma was missed in each patient, a patient sensitivity being 94%. Using ultrasonography, 87 of 100 (87%) hepatocellular carcinomas larger than 2 cm in diameter, and 14 of 57 (25%) hepatocellular carcinomas 2 cm or smaller in diameter were revealed. On the basis of segment-by-segment analysis, the sensitivity was 78% (99 of 127 segments), specificity was 97% (114 of 117 segments), accuracy was 87% (213 of 244 segments), positive predictive value was 97% (99 of 102 segments), and negative predictive value was 80% (114 of 142 segments). CONCLUSION: In patients with chronic liver disease and good hepatic function, ultrasonography has a sensitivity of 94% in the identification of affected patients, but for individual lesions, the sensitivity is only 64%

Diagnostic value of α-fetoprotein in hepatocellular carcinoma

International Nuclear Information System (INIS)

Hernández Perera, Julio César

2009-01-01

In the world the hepatocellular carcinoma (HCC) is the fifth to sixth most common malignancy. An increase in its incidence is looming in Cuba as a result of the population aging and the increase of morbi-mortality due to liver cirrhosis (CH). α-fetoprotein (AFP) by SUMA®, was used in this work as a tumor marker technique in 189 Cirrhotic patients evaluated at the CIMEQ, between January 1999 and September 2005. The main factors associated with an elevation of AFP were HCC, viral cirrhosis, and the age of 50 years or more. Presented CHC 22 (11.64%) patients, who had an average age of 55 years and the predominant sex was male (86,36%). The most important cause associated with this malignant disease was viral CH, mainly the virus of hepatitis C. This tumor marker showed a sensitivity and specificity of 68.18% and 92.17%, respectively. When combined with abdominal ultrasound was increase 86.36% sensitivity and 100% specificity. Elevated AFP levels associated with tumor prognosis factors. It can be concluded that the AFP had value in the diagnosis of HCC. This work is the first of its kind carried out in Cuba, and allows the design of a workable strategy for the research, monitoring and prognosis of HCC, having a wide network of laboratories SUMA®,, with a low cost per each determination. (author)

File list: InP.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 Input control Liver Carcinoma, Hepat...ocellular SRX467208 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: InP.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Liv.50.AllAg.Carcinoma,_Hepatocellular mm9 Input control Liver Carcinoma, Hepat...ocellular SRX467208 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Liv.50.AllAg.Carcinoma,_Hepatocellular.bed ...

Utility of Gd-EOB-DTPA-Enhanced MRI in Diagnosing Small Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Soo Ryang Kim

2009-07-01

Full Text Available We describe an 8-mm hepatocellular carcinoma (HCC with hepatitis C virus-related cirrhosis in a 74-year-old woman. Ultrasound (US revealed an 8-mm hyperechoic nodule in segment 6 of the liver. Contrast-enhanced computed tomography (CT and US revealed no hypervascularity in the early phase and no washout in the late phase and the Kupffer phase, respectively. CT during arteriography revealed no hypervascularity and CT during arterial portography disclosed no perfusion defect. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI revealed no hypervascularity in the early phase, but disclosed a defect in the hepatobiliary phase. Histologically, the nodule was diagnosed as well-differentiated HCC characterized by more than two-fold the cellularity of the non-tumorous area, with a high nuclear:cytoplasmic ratio, increased cytoplasmic eosinophilia, fatty change, and slight cell atypia with an irregular thin trabecular pattern. Our case demonstrates the utility of Gd-EOB-DTPA-enhanced MRI in the diagnosis of small HCC.

Iron overload and HFE gene mutations in Polish patients with liver cirrhosis.

Science.gov (United States)

Sikorska, Katarzyna; Romanowski, Tomasz; Stalke, Piotr; Iżycka-Świeszewska, Ewa; Bielawski, Krzysztof Piotr

2011-06-01

Increased liver iron stores may contribute to the progression of liver injury and fibrosis, and are associated with a higher risk of hepatocellular carcinoma development. Pre-transplant symptoms of iron overload in patients with liver cirrhosis are associated with higher risk of infectious and malignant complications in liver transplant recipients. HFE gene mutations may be involved in the pathogenesis of liver iron overload and influence the progression of chronic liver diseases of different origins. This study was designed to determine the prevalence of iron overload in relation to HFE gene mutations among Polish patients with liver cirrhosis. Sixty-one patients with liver cirrhosis included in the study were compared with a control group of 42 consecutive patients subjected to liver biopsy because of chronic liver diseases. Liver function tests and serum iron markers were assessed in both groups. All patients were screened for HFE mutations (C282Y, H63D, S65C). Thirty-six of 61 patients from the study group and all controls had liver biopsy performed with semiquantitative assessment of iron deposits in hepatocytes. The biochemical markers of iron overload and iron deposits in the liver were detected with a higher frequency (70% and 47% respectively) in patients with liver cirrhosis. There were no differences in the prevalence of all HFE mutations in both groups. In patients with a diagnosis of hepatocellular carcinoma, no significant associations with iron disorders and HFE gene mutations were found. Iron disorders were detected in patients with liver cirrhosis frequently but without significant association with HFE gene mutations. Only the homozygous C282Y mutation seems to occur more frequently in the selected population of patients with liver cirrhosis. As elevated biochemical iron indices accompanied liver iron deposits more frequently in liver cirrhosis compared to controls with chronic liver disease, there is a need for more extensive studies searching for

Infrequent widespread microsatellite instability in hepatocellular carcinomas.

Science.gov (United States)

Yamamoto, H; Itoh, F; Fukushima, H; Kaneto, H; Sasaki, S; Ohmura, T; Satoh, T; Karino, Y; Endo, T; Toyota, J; Imai, K

2000-03-01

Widespread or high-frequency microsatellite instability (MSI) due to the defective DNA mismatch repair (MMR) occurs in the majority of hereditary non-polyposis colorectal cancer and a subset of sporadic malignant tumors. The incidence of MSI and underlying DNA MMR defects have been well characterized in gastrointestinal carcinogenesis, but not in hepatocarcinogenesis. To address the issue, we analyzed 55 Japanese hepatocellular carcinomas using several indicators of DNA MMR defects, such as microsatellite analysis, loss of heterozygosity (LOH) and mutation analysis of MMR genes, methylation of hMLH1 promoter, and frameshift mutations of mononucleotide repeat sequences within possible target genes. Mutation of beta2-microglobulin gene, which is presumably involved in MSI-positive tumor cell escape from immune surveillance was also examined. Some of these analyses were also carried out in 9 human liver cancer cell lines. None of the 3 quasi-monomorphic mononucleotide markers sensitive for MSI, BAT26, BAT25, and BAT34C4 presented shortened unstable alleles in any of the carcinoma, cirrhosis, chronic hepatitis tissues, or cell lines. LOH at MMR genes was infrequent (4.4 approximately 7.1%), and no mutations were detected. Neither hMLH1 hypermethylation nor frameshift mutation in the target genes was detected. No mutations were found in beta2-microglobulin. Widespread MSI due to the defective DNA MMR appears to play little if any part in Japanese hepatocarcinogenesis.

Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma

International Nuclear Information System (INIS)

Sangro, Bruno; Bilbao, Jose I.; Boan, Jose; Martinez-Cuesta, Antonio; Benito, Alberto; Rodriguez, Javier; Panizo, Angel; Gil, Belen; Inarrairaegui, Mercedes; Herrero, Ignacio; Quiroga, Jorge; Prieto, Jesus

2006-01-01

Purpose: To investigate the antitumor effect of resin microspheres loaded with 90-yttrium against hepatocellular carcinoma and their safety in the setting of liver cirrhosis. Patients and Methods: Data from 24 consecutive patients with hepatocellular carcinoma (HCC) treated by radioembolization in the period from September 2003 to February 2005 were reviewed. Patients received no further antineoplastic therapy. A comprehensive evaluation was performed to prevent the risk of damage due to microsphere misplacing. Patients were discharged the day after microspheres injection. Results: Serious liver toxicity observed among cirrhotic patients in a first period was subsequently prevented by modifying the selection criteria and the method for calculating the activity to be administered. Among 21 patients evaluable for response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, a reduction in size of target lesions was observed in all but 1 patient. When considering only target lesions, disease control rate and response rate were 100% and 23.8%, respectively. However, 43% of patients progressed in the liver in the form of new lesions appearing a median time of 3 months after radioembolization. Conclusion: Our experience in these series of patients indicates that radioembolization using resin microspheres has a significant antitumor effect against HCC and that using stringent selection criteria and conservative models for calculating Radiation activity to be administered, radioembolization can be performed safely even in cirrhotic patients

Cerebrovascular Accidents Associated with Sorafenib in Hepatocellular Carcinoma

OpenAIRE

Saif, Muhammad W.; Isufi, Iris; Peccerillo, Jennifer; Syrigos, Kostas N.

2011-01-01

Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. La...

Clinical outcomes of liver transplantation for HBV-related hepatocellular carcinoma: data from the NIH HBV OLT study.

Science.gov (United States)

Han, Steven-Huy; Reddy, K Rajender; Keeffe, Emmet B; Soldevila-Pico, Consuelo; Gish, Robert; Chung, Raymond T; Degertekin, Bulent; Lok, Anna

2011-01-01

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is an indication for orthotopic liver transplantation (OLT) in patients with tumor stage within the United Network for Organ Sharing criteria. The number of patients listed for HBV-related HCC is increasing, while the number of patients listed for HBV-related cirrhosis is declining presumptively because of the availability of more effective oral nucleos(t)ide analogues. This study presents the final, long-term outcome of patients transplanted for HBV-related HCC in the National Institutes of Health (NIH) HBV OLT Study Group. Ninety-eight patients (52.4%) in the NIH HBV OLT cohort underwent OLT for HBV-related HCC. With a mean follow-up of 36.5 months post-OLT, 12 (12.2%) patients developed recurrence of HCC. Multivariate analysis did not find a statistically significant role of gender, tumor stage at OLT, pre-OLT HCC treatment, recurrence of HBV, or duration of HCC diagnosis pre-OLT in predicting HCC recurrence. Serum alpha-fetoprotein (AFP) level >200 ng/mL at transplant was found to be statistically significant in predicting HCC recurrence (p=0.003). HCC recurrence was significantly associated with decreased post-OLT survival. HCC is the most common indication for OLT in patients with chronic hepatitis B in the era of more effective oral antivirals. Serum AFP at the time of OLT is significantly associated with HCC recurrence. © 2010 John Wiley & Sons A/S.

PGK1 Drives Hepatocellular Carcinoma Metastasis by Enhancing Metabolic Process.

Science.gov (United States)

Xie, Huijun; Tong, Guihui; Zhang, Yupei; Liang, Shu; Tang, Kairui; Yang, Qinhe

2017-07-27

During the proliferation and metastasis, the tumor cells prefer glycolysis (Warburg effect), but its exact mechanism remains largely unknown. In this study, we demonstrated that phosphoglycerate kinase 1 (PGK1) is an important enzyme in the pathway of metabolic glycolysis. We observed a significant overexpression of PGK1 in hepatocellular carcinoma tissues, and a correlation between PGK1 expression and poor survival of hepatocellular carcinoma patients. Also, the depletion of PGK1 dramatically reduced cancer cell proliferation and metastasis, indicating an oncogenic role of PGK1 in liver cancer progression. Further experiments showed that PGK1 played an important role in MYC -induced metabolic reprogramming, which led to an enhanced Warburg effect. Our results revealed a new effect of PGK1, which can provide a new treatment strategy for hepatocellular carcinoma, as PGK1 is used to indicate the prognosis of hepatocellular carcinoma (HCC).

Hepatocellular carcinoma arising from hepatocellular adenoma in a hepatitis B virus-associated cirrhotic liver

International Nuclear Information System (INIS)

Seo, J.M.; Lee, S.J.; Kim, S.H.; Park, C.K.; Ha, S.Y.

2012-01-01

Hepatocellular adenoma (HCA) is a rare, benign proliferation of hepatocytes that occurs mostly in a normal liver and in extreme rare cases, occurs in a cirrhotic liver. Hepatocellular carcinomas (HCC) arising within HCA through malignant transformation is rare. The specific incidence and mechanism of malignant transformation has not been established, but the long term use of oral contraceptives is considered a causative agent. We report a case of HCC arising from HCA detected in a hepatitis B-related cirrhotic liver with serial radiologic images.

Hepatocellular carcinoma arising from hepatocellular adenoma in a hepatitis B virus-associated cirrhotic liver

Energy Technology Data Exchange (ETDEWEB)

Seo, J.M. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, S.J., E-mail: lucia@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, S.H. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, C.K.; Ha, S.Y. [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2012-04-15

Hepatocellular adenoma (HCA) is a rare, benign proliferation of hepatocytes that occurs mostly in a normal liver and in extreme rare cases, occurs in a cirrhotic liver. Hepatocellular carcinomas (HCC) arising within HCA through malignant transformation is rare. The specific incidence and mechanism of malignant transformation has not been established, but the long term use of oral contraceptives is considered a causative agent. We report a case of HCC arising from HCA detected in a hepatitis B-related cirrhotic liver with serial radiologic images.

Giant ectopic liver, hepatocellular carcinoma and pachydermia-a rare genetic syndrome?

Directory of Open Access Journals (Sweden)

Miny Peter

2011-08-01

Full Text Available Abstract Ectopic liver is a very uncommon developmental anomaly that predisposes to the development of hepatocellular carcinoma. We describe the second documented case of a hepatocellular carcinoma developing in the primary liver of a patient with a rare and uncharacterized genetic symptom complex. Also present was the largest ectopic liver ever reported, measuring 12 cm in diameter which contained a solitary focus of metastatic hepatocellular carcinoma. The primary hepatocellular carcinoma is believed to have arisen in the native liver from a hepatic adenoma that was diagnosed 15 years earlier. The patient's uncharacterised condition featured prominent thick, yellow skin over the dorsum of the fingers, and was associated with follicular hyperkeratosis, abnormal plantar creases, digital clubbing, misshaped ears, a lingua plicata and an angioleiomyolipoma of the right kidney. This unique case of hepatocellular carcinoma arising from liver cell adenoma in a patient with an uncharacterised condition featuring a large ectopic liver invites discussion of the role of local factors in carcinogenesis in the parent liver but not the ectopic liver. It also underlines the imperative ongoing need for clinical autopsies.

Correlation between interleukin-6 and primary hepatocellular carcinoma: a meta-analysis

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LI Xia

2015-06-01

Full Text Available ObjectiveTo evaluate the correlation between interleukin (IL6 and primary hepatocellular carcinoma (HCC. MethodsCase-control studies that included quantitative data on plasma or serum IL-6 levels of patients with HCC were identified from PubMed, ISI Web of Knowledge, CBM, and CNKI. A meta-analysis was performed to quantitatively and comprehensively analyze data. ResultsTwenty-five studies were included and the meta-analysis was conducted separately for 3 groups: HCC vs controls, HCC vs liver cirrhosis, and HCC vs hepatitis. The serum IL-6 levels of patients with HCC were significantly higher than those of healthy controls (25 studies, standardized mean difference (SMD 5.02, 95% CI: 4.13-5.91, Z=11.05, P＜0.000 1, patients with liver cirrhosis (15 studies, SMD=236, 95% CI: 1.54-3.19, Z=5.60, P＜0.000 1, and patients with hepatitis (7 studies, SMD=2.63, 95% CI: 1.24-4.03, Z=369, P=0.000 2. ConclusionThe inflammatory mediator, IL-6, may play an important role in the development and progression of HCC.

A clinical perspective of the link between metabolic syndrome and hepatocellular carcinoma

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Cauchy F

2015-02-01

Full Text Available François Cauchy, Jacques BelghitiHPB and Liver Transplantation Unit, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, FranceAbstract: Metabolic syndrome (MS, which is defined as a constellation of clinico-biological features closely related to insulin-resistance has reached epidemic levels in Western Europe and Northern America. Non-alcoholic fatty liver disease (NAFLD represents the hepatic manifestation of MS. As its incidence parallels that of MS, NAFLD is currently becoming one of the most frequent chronic liver diseases in Western countries. On one hand, MS favors the development of hepatocellular carcinoma (HCC either through NAFLD liver parenchymal alterations (steatosis; steatohepatitis; fibrosis, or in the absence of significant underlying liver parenchyma changes. In this setting, HCC are often diagnosed incidentally, tend to be larger than in patients developing HCC on cirrhosis and therefore frequently require major liver resections. On the other hand, MS patients are at increased risk of both liver-related postoperative complications and increased cardiorespiratory events leading to non-negligible mortality rates following liver surgery. These deleterious effects seem to be related to the existence of impaired liver function even in the absence of severe fibrosis but also higher cardiorespiratory sensitivity in a setting of MS/NAFLD. Hence, specific medical and surgical improvements in the perioperative management of these patients are required. These include complete preoperative cardiorespiratory work-up and the wide use of preoperative liver volume modulation. Finally, the long-term prognosis after curative surgery for MS-related HCC does not seem to be worse than for other HCC occurring on classical chronic liver diseases. This is probably related to less aggressive tumor behavior with lower micro vascular invasion and decreased rates of poorly differentiated lesions. In this setting, several medical therapies

Curative salvage liver transplantation in patients with cirrhosis and hepatocellular carcinoma: An intention-to-treat analysis.

Science.gov (United States)

de Haas, Robbert J; Lim, Chetana; Bhangui, Prashant; Salloum, Chady; Compagnon, Philippe; Feray, Cyrille; Calderaro, Julien; Luciani, Alain; Azoulay, Daniel

2018-01-01

The salvage liver transplantation (SLT) strategy was conceived for initially resectable and transplantable (R&T) hepatocellular carcinoma (HCC) patients, to try to obviate upfront liver transplantation, with the "safety net" of SLT in case of postresection recurrence. The SLT strategy is successful or curative when patients are recurrence free following primary resection alone, or after SLT for recurrence. The aim of the current study was to determine the SLT strategy's potential for cure in R&T HCC patients, and to identify predictors for its success. From 1994 to 2012, all R&T HCC patients with cirrhosis were enrolled in the SLT strategy. An intention-to-treat (ITT) analysis was used to determine this strategy's outcomes and predictors of success according to the above definition. In total, 110 patients were enrolled in the SLT strategy. Sixty-three patients (57%) had tumor recurrence after initial resection, and in 30 patients SLT could be performed (recurrence transplantability rate = 48%). From the time of initial resection, ITT 5-year overall and disease-free survival rates were 69% and 60%, respectively. The SLT strategy was successful in 60 patients (56%), either by resection alone (36%), or by SLT for recurrence (19%). Preresection predictors of successful SLT strategy at multivariate analysis included Model for End-Stage Liver Disease (MELD) score >10, and absence of neoadjuvant transarterial chemoembolization (TACE). Additional postresection predictive factors were absence of postresection morbidity, and T-stage 1-2 at the resection specimen. The SLT strategy is curative in only 56% of cases. Higher MELD score at inception of the strategy and no pre-resection TACE are predictors of successful SLT strategy. (Hepatology 2018;67:204-215). © 2017 by the American Association for the Study of Liver Diseases.

Improving clinical trial design for hepatocellular carcinoma treatments

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Robert G. Gish

2011-12-01

Full Text Available Despite its place as the third leading cause of cancer deaths worldwide, there are currently no approved chemotherapeutic agents, devices or techniques to treat hepatocellular carcinoma. Importantly, there have been no phase III studies demonstrating survival benefit, nor any randomized studies of treatment except for transarterial chemoembolization and most recently sorafenib. The importance of well-designed clinical trials of agents to treat HCC has never been greater. However, general clinical study design issues, combined with HCC-specific issues pose significant challenges in structuring such studies. HCC-related challenges include the heterogeneity of this cancer and the fact that it is frequently accompanied by significant comorbidities at diagnosis, such as active hepatitis B or C virus replication, substantial past or on-going alcohol use, and cirrhosis, itself often a fatal disease. The recently published comparison of a newer treatment, nolatrexed to doxorubicin, and comments about this study’s initial HCC diagnostic criteria, staging system, comparator therapy and choice of endpoints have provided a platform to discuss the challenges unique to the design of HCC clinical trials. The difficulty in accurately framing study results obtained from the constantly changing HCC clinical landscape and approaches to meet these challenges will be reviewed.

Antiviral therapy for prevention of hepatocellular carcinoma in chronic hepatitis C

DEFF Research Database (Denmark)

Kimer, Nina; Dahl, Emilie Kristine; Gluud, Lise Lotte

2012-01-01

To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C.......To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C....

Type and etiology of liver cirrhosis are not related to the presence of hepatic encephalopathy or health-related quality of life: a cross-sectional study

Directory of Open Access Journals (Sweden)

Björnsson Einar

2008-10-01

Full Text Available Abstract Background Hepatic encephalopathy has a negative impact on health-related quality of life (QoL in liver cirrhosis. There are scarce and conflicting data on whether type or etiology of liver cirrhosis could be related to hepatic encephalopathy in patients with cirrhosis. We aimed to determine the impact of cirrhosis etiology on hepatic encephalopathy and whether hepatic encephalopathy affects health-related QoL among patients with cirrhosis of different etiologies. Methods A total of 156 cirrhotic patients were prospectively evaluated for the presence of hepatic encephalopathy according to the West-Haven criteria as well as by means of two psychometric tests. Patients with cryptogenic cirrhosis or cirrhosis due to mixed hepatocellular/cholestatic etiologies were excluded. Fasting plasma glucose levels were also measured. QoL was evaluated by means of a validated questionnaire (SF-36. Results Diabetes mellitus was more common in patients with hepatocellular cirrhosis compared to those with cholestatic cirrhosis but the two groups did not differ in cirrhosis severity or the prevalence of hepatic encephalopathy (p > 0.05. The groups of patients with cirrhosis due to alcohol, hepatitis C, or cholestatic liver disease did not differ in severity of liver cirrhosis or the prevalence of hepatic encephalopathy (p > 0.05. Patients with cirrhosis of different etiologies did not differ in any SF-36 domain (p > 0.05. In multivariate analysis, performance at neuropsychological testing was independently related only to age, diabetes mellitus, and the Child-Pugh score whereas the SF-36 physical component summary only to the Child-Pugh score and hepatic encephalopathy. Conclusion Cirrhosis etiology does not seem to be related to hepatic encephalopathy or health-related QoL. Cognitive impairment is associated mainly with age, liver disease severity and diabetes mellitus.

Upregulation of MiR-212 Inhibits Migration and Tumorigenicity and Inactivates Wnt/β-Catenin Signaling in Human Hepatocellular Carcinoma.

Science.gov (United States)

Jia, Pengbo; Wei, Guangbing; Zhou, Cancan; Gao, Qi; Wu, Yunhua; Sun, Xuejun; Li, Xuqi

2018-01-01

MicroRNAs are involved in hepatocellular carcinoma metastasis, a principal cause of hepatocellular carcinoma-related death in patients worldwide. MiR-212 is a microRNA that has been identified in several types of cancers and is postulated to influence cell signaling and subsequent malignant pathogenesis. Despite emerging reports suggesting that miR-212 plays a significant role in the onset, progression, and migration of these types of malignant tumors, its involvement in the development of hepatocellular carcinoma has not been fully elucidated. Quantitative reverse transcription polymerase chain reaction, wound healing, transwell migration and invasion assays, Western blotting, and xenograft tumor growth models were performed to test the expression levels and functions of miR-212 in hepatocellular carcinoma. Luciferase reporter assay, quantitative reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry were used to identify and verify the target of miR-212. In this study, we identify significant repression of miR-212 in hepatocellular carcinoma and demonstrate that overexpression of miR-212 inhibits the migration of hepatocellular carcinoma cells in vitro and in vivo. Furthermore, we identify forkhead box M1, whose expression is inversely related to that of miR-212, as a direct target of miR-212. Additionally, reexpression of forkhead box M1 rescues the miR-212-mediated inhibition of cell migration. We observed that inhibition of miR-212 activates forkhead box M1 but inhibits the Wnt/β-catenin pathway by suppressing Wnt, LEF-1, c-Myc, and nuclear β-catenin. Finally, in vivo studies confirmed the inhibitory effect of miR-212 on hepatocellular carcinoma growth. Our present findings indicate that miR-212 is a potential prognostic biomarker of hepatocellular carcinoma and that the miR-212/forkhead box M1 regulatory axis may represent a new therapeutic objective for hepatocellular carcinoma treatment.

Selective angiography in fifty patients with primary hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Shou-Zhong, Wang; Xing-Rong, Chen; Gong-Xian, Wang

1983-06-01

Selective angiography is of great importance in the diagnosis of primary hepatocellular carcinoma. It offers information on the findings, multicentricity, localisation, extension, and type of growth. This paper discusses angiography from the methodical point of view, the findings to be obtained, the types of hepatocellular carcinoma, and the diagnostic efficiency of selective angiography in the evaluation of this type of tumour.

The multifaceted role of podoplanin expression in hepatocellular carcinoma.

Science.gov (United States)

Cioca, Andreea; Ceausu, Amalia R; Marin, Irina; Raica, Marius; Cimpean, Anca M

2017-02-13

The role of podoplanin in hepatocellular carcinoma (HCC) is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD) was increased in patients who had vascular invasion at the time of diagnosis (P=0.018) and in those with associated cirrhosis (P=0.006). Tumor cells showing podoplanin expression were correlated with histological grade (P=0.040). Podoplanin-expressing cancer associated fibroblasts (CAFs) were correlated with both LVD (P=0.019) and tumor cells (P=0.015). Our results sustain the dual role of podoplanin in HCC by its involvement in both HCC tumorigenesis, lymphatic neovascularization and tumor invasion invasiveness. A possible crosstalk between epithelial and stromal tumor cells in HCC tumor microenvironment may be mediated by podoplanin, but this hypothesis needs further studies to elucidate this interrelation.

Relationship between hepatocellular carcinoma, metabolic syndrome and non-alcoholic fatty liver disease: which clinical arguments?

Science.gov (United States)

Rosmorduc, Olivier

2013-05-01

Obesity and the metabolic syndrome are growing epidemics associated with an increased risk for many types of cancer. In the liver, inflammatory and angiogenic changes due to insulin resistance and fatty liver disease are associated with an increased incidence of liver cancer. Regardless of underlying liver disease, cirrhosis remains the most important risk factor for hepatocellular carcinoma (HCC) although are cases of HCC arising without cirrhosis raise the possibility of a direct carcinogenesis secondary to Non-alcoholic Fatty Liver Disease (NAFLD). Moreover, metabolic syndrome and its different features may also increase the risk of HCC in the setting of chronic liver diseases of other causes such as viral hepatitis or alcohol abuse. Taking into account all these data, it is necessary to better determine the risk of developing HCC in patients with metabolic syndrome to improve the screening guidelines and develop prophylactic treatments in this setting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a large case cohort study.

Science.gov (United States)

Carr, Brian I; Pancoska, Petr; Branch, Robert A

2009-12-24

967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end point. We found that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated AFP or bilirubin, or alkaline phosphatase, were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, even in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient sub groups based on liver function and tumor characteristics and found clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant factors. We also used a purely mathematical approach to derive subgroups and a prognostic model for individual patients. Interestingly, the two approaches gave similar predictive information, which opens the possibility of a more detailed mathematical analysis in the future. The results of this large dataset show that amongst non-surgical HCC patients, there are clear subsets with longer survival. The data supports the concept of heterogeneity of HCC. The three factors, bilirubin, AFP, and PVT predominate in prognosis.

Transhemangioma Ablation of Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Pua, Uei

2012-01-01

Radiofrequency ablation (RFA) is a well-established treatment modality in the treatment of early hepatocellular carcinoma (HCC) [1]. Safe trajectory of the RFA probe is crucial in decreasing collateral tissue damage and unwarranted probe transgression. As a percutaneous technique, however, the trajectory of the needle is sometimes constrained by the available imaging plane. The presence of a hemangioma beside an HCC is uncommon but poses the question of safety related to probe transgression. We hereby describe a case of transhemangioma ablation of a dome HCC.

Transhemangioma Ablation of Hepatocellular Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Pua, Uei, E-mail: druei@yahoo.com [Tan Tock Seng Hospital, Department of Diagnostic Radiology (Singapore)

2012-12-15

Radiofrequency ablation (RFA) is a well-established treatment modality in the treatment of early hepatocellular carcinoma (HCC) [1]. Safe trajectory of the RFA probe is crucial in decreasing collateral tissue damage and unwarranted probe transgression. As a percutaneous technique, however, the trajectory of the needle is sometimes constrained by the available imaging plane. The presence of a hemangioma beside an HCC is uncommon but poses the question of safety related to probe transgression. We hereby describe a case of transhemangioma ablation of a dome HCC.

Hepatocellular Carcinoma in Tyrosinemia Type 1 Without Clear Increase of AFP

NARCIS (Netherlands)

van Ginkel, Willem G.; Gouw, Annette S. H.; van der Jagt, Eric J.; de Jong, Koert P.; Verkade, Henkjan J.; van Spronsen, Francjan J.

Patients with hereditary tyrosinemia type 1 have an elevated risk of developing hepatocellular carcinoma, especially if initiation of treatment with 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione is delayed. Hepatocellular carcinoma can usually be suspected when there are increased

Theoretical analysis about early detection of hepatocellular carcinoma by medical imaging procedure

Energy Technology Data Exchange (ETDEWEB)

Odano, Ikuo; Hinata, Hiroshi; Hara, Keiji; Sakai, Kunio [Niigata Univ. (Japan). School of Medicine

1983-04-01

It is well-known that patients with chronic hepatitis and liver cirrhosis are frequently accompanied by hepatocellular carcinoma (hepatoma). They are called high risk group for hepatoma. In order to detect a small hepatoma, it is reasonable for us to perform screening examinations on these high risk group patients. Optimal screening interval, however, has not been established. In this report, a theoretical analysis was made to estimate optimal screening interval by imaging procedure such as ultrasonography, x-ray computed tomography and scintigraphy. By the analysis of eight cases, mean doubling time of hepatoma was estimated about four months (73 - 143 days). If we want to detect a hepatoma not greater than 3.0cm in diameter, medical screening procedure combining ultrasonography and scintigraphy should be performed once per about nine months.

Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis.

Science.gov (United States)

Ghouri, Yezaz Ahmed; Mian, Idrees; Rowe, Julie H

2017-01-01

Since the 1970s, the epidemic of hepatocellular carcinoma (HCC) has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US) and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments.

Dectetion of Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma

International Nuclear Information System (INIS)

Zhang Hua; Xiang Mingjie; Wang Wen; Li Yongxing; Chen Hua; Xiong Zhongxiu; Zhu Jianqian

2009-01-01

To identify serologic markers that may indicate the early presence of Hepatocellular Carcinoma (HCC) associated with Hepatitis B Virus (HBV), and analyze their clinical significance. HBV-encoded X (HBx) gene positive and negative HepG2 cells were made and subjected to cDNA subtraction. The 5 host genes, which expression were up-regulated by HBxAg, were named URG4, URG7, URG11, S15a, Suil. When specific ELISAs were constructed measuring differentially expressed antigens and corresponding antibodies in 1046 individuals from China and American Korean Immigrants (494 HBV-uninfected individuals, 400 HBV-infected individuals and 152 control samples). Individual antibodies were found in a small percentage of uninfected individuals, in HBV carriers, non-HBV hepatitis patients and other tumor patients. In contrast, antibodies to multiple up-regulated genes were detectable largely in serum samples from patients with chronic HBV hepatitis, HBV-associated cirrhosis and HCC patients (P<0.01). The number of antibodies in individual serum samples also differed in these groups. Three or more antibodies were found in 30(52.6%) of 57 HCC patients, in 35(29.2%) of 120 patients with cirrhosis, in 29 (19.0%)of 153 patients with HBV hepatitis, and only 4 (0.8%) of 494 uninfected individuals (P< 0.01). The positive rate of single antibody were 82.5%, 66.7% and 48.4% in the HCC, cirrhosis and hepatitis patients, and correspondingly the average number of antibodies were 1.37, 2.12 and 3.52 (P<0.01). Hence, antibodies were detected in HBV patients at highest risk for tumor development and in HCC patients. The number of antibodies in a sample was related to increased risk for HCC. This suggests that these antibodies may serve as preneoplastic markers for HCC in HBV-infected patients with chronic liver disease. (authors)

Hepatocellular carcinoma

International Nuclear Information System (INIS)

Farooqi, J.I.; Farooqi, R.J.

2001-01-01

Hepatocellular carcinoma (HCC) is a common cause of cancer mortality. Hepatitis B and C viruses, aflatoxin and alga toxin in the contaminated drinking water are the major etiological factors. Rapidly progressing medical imaging has resulted in the improved treatment results. Surgical resection has a major role for influencing prognosis of HCC. Local cancer therapies based on the advances in early diagnosis are progressing rapidly. Multimodality combination and sequential treatment has proved effective, unfortunately systemic chemotherapy for HCC remains disappointed. All of these have resulted in the improved prognosis of HCC. (author)

Hepatocellular carcinoma localized in the bile duct lumen: two case report

Energy Technology Data Exchange (ETDEWEB)

Bae, Kyeung Kug; Chang, Jay Chun [Yeungnam Univ. School of Medicine, Seoul (Korea, Republic of)

1998-10-01

Intrabile duct tumor growth of hepatocellular carcinoma is an uncommon manifestation, but intraluminal bile duct hepatocellular carcinoma without primary hepatic parenchymal lesions is extremely rare. To our knowledge, only a few case reports have been published. We encountered two cases of primary hepatocellular carcinoma arising in the bile duct;serum alpha-fetoprotein levels were within the normal limits. Both showed the following characteristic radiologic features: (1) Cholangiography revealed filling defects within the dilated bile duct; (2) two-phase abdominal CT showed enhancement during the arterial-dominant phase and washout during the tissue equilibrium phase, as in typical HCC; and (3) hepateic arteriography revealed hypervascular tumor staining. Surgery was performed and the resected specimen showed no detectable primary hepatic parenchymal mass;on the basis of the pathologic finding, intraluminal bile duct hepatocellular carcinoma was confirmed. We cautiously assume that this peculiar type of HCC may arise primarily from bile duct mucosa.=20.

The clinical significance and biological function of lncRNA RGMB-AS1 in hepatocellular carcinoma.

Science.gov (United States)

Sheng, Nan; Li, Yannan; Qian, Ruikun; Li, Yichun

2018-02-01

LncRNA RGMB-AS1 has been suggested to play significant roles in lung cancer progression. However, it remains unknown whether lncRNA RGMB-AS1 is involved in the development and progression of hepatocellular carcinoma. In our results, lncRNA RGMB-AS1 was low-expressed in hepatocellular carcinoma tissues and cell lines, and associated with clinical stage, tumor size and metastasis. Survival analysis indicated that lncRNA RGMB-AS1 high was an independent favorable prognostic factor for hepatocellular carcinoma patients. Gain-of-function studies showed up-regulated lncRNA RGMB-AS1 expression suppressed hepatocellular carcinoma cells proliferation, migration and invasion, and promoted cells apoptosis. There was a positively association between lncRNA RGMB-AS1 and RGMB in hepatocellular carcinoma tissues, and up-regulated lncRNA RGMB-AS1 expression increased RGMB mRNA and protein expressions in hepatocellular carcinoma cells. In conclusion, lncRNA RGMB-AS1 serves an anti-oncogenic role in hepatocellular carcinoma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Grp78 promotes the invasion of hepatocellular carcinoma

International Nuclear Information System (INIS)

Su, Rongjian; Li, Zhen; Li, Hongdan; Song, Huijuan; Bao, Cuifen; Wei, Jia; Cheng, Liufang

2010-01-01

Glucose regulated protein 78 (Grp78) is involved in the invasion and metastasis in many human cancers including gastric cancer, breast cancer, prostate cancer. But the role of Grp78 in the invasion of human hepatocellular carcinoma has not been reported. In this article, we examined if Grp78 was associated with the invasion of hepatocellular carcinoma and explored the possible underlying mechanism. The Grp78 and FAK expression levels in 44 patients with hepatocellular carcinoma were examined using immunohistochemistry. Grp78 overexpressing SMMC7721 cells were established by pcDNA3.1 (+)-Grp78 transfection and screened by G418. Grp78 and FAK levels in Grp78 overexpressing cells were down-regulated by siRNA transfection. The invasion status of tumor cells was evaluated by transwell assay in vitro, and chick embryo metastasis model in vivo. Cell spreading was determined by cell spreading assay, and quantitatively measured by Orisis software HUG. Grp78, pY397 FAK, pY576/577 FAK and FAK levels were detected by western blot. RhoA activity was detected by GST pulldown assay. The distribution of actin cytoskeleton was observed by fluorescent staining. Grp78 expression levels in 44 patients with hepatocellular carcinoma were negatively correlated with tumor grading, and positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 in SMMC7721 cells promoted the invasion of cancer cells in vitro and in vivo, and this increase in tumor cell invasion was blocked by Grp78 siRNA knockdown. Our results also revealed that overexpression of Grp78 in SMMC7721 cells accelerated the process of cell spreading and promoted lamellipodia formation. Further analysis showed that overexpression of Grp78 in SMMC7721 cells increased pY397 and pY576/577 levels of FAK. Grp78 siRNA knockdown decreased FAK activation and activity. Our results also revealed that Grp78 overexpression in SMMC7721 cells decreased RhoA-GTP level, and Grp78 siRNA knockdown rescued Rho

Grp78 promotes the invasion of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Li Hongdan

2010-01-01

Full Text Available Abstract Background Glucose regulated protein 78 (Grp78 is involved in the invasion and metastasis in many human cancers including gastric cancer, breast cancer, prostate cancer. But the role of Grp78 in the invasion of human hepatocellular carcinoma has not been reported. In this article, we examined if Grp78 was associated with the invasion of hepatocellular carcinoma and explored the possible underlying mechanism. Methods The Grp78 and FAK expression levels in 44 patients with hepatocellular carcinoma were examined using immunohistochemistry. Grp78 overexpressing SMMC7721 cells were established by pcDNA3.1 (+-Grp78 transfection and screened by G418. Grp78 and FAK levels in Grp78 overexpressing cells were down-regulated by siRNA transfection. The invasion status of tumor cells was evaluated by transwell assay in vitro, and chick embryo metastasis model in vivo. Cell spreading was determined by cell spreading assay, and quantitatively measured by Orisis software HUG. Grp78, pY397 FAK, pY576/577 FAK and FAK levels were detected by western blot. RhoA activity was detected by GST pulldown assay. The distribution of actin cytoskeleton was observed by fluorescent staining. Results Grp78 expression levels in 44 patients with hepatocellular carcinoma were negatively correlated with tumor grading, and positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 in SMMC7721 cells promoted the invasion of cancer cells in vitro and in vivo, and this increase in tumor cell invasion was blocked by Grp78 siRNA knockdown. Our results also revealed that overexpression of Grp78 in SMMC7721 cells accelerated the process of cell spreading and promoted lamellipodia formation. Further analysis showed that overexpression of Grp78 in SMMC7721 cells increased pY397 and pY576/577 levels of FAK. Grp78 siRNA knockdown decreased FAK activation and activity. Our results also revealed that Grp78 overexpression in SMMC7721 cells decreased

Design and rationale of the HCC BRIDGE study in China: a longitudinal, multicenter cohort trial in hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Qiao You-Lin

2011-05-01

HCC BRIDGE China national study, the first geographically representative study of hepatocellular carcinoma in China, will contribute to the understanding of patterns of therapy use and related clinical outcomes and will provide further information on continuing unmet needs for hepatocellular carcinoma throughout this important country.

New Insights Into the Relationships Among Alcohol Consumption, Hepatocellular Carcinoma and Hepatitis C Virus Infection

Directory of Open Access Journals (Sweden)

Sabouri Ghannad

2014-04-01

Full Text Available Context Viral hepatitis and the consumption of alcohol are recognized as important reasons for the development of liver disease throughout the world. It would also seem that chronic alcoholism causes more severe and rapid progression of liver disease in patients with chronic hepatitis C, leading to more frequent liver cirrhosis and hepatocellular carcinoma. Evidence Acquisition The data for this article were obtained through an initial Medline search and from the references of relevant articles, and used to provide updated information on the relationship between alcohol consumption and the hepatitis C virus. Results Excessive alcohol consumption among patients with chronic hepatitis C is likely to result in more severe hepatic injuries, promote pathologic progression to cirrhosis, and increase the risk of developing hepatocellular carcinoma. Although the exact mechanisms involved in the progression of chronic hepatitis C in alcoholic patients have not been definitely established, possible alcohol-induced enhancement of viral replication, iron overload, immunologic suppression, the role of NF-kappa B, and the signaling pathways involved in its activation, have been suggested. Significant correlations have been reported between hepatitis C virus RNA levels and the amount of alcohol consumed by an individual. Interferon therapy is less effective for alcohol patients, than non-alcoholic patients, even after a period of abstinence. The obtained data suggest that a hepatitis C virus infection is an important cofactor in the pathogenesis of liver disease among patients with an alcohol problem. Conclusions In light of a possible synergistic effect between alcohol and hepatitis C virus replication, total abstention ought to be recommended, and due to alcohol's inhibitory effect on interferon therapy, patients with alcohol problems should not be treated until they stop drinking.

Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma.

Science.gov (United States)

Yahagi, Naoya; Shimano, Hitoshi; Hasegawa, Kiyoshi; Ohashi, Kenichi; Matsuzaka, Takashi; Najima, Yuho; Sekiya, Motohiro; Tomita, Sachiko; Okazaki, Hiroaki; Tamura, Yoshiaki; Iizuka, Yoko; Ohashi, Ken; Nagai, Ryozo; Ishibashi, Shun; Kadowaki, Takashi; Makuuchi, Masatoshi; Ohnishi, Shin; Osuga, Jun-ichi; Yamada, Nobuhiro

2005-06-01

Hepatocellular carcinoma is a very common neoplastic disease in countries where hepatitis viruses B and/or C are prevalent. Small hepatocellular carcinoma lesions detected by ultrasonography at an early stage are often hyperechoic because they are composed of well-differentiated cancer cells that are rich in triglyceride droplets. The triglyceride content of hepatocytes depends in part on the rate of lipogenesis. Key lipogenic enzymes, such as fatty acid synthase, are co-ordinately regulated at the transcriptional level. We therefore examined the mRNA expression of lipogenic enzymes in human hepatocellular carcinoma samples from 10 patients who had undergone surgical resection. All of the samples exhibited marked elevation of expression of mRNA for lipogenic enzymes, such as fatty acid synthase, acetyl-CoA carboxylase and ATP citrate lyase, compared with surrounding non-cancerous liver tissue. In contrast, the changes in mRNA expression of SREBP-1, a transcription factor that regulates a battery of lipogenic enzymes, did not show a consistent trend. In some cases where SREBP-1 was elevated, the main contributing isoform was SREBP-1c rather than SREBP-1a. Thus, lipogenic enzymes are markedly induced in hepatocellular carcinomas, and in some cases SREBP-1c is involved in this activation.

Serum clusterin as a marker for diagnosing hepatocellular carcinoma

African Journals Online (AJOL)

Ragaa A. Ramadan

2014-06-20

Jun 20, 2014 ... tic sensitivity (95.5%) and negative predictive value (95.7%) over the single use of AFP. Conclusions: Although ... noma,12 urothelial bladder carcinoma,13 and prostate adeno- ... on top of chronic HCV infection-related cirrhosis (HCC group). ... examination and the Child-Pugh scoring system was used for.

Radiofrequency (thermal) ablation versus no intervention or other interventions for hepatocellular carcinoma

DEFF Research Database (Denmark)

Weis, Sebastian; Franke, Annegret; Mössner, Joachim

2013-01-01

Hepatocellular carcinoma is the fifth most common cancer worldwide. Percutaneous interventional therapies, such as radiofrequency (thermal) ablation (RFA), have been developed for early hepatocellular carcinoma. RFA competes with other interventional techniques such as percutaneous ethanol...

Ultrasound-guided percutaneous treatment of hepatocellular carcinoma by radiofrequency hyperthermia with a 'cooled-tip needle'. A preliminary clinical experience.

Science.gov (United States)

Francica, G; Marone, G

1999-05-01

Radiofrequency hyperthermia using the newly-developed 'cooled-tip' needle has recently been proposed as a therapeutic modality for hepatocellular carcinoma (HCC). Herein we report our preliminary results on feasibility and effectiveness of the thermal ablation of mono- or pauci-focal hepatocellular carcinoma with the cooled-tip needle. We treated 15 cirrhotic patients (mean age 68.8 years; 12 males; 14 HCV-positive; 13 in Child's Class A and 2 in Class B) with 20 hepatocellular carcinoma nodules (mean diameter 28.1 mm; range 10-43 mm; nine lesions with diameter greater than 3 cm). None of the patients had portal thrombosis and/or extrahepatic spread. We used a radiofrequency generator (100 W of power) connected to a 18 g perfusion electrode needle with an exposed tip of 2-3 cm. The circuit was closed through a dispersive electrode positioned under the patient's thighs. A peristaltic pump infused a chilled (2-5 degrees C) saline solution to guarantee the continuous cooling of the needle tip. The needle was placed into target lesions under US guidance. The interventional procedure was carried out in general anesthesia without intubation. Dynamic helical CT was carried out 15-20 days after thermal ablation to assess therapeutic efficacy. In all, 38 areas of coagulation necrosis (at 1000-1200 mA for 10-15 min) were generated in 24 sessions in the 20 hepatocellular carcinoma nodules (mean 1.9 lesions per nodule and 1.2 sessions per nodule). Complete necrosis as assessed at dynamic CT (lack of enhancement during the arteriographic phase) was achieved in 75% of cases in a single session; after a second RF session success rate was 90% (18 out of 20 nodules). A self-limited pleurisy along with a 5-fold increase in transaminases occurred in one patient; a 3-fold elevation of transaminases was encountered in three other patients. During the follow-up (median 15 months) five patients had recurrent hepatocellular carcinoma with a 1-year disease free interval of 64%. Of the

Glutathione treatment of hepatocellular carcinoma

DEFF Research Database (Denmark)

Dalhoff, K; Ranek, L; Mantoni, M

1992-01-01

This prospective study was undertaken to substantiate observations that glutathione (GSH) inhibits or reverses tumor growth in humans with hepatocellular carcinoma (HCC), a neoplasm with an extremely poor prognosis. Eight patients with biopsy-proven HCC not amenable to surgery were given 5 g of GSH...

Magnetic resonance imaging following treatment of advanced hepatocellular carcinoma with sorafenib

Directory of Open Access Journals (Sweden)

Joon-Il Choi

2014-06-01

Full Text Available Hepatocellular carcinomas are highly vascular tumors, showing progressive hypervascularity by the process of neoangiogenesis. Tumor angiogenesis is critical for tumor growth as well as metastatic spread therefore, imaging and quantification of tumor neo-angiogenesis is essential for monitoring response to targeted therapies and predicting disease progression. Sorafenib is a molecular targeting agent used for treating hypervascular tumors. This drug is now the standard of care in treatment of patients with advanced hepatocellular carcinoma. Due to its anti-angiogenic and anti-proliferative actions, imaging findings following treatment with Sorafenib are quite distinct when compared to conventional chemotherapeutic agents. Liver MRI is a widely adopted imaging modality for assessing treatment response in hepatocellular carcinoma and imaging features may reflect pathophysiological changes within the tumor. In this mini-review, we will discuss MRI findings after Sorafenib treatment in hepatocellular carcinoma and review the feasibility of MRI as an early biomarker in differentiating responders from non-responders after treatment with molecular targeting agents.

Simple Sugar Intake and Hepatocellular Carcinoma: Epidemiological and Mechanistic Insight

Directory of Open Access Journals (Sweden)

Juan Carlos Laguna

2014-12-01

Full Text Available Sugar intake has dramatically increased during the last few decades. Specifically, there has been a clear trend towards higher consumption of fructose and high fructose corn syrup, which are the most common added sugars in processed food, soft drinks and other sweetened beverages. Although still controversial, this rising trend in simple sugar consumption has been positively associated with weight gain and obesity, insulin resistance and type 2 diabetes mellitus and non-alcoholic fatty liver disease. Interestingly, all of these metabolic alterations have also been related to the development of hepatocellular carcinoma. The purpose of this review is to discuss the evidence coming from epidemiological studies and data from animal models relating the consumption of simple sugars, and specifically fructose, with an increased risk of hepatocellular carcinoma and to gain insight into the putative molecular mechanisms involved.

Mitochondrial fission promotes cell migration by Ca2+ /CaMKII/ERK/FAK pathway in hepatocellular carcinoma.

Science.gov (United States)

Sun, Xiacheng; Cao, Haiyan; Zhan, Lei; Yin, Chun; Wang, Gang; Liang, Ping; Li, Jibin; Wang, Zhe; Liu, Bingrong; Huang, Qichao; Xing, Jinliang

2018-07-01

Mitochondrial dynamics of fission and fusion plays critical roles in a diverse range of important cellular functions, and its deregulation has been increasingly implicated in human diseases. Previous studies have shown that increased mitochondrial fission significantly promoted the proliferation of hepatocellular carcinoma (HCC) cells. However, how they influence the migration of tumour cells remained largely unknown. In the present study, we further investigated the effect of mitochondrial fission on the migration and metastasis of hepatocellular carcinoma cells. Moreover, the underlying molecular mechanisms and therapeutic application were explored. Our data showed that dynamin-1-like protein expression was strongly increased in distant metastasis of hepatocellular carcinoma when compared to primary hepatocellular carcinoma. In contrast, the mitochondrial fusion protein mitofusin 1 showed an opposite trend. Moreover, the expression of dynamin-1-like protein and mitofusin 1 was significantly associated with the disease-free survival of hepatocellular carcinoma patients. In addition, our data further showed that mitochondrial fission significantly promoted the reprogramming of focal-adhesion dynamics and lamellipodia formation in hepatocellular carcinoma cells mainly by activating typical Ca 2+ /CaMKII/ERK/FAK pathway. Importantly, treatment with mitochondrial division inhibitor-1 significantly decreased calcium signalling in hepatocellular carcinoma cells and had a potential treatment effect for hepatocellular carcinoma metastasis in vivo. Taken together, our findings demonstrate that mitochondrial fission plays a critical role in the regulation of hepatocellular carcinoma cell migration, which provides strong evidence for this process as a drug target in hepatocellular carcinoma metastasis treatment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Percutaneous CT-guided high frequency induced thermotherapy as a treatment hepatocellular carcinoma and hepatic metastatic lesions

International Nuclear Information System (INIS)

Lu Ligong; Luo Pengfei; Chen Xiaoming

2004-01-01

Objective: To analyze the efficacy, side effects and complications of percutaneous high frequency induced thermotherapy (HiTT) performed under CT guidance involving 36 patients with hepatocellular carcinomas (HCC) and hepatic metastatic lesions. Methods: HiTT was performed in treatment of 36 patients (24 men and 12 women) with 42 hepatocellular carcinoma and hepatic metastatic carcinoma (six patient out of 36 had two nidi). The diameter of the tumors ranged from 1.6 to 7.8 cm (mean, 3.2 cm). The efficacy of HiTT was evaluated with triphasic spiral CT performed 1 month after the procedure. Results: The post-treatment CT scan showed complete necrosis in 33 nidi (78%) out of 42 nidi of hepatocellular carcinoma and hepatic metastatic carcinoma in 30 patients out of 36. Complete necrosis was obtained in 18 (95%) of 19 tumors no larger than 3 cm in diameter, 13 (72%) of 18 tumors between 3.0 and 5.0 cm in diameter. Eleven tumors showed incomplete necrosis. In our study, none of the patients experienced severe complications. All the patients are alive in the follow-up ranging from 2 to 12 months (mean, 7 months). Conclusion: Our research suggests that HiTT can be a safe and effective treatment of hepatocellular carcinomas and hepatic metastatic carcinoma when the lesion is no larger than 3 cm. The treatment is relatively effective for hepatocellular carcinoma between 3 and 5 cm in size. (authors)

Percutaneous electrochemotherapy in the treatment of portal vein tumor thrombosis at hepatic hilum in patients with hepatocellular carcinoma in cirrhosis: A feasibility study.

Science.gov (United States)

Tarantino, Luciano; Busto, Giuseppina; Nasto, Aurelio; Fristachi, Raffaele; Cacace, Luigi; Talamo, Maria; Accardo, Catello; Bortone, Sara; Gallo, Paolo; Tarantino, Paolo; Nasto, Riccardo Aurelio; Di Minno, Matteo Nicola Dario; Ambrosino, Pasquale

2017-02-07

To treated with electrochemotherapy (ECT) a prospective case series of patients with liver cirrhosis and Vp3-Vp4- portal vein tumor thrombus (PVTT) from hepatocellular carcinoma (HCC), in order to evaluate the feasibility, safety and efficacy of this new non thermal ablative technique in those patients. Six patients (5 males and 1 female), aged 61-85 years (mean age, 70 years), four in Child-Pugh A and two in Child-Pugh B class, entered our study series. All patients were studied with three-phase computed tomography (CT), contrast enhanced ultrasound (CEUS) and ultrasound-guided percutaneous biopsy of the thrombus before ECT. All patients underwent ECT treatment (Cliniporator Vitae ® , IGEA SpA, Carpi, Modena, Italy) of Vp3-Vp4 PVTT in a single session. At the end of the procedure a post-treatment biopsy of the thrombus was performed. Scheduled follow-up in all patients entailed: CEUS within 24 h after treatment; triphasic contrast-enhanced CT and CEUS at 3 mo after treatment and every six months thereafter. Post-treatment CEUS showed complete absence of enhancement of the treated thrombus in all cases. Post-treatment biopsy showed apoptosis and necrosis of tumor cells in all cases. The follow-up ranged from 9 to 20 mo (median, 14 mo). In 2 patients, the follow-up CT and CEUS demonstrated complete patency of the treated portal vein. Other 3 patients showed a persistent avascular non-tumoral shrinked thrombus at CEUS and CT during follow-up. No local recurrence was observed at follow-up CT and CEUS in 5/6 patients. One patient was lost to follow-up because of death from gastrointestinal hemorrage 5 wk after ECT. In patients with cirrhosis, ECT seems effective and safe for curative treatment of Vp3-Vp4 PVTT from HCC.

Hepatocellular carcinoma with neuroendocrine differentiation: clinical and imaging findings in five patients

International Nuclear Information System (INIS)

Park, Seong Hoon; Kang, Myeong Jin; Cho, Jin Han

2008-01-01

To describe the clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation, which is an extremely rare variant of hepatocellular carcinoma. We collected five patients who had histopathologically proven hepatocellular carcinoma with neuroendocrine differentiation, and described morphologic feature, enhancement pattern of tumors, extrahepatic manifestation and clinical findings. At CT, the tumor size ranged from 8 to 17 cm (mean: 12 cm) in maximum diameter. The tumor margin was well-defined and smooth in four patients and all tumors were heterogeneously hypoattenuating. Four tumor showed rim enhancement on arterial and portal phases. Local invasion to the portal vein, intrahepatic duct and gallbladder were seen. Extrahepatic manifestations included hepatic metastases, lymph node metastasis. At ultrasonography, the tumor showed heterogeneously hyperechoic in all patients and hypoechoic rim was found in four patients. Of four patients who were followed up, one survived for 16 months after initial diagnosis, while the other three died within 3 months after initial diagnosis. As described above, clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation were not specific. However, this rare variant of hepatocellular carcinoma could be considered when hepatic tumor is found in an advanced stage and shows persistent rim enhancement at CT

Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review

Energy Technology Data Exchange (ETDEWEB)

Lee, Edward Wolfgang; Alanis, Lourdes [Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Cho, Sung-Ki [Division of Interventional Radiology, Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351 (Korea, Republic of); Saab, Sammy [Division of Hepatology, Department of Medicine, Pfleger Liver Institute, University of California at Los Angeles, Los Angeles, CA 90024 (United States)

2016-11-01

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

Yttrium-90 selective internal radiation therapy with glass microspheres for hepatocellular carcinoma: Current and updated literature review

International Nuclear Information System (INIS)

Lee, Edward Wolfgang; Alanic, Lourdes; Cho, Sung Ki; Saab, Sammy

2016-01-01

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma

Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review

International Nuclear Information System (INIS)

Lee, Edward Wolfgang; Alanis, Lourdes; Cho, Sung-Ki; Saab, Sammy

2016-01-01

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma

Yttrium-90 selective internal radiation therapy with glass microspheres for hepatocellular carcinoma: Current and updated literature review

Energy Technology Data Exchange (ETDEWEB)

Lee, Edward Wolfgang; Alanic, Lourdes [Div. of Interventional Radiology, Dept. of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles (United States); Cho, Sung Ki [Div. of Interventional Radiology, Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Saab, Sammy [Div. of Hepatology, Dept. of Medicine, Pfleger Liver Institute, University of California at Los Angeles, Los Angeles (United States)

2016-07-15

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review.

Science.gov (United States)

Lee, Edward Wolfgang; Alanis, Lourdes; Cho, Sung-Ki; Saab, Sammy

2016-01-01

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

Case of small hepatocellular carcinoma detected only by dynamic sequential computed tomography with table incrementation during arterial portography (DSCTI-AP)

Energy Technology Data Exchange (ETDEWEB)

Nishijima, Hiroshi; Ida, Masahiro; Takayama, Shigeru; Yanaghi, Sekiya; Kuroda, Yuzuru [Fukui Saiseikai Hospital (Japan)

1984-05-01

A 62 years old woman was admitted for liver cirrhosis with esophageal varix. Radionuclide liver scintigram, ultrasonogram, computed tomography and infusion hepatic angiography showed no signs of hepatocellular carcinoma (HCC). But DSCTI-AP detected a small solid mass lesion about 1.5cm in diameter in the right lobe of the liver. It was difficult to diagnose this lesion as HCC because of low titer of serum ..cap alpha../sub 1/-fetoprotein. After the esophageal transection for esophageal varices, she was followed as an outpatient. Six months later, serum ..cap alpha../sub 1/-fetoprotein was slightly elevated (130 ng/ml), and all imaging methods were carried out for the detection of HCC. Ultrasonogram, computed tomography, infusion hepatic angiography, DSCTI-AP all showed hepatocellular carcinoma, about 4.5cm in diameter in the same site where a small nodule was visualized by DSCTI-AP performed 5 months ago. This case suggests that DSCTI-AP is a sensitive and useful method for detection of some type of small liver cancer.

Diagnostic and prognostic potential of serum miR-132/212 cluster in patients with hepatocellular carcinoma.

Science.gov (United States)

Wang, Feng; Wang, Jun; Ju, Linlin; Chen, Lin; Cai, Weihua; Yang, Jialin

2018-01-01

Background It has been reported that both of the miR-132/212 (micro-RNA) cluster members, miR-132 and miR-212, are downregulated in hepatocellular carcinoma. Nevertheless, the expression pattern and clinical utility of serum miR-132/212 in hepatocellular carcinoma are still unknown. Methods In this study, serum concentrations of miR-132 and miR-212 were measured in 80 hepatocellular carcinoma patients, 51 controls with chronic liver diseases and 42 healthy volunteers by using quantitative real-time polymerase chain reaction. Results In hepatocellular carcinoma patients, serum concentrations of miR-132 and miR-212 were significantly reduced and strongly correlated (r = 0.603, p hepatocellular carcinoma. Moreover, the combination of serum miR-132, miR-212 and alpha-fetoprotein improved the diagnostic efficiency for hepatocellular carcinoma, especially in sensitivity and negative predictive value. Serum miR-132 was associated with tumour differentiation degree ( p = 0.021) and tumour-node-metastasis stage ( p = 0.002); serum miR-212 correlated with tumour size ( p = 0.023) and tumour-node-metastasis stage ( p = 0.007). Kaplan-Meier analyses indicated poorer overall survival in hepatocellular carcinoma patients with lower serum concentrations of miR-132 ( p hepatocellular carcinoma.

Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma.

Science.gov (United States)

Porcu, Cristiana; Antonucci, Laura; Barbaro, Barbara; Illi, Barbara; Nasi, Sergio; Martini, Maurizio; Licata, Anna; Miele, Luca; Grieco, Antonio; Balsano, Clara

2018-02-06

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the progression of NAFLD-cirrhosis toward-HCC. We investigated whether high exogenous copper levels sensitize liver cells to transformation and if it exists an interplay between copper-related proteins and MYC oncogene. NAFLD-cirrhotic patients were characterized by a statistical significant enhancement of serum copper levels, even more evident in HCC patients. We demonstrated that high extracellular copper concentrations increase cell growth, migration, and invasion of liver cancer cells by modulating MYC/CTR1 axis. We highlighted that MYC binds a specific region of the CTR1 promoter, regulating its transcription. Accordingly, CTR1 and MYC proteins expression were progressively up-regulated in liver tissues from NAFLD-cirrhotic to HCC patients. This work provides novel insights on the molecular mechanisms by which copper may favor the progression from cirrhosis to cancer. The Cu/MYC/CTR1 interplay opens a window to refine HCC diagnosis and design new combined therapies.

Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma

Science.gov (United States)

Barbaro, Barbara; Illi, Barbara; Nasi, Sergio; Martini, Maurizio; Licata, Anna; Miele, Luca; Grieco, Antonio; Balsano, Clara

2018-01-01

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the progression of NAFLD-cirrhosis toward-HCC. We investigated whether high exogenous copper levels sensitize liver cells to transformation and if it exists an interplay between copper-related proteins and MYC oncogene. NAFLD-cirrhotic patients were characterized by a statistical significant enhancement of serum copper levels, even more evident in HCC patients. We demonstrated that high extracellular copper concentrations increase cell growth, migration, and invasion of liver cancer cells by modulating MYC/CTR1 axis. We highlighted that MYC binds a specific region of the CTR1 promoter, regulating its transcription. Accordingly, CTR1 and MYC proteins expression were progressively up-regulated in liver tissues from NAFLD-cirrhotic to HCC patients. This work provides novel insights on the molecular mechanisms by which copper may favor the progression from cirrhosis to cancer. The Cu/MYC/CTR1 interplay opens a window to refine HCC diagnosis and design new combined therapies. PMID:29507693

Gastroduodenal Complications After Concurrent Chemoradiation Therapy in Patients With Hepatocellular Carcinoma: Endoscopic Findings and Risk Factors

International Nuclear Information System (INIS)

Chon, Young Eun; Seong, Jinsil; Kim, Beom Kyung; Cha, Jihye; Kim, Seung Up; Park, Jun Yong; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon; Shin, Sung Kwan; Kim, Do Young

2011-01-01

Purpose: Concurrent chemoradiation therapy (CCRT) is useful in advanced hepatocellular carcinoma (HCC), but little is known about radiation-induced gastroduodenal complications following therapy. To determine risk factors, we investigated the prevalence and patterns of gastroduodenal complications following CCRT using endoscopy. Methods and Materials: Enrolled in the study were 123 patients treated with CCRT for unresectable HCC between January 1998 and December 2005. Radiation-induced gastroduodenal complications were defined as radiation gastritis/duodenitis, radiation gastric/duodenal ulcer, or other gastroduodenal toxicity associated with radiation, based on Common Terminology Criteria for Adverse Events (CTCAE 3.0). Serious gastroduodenal complications were defined as events occurring within 12 months from completion of CCRT, those requiring prompt therapeutic intervention, or symptoms equivalent to Grade 3 or 4 radiation-related gastroduodenal toxicity, including nausea or vomiting, based on CTCAE 3.0. Results: A month after completion of CCRT, 65 (52.8%) patients displayed endoscopic evidence of radiation-induced gastroduodenal complications. Radiation gastric and duodenal ulcers were found in 32 (26.0%) and 20 (16.3%) patients, respectively; radiation gastritis and duodenitis were found in 50 (40.7%) and 42 (34.1%) patients, respectively. Radiation-related bleeding was observed in 13 patients (10.6%). Serious gastroduodenal complications occurred in 18 patients (14.6%) and were significantly more frequent in patients with liver cirrhosis than in those without cirrhosis (p = 0.043). There were no radiation-related deaths. Conclusions: Endoscopically detectable radiation-induced gastroduodenal complications were common in HCC following CCRT. Although serious complications were uncommon, the frequency was higher in patients with liver cirrhosis; thus, these patients should be closely monitored when receiving CCRT.

Gastroduodenal Complications After Concurrent Chemoradiation Therapy in Patients With Hepatocellular Carcinoma: Endoscopic Findings and Risk Factors

Energy Technology Data Exchange (ETDEWEB)

Chon, Young Eun [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Seong, Jinsil [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Beom Kyung [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cha, Jihye [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Seung Up; Park, Jun Yong; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Liver Cirrhosis Clinical Research Center, Seoul (Korea, Republic of); Shin, Sung Kwan, E-mail: kaarma@yuhs.ac [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Do Young, E-mail: dyk1025@yuhs.ac [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Liver Cirrhosis Clinical Research Center, Seoul (Korea, Republic of)

2011-12-01

Purpose: Concurrent chemoradiation therapy (CCRT) is useful in advanced hepatocellular carcinoma (HCC), but little is known about radiation-induced gastroduodenal complications following therapy. To determine risk factors, we investigated the prevalence and patterns of gastroduodenal complications following CCRT using endoscopy. Methods and Materials: Enrolled in the study were 123 patients treated with CCRT for unresectable HCC between January 1998 and December 2005. Radiation-induced gastroduodenal complications were defined as radiation gastritis/duodenitis, radiation gastric/duodenal ulcer, or other gastroduodenal toxicity associated with radiation, based on Common Terminology Criteria for Adverse Events (CTCAE 3.0). Serious gastroduodenal complications were defined as events occurring within 12 months from completion of CCRT, those requiring prompt therapeutic intervention, or symptoms equivalent to Grade 3 or 4 radiation-related gastroduodenal toxicity, including nausea or vomiting, based on CTCAE 3.0. Results: A month after completion of CCRT, 65 (52.8%) patients displayed endoscopic evidence of radiation-induced gastroduodenal complications. Radiation gastric and duodenal ulcers were found in 32 (26.0%) and 20 (16.3%) patients, respectively; radiation gastritis and duodenitis were found in 50 (40.7%) and 42 (34.1%) patients, respectively. Radiation-related bleeding was observed in 13 patients (10.6%). Serious gastroduodenal complications occurred in 18 patients (14.6%) and were significantly more frequent in patients with liver cirrhosis than in those without cirrhosis (p = 0.043). There were no radiation-related deaths. Conclusions: Endoscopically detectable radiation-induced gastroduodenal complications were common in HCC following CCRT. Although serious complications were uncommon, the frequency was higher in patients with liver cirrhosis; thus, these patients should be closely monitored when receiving CCRT.

Diagnostic imaging and interventional radiology of hepatocellular carcinoma: A multicenter study on 290 cases

International Nuclear Information System (INIS)

Dalla Palma, Ludovico; Puzzi Mucelli, Roberto; Sponza, Massimo; De Santis, Mario; Gandini, Giovanni; Matricardi, Luigi; Rossi, Cristina

1997-01-01

The authors report of a multicenter study on the diagnosis and interventional therapy of hepatocellular carcinoma (HCC).The first aim -diagnostic - was to evaluate the sensitivity of 4 imaging techniques, namely ultrasonography (US), Computed Tomography (CT), digital arteriography (DSA) and Lipiodol CT (LCT), in hepatocellular carcinoma detection. The accuracy of these techniques was also investigated in tumor staging, which is important for treatment planning.The second aim - treatment - consisted in assessing the therapeutic efficacy of intraarterial chemoembolization (CEAT) versus percutaneous ethanol injection (PEI) in non advanced hepatocellular carcinoma and of intraarterial chemoembolization versus no treatment (NT) in advanced hepatocellular carcinoma. Treatment efficacy was evaluated with the following randomized protocols

An Ecological Study of the Association between Air Pollution and Hepatocellular Carcinoma Incidence in Texas.

Science.gov (United States)

Cicalese, Luca; Raun, Loren; Shirafkan, Ali; Campos, Laura; Zorzi, Daria; Montalbano, Mauro; Rhoads, Colin; Gazis, Valia; Ensor, Katherine; Rastellini, Cristiana

2017-11-01

Primary liver cancer is a significant cause of cancer-related death in both the United States and the world at large. Hepatocellular carcinoma comprises 90% of these primary liver cancers and has numerous known etiologies. Evaluation of these identified etiologies and other traditional risk factors cannot explain the high incidence rates of hepatocellular carcinoma in Texas. Texas is home to the second largest petrochemical industry and agricultural industry in the nation; industrial activity and exposure to pathogenic chemicals have never been assessed as potential links to the state's increased incidence rate of hepatocellular carcinoma. The association between the county-level concentrations of 4 air pollutants known to be linked to liver cancer, vinyl chloride, arsenic, benzene, and 1,3-butadiene, and hepatocellular carcinoma rates was evaluated using nonparametric generalized additive logistic regression and gamma regression models. Hepatocellular carcinoma incidence rates for 2000-2013 were evaluated in comparison to 1996 and 1999 pollution concentrations and hepatocellular carcinoma rates for the subset of 2006-2013 were evaluated in comparison to 2002 and 2005 pollution concentrations, respectively. The analysis indicates that the relationship between the incidence of liver cancer and air pollution and risk factors is nonlinear. There is a consistent significant positive association between the incidence of liver cancer and hepatitis C prevalence rates (gamma all years, p < 0.05) and vinyl chloride concentrations (logistic 2002 and 2005, p < 0.0001; gamma 2002 and 2005, p < 0.05). This study suggests that vinyl chloride is a significant contributor to the incidence of liver cancer in Texas. The relationship is notably nonlinear. Further, the study supports the association between incidence of liver cancer and prevalence of hepatitis B.

Spontaneous Rupture of Hepatocellular Carcinoma in a Young Patient with Fatal Outcome

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David F. Pinal-García

2018-01-01

Full Text Available Spontaneous rupture of hepatocellular carcinoma (HCC is a potentially life-threatening complication. Diagnosis may be difficult, particularly in the absence of known liver cirrhosis or tumor. A 20-year-old male patient presented with progressive abdominal pain and shock. His past medical history was uneventful. Anemia, acute renal failure, and abnormal liver function test were demonstrated. Mild hepatomegaly, perihepatic and flank fluid, and multiple hypodense liver lesions suggestive of intrahepatic metastases or multifocal HCC were revealed by computed tomography. Two actively bleeding liver tumors and multiple tumors in a noncirrhotic liver were found. Hemostatic suture and perihepatic packing were performed. The patient remained in critical condition, with a fatal outcome 48 h later. Histopathologic analysis reported HCC and absence of cirrhotic changes. HCC spontaneous rupture incidence is reported between 2.3 and 26%. Median age is 65 years. No liver cirrhosis is found in one-third of patients, with a median age of 51 years. Sudden onset of abdominal pain and shock is observed in the majority of cases. An accurate preoperative diagnosis improves to 75% with ultrasound and computed tomography. Besides hemodynamic stabilization, there is no general agreement on the best treatment option. Transarterial embolization, surgical perihepatic packing, suture plication, and hepatic artery ligation are useful methods of hemostasis in unstable patients. Mortality has been reported from 16.5 to 100%. The histopathologic finding of HCC in a noncirrhotic liver represents a less frequent presentation. A case of spontaneous rupture of HCC carcinoma and a noncirrhotic liver in a young patient is herein reported.

Diagnosis of small hepatocellular carcinoma by incremental dynamic CT

International Nuclear Information System (INIS)

Uchida, Masafumi; Kumabe, Tsutomu; Edamitsu, Osamu

1993-01-01

Thirty cases of pathologically confirmed small hepatocellular carcinoma were examined by Incremental Dynamic CT (ICT). ICT scanned the whole liver with single-breath-hold technique; therefore, effective early contrast enhancement could be obtained for diagnosis. Among the 30 tumors, 26 were detected. The detection rate was 87%. A high detection rate was obtained in tumors more than 20 mm in diameter. Twenty-two of 26 tumors could be diagnosed correctly. ICT examination was useful for detection of small hepatocellular carcinoma. (author)

Serum immunoreactive calcitonin concentration in hepatocellular carcinoma

International Nuclear Information System (INIS)

Dugard, J.; Kew, M.C.; Da Fonseca, M.; Levin, J.

1982-01-01

Having found raised serum calcitonin concentrations is 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154,6 pg/ml). Values in the tumour patients ranged from 10 to 1 650 pg/ml (mean 302,6 pg/ml). The mean figures were significantly higher in the tumour patients (P smaller than 0,001), 35,5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10780 pg/ml (mean 2 179 pg/ml). If 1 000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r=0,67; P smaller than 0,001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma

Serum immunoreactive calcitonin concentration in hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Dugard, J; Kew, M C; Da Fonseca, M; Levin, J [University of the Witwatersrand, Johannesburg (South Africa)

1982-08-21

Having found raised serum calcitonin concentrations in 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154,6 pg/ml). Values in the tumour patients ranged from 10 to 1,650 pg/ml (mean 302,6 pg/ml). The mean figures were significantly higher in the tumour patients (P smaller than 0,001), 35.5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10780 pg/ml (mean 2,179 pg/ml). If 1,000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r=0,67; P smaller than 0,001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma.

The multifaceted role of podoplanin expression in hepatocellular carcinoma

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Andreea Cioca

2017-02-01

Full Text Available The role of podoplanin in hepatocellular carcinoma (HCC is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD was increased in patients who had vascular invasion at the time of diagnosis (P=0.018 and in those with associated cirrhosis (P=0.006. Tumor cells showing podoplanin expression were correlated with histological grade (P=0.040. Podoplanin-expressing cancer associated fibroblasts (CAFs were correlated with both LVD (P=0.019 and tumor cells (P=0.015. Our results sustain the dual role of podoplanin in HCC by its involvement in both HCC tumorigenesis, lymphatic neovascularization and tumor invasion invasiveness. A possible crosstalk between epithelial and stromal tumor cells in HCC tumor microenvironment may be mediated by podoplanin, but this hypothesis needs further studies to elucidate this interrelation.

Haptocorrin as marker of disease progression in fibrolamellar hepatocellular carcinoma

DEFF Research Database (Denmark)

Lildballe, Dorte Launholt; Nguyen, Khoa Tran; Poulsen, Steen Seier

2011-01-01

No valid markers are routinely available to follow disease progression in patients with fibrolamellar hepatocellular carcinoma (FLHCC). We report data suggesting that the vitamin B12 binding protein haptocorrin (HC) may prove a suitable marker.......No valid markers are routinely available to follow disease progression in patients with fibrolamellar hepatocellular carcinoma (FLHCC). We report data suggesting that the vitamin B12 binding protein haptocorrin (HC) may prove a suitable marker....

Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma

Science.gov (United States)

2015-12-01

Hepatocellular Carcinoma; Hepatoma; Liver Cancer, Adult; Liver Cell Carcinoma; Liver Cell Carcinoma, Adult; Cancer of Liver; Cancer of the Liver; Cancer, Hepatocellular; Hepatic Cancer; Hepatic Neoplasms; Hepatocellular Cancer; Liver Cancer; Neoplasms, Hepatic; Neoplasms, Liver

Activity of serum angiotensin-converting enzyme as a tumour marker of hepatocellular carcinoma.

Science.gov (United States)

Kardum, D; Huskic, J; Fabijanic, D; Banic, M; Buljevac, M; Kujundzic, M; Loncar, B

1999-11-01

Previous studies have pointed to the changes of serum angiotensin-converting enzyme (SACE) values in patients with liver disease and cancer located in different sites. The aim of this study was to determine the changes in SACE values in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. The study comprised 30 patients with HCC (22 men and eight women) of average age 48.6 +/- 9.0 years and 30 patients with liver cirrhosis (21 men, nine women) of average age 49.1 +/- 9.5 years. The control group consisted of 30 healthy volunteers with matching anthropometric characteristics. SACE activity was determined by a spectrophotometric method using synthetic hippuryl-glycyl-glycine as substrate. The mean SACE value was considerably lower in patients with HCC, 22.8 U/ml (95% CI, 22.5-23.9), both those in whom HCC developed in cirrhotic liver (n = 23), 23.7 (22.9-24.5) as well as those with HCC without cirrhosis (n = 7), 21.8 (21.0-22.6), with regard to patients with liver cirrhosis, 37.2 (36.6-37.8) (P SACE value was increased in accordance with the severity of the disease expressed by Child's classification; however, at each stage SACE values were considerably lower in patients with HCC in cirrhotic liver (Child A, 35.8 vs 22.1; Child B, 38.7 vs 24.2; Child C, 40.0 vs 28.3) (P SACE activity. The SACE value was also significantly decreased in patients with HCC whose AFP were not altered. The study has shown that SACE values are low in patients with advanced HCC. It may be helpful in detecting HCC in patients with cirrhosis, where it can be difficult to differentiate between small HCC tumours and regeneration nodules.

Midkine Increases Diagnostic Yield in AFP Negative and NASH-Related Hepatocellular Carcinoma.

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Roslyn Vongsuvanh

Full Text Available Robust biomarkers for population-level hepatocellular carcinoma (HCC surveillance are lacking. We compared serum midkine (MDK, dickkopf-1 (DKK1, osteopontin (OPN and AFP for HCC diagnosis in 86 HCC patients matched to 86 cirrhotics, 86 with chronic liver disease (CLD and 86 healthy controls (HC. Based on the performance of each biomarker, we assessed a separate longitudinal cohort of 28 HCC patients, at and before cancer diagnosis. Serum levels of MDK and OPN were higher in HCC patients compared to cirrhosis, CLD and HC groups. DKK1 was not different between cases and controls. More than half of HCC patients had normal AFP. In this AFP-negative HCC cohort, 59.18% (n = 29/49 had elevated MDK, applying the optimal cut-off of 0.44 ng/ml. Using AFP ≥ 20 IU/ml or MDK ≥ 0.44 ng/ml, a significantly greater number (76.7%; n = 66/86 of HCC cases were detected. The area under the receiver operating curve for MDK was superior to AFP and OPN in NASH-HCC diagnosis. In the longitudinal cohort, MDK was elevated in 15/28 (54% of HCC patients at diagnosis, of whom 67% had elevated MDK 6 months prior.AFP and MDK have a complementary role in HCC detection. MDK increases the diagnostic yield in AFP-negative HCC and has greater diagnostic performance than AFP, OPN and DKK-1 in the diagnosis of NASH-HCC. Additionally, MDK has a promising role in the pre-clinical diagnosis of HCC.

Expression characteristics and diagnostic value of annexin A2 in hepatocellular carcinoma

OpenAIRE

Zhang, Hai-Jian; Yao, Deng-Fu; Yao, Min; Huang, Hua; Wu, Wei; Yan, Mei-Juan; Yan, Xiao-Di; Chen, Jie

2012-01-01

AIM: To investigate the characteristics and diagnostic value of annexin A2 (ANXA2) expression in cancerous tissues and sera of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis

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Yezaz Ahmed Ghouri

2017-01-01

Full Text Available Since the 1970s, the epidemic of hepatocellular carcinoma (HCC has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments.

[{sup 68}Ga]NODAGA-RGD - Metabolic stability, biodistribution, and dosimetry data from patients with hepatocellular carcinoma and liver cirrhosis

Energy Technology Data Exchange (ETDEWEB)

Haubner, Roland; Rangger, Christine; Decristoforo, Clemens; Virgolini, Irene J. [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Finkenstedt, Armin; Zoller, Heinz [Medical University of Innsbruck, Department of Internal Medicine II, Innsbruck (Austria); Stegmayr, Armin [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); FH Gesundheit/University of Applied Sciences Tyrol, Innsbruck (Austria)

2016-10-15

This study was designed to determine safety, tolerability, and radiation burden of a [{sup 68}Ga]NODAGA-RGD-PET for imaging integrin α{sub v}β{sub 3} expression in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Moreover, metabolic stability and biokinetic data were compiled. After injection of 154-184 MBq [{sup 68}Ga]NODAGA-RGD three consecutive PET/CT scans were acquired starting 8.3 ± 2.1, 36.9 ± 2.8, and 75.1 ± 3.4 min after tracer injection. For metabolite analysis, blood and urine samples were analyzed by HPLC. For dosimetry studies, residence time VOIs were placed in the corresponding organs. The OLINDA/EXM program was used to estimate the absorbed radiation dose. The radiopharmaceutical was well tolerated and no drug-related adverse effects were observed. No metabolites could be detected in blood (30 and 60 min p.i.) and urine (60 min p.i.). [{sup 68}Ga]NODAGA-RGD showed rapid and predominantly renal elimination. Background radioactivity in blood, intestine, lung, and muscle tissue was low (%ID/l 60 min p.i. was 0.56 ± 0.43, 0.54 ± 0.39, 0.22 ± 0.05, and 0.16 ± 0.8, respectively). The calculated effective dose was 21.5 ± 5.4 μSv/MBq, and the highest absorbed radiation dose was found for the urinary bladder wall (0.26 ± 0.09 mSv/MBq). No increased uptake of the tracer was found in HCC compared with the background liver tissue. [{sup 68}Ga]NODAGA-RGD uptake in the HCCs lesions was not sufficient to use this tracer for imaging these tumors. [{sup 68}Ga]NODAGA-RGD was well tolerated and metabolically stable. Due to rapid renal excretion, background radioactivity was low in most of the body, resulting in low radiation burden and indicating the potential of [{sup 68}Ga]NODAGA-RGD PET for non-invasive determination of integrin α{sub v}β{sub 3} expression. (orig.)

Differential expression of OPN, VEGF-A, and HIF-1α and its clinical significance in hepatocellular carcinoma

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ZHENG Yan

2013-01-01

Full Text Available ObjectiveTo investigate the expression patterns of osteopontin (OPN, vascular endothelial growth factor-A (VEGF-A, and hypoxia-inducible factor-1α(HIF-1α in primary hepatocellular carcinoma (HCC and determine the clinical significance of this differential expression profile. MethodsImmunohistochemical staining of OPN, VEGF-A, and HIF-1α was carried out on primary HCC tissues from 90 patients, HCC-adjacent cirrhosis tissues from 20 of those patients, and normal liver tissues from 15 healthy controls. Correlations between expression levels and HCC clinicopathological characteristics were assessed by Spearman's correlation coefficient. ResultsThe majority of HCC tissues showed positive immunostaining for OPN (69/90, 76.67%, VEGF-A (64/90, 71.11%, and HIF-1α (66/90, 73.33%. OPN- and VEGF-A-positivity were significantly higher than the results from the cirrhosis tissues and normal tissues. HIF-1α-positivity was similar between the HCC and cirrhosis tissues, but both were significantly different from the normal tissues. The differential expressions of OPN, VEGF-A, and HIF-1α were significantly correlated with tumor thrombus, capsular integrity, tumor differentiation and stage, and metastasis (P＜0.05. ConclusionHCC tissues overexpress OPN, VEGF-A, and HIF-1α and this differential profile may be related to HCC progression. Future investigations of this triad of factors may provide novel insights into the biological characteristics of HCC and reveal important targets of molecular therapy.

Targeting the gut-liver axis in cirrhosis

DEFF Research Database (Denmark)

Madsen, Bjørn S; Havelund, Troels; Krag, Aleksander

2013-01-01

The gut-liver axis in cirrhosis and portal hypertension is gaining increasing attention as a key pathophysiological mechanism responsible for progression of liver failure and development of complications such as spontaneous infections and hepatocellular carcinoma. Antibiotics and non-selective β......-blockers (NSBB) intercept this axis and each drug has proven efficacy in clinical trials. A synergistic effect is a hitherto unproven possibility. There is an increasing body of evidence supporting improved outcome with expanded use of NSBB and antibiotic therapy beyond current indications. This review addresses...... the issue of pharmacological treatment of cirrhosis and portal hypertension with antibiotics and NSBB. We discuss their mechanism of action and suggest that combining the two treatment modalities could potentially reduce the risk of complications....

New hallmark of hepatocellular carcinoma, early hepatocellular carcinoma and high-grade dysplastic nodules on Gd-EOB-DTPA MRI in patients with cirrhosis: a new diagnostic algorithm.

Science.gov (United States)

Renzulli, Matteo; Biselli, Maurizio; Brocchi, Stefano; Granito, Alessandro; Vasuri, Francesco; Tovoli, Francesco; Sessagesimi, Elisa; Piscaglia, Fabio; D'Errico, Antonietta; Bolondi, Luigi; Golfieri, Rita

2018-02-03

Many improvements have been made in diagnosing hepatocellular carcinoma (HCC), but the radiological hallmarks of HCC have remained the same for many years. We prospectively evaluated the imaging criteria of HCC, early HCC and high-grade dysplastic nodules (HGDNs) in patients under surveillance for chronic liver disease, using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and diffusion-weighted imaging. Our study population included 420 nodules >1 cm in 228 patients. The MRI findings of each nodule were collected in all sequences/phases. The diagnosis of HCC was made according to the American Association for the Study of Liver Diseases (AASLD) criteria; all atypical nodules were diagnosed using histology. A classification and regression tree was developed using three MRI findings which were independently significant correlated variables for early HCC/HCC, and the best sequence of their application in a new diagnostic algorithm (hepatobiliary hypointensity, arterial hyperintensity and diffusion restriction) was suggested. This algorithm demonstrated, both in the entire study population and for nodules ≤2 cm, higher sensitivity (96% [95% CI 93.5% to 97.6%] and 96.6% [95% CI 93.9% to 98.5%], P<0.001, respectively) and slightly lower specificity (91.8% [95% CI 88.6% to 94.1%], P=0.063, and 92.7% [95% CI 88.9% to 95.4%], P=0.125, respectively) than those of the AASLD criteria. Our new diagnostic algorithm also showed a very high sensitivity (94.7%; 95% CI 92% to 96.6%) and specificity (99.3%; 95% CI 97.7% to 99.8%) in classifying HGDN. Our new diagnostic algorithm demonstrated significantly higher sensitivity and comparable specificity than those of the AASLD imaging criteria for HCC in patients with cirrhosis evaluated using Gd-EOB-DTPA MRI, even for lesions ≤2 cm. Moreover, this diagnostic algorithm allowed evaluating other lesions which could arise in a cirrhotic liver, such as early HCC and HGDN. © Article author

Using transient elastography to predict hepatocellular carcinoma recurrence after radiofrequency ablation.

Science.gov (United States)

Lee, Yu Rim; Park, Soo Young; Kim, Seung Up; Jang, Se Young; Tak, Won Young; Kweon, Young Oh; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang-Hyub; Hur, Keun

2017-05-01

Liver stiffness (LS) value determined using transient elastography (TE) can be used to assess the degree of liver fibrosis. The study investigated whether TE can predict the recurrence of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). This study retrospectively enrolled 228 patients with HCC who received TE and RFA as the first-line treatment for HCC between 2008 and 2015. Cox regression analysis was used to identify independent predictors of HCC recurrence. The median age of the study population (170 men and 58 women) was 61 years. During the study period, HCC recurrence and mortality developed in 125 (54.8%) and 37 (16.2%) patients after RFA, respectively. Liver cirrhosis, platelet count, multiple tumors, and LS value were the independent predictors of HCC recurrence. When the study population was stratified into early (measurement using TE can be a useful predictor of HCC recurrence after RFA. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

PARP-1 serves as a novel molecular marker for hepatocellular carcinoma in a Southern Chinese Zhuang population.

Science.gov (United States)

Li, Jiatong; Dou, Dongwei; Li, Ping; Luo, Wenqi; Lv, Wenxin; Zhang, Chengdong; Song, Xiaowei; Yang, Yuan; Zhang, Yuening; Xu, Yanzhen; Xiao, Feifan; Wei, Yan; Qin, Jian; Li, Hongtao; Yang, Xiaoli

2017-07-01

PARP-1 (poly(ADP-ribose) polymerase-1) plays an important role in tumorigenesis. Since its effects on different populations are varied, this study investigated the impact of PARP-1 on primary hepatocellular carcinoma in a Southern Chinese Zhuang population. We assessed the global PARP-1 messenger RNA expression in patients with hepatocellular carcinoma using The Cancer Genome Atlas dataset. Increased PARP-1 expression, related to alpha-fetoprotein level, was observed. The area under the receiver operating characteristic curve value was 0.833. Kaplan-Meier survival curves indicated that higher PARP-1 expression was not correlated with poorer overall survival and recurrence-free survival. In a Zhuang population, PARP-1 messenger RNA and protein levels were increased in the hepatocellular carcinoma tissue and its adjacent liver tissues as assessed by quantitative polymerase chain reaction, immunohistochemistry, and western blotting. Higher PARP-1 level was associated with a higher tumor stage (p  0.05). Further analysis suggested that H2AX, a PARP-1 protein interaction partner, was coordinated with PARP-1 in hepatocellular carcinoma tumorigenesis. Overall, some new characteristics of PARP-1 expression were noted in the Zhuang population. PARP-1 is a novel promising diagnostic marker for hepatocellular carcinoma in the Southern Chinese Zhuang population.

Molecular mechanism for the involvement of nuclear receptor FXR in HBV-associated hepatocellular carcinoma

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Yong-dong Niu

2011-08-01

Full Text Available Farnesoid X receptor (FXR, also termed nuclear receptor NR1H4 is critically involved in the regulation of nascent bile formation and bile acid enterohepatic circulation. FXR and bile acids have been shown to play roles in liver regeneration and inflammatory responses. There is increasing evidence suggesting that FXR and the FXR signaling pathway are involved in the pathophysiology of a wide range of liver diseases, such as viral hepatitis, cirrhosis, and hepatocellular carcinoma (HCC. Here we discuss the latest discoveries of FXR functions with relevance to bile acid metabolism and HBV-associated HCC. More specifically, the goal of this review is to discuss the roles of FXR and bile acids in regulating HBV replication and how disregulation of the FXR-bile acid signaling pathway is involved in HBV-associated hepatocarcinogenesis.

MicroRNA gene polymorphisms and environmental factors increase patient susceptibility to hepatocellular carcinoma.

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Yin-Hung Chu

Full Text Available BACKGROUND: Micro RNAs (miRNAs are small RNA fragments that naturally exist in the human body. Through various physiological mechanisms, miRNAs can generate different functions for regulating RNA protein levels and balancing abnormalities. Abnormal miRNA expression has been reported to be highly related to several diseases and cancers. Single-nucleotide polymorphisms (SNPs in miRNAs have been reported to increase patient susceptibility and affect patient prognosis and survival. We adopted a case-control research design to verify the relationship between miRNAs and hepatocellular carcinoma. METHODOLOGY/PRINCIPAL FINDINGS: A total of 525 subjects, including 377 controls and 188 hepatocellular carcinoma patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and real-time PCR were used to analyze miRNA146a (rs2910164, miRNA149 (rs2292832, miRNA196 (rs11614913, and miRNA499 (rs3746444 genetic polymorphisms between the control group and the case group. The results indicate that people who carry the rs3746444 CT or CC genotypes may have a significantly increased susceptibility to hepatocellular carcinoma (adjusted odds ratio [AOR] = 2.84, 95% confidence interval [CI] = 1.88-4.30. In addition, when combined with environmental risk factors, such as smoking and alcohol consumption, interaction effects were observed between gene polymorphisms and environmental factors (odds ratio [OR] = 4.69, 95% CI = 2.52-8.70; AOR = 3.38, 95% CI = 1.68-6.80. CONCLUSIONS: These results suggest that a significant association exists between miRNA499 SNPs and hepatocellular carcinoma. Gene-environment interactions of miRNA499 polymorphisms, smoking, and alcohol consumption might alter hepatocellular carcinoma susceptibility.

Histopathology of hepatocellular carcinoma.

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Schlageter, Manuel; Terracciano, Luigi Maria; D'Angelo, Salvatore; Sorrentino, Paolo

2014-11-21

Hepatocellular carcinoma (HCC) is currently the sixth most common type of cancer with a high mortality rate and an increasing incidence worldwide. Its etiology is usually linked to environmental, dietary or life-style factors. HCC most commonly arises in a cirrhotic liver but interestingly an increasing proportion of HCCs develop in the non-fibrotic or minimal fibrotic liver and a shift in the underlying etiology can be observed. Although this process is yet to be completely understood, this changing scenario also has impact on the material seen by pathologists, presenting them with new diagnostic dilemmas. Histopathologic criteria for diagnosing classical, progressed HCC are well established and known, but with an increase in detection of small and early HCCs due to routine screening programs, the diagnosis of these small lesions in core needle biopsies poses a difficult challenge. These lesions can be far more difficult to distinguish from one another than progressed HCC, which is usually a clear cut hematoxylin and eosin diagnosis. Furthermore lesions thought to derive from progenitor cells have recently been reclassified in the WHO. This review summarizes recent developments and tries to put new HCC biomarkers in context with the WHOs reclassification. Furthermore it also addresses the group of tumors known as combined hepatocellular-cholangiocellular carcinomas.

Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report

International Nuclear Information System (INIS)

Tanaka, Tomoko; Hiramatsu, Katsushi; Nosaka, Takuto; Saito, Yasushi; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Matsuda, Hidetaka; Ohtani, Masahiro; Nemoto, Tomoyuki; Suto, Hiroyuki; Yamamoto, Tatsuya; Kimura, Hirohiko; Nakamoto, Yasunari

2015-01-01

Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin-labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism

Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report.

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Tanaka, Tomoko; Hiramatsu, Katsushi; Nosaka, Takuto; Saito, Yasushi; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Matsuda, Hidetaka; Ohtani, Masahiro; Nemoto, Tomoyuki; Suto, Hiroyuki; Yamamoto, Tatsuya; Kimura, Hirohiko; Nakamoto, Yasunari

2015-11-06

Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin-labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism.

High-resolution characterization of a hepatocellular carcinoma genome.

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Totoki, Yasushi; Tatsuno, Kenji; Yamamoto, Shogo; Arai, Yasuhito; Hosoda, Fumie; Ishikawa, Shumpei; Tsutsumi, Shuichi; Sonoda, Kohtaro; Totsuka, Hirohiko; Shirakihara, Takuya; Sakamoto, Hiromi; Wang, Linghua; Ojima, Hidenori; Shimada, Kazuaki; Kosuge, Tomoo; Okusaka, Takuji; Kato, Kazuto; Kusuda, Jun; Yoshida, Teruhiko; Aburatani, Hiroyuki; Shibata, Tatsuhiro

2011-05-01

Hepatocellular carcinoma, one of the most common virus-associated cancers, is the third most frequent cause of cancer-related death worldwide. By massively parallel sequencing of a primary hepatitis C virus-positive hepatocellular carcinoma (36× coverage) and matched lymphocytes (>28× coverage) from the same individual, we identified more than 11,000 somatic substitutions of the tumor genome that showed predominance of T>C/A>G transition and a decrease of the T>C substitution on the transcribed strand, suggesting preferential DNA repair. Gene annotation enrichment analysis of 63 validated non-synonymous substitutions revealed enrichment of phosphoproteins. We further validated 22 chromosomal rearrangements, generating four fusion transcripts that had altered transcriptional regulation (BCORL1-ELF4) or promoter activity. Whole-exome sequencing at a higher sequence depth (>76× coverage) revealed a TSC1 nonsense substitution in a subpopulation of the tumor cells. This first high-resolution characterization of a virus-associated cancer genome identified previously uncharacterized mutation patterns, intra-chromosomal rearrangements and fusion genes, as well as genetic heterogeneity within the tumor.

[Care pathway of patients with hepatocellular carcinoma in France: State of play in 2017].

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Costentin, Charlotte; Ganne-Carrié, Nathalie; Rousseau, Benoit; Gérolami, René; Barbare, Jean-Claude

2017-09-01

Hepatocellular carcinoma is a major public health problem with one of the highest overall mortality compared to other cancers. The median overall survival in France in a hospital population with hepatocellular carcinoma is 9.4 months. Several publications reported a positive impact of hepatocellular carcinoma screening on diagnosis at an early-stage, eligibility for curative treatment and overall survival. However, the identification of patients to be included in a hepatocellular carcinoma screening program and the application of screening recommendations are not optimal. Other studies suggest a potentially negative impact of delayed diagnosis or treatment initiation on the patient's prognosis. Finally, marked variations between French regions and departments have been described in terms of access to curative treatment and overall survival. In this review article, we propose a state of play of the hepatocellular carcinoma patient's care pathway in France with the aim of identifying potential breaking points with negative impact on prognosis and of developing proposals for improvement. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Machine Learning Algorithms Outperform Conventional Regression Models in Predicting Development of Hepatocellular Carcinoma

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Singal, Amit G.; Mukherjee, Ashin; Elmunzer, B. Joseph; Higgins, Peter DR; Lok, Anna S.; Zhu, Ji; Marrero, Jorge A; Waljee, Akbar K

2015-01-01

Background Predictive models for hepatocellular carcinoma (HCC) have been limited by modest accuracy and lack of validation. Machine learning algorithms offer a novel methodology, which may improve HCC risk prognostication among patients with cirrhosis. Our study's aim was to develop and compare predictive models for HCC development among cirrhotic patients, using conventional regression analysis and machine learning algorithms. Methods We enrolled 442 patients with Child A or B cirrhosis at the University of Michigan between January 2004 and September 2006 (UM cohort) and prospectively followed them until HCC development, liver transplantation, death, or study termination. Regression analysis and machine learning algorithms were used to construct predictive models for HCC development, which were tested on an independent validation cohort from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. Both models were also compared to the previously published HALT-C model. Discrimination was assessed using receiver operating characteristic curve analysis and diagnostic accuracy was assessed with net reclassification improvement and integrated discrimination improvement statistics. Results After a median follow-up of 3.5 years, 41 patients developed HCC. The UM regression model had a c-statistic of 0.61 (95%CI 0.56-0.67), whereas the machine learning algorithm had a c-statistic of 0.64 (95%CI 0.60–0.69) in the validation cohort. The machine learning algorithm had significantly better diagnostic accuracy as assessed by net reclassification improvement (pmachine learning algorithm (p=0.047). Conclusion Machine learning algorithms improve the accuracy of risk stratifying patients with cirrhosis and can be used to accurately identify patients at high-risk for developing HCC. PMID:24169273

Knockdown of long noncoding RNA linc-ITGB1 suppresses migration, invasion of hepatocellular carcinoma via regulating ZEB1.

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Yu, W-W; Wang, K; Liao, G-J

2017-11-01

This research focuses on the influence of linc-ITGB1 on the metastasis of hepatocellular carcinoma and further explores its underlying mechanism. A total of 70 hepatocellular carcinoma patients were chosen for our study. RT-qPCR was used for detecting the expression level of linc-ITGB1 in their cancer tissues. Moreover, the expression level of linc-ITGB1 was also detected in hepatocellular carcinoma cell lines. Furthermore, whether linc-ITGB1 could affect the migrated and invaded ability of hepatocellular carcinoma cells was determined by wound healing assay and transwell assay. We further explored the potential mechanism by RT-qPCR and Western blot assay. Linc-ITGB1 expression level in hepatocellular carcinoma tissues was remarkably higher than that in adjacent tissues. Moreover, migrated and invaded ability of hepatocellular carcinoma cells was inhibited through knockdown of linc-ITGB1. Further study revealed that silenced linc-ITGB1 inhibited the expression of ZEB1 and then suppressed epithelial to mesenchymal transition (EMT), which was important during the metastasis of hepatocellular carcinoma. Moreover, the inhibition of cell invasion by silenced linc-ITGB1 could be rescued through overexpression of ZEB1 in hepatocellular carcinoma. The results indicate that linc-ITGB1, a novel oncogene in tumorigenesis, could promote the metastasis and EMT via ZEB1, which may offer a possible therapeutic target in hepatocellular carcinoma.

Scintigraphic demonstration of a metastasizing hepato-cellular carcinoma

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Heintz, P; Gratz, K F; Schwarzrock, R; Schober, O; Neuhaus, P; Creutzig, H

1986-01-01

Adenomas and hepato cellular carcinomas cannot be differentiated by nuclear medicine: both exhibit masked radiodrug trapping at reduced perfusion. Two patients revealed specific accumulation in extrahepatic foci unknown before; hence, the diagnosis of a metastasizing hepatocellular carcinoma had to be verified. One case is demonstrated in full detail. (orig./SHA).

Characterization of Hepatocellular Carcinoma Related Genes and Metabolites in Human Nonalcoholic Fatty Liver Disease

Czech Academy of Sciences Publication Activity Database

Clarke, D. J.; Novák, Petr; Lake, A.D.; Shipkova, P.; Aranibar, N.; Robertson, D.; Severson, P.L.; Reily, M.D.; Futscher, B. W.; Lehman-McKeeman, L.D.; Cherrington, N.J.

2014-01-01

Roč. 59, č. 2 (2014), s. 365-374 ISSN 0163-2116 Institutional research plan: CEZ:AV0Z50510513 Institutional support: RVO:60077344 Keywords : nonalcoholic fatty liver disease * nonalcoholic steatohepatitis * hepatocellular carcinoma * metabolomics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.613, year: 2014

Brazilian society of hepatology recommendations for the diagnosis and treatment of hepatocellular carcinoma

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Flair J Carrilho

Full Text Available ABSTRACT Hepatocellular carcinoma is a malignancy of global importance and is associated with a high rate of mortality. Recent advances in the diagnosis and treatment of this disease make it imperative to update the recommendations on the management of the disease. In order to draw evidence-based recommendations concering the diagnosis and management of hepatocellular carcinoma, the Brazilian Society of Hepatology has sponsored a single-topic meeting in João Pessoa (PB. All the invited pannelists were asked to make a systematic review of the literature and to present topics related to the risk factors for its development, methods of screening, radiological diagnosis, staging systems, curative and palliative treatments and hepatocellular carcinoma in noncirrhotic liver. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript containing the recommendations of the Brazilian Society of Hepatology.

DNAJC6 promotes hepatocellular carcinoma progression through induction of epithelial–mesenchymal transition

International Nuclear Information System (INIS)

Yang, Tao; Li, Xiao-Na; Li, Xing-Guang; Li, Ming; Gao, Peng-Zhi

2014-01-01

Highlights: • DNAJC6 is up-regulated in hepatocellular carcinoma tissues. • DNAJC6 promotes hepatocellular carcinoma cell proliferation and invasion. • DNAJC6 induces epithelial–mesenchymal transition by activating transforming growth factor β signaling. - Abstract: Epithelial–mesenchymal transition (EMT) is a developmental program, which is associated with hepatocellular carcinoma (HCC) development and progression. DNAJC6 (DNA/HSP40 homolog subfamily C member 6) encodes auxilin, which is responsible for juvenile Parkinsonism with phenotypic variability. However, the role of DNAJC6 in HCC development and progression is limited. Here, we report that DNAJC6 is up-regulated in HCC tissues and up-regulation of DNAJC6 expression predicts poor outcome in patients with HCC. Furthermore, overexpression of DNAJC6 enhances the ability for acquisition of mesenchymal traits, enhanced cell proliferation and invasion. DNAJC6 positively regulated expression of EMT-related transcription factor, also activating transforming growth factor β (TGF-β) pathway to contribute to EMT. Our findings demonstrated an important function of DNAJC6 in the progression of HCC by induction of EMT, and they implicate DNAJC6 as a marker of poor outcome in HCC

DNAJC6 promotes hepatocellular carcinoma progression through induction of epithelial–mesenchymal transition

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Yang, Tao [Hepatobiliary Surgery, The First Hospital of Shijiazhuang City, Shijiazhuang 050011 (China); Li, Xiao-Na [General Surgery, Sports Science Institute of Hebei Province, Shijiazhuang 050011 (China); Li, Xing-Guang; Li, Ming [General Surgery, The First Hospital of Shijiazhuang City, Shijiazhuang 050011 (China); Gao, Peng-Zhi, E-mail: pengzhigaovip@163.com [Hepatobiliary Surgery, The First Hospital of Shijiazhuang City, Shijiazhuang 050011 (China)

2014-12-12

Highlights: • DNAJC6 is up-regulated in hepatocellular carcinoma tissues. • DNAJC6 promotes hepatocellular carcinoma cell proliferation and invasion. • DNAJC6 induces epithelial–mesenchymal transition by activating transforming growth factor β signaling. - Abstract: Epithelial–mesenchymal transition (EMT) is a developmental program, which is associated with hepatocellular carcinoma (HCC) development and progression. DNAJC6 (DNA/HSP40 homolog subfamily C member 6) encodes auxilin, which is responsible for juvenile Parkinsonism with phenotypic variability. However, the role of DNAJC6 in HCC development and progression is limited. Here, we report that DNAJC6 is up-regulated in HCC tissues and up-regulation of DNAJC6 expression predicts poor outcome in patients with HCC. Furthermore, overexpression of DNAJC6 enhances the ability for acquisition of mesenchymal traits, enhanced cell proliferation and invasion. DNAJC6 positively regulated expression of EMT-related transcription factor, also activating transforming growth factor β (TGF-β) pathway to contribute to EMT. Our findings demonstrated an important function of DNAJC6 in the progression of HCC by induction of EMT, and they implicate DNAJC6 as a marker of poor outcome in HCC.

The application of Fasudil in treating vascular spasm occurred in interventional treatment for hepatocellular carcinomas

International Nuclear Information System (INIS)

Fan Xiaoqiang; Shen Jie; Zhang Xuena; Liu Qiuru; Ma Aiying

2011-01-01

Objective: To explore an effective way to treat the vascular spasm occurred during TACE for hepatocellular carcinomas. Methods: During interventional chemoembolization for hepatocellular carcinomas, Fasudil of 2.5 mg was injected via the catheter if vessel spasm occurred, which was followed by DSA to determine the dilatation of the arteries. Adverse effect was observed and recorded. Results: After the injection of Fasudil the vascular spasm was completely relieved in all the 30 cases. The interventional procedure for hepatocellular carcinomas was successfully accomplished in all patients. No obvious side effect occurred. Conclusion: The injection of Fasudil via the catheter is an effective and safe method to eliminate vessel spasm occurred during TACE for hepatocellular carcinomas. (authors)

Association between hepatitis B virus/hepatitis C virus infection and primary hepatocellular carcinoma risk: A meta-analysis based on Chinese population.

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Li, Libo; Lan, Xiaolin

2016-12-01

To assess the relationship between hepatitis B virus (HBV), hepatitis C virus (HCV), and HBV/HCV double infection and hepatocellular carcinoma risk in Chinese population. The databases of PubMed and CNKI were electronic searched by reviewers according to the searching words of HBV, HCV, and hepatocellular carcinoma. The related case-control studies or cohort studies were included. The association between virus infection and hepatocellular carcinoma risk was demonstrated by odds ratio (OR) and 95% confidence interval (95% CI). The data were pooled by fixed or random effects model according to the statistical heterogeneity. The publication bias was assessed by Begg's funnel plot and Egger's linear regression test. Finally, 13 publications were included in this meta-analysis. For significant statistical heterogeneity (I2 = 99.8%,P = 0.00), the OR was pooled by random effects model. The pooled results showed that HBV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 58.01, 95% CI: 44.27-71.75); statistical heterogeneity analysis showed that significant heterogeneity existed in evaluation of HCV infection and hepatocellular carcinoma risk across the included 13 studies I2 = 77.78%, P = 0.00). The OR was pooled by random effects model. The pooled results showed that HCV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 2.34, 95% CI: 1.20-3.47); significant heterogeneity did not exist in evaluation HBV/HCV double infection and hepatocellular carcinoma risk for the included 13 studies (I2 = 0.00%,P = 0.80). The OR was pooled by fixed effects model. The pooled results showed that HBV/HCV double infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 11.39, 95% CI: 4.58-18.20). No publication bias was found in the aspects of HBV, HCV, and HBV/HCV double infection and hepatocellular carcinoma. For Chinese population, HBV, HCV or HBV/HCV double infection can

Intra-arterial injection of iodine-131-labeled lipiodol for treatment of hepatocellular carcinoma

International Nuclear Information System (INIS)

Boucher, Eveline; Garin, Etienne; Guylligomarc'h, Anne; Olivie, Damien; Boudjema, Karim; Raoul, Jean-Luc

2007-01-01

Background/Aim: The therapeutic effect of intra-arterial injection of 131-iodine-labeled lipiodol for treatment of hepatocellular carcinoma in palliative or adjuvant settings has been promising. We report, the results of an open study of this therapy in cirrhotic patients with small hepatocellular carcinoma. Patients and method: Forty patients with hepatocellular carcinoma were given intra-arterial injections of 131-iodine-labeled lipiodol. These injections were repeated if necessary every 3 months. Tumor response (WHO criteria) was determined on CT scans performed after each treatment and every 3 months during the follow-up. Side effects and the cause of death were recorded. Therapeutic response and survival were analyzed. Results: The median number of treatment was 2 (1-4). There was one complete response, 18 partial responses (47.5% response rate); 19 had stable disease and 2 progressions. Overall survival rates (±CI 95%) at 1, 2 and 3 years were: 90 ± 4.7%, 60.3 ± 8%, and 39 ± 8.3%, respectively. Median survival was 27 months; 25 patients have died (4-56 months), 8 of tumor progression with a multifocal spread in the liver. Tolerance was good except for 2 patients who develop a fatal drug-related pulmonary insufficiency. Conclusion: These data suggest that intra-arterial therapeutic injection of 131-iodine-labeled lipiodol for treatment of hepatocellular carcinoma can provide high rate response and long survival for individuals not eligible for surgery or local treatment

Computed tomography of liver tumors, 2. Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor by dynamic CT scanning

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Naito, Akira; Fukuoka, Haruhito; Kashiwado, Kouzou; Ichiki, Toshio; Makidono, Yoko [Hiroshima Red Cross Hospital (Japan)

1984-02-01

Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor was attempted using dynamic CT scanning. Homogeneous and patchy types were peculiar to hepatocellular carcinoma, and ring-like type to metastatic hepatic tumor. However, with no enhancement, hepatocellular carcinoma could not be denied. Hepatocellular carcinoma was characterized by the enhancement shown on the early stage of dynamic CT. Ring enhancement was not visualized on dynamic CT but visualized on conventional contrast enhanced CT in hepatocellular carcinomas; it was visualized on conventional contrast enhanced CT and on dynamic CT in metastatic hepatic tumors.

Genome-wide transcriptional reorganization associated with senescence-to-immortality switch during human hepatocellular carcinogenesis.

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Gokhan Yildiz

Full Text Available Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal" by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15

Evaluation of arterial embolization therapy of hepatocellular carcinoma by computed tomography

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Ohishi, H; Ohue, S; Ide, K [Nara Medical Univ., Kashihara (Japan)

1981-11-01

The therapeutic effect of arterial embolization performed to 18 patients with hepatocellular carcinoma was evaluated by means of computed tomography (CT). 1) After embolization, the tumor was observed to have been reduced in size in all the cases. The relative attenuation coefficients of the tumor region to surrounding liver tissue was decreased at initial stage after arterial embolization, however, it showed a tendency of more elevation than the initial stage in the cases performed follow-up CT. The decrease of the attenuation values at the initial stage suggests the ischemic necrosis, while its elevation is considered attributable to subsequent histologic change and tumor shrinkage. 2) The follow-up CT examination after the arterial embolization on hepatocellular carcinoma provides significant facility for evaluation of its effectiveness and judgement of the time for the repeat arterial embolization.

Carcinoma hepatocelular, alcoholismo y virus de la hepatitis C Hepatocellular carcinoma, alcoholism and hepatitis C virus infection

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John Jairo Orrego B.

1994-02-01

Full Text Available Presentamos el caso de un paciente de 64 años, con el antecedente de consumo excesivo de alcohol, quien consulta por dolor localizado en el cuadrante superior derecho, de varios meses de evolución. En la laparoscopia se aprecian cirrosis macronodular y una masa localizada en el lóbulo Izquierdo del hígado, previamente detectada por ecografía. El estudio histológico demostró un carcinoma hepatocelular. Los estudios metabólicos, Inmunológicos y sexológicos permitieron documentar solamente la asociación con anticuerpos contra el virus de la Hepatitis C.

We report on the case of a sixty-four year old man who drank alcohol chronically. For several months he had suffered pain in his right upper abdominal quadrant. At laparoscopy macronodular cirrhosis and a mass 10-calized on the left hepatic lobe were observed; the mass had previously been identified by ultrasound examination. Histologic examination of the lesion established the presence of a hepatocellular carcinoma. Metabolic, Immunologic and serologic studies documented only the association with antibodies to hepatitis C virus.

Linc-POU3F3 is overexpressed in hepatocellular carcinoma and regulates cell proliferation, migration and invasion.

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Li, Yichun; Li, Yannan; Wang, Dan; Meng, Qingdong

2018-06-12

Linc-POU3F3 showed an up-regulated tendency and functioned as tumor promoter in glioma, esophageal cancer and colorectal cancer. There was no report about the expression pattern and clinical value of linc-POU3F3 in hepatocellular carcinoma. Thus, the purpose of our study is to explore the clinical significance and biological role of linc-POU3F3 in hepatocellular carcinoma. Our results suggested that levels of linc-POU3F3 were dramatically increased in hepatocellular carcinoma tissues and cell lines compared with paired normal hepatic tissues and normal hepatic cell line, respectively. Levels of linc-POU3F3 were positively correlated with clinical stage, tumor size, vascular invasion and metastasis. Moreover, high-expression of linc-POU3F3 was an independent prognostic factor for hepatocellular carcinoma patients. The gain- and loss-of-function experiments showed that linc-POU3F3 expression significantly promoted tumor cell proliferation, migration and invasion. In addition, linc-POU3F3 expression was negatively correlated with POU3F3 mRNA and protein expressions in hepatocellular carcinoma tissues, and negatively regulated POU3F3 mRNA and protein expressions in hepatocellular carcinoma cells. In conclusion, our study supports the first evidence that linc-POU3F3 plays an oncogenic role in hepatocellular carcinoma, and represents a potential therapeutic strategy for hepatocellular carcinoma patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Cirrhosis: CT and MR imaging evaluation

International Nuclear Information System (INIS)

Brancatelli, Giuseppe; Federle, Michael P.; Ambrosini, Roberta; Lagalla, Roberto; Carriero, Alessandro; Midiri, Massimo; Vilgrain, Valerie

2007-01-01

In this article, we present the CT and MR imaging characteristics of the cirrhotic liver. We describe the altered liver morphology in different forms of viral, alcoholic and autoimmune end-stage liver disease. We present the spectrum of imaging findings in portal hypertension, such as splenomegaly, ascites and varices. We describe the patchy and lacelike patterns of fibrosis, along with the focal confluent form. The process of hepatocarcinogenesis is detailed, from regenerative to dysplastic nodules to overt hepatocellular carcinoma. Different types of non-neoplastic focal liver lesions occurring in the cirrhotic liver are discussed, including arterially enhancing nodules, hemangiomas and peribiliary cysts. We show different conditions causing liver morphology changes that can mimic cirrhosis, such as congenital hepatic fibrosis, 'pseudo-cirrhosis' due to breast metastases treated with chemotherapy, Budd-Chiari syndrome, sarcoidosis and cavernous transformation of the portal vein

Cirrhosis: CT and MR imaging evaluation

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Brancatelli, Giuseppe [Sezione di Radiologia, Ospedale Specializzato in Gastroenterologia, ' Saverio de Bellis' -IRCCS, 70013 Castellana Grotte (Bari) (Italy) and Sezione di Scienze Radiologiche, Dipartimento di Biotecnologie Mediche e Medicina Legale, Universita di Palermo, Via del Vespro 127, 90127 Palermo (Italy) and Department of Radiology, University of Pittsburgh Medical Center, 200 Lothrop Street, 15213 Pittsburgh, PA (United States)]. E-mail: gbranca@yahoo.com; Federle, Michael P. [Department of Radiology, University of Pittsburgh Medical Center, 200 Lothrop Street, 15213 Pittsburgh, PA (United States); Ambrosini, Roberta [Department of Diagnostic and Interventional Radiology, ' Maggiore della Carita' University Hospital, ' A.Avogadro' Eastern Piemonte University, Corso Mazzini 18, Novara (Italy); Lagalla, Roberto [Sezione di Scienze Radiologiche, Dipartimento di Biotecnologie Mediche e Medicina Legale, Universita di Palermo, Via del Vespro 127, 90127 Palermo (Italy); Carriero, Alessandro [Department of Diagnostic and Interventional Radiology, ' Maggiore della Carita' University Hospital, ' A.Avogadro' Eastern Piemonte University, Corso Mazzini 18, Novara (Italy); Midiri, Massimo [Sezione di Scienze Radiologiche, Dipartimento di Biotecnologie Mediche e Medicina Legale, Universita di Palermo, Via del Vespro 127, 90127 Palermo (Italy); Vilgrain, Valerie [Service de Radiologie, Hopital Beaujon, 100 Boulevard du General Leclerc, 92118 Clichy (France)

2007-01-15

In this article, we present the CT and MR imaging characteristics of the cirrhotic liver. We describe the altered liver morphology in different forms of viral, alcoholic and autoimmune end-stage liver disease. We present the spectrum of imaging findings in portal hypertension, such as splenomegaly, ascites and varices. We describe the patchy and lacelike patterns of fibrosis, along with the focal confluent form. The process of hepatocarcinogenesis is detailed, from regenerative to dysplastic nodules to overt hepatocellular carcinoma. Different types of non-neoplastic focal liver lesions occurring in the cirrhotic liver are discussed, including arterially enhancing nodules, hemangiomas and peribiliary cysts. We show different conditions causing liver morphology changes that can mimic cirrhosis, such as congenital hepatic fibrosis, 'pseudo-cirrhosis' due to breast metastases treated with chemotherapy, Budd-Chiari syndrome, sarcoidosis and cavernous transformation of the portal vein.

Curative Intent Treatment of Hepatocellular Carcinoma - 844 Cases Treated in a General Surgery and Liver Transplantation Center.

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Grigorie, Răzvan; Alexandrescu, Sorin; Smira, Gabriela; Ionescu, Mihnea; Hrehoreţ, Doina; Braşoveanu, Vladislav; Dima, Simona; Ciurea, Silviu; Boeţi, Patricia; Dudus, Ionut; Picu, Nausica; Zamfir, Radu; David, Leonard; Botea, Florin; Gheorghe, Liana; Tomescu, Dana; Lupescu, Ioana; Boroş, Mirela; Grasu, Mugur; Dumitru, Radu; Toma, Mihai; Croitoru, Adina; Herlea, Vlad; Pechianu, Cătălin; Năstase, Anca; Popescu, Irinel

2017-01-01

Background: The objective of this study is to assess the outcome of the patients treated for hepatocellular carcinoma (HCC) in a General Surgery and Liver Transplantation Center. Methods: This retrospective study includes 844 patients diagnosed with HCC and surgically treated with curative intent methods. Curative intent treatment is mainly based on surgery, consisting of liver resection (LR), liver transplantation (LT). Tumor ablation could become the choice of treatment in HCC cases not manageable for surgery (LT or LR). 518 patients underwent LR, 162 patients benefited from LT and in 164 patients radiofrequency ablation (RFA) was performed. 615 patients (73%) presented liver cirrhosis. Results: Mordidity rates of patient treated for HCC was 30% and mortality was 4,3% for the entire study population. Five year overall survival rate was 39 % with statistically significant differences between transplanted, resected, or ablated patients (p 0.05) with better results in case of LT followed by LR and RFA. Conclusions: In HCC patients without liver cirrhosis, liver resection is the treatment of choice. For early HCC occurred on cirrhosis, LT offers the best outcome in terms of overall and disease free survival. RFA colud be a curative method for HCC patients not amenable for LT of LR. Celsius.

GC-MS Based Plasma Metabolomics for Identification of Candidate Biomarkers for Hepatocellular Carcinoma in Egyptian Cohort.

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Mohammad R Nezami Ranjbar

Full Text Available This study evaluates changes in metabolite levels in hepatocellular carcinoma (HCC cases vs. patients with liver cirrhosis by analysis of human blood plasma using gas chromatography coupled with mass spectrometry (GC-MS. Untargeted metabolomic analysis of plasma samples from participants recruited in Egypt was performed using two GC-MS platforms: a GC coupled to single quadruple mass spectrometer (GC-qMS and a GC coupled to a time-of-flight mass spectrometer (GC-TOFMS. Analytes that showed statistically significant changes in ion intensities were selected using ANOVA models. These analytes and other candidates selected from related studies were further evaluated by targeted analysis in plasma samples from the same participants as in the untargeted metabolomic analysis. The targeted analysis was performed using the GC-qMS in selected ion monitoring (SIM mode. The method confirmed significant changes in the levels of glutamic acid, citric acid, lactic acid, valine, isoleucine, leucine, alpha tocopherol, cholesterol, and sorbose in HCC cases vs. patients with liver cirrhosis. Specifically, our findings indicate up-regulation of metabolites involved in branched-chain amino acid (BCAA metabolism. Although BCAAs are increasingly used as a treatment for cancer cachexia, others have shown that BCAA supplementation caused significant enhancement of tumor growth via activation of mTOR/AKT pathway, which is consistent with our results that BCAAs are up-regulated in HCC.

Radiation recall dermatitis triggered by sorafenib after radiation therapy for hepatocellular carcinoma

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Kim, Gwi Eon; Song, Hee Sung; Kim, Young Suk [Jeju National University Hospital, Jeju National University School of Medicine, Jeju (Korea, Republic of); Ahn, Ki Jung [Dept. of Radiation Oncology, Inje University Busan Paik Hospital, Inje University of Medicine, Busan (Korea, Republic of)

2017-09-15

Sorafenib is widely used for unresectable and metastatic hepatocellular carcinomas. Radiation recall dermatitis (RRD) is an acute inflammatory reaction confined to previously irradiated skin that occurs after the administration of certain drugs. RRD after sorafenib treatment is rare; five cases have been reported thus far. We describe a 44-year-old man irradiated for chest wall bone metastasis from hepatocellular carcinoma. Eight days after radiotherapy completion, systemic therapy for metastatic hepatocellular carcinoma was initiated with sorafenib treatment. Eleven days after starting sorafenib, the patient complained of erythematous rash with pruritus in the chest wall, in a location consistent with the previous radiation field. Sorafenib was continued at the same dose, despite the RRD. The skin reaction subsided over the next 2 weeks without any medical intervention.

Abdominal lymph node metastases of hepatocellular carcinoma diagnosed by computed tomography and angiography

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Nakamura, Hironobu; Oi, Hiromichi [Osaka Univ. (Japan). Research Inst. for Microbial Diseases; Tanaka, Takeshi; Sai, Soomi; Hori, Shinichi

1984-04-01

CT scans of 164 patients with hepatocellular carcinoma were studied, and abdominal lymph node metastases were detected in 13 cases. Most of these lymph node metastases occured in periportal, peripancreatic and paraaortic lymph nodes. Ten instances of each these metastases were identified by CT. Six of the patients had metastases in all three sites. In 9 of 13 cases, lymph node metastases were demonstrated by angiography and various degrees of contrast material stain were seen. Lymph node metastasis of hepatocellular carcinoma is apt to be hypervascular. Most of hepatocellular carcinoma with lymph node metastasis showed infiltrative growth, and tumor thrombosis in the portal vein was commonly complicated.

Clinicopathological and prognostic significance of OCT4 in patients with hepatocellular carcinoma: a meta-analysis

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Liang CJ

2017-12-01

Full Text Available Chaojie Liang,* Yingchen Xu,* Hua Ge, Guangming Li, Jixiang Wu Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China *These authors contributed equally to this work Background and aims: Octamer-binding transcription factor 4 (OCT4 has been implicated in the development of hepatocellular carcinoma (HCC, although the findings are controversial. We conducted a meta-analysis to assess the correlation between OCT4 and the clinicopathological characteristics and the prognostic value in HCC.Methods: An electronic search for relevant articles was conducted in PubMed, Cochrane Library, Web of Science, EMBASE database, Chinese CNKI, and Chinese WanFang database. Correlations between OCT4 expression and clinicopathological features and survival outcomes were analyzed. Pooled odds ratios and hazard ratios with 95% CIs were calculated using STATA 14.2 software.Results: A total of 10 trials with 985 patients were included. Positive OCT4 expression was correlated with tumor size, tumor numbers, differentiation, and TNM stage. OCT4 expression was not correlated with gender, age, hepatitis B surface antigen, alfa-fetoprotein, liver cirrhosis, vascular invasion, or tumor encapsulation. OCT4 expression was associated with poor 3- and 5-year overall survival, and disease-free survival rate.Conclusion: OCT4 expression was associated with tumor size, tumor numbers, differentiation, and TNM stage in HCC. OCT4 may be a useful prognostic biomarker for HCC. Keywords: octamer-binding transcription factor 4, hepatocellular carcinoma, prognosis, meta-analysis

Association of social class in HBsAg and hepatocellular carcinoma

International Nuclear Information System (INIS)

Pervez, T.; Anwar, M. S.

2001-01-01

Objective: To find out the social class difference in relation to frequency of HBsAg and hepatocellular carcinoma in our population. Design: An analytical study. Place and Duration of Study: This study was conducted in Oncology Department, Services Hospital, Lahore from December 1997 to December 2000. Subjects and Methods: The HBsAg positive voluntary and apparently healthy blood donors were grouped into three, based on monthly income. Lower socioeconomic group and had monthly income less than 3,000 Pakistani rupees, middle socioeconomic group had monthly income between 3,000-10,000 rupees and upper socioeconomic group had income of more than 10,000 Pakistani rupees. On the same pattern patients suffering from hepatocellular carcinoma coming for treatment were also grouped. During this period, 1000 blood donors were screened for HBsAg and 95 biopsy proven liver cancer by causes were treated. Medical and demographic data of all subjects were recorded. HBsAg test was performed immuno-chromatographic technique using Daina Screen HBsAg kit manufactured by Dainabot Co. Ltd, Tokyo, Japan. Results: Patients from lower and middle social class had higher percentage (80% and 75%) of hepatocellular carcinoma as compared to higher social class (66.6%). In the healthy asymptomatic blood donors lower social class had higher (13.76%) HBsAg positively as compared to middle social class (11.25%) and higher social class (8.06%). Conclusion: Preventive measures should be taken in identifying and reducing factors predisposing high frequency of these conditions. (author)

Hepatocellular carcinoma risk in relation to atomic-bomb radiation and hepatitis virus infections

International Nuclear Information System (INIS)

Fujiwara, S.; Cologne, J.B.; Hattori, N.; Suzuki, G.

2003-01-01

In Japan, most cases of hepatocellular carcinoma (HCC) are related to chronic hepatitis C (HCV) or B (HBV) virus infections. Increased liver cancer risk among atomic-bomb survivors has been reported based on mortality studies or tumor registries, but virus infection status-particularly B, which is associated with radiation dose-was not taken account. The objectives of this study were to determine HCC risk in relation to radiation exposure, after adjusting for virus infection in a cohort follow-up study. The study subjects were 6,121 Adult Health Study participants who received tests for hepatitis C and B virus antigen or antibody in 1993-5. A total of 58 HCC cases were newly diagnosed during 1993-2002. As of August 2002, 8% of individuals positive for HCV antibody subsequently developed HCC, compared with less than 1% of individuals who were negative for HCV antibody. Cox regression analysis revealed that the incidence of HCC was 27 times higher among HCV antibody positive individuals and 7 times higher among HBV surface antigen positive individuals. Men had 1.6 times higher risk than women. The risk of HCC increased with age at exam overall but declined with age at exam among the HCV-infected persons. Risk of HCC was 1.3 times higher on average among individuals exposed to radiation, but persons who were younger at the time of bombing had a higher risk of HCC for radiation. There was no evidence of interaction between HCV and radiation exposure. In conclusion, hepatocellular carcinoma risk increased with radiation exposure among persons exposed at young ages, even after adjusting for hepatitis virus infection. There was no evidence of synergy between radiation and HCV infection in this late follow-up. Further study including earlier diagnosed cases is needed to clarify this issue

Factors related to postoperative pain among patients who underwent radiofrequency ablation of hepatocellular carcinoma

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Hsieh, Y.-C.; Yap, Y.-S.; Hung, C.-H.; Chen, C.-H.; Lu, S.-N.; Wang, J.-H.

2013-01-01

Aim: To evaluate the incidence and associated factors of postoperative intense pain and haemodynamic changes during radiofrequency ablation of hepatocellular carcinoma. Materials and methods: A total of 123 consecutive hepatocellular carcinoma patients who underwent radiofrequency ablation were prospectively recruited. Patient factors, tumour characteristics, procedural factors, intraoperative haemodynamic changes, complications, postoperative events, laboratory values before and after ablation, and postoperative pain were evaluated. Postoperative pain was scored using a visual analogue scale after the procedure. Results: The mean age of the patients was 65.6 ± 9.6 years. In multiple logistic regression analysis, patients who underwent general anaesthesia [odds ratio (95% CI): 2.68 (1.23–5.81); p = 0.013] and had more postoperative nausea and vomiting episodes [3.10 (1.11–8.63); p = 0.036] were associated with intense pain. These findings remain robust after propensity score matching. For mean difference values between before and after RFA, higher in change in aspartate transaminase (p = 0.026), alanine transaminase (p = 0.016) and white blood cell count (p = 0.015), and lower in change in haemoglobin (p = 0.009) were also correlated with intense pain. There was no significant difference in haemodynamic changes between the general anaesthesia and local anaesthesia group during ablation. Conclusion: General anaesthesia, postoperative nausea and vomiting, and laboratory factors were associated with postoperative intense pain in patients who underwent radiofrequency ablation. Counselling and modification of analgesics should be considered in patients with related factors for intense pain

Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma

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Gao, Rong; Cheng, Jianhua; Fan, Chunlei; Shi, Xiaofeng; Cao, Yuan; Sun, Bo; Ding, Huiguo; Hu, Chengjin; Dong, Fangting; Yan, Xianzhong

2015-12-01

Hepatocellular carcinoma (HCC) is a common malignancy that has region specific etiologies. Unfortunately, 85% of cases of HCC are diagnosed at an advanced stage. Reliable biomarkers for the early diagnosis of HCC are urgently required to reduced mortality and therapeutic expenditure. We established a non-targeted gas chromatography-time of flight-mass spectrometry (GC-TOFMS) metabolomics method in conjunction with Random Forests (RF) analysis based on 201 serum samples from healthy controls (NC), hepatitis B virus (HBV), liver cirrhosis (LC) and HCC patients to explore the metabolic characteristics in the progression of hepatocellular carcinogenesis. Ultimately, 15 metabolites were identified intimately associated with the process. Phenylalanine, malic acid and 5-methoxytryptamine for HBV vs. NC, palmitic acid for LC vs. HBV, and asparagine and β-glutamate for HCC vs. LC were screened as the liver disease-specific potential biomarkers with an excellent discriminant performance. All the metabolic perturbations in these liver diseases are associated with pathways for energy metabolism, macromolecular synthesis, and maintaining the redox balance to protect tumor cells from oxidative stress.

Detection of hepatocellular carcinoma with multi-slice spiral CT by ...

African Journals Online (AJOL)

STORAGESEVER

2010-06-07

Jun 7, 2010 ... The purpose of the study is to evaluate the effect of iodine concentration of contrast material on detection of hepatocellular carcinoma with multi-slice spiral computed tomography (CT) by using double-arterial phase and portal venous phase enhanced scanning. Ninety-four (94) patients with hepatocellular ...

Overexpression of Rabl3 and Cullin7 is associated with pathogenesis and poor prognosis in hepatocellular carcinoma.

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An, Jun; Liu, Zhiyong; Liang, Qiong; Pan, Yuhang; Li, Haifeng; Wang, Ruizhi; Jin, Yi

2017-09-01

The expression of Rabl3 and Cullin7 is relevant to the carcinogenesis of certain cancers. However, the relationship of this expression with hepatocellular carcinoma remains unclear. To study the protein expression of Rabl3 and Cullin7 and to evaluate their role in hepatocarcinogenesis, in 162 cases of hepatocellular carcinoma, we used immunohistochemistry to investigate the expression of Rabl3 and Cullin7 in both the cancer tissues and the normal hepatic tissues around the hepatocellular carcinoma. The results demonstrated that the rates of positive Rabl3 and Cullin7 expression were 80.2% and 69.1%, respectively, in hepatocellular carcinoma tissues. However, the rates of positive Rabl3 and Cullin7 expression were 31.5% and 29.0%, respectively, in adjacent normal hepatic tissues. Rabl3 and Cullin7 were expressed at significantly higher rates in hepatocellular carcinoma compared with adjacent normal hepatic tissues (Phepatocellular carcinoma tissues of patients with lymph node metastasis, tumor thrombi in the portal vein and an advanced clinical stage (Phepatocellular carcinoma cohort. Moreover, patients with positive expression for both Rabl3 and Cullin7 had a remarkably shorter survival time compared with patients with negative expression for both proteins (Phepatocellular carcinoma and could be used as a prognostic indicator in patients with hepatocellular carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Serum transforming growth factor beta 1 in hepatitis c virus related chronic liver disease and hepatocellular carcinoma patients

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El-fouly, N.F.

2007-01-01

hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of the most frequent human malignant neoplasms. it is estimated to cause more than a quarter of a million deaths each year throughout the world. the aim of the present work was to assess the value of serum level of TGF-betal in patients with HCV related CLD and its level in patients with HCC and to evaluate its sensitivity and specificity in comparison to AFP in early diagnosis of HCC. the study was performed on two groups of egyptian patients, from the tropical medicine department and outpatient,s clinic for early detection of hepatocellular carcinoma (HCC), Ain Shams university hospitals; croup 1 consisted of forty patients with chronic liver disease, their ages ranged between 85 and 35 years (mean 51.8+ 9.2 years) included 23 male patients (57.5%) and 17 female patients (42.5%), group 11 consisted of forty patients with HCC, their age ranged between 72 and 42 years (mean 54.0+ 7.5 years) included 30 male patients (75%) and 10 female patients (25%)

Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling

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2015-01-01

Hepatocellular carcinoma (HCC) is the most common form of liver cancer (~80%), and it is one of the few cancer types with rising incidence in the United States. This highly invasive cancer is very difficult to detect until its later stages, resulting in limited treatment options and low survival rates. There is a dearth of knowledge regarding the mechanisms associated with the effects of biomechanical forces such as interstitial fluid flow (IFF) on hepatocellular carcinoma invasion. We hypothesized that interstitial fluid flow enhanced hepatocellular carcinoma cell invasion through chemokine-mediated autologous chemotaxis. Utilizing a 3D in vitro invasion assay, we demonstrated that interstitial fluid flow promoted invasion of hepatocellular carcinoma derived cell lines. Furthermore, we showed that autologous chemotaxis influences this interstitial fluid flow-induced invasion of hepatocellular carcinoma derived cell lines via the C-X-C chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12) signaling axis. We also demonstrated that mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling affects interstitial fluid flow-induced invasion; however, this pathway was separate from CXCR4/CXCL12 signaling. This study demonstrates, for the first time, the potential role of interstitial fluid flow in hepatocellular carcinoma invasion. Uncovering the mechanisms that control hepatocellular carcinoma invasion will aid in enhancing current liver cancer therapies and provide better treatment options for patients. PMID:26560447

CASC2/miR-24/miR-221 modulates the TRAIL resistance of hepatocellular carcinoma cell through caspase-8/caspase-3.

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Jin, Xiaoxin; Cai, Lifeng; Wang, Changfa; Deng, Xiaofeng; Yi, Shengen; Lei, Zhao; Xiao, Qiangsheng; Xu, Hongbo; Luo, Hongwu; Sun, Jichun

2018-02-23

Hepatocellular carcinoma is one of the most common solid tumors in the digestive system. The prognosis of patients with hepatocellular carcinoma is still poor due to the acquisition of multi-drug resistance. TNF Related Apoptosis Inducing Ligand (TRAIL), an attractive anticancer agent, exerts its effect of selectively inducing apoptosis in tumor cells through death receptors and the formation of the downstream death-inducing signaling complex, which activates apical caspases 3/8 and leads to apoptosis. However, hepatocellular carcinoma cells are resistant to TRAIL. Non-coding RNAs, including long non-coding RNAs (lncRNAs) and miRNAs have been regarded as major regulators of normal development and diseases, including cancers. Moreover, lncRNAs and miRNAs have been reported to be associated with multi-drug resistance. In the present study, we investigated the mechanism by which TRAIL resistance of hepatocellular carcinoma is affected from the view of non-coding RNA regulation. We selected and validated candidate miRNAs, miR-24 and miR-221, that regulated caspase 3/8 expression through direct targeting, and thereby affecting TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. In addition, we revealed that CASC2, a well-established tumor suppressive long non-coding RNA, could serve as a "Sponge" of miR-24 and miR-221, thus modulating TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. Taken together, we demonstrated a CASC2/miR-24/miR-221 axis, which can affect the TRAIL resistance of hepatocellular carcinoma through regulating caspase 3/8; through acting as a "Sponge" of miR-24 and miR-221, CASC2 may contribute to improving hepatocellular carcinoma TRAIL resistance, and finally promoting the treatment efficiency of TRAIL-based therapies.

Yttrium-90 microspheres for the treatment of hepatocellular carcinoma.

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Geschwind, Jean Francois H; Salem, Riad; Carr, Brian I; Soulen, Michael C; Thurston, Kenneth G; Goin, Kathleen A; Van Buskirk, Mark; Roberts, Carol A; Goin, James E

2004-11-01

Unresectable hepatocellular carcinoma is extremely difficult to treat. TheraSphere consists of yttrium-90 (a pure beta emitter) microspheres, which are injected into the hepatic arteries. This article reviews the safety and survival of patients with hepatocellular carcinoma who were treated with yttrium-90 microspheres. Eighty patients were selected from a database of 108 yttrium-90 microsphere-treated patients and were staged by using Child-Pugh, Okuda, and Cancer of the Liver Italian Program scoring systems. Patients were treated with local, regional, and whole-liver approaches. Survival from first treatment was analyzed with Kaplan-Meier and Cox regression methods. Adverse events and complications of treatment were coded by using the Southwest Oncology Group toxicity scoring system. Patients received liver doses ranging from 47 to 270 Gy. Thirty-two patients (40%) received more than 1 treatment. Survival correlated with pretreatment Cancer of the Liver Italian Program scores ( P = .002), as well as with the individual Cancer of the Liver Italian Program components, Child-Pugh class, alpha-fetoprotein levels, and percentage of tumor replacement. Patients classified as Okuda stage I (n = 54) and II (n = 26) had median survival durations and 1-year survival rates of 628 days and 63%, and 384 days and 51%, respectively ( P = .02). One patient died of liver failure judged as possibly related to treatment. Thus, in selected patients with hepatocellular carcinoma, yttrium-90 microsphere treatment is safe and well tolerated. On the basis of these results, a randomized controlled trial is warranted comparing yttrium-90 microsphere treatment with transarterial chemoembolization by using the Cancer of the Liver Italian Program system for prospective stratified randomization.

Helical CT appearance of hypovascular small hepatocellular carcinoma with pathologic correlation

International Nuclear Information System (INIS)

Zheng Keguo; Xu Dasheng; Shen Jingxian

2003-01-01

Objective: To study the helical CT dual-phase enhancement manifestation of the hypodense small hepatocellular carcinoma, and to evaluate its correlation with the histopathology. Methods: The CT signs and its histopathologic changes were analyzed in 25 cases with 27 hypodense lesions in helical CT dual-phase enhancement. All the lesions were confirmed as small hepatocellular carcinoma by operation and histopathology. Results: (1) On unenhanced scan, 16 lesions were with obscure borders and 11 lesions were with well-delineated borders. On enhanced scan, only 7 lesions were with obscure borders and the other 20 lesions were with well-delineated borders, and their contours were slightly irregular. (2) On unenhanced scan, 18 lesions showed homogeneous hypodensity and 9 lesions showed heterogeneous hypodensity. On enhanced scan, only 6 lesions showed homogeneous hypodensity and the other 21 lesions showed heterogeneous hypodensity with multiple flecks of more hypodense areas. Conclusion: The helical CT dual-phase enhancement characteristic manifestations of hypodense small hepatocellular carcinoma were as follows: the border of the lesion was obscure on unenhanced scan, however the border of the lesion became well-delineated and slightly irregular, and there were multiple flecks of more hypodense areas in the lesions after enhancement. This might be an important character in distinguishing hypodense small hepatocellular carcinoma from other hypodense diseases in the liver

Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis.

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Tang, An; Hallouch, Oussama; Chernyak, Victoria; Kamaya, Aya; Sirlin, Claude B

2018-01-01

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer mortality worldwide. Incidence rates of liver cancer vary widely between geographic regions and are highest in Eastern Asia and sub-Saharan Africa. In the United States, the incidence of HCC has increased since the 1980s. HCC detection at an early stage through surveillance and curative therapy has considerably improved the 5-year survival. Therefore, medical societies advocate systematic screening and surveillance of target populations at particularly high risk for developing HCC to facilitate early-stage detection. Risk factors for HCC include cirrhosis, chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), excess alcohol consumption, non-alcoholic fatty liver disease, family history of HCC, obesity, type 2 diabetes mellitus, and smoking. Medical societies utilize risk estimates to define target patient populations in which imaging surveillance is recommended (risk above threshold) or in which the benefits of surveillance are uncertain (risk unknown or below threshold). All medical societies currently recommend screening and surveillance in patients with cirrhosis and subsets of patients with chronic HBV; some societies also include patients with stage 3 fibrosis due to HCV as well as additional groups. Thus, target population definitions vary between regions, reflecting cultural, demographic, economic, healthcare priority, and biological differences. The Liver Imaging Reporting and Data System (LI-RADS) defines different patient populations for surveillance and for diagnosis and staging. We also discuss general trends pertaining to geographic region, age, gender, ethnicity, impact of surveillance on survival, mortality, and future trends.

Intra-arterial cis-diamminedichloroplatinum infusion treatment for widespread hepatocellular carcinoma

International Nuclear Information System (INIS)

Park, Sung Il; Yang, Hee Chul; Lee, Do Yon; Shim, Yong Woon; Kim, Sang Heum; Kim, Myeong Jin; Lee, Jong Tae; Yoo, Hyung Sik

1997-01-01

The purpose of this study is to evaluate the therapeutic efficacy of intra-arterial infusion of Cis-diamminedichloroplatinum (C-DDP) for the treatment of hepatocellular carcinomas with widespread involvement. We retrospectively analyzed 22 patients who between July 1994 and June 1996 had undergone intra-arterial c-DDP infusion therapy for the treatment of hepatocellular carcinomas with widespread involvement. The hepatomas involved both lobes in ten, portal venous obstructions in fourteen, arterio-portal shunts in nine, and arterio-venous shunts in two. Proper hepatic artery was selected for infusion of 100 mg/BSA of C-DDP. The same procedure was repeated every 3 to 4 weeks, and the total number of infusions was 65. On the basis of WHO criteria, response was classified as complete remission, partial remission, stable, or progression of the disease. Six-month and one-year survival rates were estimated, and adverse reactions were evaluated. Although the response rate is not high, intra-arterial C-DDP infusion therapy can be used as an alternative treatment for hepatocellular carcinomas with widespread involvement; adverse reactions are tolerable. (author). 16 refs., 3 figs

Contrast-enhanced dynamic magnetic resonance imaging findings of hepatocellular carcinoma and their correlation with histopathologic findings

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Karahan, Okkes I. [Department of Radiology, Erciyes University Medical Faculty, PK: 18 Talas 38280, Kayseri (Turkey)]. E-mail: oikarahan@yahoo.com; Yikilmaz, Ali [Department of Radiology, Erciyes University Medical Faculty, PK: 18 Talas 38280, Kayseri (Turkey); Artis, Tarik [Department of General Surgery, Erciyes University Medical Faculty, PK: 18 Talas 38280, Kayseri (Turkey); Canoz, Ozlem [Department of Pathology, Erciyes University Medical Faculty, PK: 18 Talas 38280, Kayseri (Turkey); Coskun, Abdulhakim [Department of Radiology, Erciyes University Medical Faculty, PK: 18 Talas 38280, Kayseri (Turkey); Torun, Edip [Department of Internal Medicine, Division of Gastrenterology, Erciyes University Medical Faculty, PK: 18 Talas 38280, Kayseri (Turkey)

2006-03-15

Purpose: To investigate the correlations of contrast-enhanced magnetic resonance (MR) imaging findings of large (>5 cm) hepatocellular carcinomas with tumor size and histopathologic findings. Materials and methods: MR imaging was performed in 30 patients with a histopathologic diagnosis of hepatocellular carcinoma. The imaging protocol included non-contrast, hepatic arterial, portal venous and late phases. The signal intensities relative to the liver, enhancement patterns and the morphologic features of the lesions were evaluated in relation to size and degree of differentiation. Results: On histopathologic examination, 12 of 30 (40%) tumors were well-differentiated (grade 1), 6 of 30 (20%) were moderately differentiated (grades 2 and 3) and 12 of 30 (40%) were poorly differentiated (grade 4). Tumor size, tumor boundary, serum alpha-fetoprotein level and portal vein invasion were found to have statistically significant correlations with the degree of differentiation (p < 0.05). Portal vein invasion, capsule formation and tumor surface characteristics showed statistically significant correlations with tumor size (p < 0.05). Conclusion: MR imaging findings of hepatocellular carcinomas larger than 5 cm are partially dependent on tumor size and degree of differentiation.

Skeletal metastases from primary hepatocellular carcinoma

International Nuclear Information System (INIS)

Kim, So Sun; Huh, Jin Do; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk; Chang, Hee Kyung; Huh, Man Ha

1988-01-01

In order to detect and to evaluate the frequency, the distribution, and the radiological findings of skeletal metastases from hepatocellular carcinoma, the authors retrospectively analyzed radiographic, scintigraphic, and CT findings of 257 patients with hepatocellular carcinoma. The results were as follows: 1. Skeletal metastases were demonstrated in 21 patients (8.2%). 2. Frequent symptoms were pain, limitation of motion, paralysis, and mass. In nine of them the initial symptoms were due to skeletal metastases. 3. The common sites of metastases were spine (13 cases), ribs (8 cases), pelvis (8 cases) and femur (6 cases). Humerus, skull and sternum were also frequently involved. 4. Plain film findings were purely osteolytic in all cases and pathologic fractures were noted in 5 cases. 5. The lesions appear expansible in 7 cases, and 4 of them showed associated soft tissue masses on CT scans. 6. Bone scans were performed in 13 cases of them and showed increased radiotracer uptake in all. 7. Angiographic studies of 3 cases showed hypervascularity of the metastatic lesions as well as the primary hepatic tumor.

Glycogen metabolism in radiation induced hepatocellular carcinoma in Swiss albino mice

International Nuclear Information System (INIS)

Gupta, N.K.; Kumar, Ashok

1988-01-01

Glycogen content and the activities of phosphorylase, glycogen sythetase (GS), glucose 6-phosphatase (G6Pase), phosphohexose isomerase (PHI), glucose 6-phosphodehydrogenase were biochemically determined in the heparocellular carcinoma induced in swiss albino mice following radiocalcium internal irradiation. The content glycogen and the activities of phosphorylase, glycogen synthetase, G6Pase, PHI, GPT and GOT are considerably reduced in the hepatocellular carcinoma compared to that in control liver. However, the activity of G6PDH shows an increased activity. Results indicate that the decreas ed glycogen content in the hepatocellular carcinoma is due to the reduced glycogen synthetase activity and utilization of glucose by HMP pathway. (author). 2 tabs., 24 refs

Synergistic growth inhibition by sorafenib and vitamin K2 in human hepatocellular carcinoma cells.

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Zhang, Yafei; Zhang, Bicheng; Zhang, Anran; Zhao, Yong; Zhao, Jie; Liu, Jian; Gao, Jianfei; Fang, Dianchun; Rao, Zhiguo

2012-09-01

Sorafenib is an oral multikinase inhibitor that has been proven effective as a single-agent therapy in hepatocellular carcinoma, and there is a strong rationale for investigating its use in combination with other agents. Vitamin K2 is nearly non-toxic to humans and has been shown to inhibit the growth of hepatocellular carcinoma. In this study, we evaluated the effects of a combination of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. Flow cytometry, 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) and nude mouse xenograft assays were used to examine the effects of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. Western blotting was used to elucidate the possible mechanisms underlying these effects. Assays for 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) revealed a strong synergistic growth-inhibitory effect between sorafenib and vitamin K2. Flow cytometry showed an increase in cell cycle arrest and apoptosis after treatment with a combination of these two drugs at low concentrations. Sorafenib-mediated inhibition of extracellular signal-regulated kinase phosphorylation was promoted by vitamin K2, and downregulation of Mcl-1, which is required for sorafenib-induced apoptosis, was observed after combined treatment. Vitamin K2 also attenuated the downregulation of p21 expression induced by sorafenib, which may represent the mechanism by which vitamin K2 promotes the inhibitory effects of sorafenib on cell proliferation. Moreover, the combination of sorafenib and vitamin K2 significantly inhibited the growth of hepatocellular carcinoma xenografts in nude mice. Our results determined that combined treatment with sorafenib and vitamin K2 can work synergistically to inhibit the growth of hepatocellular carcinoma cells. This finding raises the possibility that this combined treatment strategy might be promising as a new therapy against hepatocellular carcinoma, especially for patients

Small Molecule Targeting of a MicroRNA Associated with Hepatocellular Carcinoma.

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Childs-Disney, Jessica L; Disney, Matthew D

2016-02-19

Development of precision therapeutics is of immense interest, particularly as applied to the treatment of cancer. By analyzing the preferred cellular RNA targets of small molecules, we discovered that 5"-azido neomycin B binds the Drosha processing site in the microRNA (miR)-525 precursor. MiR-525 confers invasive properties to hepatocellular carcinoma (HCC) cells. Although HCC is one of the most common cancers, treatment options are limited, making the disease often fatal. Herein, we find that addition of 5"-azido neomycin B and its FDA-approved precursor, neomycin B, to an HCC cell line selectively inhibits production of the mature miRNA, boosts a downstream protein, and inhibits invasion. Interestingly, neomycin B is a second-line agent for hepatic encephalopathy (HE) and bacterial infections due to cirrhosis. Our results provocatively suggest that neomycin B, or second-generation derivatives, may be dual functioning molecules to treat both HE and HCC. Collectively, these studies show that rational design approaches can be tailored to disease-associated RNAs to afford potential lead therapeutics.

TMEM88, CCL14 and CLEC3B as prognostic biomarkers for prognosis and palindromia of human hepatocellular carcinoma.

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Zhang, Xin; Wan, Jin-Xiang; Ke, Zun-Ping; Wang, Feng; Chai, Hai-Xia; Liu, Jia-Qiang

2017-07-01

Hepatocellular carcinoma is one of the most mortal and prevalent cancers with increasing incidence worldwide. Elucidating genetic driver genes for prognosis and palindromia of hepatocellular carcinoma helps managing clinical decisions for patients. In this study, the high-throughput RNA sequencing data on platform IlluminaHiSeq of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas with 330 primary hepatocellular carcinoma patient samples. Stable key genes with differential expressions were identified with which Kaplan-Meier survival analysis was performed using Cox proportional hazards test in R language. Driver genes influencing the prognosis of this disease were determined using clustering analysis. Functional analysis of driver genes was performed by literature search and Gene Set Enrichment Analysis. Finally, the selected driver genes were verified using external dataset GSE40873. A total of 5781 stable key genes were identified, including 156 genes definitely related to prognoses of hepatocellular carcinoma. Based on the significant key genes, samples were grouped into five clusters which were further integrated into high- and low-risk classes based on clinical features. TMEM88, CCL14, and CLEC3B were selected as driver genes which clustered high-/low-risk patients successfully (generally, p = 0.0005124445). Finally, survival analysis of the high-/low-risk samples from external database illustrated significant difference with p value 0.0198. In conclusion, TMEM88, CCL14, and CLEC3B genes were stable and available in predicting the survival and palindromia time of hepatocellular carcinoma. These genes could function as potential prognostic genes contributing to improve patients' outcomes and survival.

Liver transplantation in patients with hepatocellular carcinoma

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Polak, Wojciech G.; Soyama, Akihiko; Slooff, Maarten J. H.

2008-01-01

Liver transplantation has a definitive place in the treatment of patients with hepatocellular carcinoma (HCC) in a cirrhotic liver. Patients with a tumor load within the Milan criteria have excellent survival comparable to survival in patients with benign indications. When tumor load exceeds the

Hyperkalaemia after radiofrequency ablation of hepatocellular carcinoma

NARCIS (Netherlands)

Verhoevena, BH; Haagsma, EB; Appeltans, BMG; Slooff, MJH; de Jong, KP

Radiofrequency ablation of liver tumours is a useful therapy for otherwise unresectable tumours. The complication rate is said to be low. In this case report we describe hyperkalaemia after radiofrequency ablation of a hepatocellular carcinoma in a patient with end-stage renal insufficiency. (C)

Factors Predicting Survival after Transarterial Chemoembolization of Unresectable Hepatocellular Carcinoma

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Farina M. Hanif

2014-10-01

Full Text Available Background: Transarterial chemoembolization is the preferred treatment for unresectable, intermediate-stage hepatocellular carcinoma. Survival after transarterial chemoembolization can be highly variable. The purpose of this study is to identify the factors that predict overall survival of patients with unresectable hepatocellular carcinoma who undergo transarterial chemoembolization as the initial therapy. Methods:We included patients who underwent transarterial chemoembolization from 2007 to 2012 in this study. Patient’s age, gender, cause of cirrhosis, Child-Turcotte-Pugh score, model of end-stage liver disease score, Cancer of the Liver Italian Program score, Okuda stage, alpha- fetoprotein level, site, size and number of tumors were recorded. Radiological response to transarterial chemoembolization was assessed by computerized tomography scan at 1 and 3 months after the procedure. Repeat sessions of transarterial chemoembolization were performed according to the response. We performed survival assessment and all patients were assessed for survival at the last follow-up. Results: Included in this study were 71 patients of whom there were 57 (80.3 % males, with a mean age of 51.9±12.1 years (range: 18-76 years. The mean follow-up period was 12.5±10.7 months. A total of 31 (43.7% patients had only one session of transarterial chemoembolization, 17 (23.9% underwent 2 and 11 (15.5% had 3 or more sessions. On univariate analysis, significant factors that predicted survival included serum bilirubin (P=0.02, esophageal varices (P=0.002, Cancer of the Liver Italian Program score (P=0.003, tumor size (P=0.005, >3 sessions of transarterial chemoembolization (P=0.006 and patient's age (P=0.001. Cox regression analysis showed that tumor size of 1 transarterial chemoembolization session (P=0.004 were associated with better survival. Conclusion: Our study demonstrates that survival after transarterial chemoem- bolization is predicted by tumor size

Triclosan treatment decreased the antitumor effect of sorafenib on hepatocellular carcinoma cells

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Wu M

2018-05-01

Full Text Available Man Wu,1,2 Guanren Zhao,2 Xiaomei Zhuang,1 Tianhong Zhang,1 Ce Zhang,2 Wenpeng Zhang,1 Zhenqing Zhang1 1State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China; 2Department of Pharmacy, The 309th Hospital of PLA, Beijing, China Background: Triclosan is a widely applied antimicrobial agent which affects the endocrine system and homeostasis; it may also promote the cirrhosis and hepatocellular carcinoma (HCC growth in a mice model. The exact roles of triclosan in regulating human hepatocellular carcinoma development and treatment remain unknown. Methods: MHCC97-H, a highly aggressive HCC cell line, was treated with indicated concentration of triclosan or sorafenib. The expression of drug-resistance genes was examined by qPCR. The clearance or metabolism of sorafenib was determined by liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS. MTT assay was used to examine the MHCC97-H cell proliferation. Nude mice were used to exam the anti-tumor effect of sorafenib on subcutaneous and intrahepatic growth of MHCC97-H cells. Results: In the present study, triclosan could induce the expression of drug-resistance genes in MHCC97-H cells (a highly aggressive HCC cell line, accelerate the clearance of sorafenib, and attenuate the anti-proliferation effect of this molecular targeted agent in MHCC97-H cells. Triclosan decreased the antitumor effect of sorafenib on subcutaneous and intrahepatic growth of MHCC97-H in nude mice. Conclusion: By discovering the fact that triclosan treatment enhances sorafenib resistance in HCC cells, this work suggests exposure of triclosan is detrimental to HCC patients during chemotherapy. Keywords: HCC, triclosan, sorafenib resistance, drug clearance 

GPX4 and GPX7 Over-Expression in Human Hepatocellular Carcinoma Tissues

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Guerriero, E.; Capone, F.; Accardo, M.; Sorice, A.; Costantini, M.; Colonna, G.; Castello, G.

2015-01-01

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is still one of the most fatal cancers. Hence, it needs to identify always new putative markers to improve its diagnosis and prognosis. The selenium is an essential trace mineral implicated as a key factor in the early stage of cancer and exerts its biological function through the selenoproteins. In the last years our group has been studying the involvement of some selenoproteins in HCC. However, no many data are reported in literature about the correlation between HCC and the glutathione peroxidases (GPXs), both selenium and non selenium-containing GPXs. In this paper we have evaluated the GPX4 and GPX7 expression in some paraffin-embedded tissues from liver biopsy of patients with hepatitis C virus (HCV)-related cirrhosis and HCC by immunohistochemistry and RT-qPCR analysis. Our results evidenced that i) GPX4 and GPX7 had a statistically significant over-expression in HCC tissues compared to cirrhotic counterparts used as non tumor tissues, and ii) their expression was higher in grade III HCC tissues with respect to grade I-II samples. Therefore, we propose to use GPX4 and GPX7 as possible markers for improving HCC diagnosis/prognosis. PMID:26708178

Hepatocellular carcinoma: risk groups, surveillance and outcome

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van Meer, S

2016-01-01

The burden of hepatocellular carcinoma (HCC) has changed in the past few decades. Although the majority of HCC cases develops in East Asia and Sub-Saharan Africa, HCC has become an increasing problem in Western countries such as the Netherlands. Surveillance for HCC is controversial because of

Detection of hepatocellular carcinoma: comparison of Gd-DTPA- and ferumoxides-enhanced MR imaging

International Nuclear Information System (INIS)

Simon, G.; Link, T.M.; Daldrup-Link, H.; Settles, M.; Woertler, K.; Doebereiner, F.; Schulte-Frohlinde, E.; Rummeny, E.J.

2005-01-01

The aim was to compare the diagnostic performance of dynamic Gd-DTPA- and ferumoxides-enhanced MRI for hepatocellular carcinoma (HCC). Twenty-five patients with chronic hepatitis or liver cirrhosis underwent both dynamic gadopentetate- and ferumoxides-enhanced MRI studies of the liver for HCC detection on the same day. MR data of both studies were retrospectively and independently analyzed. Two observers determined in consensus the grade of diffuse fibrotic liver changes (mild, moderate or severe) and the number of focal lesions. HCCs were confirmed by histology (n=22) and/or follow-up studies for at least six months (n=64). Differences in results obtained from both MR data sets were tested for significance with the McNemar's test (p 0.05) and Gd-DTPA-enhanced scans (94.2%). Gd-DTPA- and ferumoxides-enhanced MRI perform equally well for HCC detection. The majority of small hypervascular hepatic lesions, detected on dynamic Gd-DTPA-enhanced MRI but not on ferumoxides-enhanced MRI, represent no HCCs. (orig.)

Dynamic computed tomography of hepatocellular carcinoma with particular reference to capsule

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Otsuji, Hideaki [Nara Prefectural Hospital (Japan); Uchida, Hideo; Ohishi, H

1983-11-01

Dynamic CT of 117 hepatocellular carcinoma was analyzed about the capsule. Capsules were detected in 57 cases (49%) and they were classified into three types. The tumor showed high density during 15 to 26 sec after bolus injection of conrast medium, but the capsule was not enhanced. Incidence of the capsule enhanced as ring high density was 73% during 37 to 90 sec and over 90% after 4 min. Dynamic CT was very useful in the elucidation of hemodynamics of capsules of hepatocellular carcinoma.

A hepatectomized case of hepatocellular carcinoma after fast neutron irradiation therapy

International Nuclear Information System (INIS)

Nagashima, Tohru; Ryu, Takamasa; Watanabe, Yoshiji

1985-01-01

A 51-year-old male patient with hepatocellular carcinoma was treated preoperatively by fast neutron radiotherapy (910 rad/7 fractions/15 days) with a field of 8 x 6 cm. Radiation-associated liver function disturbance was scarcely observed. No side effect, such as loss of appetite and general fatigue, was encountered. According to the classification of Ohoshi and Shimosato, histological effect of radiation was graded as II sub(A). There is no preoperative fast neutron radiotherapy for hepatocellular carcinoma in Japan in the literature. (Namekawa, K.)

Value of infusion-DSA (Digital Subtraction Angiography) in diagnosis of primary hepatocellular carcinoma

International Nuclear Information System (INIS)

Kwon, Jeong Mi; Kim, So Sun; Huh, Jin Do; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk

1991-01-01

In order to evaluate diagnostic effectiveness of the infusion-study, the authors prospectively evaluated hepatic digital subtraction angiography of bolus and infusion studies in 71 patients with hepatocellular carcinoma. In contrast to Bolus-DSA, which involves a 2 second injection of 10cc of contrast medium, the Infusion-DSA uses a protracted (10sec) injection, a lower injection rate, and larger total dose of contrast medium (20cc). The information yield of arterial and capillary phases of Infusion-DSA was compared with that of Bolus-DSA and graded as 'improved(+)', 'equivalent( ± )', or 'poor(-)'. Also, the contribution of Infusion-DSA to the diagnosis was classified into one of five in a graded system. In 29 hepatocellular patients, the Infusion-DSA was helpful in detecting daughter nodules, fibrous capsule and arteriovenous shunt. Infusion-DSA is a useful complementary technique in the diagnosis of hepatocellular carcinoma and was also helpful in determining the selection of the therapeutic modality of hepatocellular carcinoma

Anticancer effects of deproteinized asparagus polysaccharide on hepatocellular carcinoma in vitro and in vivo.

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Xiang, Jianfeng; Xiang, Yanjie; Lin, Shengming; Xin, Dongwei; Liu, Xiaoyu; Weng, Lingling; Chen, Tao; Zhang, Minguang

2014-04-01

Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world whose chemoprevention became increasingly important in HCC treatment. Although the anticancer effects of asparagus constituents have been investigated in several cancers, its effects on hepatocellular carcinoma have not been fully studied. In this study, we investigated the anticancer effects of the deproteinized asparagus polysaccharide on the hepatocellular carcinoma cells using the in vitro and in vivo experimental model. Our data showed that deproteinized asparagus polysaccharide might act as an effective inhibitor on cell growth in vitro and in vivo and exert potent selective cytotoxicity against human hepatocellular carcinoma Hep3B and HepG2 cells. Further study showed that it could potently induce cell apoptosis and G2/M cell cycle arrest in the more sensitive Hep3B and HepG2 cell lines. Moreover, deproteinized asparagus polysaccharide potentiated the effects of mitomycin both in vitro and in vivo. Mechanistic studies revealed that deproteinized asparagus polysaccharide might exert its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. In conclusion, deproteinized asparagus polysaccharide exhibited significant anticancer activity against hepatocellular carcinoma cells and could sensitize the tumoricidal effects of mitomycin, indicating that it is a potential therapeutic agent (or chemosensitizer) for liver cancer therapy.

Multiple infarcted regenerative nodules in liver cirrhosis after decompensation of cirrhosis: a case series

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Müllhaupt Beat

2010-11-01

Full Text Available Abstract Introduction Liver cirrhosis is a common disease with many known complications. Cirrhosis represents a clinical spectrum, ranging from asymptomatic liver disease to hepatic decompensation. Manifestations of hepatic decompensation include variceal bleeding, ascites, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, portopulmonary hypertension and hepatocellular carcinoma. There are reports about infarcted regenerative nodules in cirrhotic livers after gastrointestinal hemorrhage. Case presentation We report three Caucasian patients (one female and two male patients; ages: 52, 54 and 60 years with decompensated liver cirrhosis, who showed newly infarcted regenerative nodules at necropsy. Two of them suffered from gastric variceal bleeding. Histopathology showed extensive infarction in all three cases. Hemorrhage and inflammatory changes were also observed around the infarcted regenerative nodules. Conclusion These patients showed focal liver lesions, to be considered in the differential diagnosis of cirrhotic livers. Infarcted regenerative nodules may be underdiagnosed in patients with decompensation of cirrhosis. In order to differentiate these lesions from malignant tumors, serial imaging seems to be helpful. However, the main differential diagnosis should be an abscess. It is important to know the wide spectrum of image appearances of these lesions. Hypotension can lead to a reduction of portal and arterial liver flow. Since variceal bleeding or septic shock can induce hypotension - as observed in our patients - we conclude that this leads to infarction of such nodules.

Chondroitin sulfate iron colloid as MR contrast agent in differentiation between hepatocellular carcinoma and adenomatous hyperplasia

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Suto, Y. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Kato, T. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Matsuo, T. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Kamba, M. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Shimatani, Y. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Ohuchi, Y. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Nakamura, K. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Ohta, Y. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan))

1993-05-01

Using a 1.5 T MR imaging unit, T1- and T2-weighted images were obtained before and after i.v. administration of chondroitin sulfate iron colloid (CSIC) in order to differentiate hepatocellular carcinoma (n=20) from adenomatous hyperplasia without atypia (n=16). Differentiation was made from the tumor-liver contrast to noise ratio (CNR) and visual evaluation of the nodule, with reference to signal intensity relative to that of the surrounding liver. The CNR of adenomatous hyperplasia was on T1-weighted images significantly decreased after CSIC administration (p<0.01). On T2-weighted images, there was no significant difference in CNR after CSIC administration. On the other hand, the CNR of hepatocellular carcinoma was significantly increased after CSIC administration on both T1- and T2-weighted images (p<0.01). CSIC reflects intratumor reticuloendothelial cellular functions, and is therefore useful in differentiating hepatocellular carcinoma from adenomatous hyperplasia without atypia. (orig.).

Spontaneous rupture of adrenal metastasis from hepatocellular carcinoma

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Lim, Chae Hun; Kim, Hyun Jin; Park, Soo Youn; Hwang, Seong Su; Choi, Hyun Joo [St. Vincent Hospital, Suwon (Korea, Republic of)

2007-03-15

Rupture of adrenal tumor from various primary origins is a rather rare event. We report here on a ruptured adrenal metastasis from hepatocellular carcinoma, and this ruptured metastasis was observed at the time of the initial diagnosis.

Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: limited role for risk scores in Caucasians.

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Arends, Pauline; Sonneveld, Milan J; Zoutendijk, Roeland; Carey, Ivana; Brown, Ashley; Fasano, Massimo; Mutimer, David; Deterding, Katja; Reijnders, Jurriën G P; Oo, Ye; Petersen, Jörg; van Bömmel, Florian; de Knegt, Robert J; Santantonio, Teresa; Berg, Thomas; Welzel, Tania M; Wedemeyer, Heiner; Buti, Maria; Pradat, Pierre; Zoulim, Fabien; Hansen, Bettina; Janssen, Harry L A

2015-08-01

Hepatocellular carcinoma (HCC) risk-scores may predict HCC in Asian entecavir (ETV)-treated patients. We aimed to study risk factors and performance of risk scores during ETV treatment in an ethnically diverse Western population. We studied all HBV monoinfected patients treated with ETV from 11 European referral centres within the VIRGIL Network. A total of 744 patients were included; 42% Caucasian, 29% Asian, 19% other, 10% unknown. At baseline, 164 patients (22%) had cirrhosis. During a median follow-up of 167 (IQR 82-212) weeks, 14 patients developed HCC of whom nine (64%) had cirrhosis at baseline. The 5-year cumulative incidence rate of HCC was 2.1% for non-cirrhotic and 10.9% for cirrhotic patients (peliminate the risk of HCC. Discriminatory performance of HCC risk scores was limited, particularly in Caucasians, at baseline and during therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?

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A.L. Chagas

2009-10-01

Full Text Available Non-alcoholic steatohepatitis (NASH has been associated with hepatocellular carcinoma (HCC often arising in histologically advanced disease when steatohepatitis is not active (cryptogenic cirrhosis. Our objective was to characterize patients with HCC and active, histologically defined steatohepatitis. Among 394 patients with HCC detected by ultrasound imaging over 8 years and staged by the Barcelona Clinic Liver Cancer (BCLC criteria, we identified 7 cases (1.7% with HCC occurring in the setting of active biopsy-proven NASH. All were negative for other liver diseases such as hepatitis C, hepatitis B, autoimmune hepatitis, Wilson disease, and hemochromatosis. The patients (4 males and 3 females, age 63 ± 13 years were either overweight (4 or obese (3; 57% were diabetic and 28.5% had dyslipidemia. Cirrhosis was present in 6 of 7 patients, but 1 patient had well-differentiated HCC in the setting of NASH without cirrhosis (fibrosis stage 1 based on repeated liver biopsies, the absence of portal hypertension by clinical and radiographic evaluations and by direct surgical inspection. Among the cirrhotic patients, 71.4% were clinically staged as Child A and 14.2% as Child B. Tumor size ranged from 1.0 to 5.2 cm and 5 of 7 patients were classified as early stage; 46% of all nodules were hyper-echoic and 57% were <3 cm. HCC was well differentiated in 1/6 and moderately differentiated in 5/6. Alpha-fetoprotein was <100 ng/mL in all patients. HCC in patients with active steatohepatitis is often multifocal, may precede clinically advanced disease and occurs without diagnostic levels of alpha-fetoprotein. Importantly, HCC may occur in NASH in the absence of cirrhosis. More aggressive screening of NASH patients may be warranted.

Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?

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A.L. Chagas

Full Text Available Non-alcoholic steatohepatitis (NASH has been associated with hepatocellular carcinoma (HCC often arising in histologically advanced disease when steatohepatitis is not active (cryptogenic cirrhosis. Our objective was to characterize patients with HCC and active, histologically defined steatohepatitis. Among 394 patients with HCC detected by ultrasound imaging over 8 years and staged by the Barcelona Clinic Liver Cancer (BCLC criteria, we identified 7 cases (1.7% with HCC occurring in the setting of active biopsy-proven NASH. All were negative for other liver diseases such as hepatitis C, hepatitis B, autoimmune hepatitis, Wilson disease, and hemochromatosis. The patients (4 males and 3 females, age 63 ± 13 years were either overweight (4 or obese (3; 57% were diabetic and 28.5% had dyslipidemia. Cirrhosis was present in 6 of 7 patients, but 1 patient had well-differentiated HCC in the setting of NASH without cirrhosis (fibrosis stage 1 based on repeated liver biopsies, the absence of portal hypertension by clinical and radiographic evaluations and by direct surgical inspection. Among the cirrhotic patients, 71.4% were clinically staged as Child A and 14.2% as Child B. Tumor size ranged from 1.0 to 5.2 cm and 5 of 7 patients were classified as early stage; 46% of all nodules were hyper-echoic and 57% were <3 cm. HCC was well differentiated in 1/6 and moderately differentiated in 5/6. Alpha-fetoprotein was <100 ng/mL in all patients. HCC in patients with active steatohepatitis is often multifocal, may precede clinically advanced disease and occurs without diagnostic levels of alpha-fetoprotein. Importantly, HCC may occur in NASH in the absence of cirrhosis. More aggressive screening of NASH patients may be warranted.

Radiofrequency ablation of hepatocellular carcinoma: Mono or multipolar?

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Cartier, Victoire; Boursier, Jérôme; Lebigot, Jérôme; Oberti, Frédéric; Fouchard-Hubert, Isabelle; Aubé, Christophe

2016-03-01

Thermo-ablation by radiofrequency is recognized as a curative treatment for early-stage hepatocellular carcinoma. However, local recurrence may occur because of incomplete peripheral tumor destruction. Multipolar radiofrequency has been developed to increase the size of the maximal ablation zone. We aimed to compare the efficacy of monopolar and multipolar radiofrequency for the treatment of hepatocellular carcinoma and determine factors predicting failure. A total of 171 consecutive patients with 214 hepatocellular carcinomas were retrospectively included. One hundred fifty-eight tumors were treated with an expandable monopolar electrode and 56 with a multipolar technique using several linear bipolar electrodes. Imaging studies at 6 weeks after treatment, then every 3 months, assessed local effectiveness. Radiofrequency failure was defined as persistent residual tumor after two sessions (primary radiofrequency failure) or local tumor recurrence during follow-up. This study received institutional review board approval (number 2014/77). Imaging showed complete tumor ablation in 207 of 214 lesions after the first session of radiofrequency. After a second session, only two cases of residual viable tumor were observed. During follow-up, there were 46 local tumor recurrences. Thus, radiofrequency failure occurred in 48/214 (22.4%) cases. By multivariate analysis, technique (P radiofrequency failure. Failure rate was lower with the multipolar technique for tumors radiofrequency, multipolar radiofrequency improves tumor ablation with a subsequent lower rate of local tumor recurrence. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

[Cellular adhesion signal transduction network of tumor necrosis factor-alpha induced hepatocellular carcinoma cells].

Science.gov (United States)

Zheng, Yongchang; Du, Shunda; Xu, Haifeng; Xu, Yiyao; Zhao, Haitao; Chi, Tianyi; Lu, Xin; Sang, Xinting; Mao, Yilei

2014-11-18

To systemically explore the cellular adhesion signal transduction network of tumor necrosis factor-alpha (TNF-α)-induced hepatocellular carcinoma cells with bioinformatics tools. Published microarray dataset of TNF-α-induced HepG2, human transcription factor database HTRI and human protein-protein interaction database HPRD were used to construct and analyze the signal transduction network. In the signal transduction network, MYC and SP1 were the key nodes of signaling transduction. Several genes from the network were closely related with cellular adhesion.Epidermal growth factor receptor (EGFR) is a possible key gene of effectively regulating cellular adhesion during the induction of TNF-α. EGFR is a possible key gene for TNF-α-induced metastasis of hepatocellular carcinoma.

Cerebrovascular accidents associated with sorafenib in hepatocellular carcinoma.

Science.gov (United States)

Saif, Muhammad W; Isufi, Iris; Peccerillo, Jennifer; Syrigos, Kostas N

2011-01-01

Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. Laboratory data were noncontributory. The head CT scan did not reveal acute abnormalities. No hemodynamically significant stenosis was visible in the carotid ultrasound, and the echocardiogram showed normal size of the heart chambers and normal systolic function of the left ventricle. Sorafenib was discontinued in both cases. Physicians should monitor patients receiving sorafenib for neurologic symptoms, and in the absence of other etiology, prompt discontinuation of this drug should be considered.

Correlations of matrix metalloproteinase content and expression with invasion and metastasis of hepatocellular carcinoma

International Nuclear Information System (INIS)

Zhang Zhichao; Jia Mingku; Sun Yaxin

2006-01-01

Objective: To investigate the correlations of serum matrix metalloproteinase-2, -9 (MMP-2, MMP-9) contents and tissue expressions in hepatocellular carcinoma with tumor invasion and metastasis. Methods: Serum MMP-2, MMP-9 contents were detected in 40 patient with hepatocellular carcinoma and 20 healthy controls by ELISA; the expressions and distributions of MMP-2 and MMP-9 in 40 patients and 10 normal tissues were detected by immunohistochemical method. Results: Serum MMP-2, MMP-9 contents were significantly elevated in cancer samples compared with normal serum (P<0.01), the significant difference was found between contents in the presence and the absence of lymph node metastasis (P<0.05). In hepatocellular carcinoma, the expressions of MMP-2, MMP-9 were increased significantly compared with normal tissue. The expressions of MMP-2, MMP-9 were correlated with histological grade and lymph node metastasis (P<0.05). Conclusion: The serum of MMP-2 and MMP-9 contents and their expressions may provide reliable information for hepatocellular carcinoma prognosis. (authors)

Intravenous miR-144 inhibits tumor growth in diethylnitrosamine-induced hepatocellular carcinoma in mice.

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He, Quan; Wang, Fangfei; Honda, Takashi; Lindquist, Diana M; Dillman, Jonathan R; Timchenko, Nikolai A; Redington, Andrew N

2017-10-01

Previous in vitro studies have demonstrated that miR-144 inhibits hepatocellular carcinoma cell proliferation, invasion, and migration. We have shown that miR-144, injected intravenously, is taken up by the liver and induces endogenous hepatic synthesis of miR-144. We hypothesized that administered miR-144 has tumor-suppressive effects on liver tumor development in vivo. The effects of miR-144 on tumorigenesis and tumor growth were tested in a diethylnitrosamine-induced hepatocellular carcinoma mouse model. MiR-144 injection had no effect on body weight but significantly reduced diethylnitrosamine-induced liver enlargement compared with scrambled microRNA. MiR-144 had no effect on diethylnitrosamine-induced liver tumor number but reduced the tumor size above 50%, as evaluated by magnetic resonance imaging (scrambled microRNA 23.07 ± 5.67 vs miR-144 10.38 ± 2.62, p hepatocellular carcinoma tumorigenesis. Exogenously delivered miR-144 may be a therapeutic strategy to suppress tumor growth in hepatocellular carcinoma.

Alpha-fetoprotein still is a valuable diagnostic and prognosis predicting biomarker in hepatitis B virus infection-related hepatocellular carcinoma.

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Yao, Mingjie; Zhao, Jingmin; Lu, Fengmin

2016-01-26

Use of serum alpha-fetoprotein (AFP) in clinical practices has been challenged in recent years, due to the lack of specificity and sensitivity. Here we conducted a retrospective study to evaluate the diagnostic and prognostic value of serum AFP among hepatocellular carcinoma (HCC) patients with their pathogenic features taken into consideration. The cohort for this study comprised 318 cases of hepatitis and 731 cases of cirrhosis, as well as 796 HCC patients. Using 11.62ng/mL as a cut-off value, the positive rate of AFP test among serum hepatitis B surface antigen (HBsAg) positive HCC patients was significantly higher than that in those HBsAg negative HCC patients (79.55% vs 56.49%, P < 0.000). Similarly, the median serum AFP level in HCC patients with serum HBsAg positive was significantly higher than that in those HBsAg negative HCC patients (423.89ng/ml vs 40.82ng/ml, P < 0.000). In addition, Kaplan-Meier curve analysis revealed that lower preoperative AFP level implicated a much higher overall survival rate. Of note, such prognosis predicting value was only seen in those chronic HBV infection-related HCC patients, but not among the HCC patients etiologically irrelevant to HBV infection. We believe that serum AFP is of diagnosis and prognostic predicting value for HCC with chronic HBV infection, and strongly suggest use of serum AFP as a biomarker in China and other HBV infection endemic area like Southeast Asia.

Downstaging therapy followed by liver transplantation for hepatocellular carcinoma beyond Milan criteria.

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Kim, Young; Stahl, Christopher C; Makramalla, Abouelmagd; Olowokure, Olugbenga O; Ristagno, Ross L; Dhar, Vikrom K; Schoech, Michael R; Chadalavada, Seetharam; Latif, Tahir; Kharofa, Jordan; Bari, Khurram; Shah, Shimul A

2017-12-01

Orthotopic liver transplantation is a curative treatment for hepatocellular carcinoma within Milan criteria, but these criteria preclude many patients from transplant candidacy. Recent studies have demonstrated that downstaging therapy can reduce tumor burden to meet conventional criteria. The present study reports a single-center experience with tumor downstaging and its effects on post-orthotopic liver transplantation outcomes. All patients with hepatocellular carcinoma who were evaluated by our multidisciplinary liver services team from 2012 to 2016 were identified (N = 214). Orthotopic liver transplantation candidates presenting outside of Milan criteria at initial radiographic diagnosis and/or an initial alpha-fetoprotein >400 ng/mL were categorized as at high risk for tumor recurrence and post-transplant mortality. Of the 214 patients newly diagnosed with hepatocellular carcinoma, 73 (34.1%) eventually underwent orthotopic liver transplantation. The majority of patients who did not undergo orthotopic liver transplantation were deceased or lost to follow-up (47.5%), with 14 of 141 (9.9%) currently listed for transplantation. Among transplanted patients, 21 of 73 (28.8%) were considered high-risk candidates. All 21 patients were downstaged to within Milan criteria with an alpha-fetoprotein hepatocellular carcinoma was higher but acceptable between downstaged high-risk and traditional candidates (9.5% vs 1.9%; P > .05) at a median follow-up period of 17 months. Downstaged high-risk candidates had a similar overall survival compared with those transplanted within Milan criteria (log-rank P > .05). In highly selected cases, patients with hepatocellular carcinoma outside of traditional criteria for orthotopic liver transplantation may undergo downstaging therapy in a multidisciplinary fashion with excellent post-transplant outcomes. These data support an aggressive downstaging approach for selected patients who would otherwise be deemed ineligible for

Efficacy of intrahepatic absolute alcohol in unrespectable hepatocellular carcinoma

International Nuclear Information System (INIS)

Farooqi, J.I.; Hameed, K.; Khan, I.U.; Shah, S.

2001-01-01

To determine efficacy of intrahepatic absolute alcohol injection in researchable hepatocellular carcinoma. A randomized, controlled, experimental and interventional clinical trial. Gastroenterology Department, PGMI, Hayatabad Medical Complex, Peshawar during the period from June, 1998 to June, 2000. Thirty patients were treated by percutaneous, intrahepatic absolute alcohol injection sin repeated sessions, 33 patients were not given or treated with alcohol to serve as control. Both the groups were comparable for age, sex and other baseline characteristics. Absolute alcohol therapy significantly improved quality of life of patients, reduced the tumor size and mortality as well as showed significantly better results regarding survival (P< 0.05) than the patients of control group. We conclude that absolute alcohol is a beneficial and safe palliative treatment measure in advanced hepatocellular carcinoma (HCC). (author)

A case-control study on the association of hepatitis B virus infection and hepatocellular carcinoma in Northeast Brazil

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Cotrim Helma

1992-01-01

Full Text Available Hepatitis B virus (HBV serological markers were investigated in 40 incident cases of hepatocellular carcinoma (HCC and in two age and sex matched control groups, comprising 40 patients with other cancers and 80 healthy individuals, resident in Bahia, Brazil. Serologic tests were done by radioimmunoassay. The study observed high proportion of seropositivity to HBsAg (42.5% and of those presenting HBsAg or antiHBc (65.0% among HCC cases, higher in men than women and in those aged 17 to 30 years old. HBsAg seropositivity among HCC patients was greater than in the control group with other cancers (7.5% and in healthy controls (2.5%, corresponding to odds ratio estimates of 15.0 (95% CI 3.29, 68.30 and 33.0 (95% CI 9.13, 119.28, both statistically significant. HBeAg was not observed and antiHBe was present in 41.2% of cases, suggesting the absence of viral replication, possibly with viral DNA intergration into the hepatocyte genome. The presence of cirrhosis was associated with HBsAg seropositivity among HCC cases. A history of chronic alcoholism is shown to be more frequently related to those cases with cirrhosis. This study highlights the relevant association between HCC and HBV in Northeast Brazil, particularly for young individuals, and the high risk of development of HCC for HBsAg carriers.

Targeting hepatocellular carcinoma: what did we discover so far?

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Ana Filipa Brito

2016-10-01

Full Text Available Hepatocellular carcinoma (HCC is increasingly considered an issue of global importance. Its rates of incidence and mortality have been markedly increasing over the last decades. Among risk factors, some should be highlighted, namely the infections by hepatitis B and C virus, as well as clinical cases of cirrhosis. HCC is characterized as asymptomatic disease in the initial stages which most often leads to a late diagnosis. At molecular and genetic level HCC represents a highly complex tumor entity, including a wide variety of mutations, thus accounting for different mechanisms of resistance towards therapeutic approaches. In particular, mutations of the TP53 gene, as well as a deregulation between the expression of pro- and anti-apoptotic proteins of the BCL-2 family are observed. Regarding treatment modalities, surgical procedures offer the best chance of cure, however, due to a late diagnosis, most of concerned patients cannot be subjected to them. Chemotherapy and radiotherapy are also ineffective, and currently, the treatment with sorafenib is the most commonly used systemic therapy although it can only increase the patient survival for some months. In this sense, a quick and accurate investigation is of utmost importance in order to develop ways of early diagnosis as well as new therapies for HCC.

Proteomic Studies of Cholangiocarcinoma and Hepatocellular Carcinoma Cell Secretomes

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Chantragan Srisomsap

2010-01-01

Full Text Available Cholangiocarcinoma (CCA and hepatocellular carcinoma (HCC occur with relatively high incidence in Thailand. The secretome, proteins secreted from cancer cells, are potentially useful as biomarkers of the diseases. Proteomic analysis was performed on the secreted proteins of cholangiocarcinoma (HuCCA-1 and hepatocellular carcinoma (HCC-S102, HepG2, SK-Hep-1, and Alexander cell lines. The secretomes of the five cancer cell lines were analyzed by SDS-PAGE combined with LC/MS/MS. Sixty-eight proteins were found to be expressed only in HuCCA-1. Examples include neutrophil gelatinase-associated lipocalin (lipocalin 2, laminin 5 beta 3, cathepsin D precursor, desmoplakin, annexin IV variant, and annexin A5. Immunoblotting was used to confirm the presence of lipocalin 2 in conditioned media and cell lysate of 5 cell lines. The results showed that lipocalin 2 was a secreted protein which is expressed only in the conditioned media of the cholangiocarcinoma cell line. Study of lipocalin 2 expression in different types of cancer and normal tissues from cholangiocarcinoma patients showed that lipocalin 2 was expressed only in the cancer tissues. We suggest that lipocalin 2 may be a potential biomarker for cholangiocarcinoma.

[A single metastasis in the carpal bones as the first clinical manifestation of a hepatocellular carcinoma].

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Corrales Pinzón, R; Alonso Sánchez, J M; de la Mano González, S; El Karzazi Tarazona, K

2014-01-01

Hepatocellular carcinoma is the most common primary tumor of the liver. Spreading outside the liver usually takes place in advanced stages of the disease, and bone is the third most common site of metastases. We present a case of hepatocellular carcinoma in which the first clinical manifestation was a single metastasis to the carpal bones. The interest of this case lies in the way this hepatocellular carcinoma manifested as well as in the unusual site of the metastasis. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Coffee consumption and risk of hepatocellular carcinoma: a meta-analysis of eleven epidemiological studies

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Bai K

2016-07-01

Full Text Available Kai Bai,* Qiucheng Cai,* Yi Jiang, Lizhi Lv Department of Hepatobiliary Surgery, Fuzong Clinical College, Fujian Medical University, Fuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Growing evidence has shown that coffee consumption is inversely related with the risk of hepatocellular carcinoma. It is suggested that caffeine maintains strong antioxidative activity. With this property, coffee intake may lead to the inhibition of cell proliferation of liver cancer cells; also, some compounds contained in coffee can reduce the genotoxicity of aflatoxin B1 in vitro and lower the damage caused by some carcinogens. A computerized search was performed in PubMed to identify relevant articles published before August 2015. Eleven relevant studies were included with a total of 2,795 cases and 340,749 control subjects. According to the meta-analysis we performed, the pooled odds ratio (OR from all included studies was 0.49 (95% confidence interval [CI] =0.46–0.52. The subgroup analysis indicated that the pooled ORs for Asian studies and other populations were 0.27 (95% CI =0.23–0.31 and 0.82 (95% CI =0.77–0.87, respectively. The overall pooled OR for high consumption was decreased to 0.21 (95% CI =0.18–0.25 and significance was observed. Among other populations, the pooled OR of subjects with high coffee consumption was 0.65 (95% CI =0.56–0.73 compared to the nondrinker. The corresponding OR of five Asian studies was 0.13 (95% CI =0.09–0.17. The findings from this meta-analysis further confirmed the inverse association between the coffee consumption and hepatocellular carcinoma risk with quantitative evidence. The protective effect can be detected among healthy population and patients with chronic liver diseases, and the consumption can also prevent the development of liver cirrhosis. Keywords: hepatocarcinogenesis, meta-analysis, coffee, antioxidant

Serine/arginine rich splicing factor 2 expression and clinic pathological features indicating a prognostic factor in human hepatocellular carcinoma patients.

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Wang, Pingan; Guo, Lingyu; Li, Kaipeng; Ning, Shanglei; Shi, Weichen; Liu, Zhaochen; Chen, Yuxin

2018-02-14

This research was aimed to study the expression of Serine/arginine rich splicing factor 2 (SRSF2) in tissues of hepatocellular carcinoma, and explore the relationship between the expression and the clinic pathological and prognosis of human hepatocellular carcinoma (HCC). One hundred and fifty-three pairs HCC tissues and adjacent normal tissue were collected from January 2010 to March 2013. The expression of SRSF2 gene was detected by immunohistochemistry, western blotting and real-time quantitative polymerase chain reaction (PCR), and the relationship between the expression and the clinic pathological and prognosis of HCC being analyzed. In 153 cases of hepatocellular carcinoma, SRSF2 was highly expressed in 93 cases, low expression of 60 cases, immunohistochemistry score (6.50 ± 2.82), which was significantly higher than that in adjacent normal tissues (2.94 ± 1.23) (Phepatocellular carcinoma was positively correlated (r = 0.704, Phepatocellular carcinoma were 74.19%, 44.09%, 26.88%, 24.73% and 21.51% at 1 year, 2 years, 3 years, 4 years and 5 years respectively, which were lower than those of SRSF2 low expression group (93.33%, 71.67%, 56.67%, 51.67% and 50.00%). SRSF2 is highly expressed in hepatocellular carcinoma and its expression increases with the degree of tumor differentiation and TNM staging. It is related to lymph node metastasis and metastasis of tumor cells, and is positively related to serum alpha fetoprotein content, and affects the postoperative survival time of HCC patients.

An efficient model for auxiliary diagnosis of hepatocellular carcinoma based on gene expression programming.

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Zhang, Li; Chen, Jiasheng; Gao, Chunming; Liu, Chuanmiao; Xu, Kuihua

2018-03-16

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. The early diagnosis of HCC is greatly helpful to achieve long-term disease-free survival. However, HCC is usually difficult to be diagnosed at an early stage. The aim of this study was to create the prediction model to diagnose HCC based on gene expression programming (GEP). GEP is an evolutionary algorithm and a domain-independent problem-solving technique. Clinical data show that six serum biomarkers, including gamma-glutamyl transferase, C-reaction protein, carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 153, and carbohydrate antigen 199, are related to HCC characteristics. In this study, the prediction of HCC was made based on these six biomarkers (195 HCC patients and 215 non-HCC controls) by setting up optimal joint models with GEP. The GEP model discriminated 353 out of 410 subjects, representing a determination coefficient of 86.28% (283/328) and 85.37% (70/82) for training and test sets, respectively. Compared to the results from the support vector machine, the artificial neural network, and the multilayer perceptron, GEP showed a better outcome. The results suggested that GEP modeling was a promising and excellent tool in diagnosis of hepatocellular carcinoma, and it could be widely used in HCC auxiliary diagnosis. Graphical abstract The process to establish an efficient model for auxiliary diagnosis of hepatocellular carcinoma.

Prognosis and therapy for ruptured hepatocellular carcinoma: Problems with staging and treatment strategy

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Hiraoka, Atsushi, E-mail: hirage@m.ehime-u.ac.jp [Gastroenterology Center, Ehime Prefectural Central Hospital, Kasuga-cho 83, Matsuyama, Ehime 790-0024 (Japan); Kawamura, Tomoe; Aibiki, Toshihiko; Okudaira, Tomonari; Toshimori, Akiko; Yamago, Hiroka; Nakahara, Hiromasa; Suga, Yoshifumi; Azemoto, Nobuaki; Miyata, Hideki; Miyamoto, Yasunao; Ninomiya, Tomoyuki [Gastroenterology Center, Ehime Prefectural Central Hospital, Kasuga-cho 83, Matsuyama, Ehime 790-0024 (Japan); Murakami, Tadashi; Ishimaru, Yoshihiro [Department of Radiology, Ehime Prefectural Central Hospital (Japan); Kawasaki, Hideki [Department of Surgery, Ehime Prefectural Central Hospital (Japan); Hirooka, Masashi; Abe, Masanori; Matsuura, Bunzo; Hiasa, Yoichi [Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime (Japan); Michitaka, Kojiro [Gastroenterology Center, Ehime Prefectural Central Hospital, Kasuga-cho 83, Matsuyama, Ehime 790-0024 (Japan)

2015-03-15

Highlights: •Although a patient with a ruptured HCC is generally considered to have a poor prognosis and treated as T4 in the 7th edition of the AJCC/UICC, some ruptured cases show a good clinical course. •There are no clear criteria established for treating a ruptured hepatocellular carcinoma (HCC) which is classified as T4 in TNM stage of UICC 7th. •This article describes that better prognosis can be expected with curative treatment in patients with a ruptured HCC, especially those with a single tumor, and without decompensated liver cirrhosis and PVTT/extrahepatic metastasis. T4 classification should not include all types of ruptured HCC. -- Abstract: Background: There are no clear criteria established for treating a ruptured hepatocellular carcinoma (HCC). To elucidate the clinical features of affected patients, we examined prognosis and therapy choices. Materials/methods: We enrolled 67 patients treated for a ruptured HCC (HCV 44, HBV 5, HBV + HCV 1, alcohol 2, others 15; naïve HCC 34, recurrent 33) from 2000 to 2013, and investigated their clinical background and prognosis. Results: Median survival time (MST) for all cases was 4 months. For patients who survived for more than 1 year after rupture, the percentages of Child-Pugh C and positive for portal vein tumor thrombosis (PVTT)/extrahepatic metastasis were less than for those who died within 1 year. Child-Pugh classification (A:B:C = 14:15:5 vs. 4:9:20, P < 0.001) was better, while the percentage of patients with multiple tumors was lower [19/34 (55.9%) vs. 29/33 (87.9%), respectively; P < 0.001] in the naïve group. The 1- and 3-year survival rates were better in the naïve as compared to the recurrent group (60.6% and 33.3% vs. 12.6% and 0%, respectively; P < 0.01). MST according to modified TNM stage (UICC 7th) calculated after exclusion of T4 factor of rupture, stage I was better than others (22.7 vs. (II) 2.2, (III) 1.2, and (IV) 0.7 months) (P = 0.010). Conclusion: In patients with a ruptured

Serologic and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation

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Pommergaard, Hans-Christian; Burcharth, Jakob Hornstrup Frølunde; Rosenberg, Jacob

2016-01-01

INTRODUCTION: Recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC) is a major cause of mortality. Knowledge on biomarkers may contribute to better surveillance based on the patients' risk of recurrence. Reviewing the literature, we aimed to identify serological...... and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation. METHODS: A literature search was performed in the databases PubMed and Scopus to identify observational studies evaluating serological or molecular biomarkers for recurrence of HCC after LT using adjusted analysis...

Hepatocellular carcinoma. Comparison between gadolinium and ironoxide enhanced MR imaging

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Castoldi, M.C.; Fauda, V.; Scaramuzza, D.; Vergnaghi, D.

2000-01-01

Purpose of this work is to compare prospectively dynamic gadolinium (Gd)-enhanced with superparamagnetic iron oxide (SPIO)-enhanced MRI for the detection of hepatocellular carcinoma (HCC). Twenty-five patients with histologically proven HCC and liver cirrhosis (28% of them in B or C Child class) underwent dynamic Gd-enhanced MRI and, a few days later, (mean interval: three days) SPIO-enhanced MRI. Only patients with availability of clinical and imaging follow-up for at least seven months were enrolled in this prospective study. MR images were reviewed by two independent radiologists. The readers scored each lesion for the presence of HCC and assigned confidence levels based on a five-grade scale: 1, definitely or almost definitely absent; 2, possibly present; 3, probably present; 4, definitely present; 5, definitely present with optimal liver/lesion contrast or good liver/lesion contrast and morphological signs (intact capsule, intranodular septa, extracapsular infiltration), useful for locoregional treatment planning. A positive diagnostic value was assessed for scores of 3 or higher. Gd-enhanced and SPIO-enhanced MRI found 44 lesions. Eight of twelve lesions visible with a single contrast agent measured less than 1 cm in diameter. HCC detectability was 75% with Gd-enhanced MRI and 97.7% with SPIO-enhanced MRI. SPIO-enhanced T2-weighted TSE images showed significantly higher diagnostic value than SPIO-enhanced T1-T2*GRE images only in three cases, while nodule morphological characteristics (capsule, septa, different cell differentiation components) were better depicted by TSE images. In thi study the combined use of SPIO-enhanced T2-weighted TSE and T1-T2*-weighted GRE sequences showed higher sensitivity than gadolinium-enhanced GRE dynamic imaging (97.7% versus 75%). These results are at least partly related to our study conditions, that is: 1)MRI was performed with a 1T system, 2) both axial and sagittal SPIO-enhanced imaging were performed with respiratory

Living-donor vs deceased-donor liver transplantation for patients with hepatocellular carcinoma.

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Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Kokudo, Norihiro

2014-09-27

With the increasing prevalence of living-donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC), some authors have reported a potential increase in the HCC recurrence rates among LDLT recipients compared to deceased-donor liver transplantation (DDLT) recipients. The aim of this review is to encompass current opinions and clinical reports regarding differences in the outcome, especially the recurrence of HCC, between LDLT and DDLT. While some studies report impaired recurrence - free survival and increased recurrence rates among LDLT recipients, others, including large database studies, report comparable recurrence - free survival and recurrence rates between LDLT and DDLT. Studies supporting the increased recurrence in LDLT have linked graft regeneration to tumor progression, but we found no association between graft regeneration/initial graft volume and tumor recurrence among our 125 consecutive LDLTs for HCC cases. In the absence of a prospective study regarding the use of LDLT vs DDLT for HCC patients, there is no evidence to support the higher HCC recurrence after LDLT than DDLT, and LDLT remains a reasonable treatment option for HCC patients with cirrhosis.

Orthotopic liver transplantation after the combined use of locoregional therapy and sorafenib for advanced hepatocellular carcinoma

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Yoo EJ

2013-06-01

Full Text Available Eun Jin Yoo,1,* Hye Sun Shin,1,* Seung Up Kim,1,2,7 Dong Jin Joo,3,4 Jun Yong Park,1,2,7 Gi Hong Choi,3 Do Young Kim,1,2,7 Sang Hoon Ahn,1,2,7 Jinsil Seong,5 Myung Joo Koh,6 Kwang-Hyub Han,1,2,7 Chae Yoon Chon1,2,7 1Department of Internal Medicine, 2Institute of Gastroenterology, 3Department of Surgery, 4Research Institute for Transplantation, 5Department of Radiation Oncology, 6Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea; 7Liver Cirrhosis Clinical Research Center, Seoul, South Korea *These authors contributed equally to this work Abstract: We herein report a patient with advanced hepatitis B virus-related hepatocellular carcinoma (HCC beyond the Milan criteria. He underwent orthotopic liver transplantation after successful HCC downstaging that satisfied the University of California, San Francisco criteria, using concurrent chemoradiation therapy with a combination of repeated hepatic arterial infusion chemotherapy (HAIC and sorafenib. A 52-year-old male was diagnosed with advanced hepatitis B virus-related HCC beyond the Milan criteria. He underwent concurrent chemoradiation therapy (50 Gy with 20 fractions over 5 weeks with HAIC using 5-fluorouracil at a dose of 500 mg/day, which was administered during the first and fifth weeks of radiation therapy as an initial treatment modality. This was followed by the combined use of HAIC using 5-fluorouracil (500 mg/m2 for 5 hours on days 1–3 and cisplatin (60 mg/m2 for 2 hours on day 2 every 4 weeks (twelve cycles and sorafenib (from the third to the twelfth cycle of HAIC to treat the remaining HCC. Because a remarkable decrease in the tumor burden that satisfied the University of California, San Francisco criteria was observed after these combination treatments, the patient underwent orthotopic liver transplantation with curative aim and survived for 11 months without evidence of HCC recurrence. Keywords: hepatocellular carcinoma, liver transplantation

Magnetic Nanoparticles for Hepatocellular Carcinoma Diagnosis and Therapy

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Ungureanu, Bogdan Silviu; Teodorescu, Cristian-Mihail; Săftoiu, Adrian

2016-01-01

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver, ranking as the second most common cause of death from cancer worldwide. Magnetic nanoparticles (MNPs) have been used so far in tumor diagnosis and treatment, demonstrating great potential and promising results...

Cost-effectiveness of sorafenib versus SBRT for unresectable advanced hepatocellular carcinoma

International Nuclear Information System (INIS)

Leung, Henry W. C.; Liu, Chung-Feng; Chan, Agnes L. F.

2016-01-01

Stereotactic body radiotherapy (SBRT) has been shown to improve overall survival in patients with advanced hepatocellular carcinoma. This study aimed to assess the cost-effectiveness of SBRT compared to sorafenib which is the only drug for advanced hepatocellular carcinoma. A Markov decision-analytic model was performed to compare the cost-effectiveness of SBRT and sorafenib for unresectable advanced hepatocellular carcinoma. Patients transitioned between three health states: stable disease, progression disease and death. We calculated the data on cost from the perspective of our National Health Insurance Bureau. Sensitivity analyses were conducted to determine the impact of several variables. The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was NT$3,788,238 per quality-adjusted life year gained (cost/QALY), which was higher than the willingness to pay threshold of Taiwan according to WHO’s guideline. One-way sensitivity analysis revealed that the utility of progression disease for the sorafenib treatment, utility of progression free survival for SBRT, utility of progression free survival for sorafenib, utility of PFS to progression disease for SBRT and transition probability of progression disease to dead for SBRT were the most sensitive parameters in all cost scenarios. The Monte-Carlo simulation demonstrated that the probability of cost-effectiveness at a willingness to pay threshold of NT$ 2,213,145 per QALY was 100 % and 0 % chance for SBRT and sorafenib. This study indicated that SBRT for advanced hepatocellular carcinoma is cost-effective at a willingness to pay threshold as defined by WHO guideline in Taiwan

Leptomeningeal metastasis from hepatocellular carcinoma with other unusual metastases: a case report

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Pan, Zhenyu; Yang, Guozi; Yuan, Tingting; Pang, Xiaochuan; Wang, Yongxiang; Qu, Limei; Dong, Lihua

2014-01-01

Leptomeningeal metastasis, which results from metastasis of tumors to the arachnoid and pia mater, can lead to the dissemination of tumor cells throughout the subarachnoid space via the cerebral spinal fluid, and frequently with a poor prognosis. The primary tumor in adults is most often breast cancer, lung cancer, or melanoma. Although leptomeningeal metastasis due to cholangiocarcinoma has been reported, to the best of our knowledge there is no cytologically confirmed report of leptomeningeal metastasis from hepatocellular carcinoma. We herein report a case of leptomeningeal metastasis from hepatocellular carcinoma in a 53-year-old woman with concomitant systemic metastases to the lung, bone, brain, kidney, adrenal gland, subcutaneous tissues, and abdominal pelvis. The neurological symptoms of the patient were relieved after treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy. To our knowledge this is the first report of leptomeningeal metastasis from hepatocellular carcinoma confirmed by cytology. Treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy was effective

Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes.

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Markowitz, Geoffrey J; Yang, Pengyuan; Fu, Jing; Michelotti, Gregory A; Chen, Rui; Sui, Jianhua; Yang, Bin; Qin, Wen-Hao; Zhang, Zheng; Wang, Fu-Sheng; Diehl, Anna Mae; Li, Qi-Jing; Wang, Hongyang; Wang, Xiao-Fan

2016-04-15

Chronic inflammation in liver tissue is an underlying cause of hepatocellular carcinoma. High levels of inflammatory cytokine IL18 in the circulation of patients with hepatocellular carcinoma correlates with poor prognosis. However, conflicting results have been reported for IL18 in hepatocellular carcinoma development and progression. In this study, we used tissue specimens from hepatocellular carcinoma patients and clinically relevant mouse models of hepatocellular carcinoma to evaluate IL18 expression and function. In a mouse model of liver fibrosis that recapitulates a tumor-promoting microenvironment, global deletion of the IL18 receptor IL18R1 enhanced tumor growth and burden. Similarly, in a carcinogen-induced model of liver tumorigenesis, IL18R1 deletion increased tumor burden. Mechanistically, we found that IL18 exerted inflammation-dependent tumor-suppressive effects largely by promoting the differentiation, activity, and survival of tumor-infiltrating T cells. Finally, differences in the expression of IL18 in tumor tissue versus nontumor tissue were more predictive of patient outcome than overall tissue expression. Taken together, our findings resolve a long-standing contradiction regarding a tumor-suppressive role for IL18 in established hepatocellular carcinoma and provide a mechanistic explanation for the complex relationship between its expression pattern and hepatocellular carcinoma prognosis. Cancer Res; 76(8); 2394-405. ©2016 AACR. ©2016 American Association for Cancer Research.

Knockdown of TMEM16A suppressed MAPK and inhibited cell proliferation and migration in hepatocellular carcinoma

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Deng L

2016-01-01

Full Text Available Liang Deng,1,* Jihong Yang,2,* Hongwu Chen,3 Bo Ma,4 Kangming Pan,1 Caikun Su,1 Fengfeng Xu,1 Jihong Zhang1 1Department of Hepatobiliary Surgery, The Eastern Hospital of the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 2Department of General Surgery, The Affiliated Hospital of Hebei University, Baoding, 3Department of Emergency, 4Department of Gastroenterology, The Eastern Hospital of the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: TMEM16A plays an important role in cell proliferation in various cancers. However, less was known about the expression and role of TMEM16A in hepatocellular carcinoma. We screened the expression of TMEM16A in patients’ hepatocellular carcinoma tissues, and also analyzed the biological function of hepatocellular carcinoma cells by knockdown of TMEM16A, as well as the expression of MAPK signaling proteins, including p38, p-p38, ERK1/2, p-ERK1/2, JNK, and p-JNK, and cell cycle regulatory protein cyclin D1 in TMEM16A siRNA-transfected SMMC-7721 cells by Western blot. Our results showed that TMEM16A was overexpressed in hepatocellular carcinoma tissues. Inhibition of TMEM16A suppressed the cell proliferation, migration, and invasion, and cell cycle progression but did not influence the cell apoptosis. TMEM16A siRNA-suppressed cancer cell proliferation and tumor growth were accompanied by a reduction of p38 and ERK1/2 activation and cyclin D1 induction, and were not influenced by other tested MAPK signaling proteins. In addition, inhibition of TMEM16A suppressed tumorigenicity in vivo. TMEM16A is overexpressed in hepatocellular carcinoma, and that inhibition of TMEM16A suppressed MAPK and growth of hepatocellular carcinoma. TMEM16A could be a potentially novel therapeutic target for human cancers, including hepatocellular carcinoma.Keywords: TMEM16A, cell cycle, proliferation, apoptosis

Serum Autoantibody Measurement for the Detection of Hepatocellular Carcinoma

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Middleton, Catrin H.; Irving, William; Robertson, John F. R.; Murray, Andrea; Parsy-Kowalska, Celine B.; Macdonald, Isabel K.; McElveen, Jane; Allen, Jared; Healey, Graham F.; Thomson, Brian J.; Ryder, Stephen J.; Holdenrieder, Stefan; Chapman, Caroline J.

2014-01-01

Background Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC) which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs) in the serum of patients with HCC. Methods Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA. Results Varying autoantibody specificities (97–100%) and sensitivities (0–10%) were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel. Conclusions This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography) and to similar tests in other cancers (EarlyCDT-Lung). PMID:25093332

Serum autoantibody measurement for the detection of hepatocellular carcinoma.

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Catrin H Middleton

Full Text Available BACKGROUND: Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs in the serum of patients with HCC. METHODS: Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA. RESULTS: Varying autoantibody specificities (97-100% and sensitivities (0-10% were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel. CONCLUSIONS: This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography and to similar tests in other cancers (EarlyCDT-Lung.

Liver surgery in cirrhosis and portal hypertension.

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Hackl, Christina; Schlitt, Hans J; Renner, Philipp; Lang, Sven A

2016-03-07

The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary or metastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis.

Hepatocellular carcinoma: computed tomography assessment after invasive treatment

International Nuclear Information System (INIS)

Kozima, Shigeru; Larranaga, Nebil; Wulfson, Gabriela; Eisele, Guillermo; Ridruejo, Ezequiel; Mando, Oscar; Perazzo, Florencia

2008-01-01

Objective: To show the computed tomography (CT) usefulness after treatment with transcatheter arterial quimioembolization and radiofrequency ablation of hepatocellular carcinoma. Material and methods: In a period between march 2006 to april 2008 a total of 90 patient presenting 148 nodular lesions with diagnosis of hepatocellular carcinoma were controlled with triphasic CT. All the lesions were treated with minimally invasive procedure. For the treatment, the patients were classified in two groups following Milan criteria. The first group, constituted by 75 patients with 109 nodules, was treated with quimioembolization. The second group, of 15 patients with 25 nodules, was treated with radiofrequency ablation. In our population, a subgroup of 10 patients was treated with both methods. Results: Of 90 patients after CT control on a month, 3 months and for each 3 months during 2 years, on 63 cases (70%) was observed homogeneous accumulation of iodized oil, partial defect without enhancement or absence of enhancement on treated lesions. In these patients a new treatment after initial one was not performed. The remaining 27 patients (30%) underwent new treatment because we founded partial defect or absence of iodized oil with enhancement or peripheral enhancement on arterial phase in treated lesions. In this last group, 16 treated patients (17.7%) had new nodular enhancement on the remaining hepatic parenquimal. Conclusion: The CT unenhanced and the arterial phase on a month and for each 3 months, allow monitoring the effectiveness, residual disease and/or relapse of hepatocellular carcinoma after minimally invasive treatment. (authors) [es

Radioembolisation for treatment of pediatric hepatocellular carcinoma

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Hawkins, Clifford Matthew; Kukreja, Kamlesh [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Geller, James I. [Cincinnati Children' s Hospital Medical Center, Department of Hematology/Oncology, Cincinnati, OH (United States); Schatzman, Carmen; Ristagno, Ross [University of Cincinnati, UC Health, Department of Radiology, Division of Interventional Radiology, Cincinnati, OH (United States)

2013-07-15

Transarterial radioembolisation with yttrium-90 (TARE-Y90), a catheter-directed therapy, has been used extensively in adults to treat primary and secondary hepatic malignancies. To our knowledge, the use of this palliative technique has not been described in children. We present two children with unresectable hepatocellular carcinoma (HCC) treated with TARE-Y90. (orig.)

CTP synthase forms the cytoophidium in human hepatocellular carcinoma.

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Chang, Chia-Chun; Jeng, Yung-Ming; Peng, Min; Keppeke, Gerson Dierley; Sung, Li-Ying; Liu, Ji-Long

2017-12-15

CTP synthase (CTPS) can aggregate into an intracellular macrostructure, the cytoophidium, in various organisms including human cells. Previous studies have shown that assembly of human CTPS cytoophidia may be correlated with the cellular metabolic status, and is able to promote the activity of CTPS. A correlation between the cytoophidium and cancer metabolism has been proposed but not yet been revealed. In the current study we provide clear evidence of the presence of CTPS cytoophidia in various human cancers and some non-cancerous tissues. Moreover, among 203 tissue samples of hepatocellular carcinoma, 56 (28%) samples exhibited many cytoophidia, whereas no cytoophidia were detected in adjacent non-cancerous hepatocytes for all samples. Our findings suggest that the CTPS cytoophidium may participate in the adaptive metabolism of human hepatocellular carcinoma. Copyright © 2017. Published by Elsevier Inc.

Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma

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Seo, Seung In; Kim, Hyoung Su; Kim, Won Jin; Shin, Woon Geon; Kim, Doo Jin; Kim, Kyung Ho; Jang, Myoung Kuk; Lee, Jin Heon; Kim, Joo Seop; Kim, Hak Yang; Kim, Dong Joon; Lee, Myung Seok; Park, Choong Kee

2015-01-01

AIM: To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) in chronic hepatitis B (CHB). METHODS: A total of 1255 patients with CHB, including 157 patients with hepatocellular carcinoma (HCC), 879 with non-cirrhotic CHB and 219 with cirrhosis without HCC, were retrospectively enrolled. The areas under the receiver operating characteristic (AUROC) curves of PIVKA-II, AFP and their combination were calculated and compared. RESULTS: The optimal cutoff values for PIVKA-II and AFP were 40 mAU/mL and 10 ng/mL, respectively, for the differentiation of HCC from nonmalignant CHB. The sensitivity and specificity were 73.9% and 89.7%, respectively, for PIVKA-II and 67.5% and 90.3% for AFP, respectively. The AUROC curves of both PIVKA-II and AFP were not significantly different (0.854 vs 0.853, P = 0.965) for the differentiation of HCC from nonmalignant CHB, whereas the AUROC of PIVKA-II was significantly better than that of AFP in patients with cirrhosis (0.870 vs 0.812, P = 0.042). When PIVKA-II and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-II alone for the differentiation of HCC from nonmalignant CHB (P < 0.05), especially when cirrhosis was present (P < 0.05). CONCLUSION: Serum PIVKA-II might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB. PMID:25852278

Overexpression of Zwint predicts poor prognosis and promotes the proliferation of hepatocellular carcinoma by regulating cell-cycle-related proteins

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Ying H

2018-02-01

Full Text Available Hanning Ying,1,2 Zhiyao Xu,3 Mingming Chen,1,2 Senjun Zhou,1,2 Xiao Liang,1,2 Xiujun Cai1,2 1Department of General Surgery, 2Key Laboratory of Endoscopic Technique Research of Zhejiang Province, 3Central Lab of Biomedical Research Center, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China Introduction: Zwint, a centromere-complex component required for the mitotic spindle checkpoint, has been reported to be overexpressed in different human cancers, but it has not been studied in human hepatocellular carcinoma (HCC.Materials and methods: The role of Zwint in hepatocellular carcinoma cell proliferation capacities was evaluated by using cell counting kit-8 (CCK8, flow cytometry, clone formation and tumor formation assay in nude mice. Western blot analysis and qPCR assay were performed to assess Zwint interacting with cell-cycle-related proteins.Results: We report that ZWINT mRNA and protein expression were upregulated in HCC samples and cell lines. An independent set of 106 HCC-tissue pairs and corresponding noncancerous tissues was evaluated for Zwint expression using immunohistochemistry, and elevated Zwint expression in HCC tissues was significantly correlated with clinicopathological features, such as tumor size and number. Kaplan–Meier survival and Cox regression analysis revealed that high expression of Zwint was correlated with poor overall survival and a greater tendency for tumor recurrence. Ectopic expression of Zwint promoted HCC-cell proliferation, and Zwint expression affected the expression of several cell-cycle proteins, including PCNA, cyclin B1, Cdc25C and CDK1.Conclusion: Our findings suggest that upregulation of Zwint may contribute to the progression of HCC and may be a prognostic biomarker and potential therapeutic target for treating HCC. Keywords: Zwint, hepatocellular carcinoma, HCC, prognosis, cell proliferation, cell cycle

Tie2-Expressing Monocytes Are Associated with Identification and Prognoses of Hepatitis B Virus Related Hepatocellular Carcinoma after Resection

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He, Yi-Feng; Wang, Chao-Qun; Yu, Yao; Qian, Jing; Song, Kang; Sun, Qi-Man; Zhou, Jian

2015-01-01

Background Tie2-expressing monocytes (TEMs) are found in various tumors, involved in forming tumor blood vessels and expressing several important proangiogenic factors. The goals of this study were to evaluate the value of TEMs in diagnosing and predicting the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods Flow cytometry was performed to identify and count TEMs in peripheral blood monocytes from HCC patients (n = 84) receiving hepatectomy, HBV cirrhotic p...

Induction of apoptosis by Armillaria mellea constituent armillarikin in human hepatocellular carcinoma

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Chen YJ

2016-08-01

Full Text Available Yu-Jen Chen,1–4 Chien-Chih Chen,5 Huey-Lan Huang6 1Department of Medical Research, 2Department of Radiation Oncology, Mackay Memorial Hospital, 3Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 4Institute of Pharmacology, Taipei Medical University, Taipei, 5Department of Biotechnology, HungKuang University, Taichung, 6Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan, Taiwan Abstract: Armillaria mellea is a honey mushroom often used in the traditional Chinese medicine “Tianma”. Currently, this medicinal mushroom is also used as a dietary supplement in numerous Western and Eastern countries. Armillarikin was isolated from A. mellea, and we previously discovered that it induced cytotoxicity in human leukemia cells. In this study, we further investigated the cytotoxicity of armillarikin against liver and intrahepatic bile duct cancer cells. Armillarikin was cytotoxic against human hepatocellular carcinoma Huh7, HA22T, and HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium and alamarBlue® assays. Armillarikin treatment also induced the collapse of the mitochondrial transmembrane potential of these cells. Furthermore, armillarikin-induced apoptotic cell death was demonstrated by sub-G1 chromosomal DNA formation by using flow cytometry. In addition, the apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-fmk. Immunoblotting also revealed the armillarikin-induced activation of procaspase-3, -8, and -9 and upregulation of the apoptosis- and cell cycle arrest-related phospho-histones 2 and 3, respectively. Moreover, reactive oxygen species scavengers also inhibited the armillarikin-induced apoptosis in human hepatocellular carcinoma, suggesting that reactive oxygen species formation played an important role in the armillarikin-induced apoptosis of human hepatocellular carcinoma. In

Metronomic capecitabine as second-line treatment in hepatocellular carcinoma after sorafenib failure.

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Granito, Alessandro; Marinelli, Sara; Terzi, Eleonora; Piscaglia, Fabio; Renzulli, Matteo; Venerandi, Laura; Benevento, Francesca; Bolondi, Luigi

2015-06-01

No standard second-line treatments are available for hepatocellular carcinoma patients who fail sorafenib therapy. We assessed the safety and efficacy of metronomic capecitabine after first-line sorafenib failure. Retrospective analysis of consecutive hepatocellular carcinoma patients receiving metronomic capecitabine between January 2012 and November 2014. The primary end-point was safety, secondary end-point was efficacy, including time-to-progression and overall survival. Twenty-six patients (80% Child-Pugh A, 80% Barcelona Clinic Liver Cancer stage C) received metronomic capecitabine (500 mg/bid). Median treatment duration was 3.2 months (range 0.6-31). Fourteen (53%) patients experienced at least one adverse event. The most frequent drug-related adverse events were bilirubin elevation (23%), fatigue (15%), anaemia (11%), lymphoedema (11%), and hand-foot syndrome (7.6%). Treatment was interrupted in 19 (73%) for disease progression, in 4 (15%) for liver deterioration, and in 1 (3.8%) for adverse event. Disease control was achieved in 6 (23%) patients. Median time-to-progression was 4 months (95% confidence interval 3.2-4.7). Median overall survival was 8 months (95% confidence interval 3.7-12.3). Metronomic capecitabine was well tolerated in hepatocellular carcinoma patients who had been treated with sorafenib. Preliminary data show potential anti-tumour activity with long-lasting disease control in a subgroup of patients that warrants further evaluation in a phase III study. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Association between the HFE C282Y, H63D Polymorphisms and the Risks of Non-Alcoholic Fatty Liver Disease, Liver Cirrhosis and Hepatocellular Carcinoma: An Updated Systematic Review and Meta-Analysis of 5,758 Cases and 14,741 Controls

Science.gov (United States)

Yin, Wei-Li; Wang, Feng-Mei; Han, Tao

2016-01-01

Background Conflicting results have been obtained for the association between two common polymorphisms (C282Y, H63D) of human HFE (hereditary hemochromatosis) gene and the risks of the liver diseases, including non-alcoholic fatty liver disease (NAFLD), liver cirrhosis and hepatocellular carcinoma (HCC). Methods An updated systematic review and meta-analysis was conducted to evaluate the potential role of HFE polymorphisms in the susceptibility to NAFLD, liver cirrhosis and HCC. After retrieving articles from online databases, eligible studies were enrolled according to the selection criteria. Stata/SE 12.0 software was utilized to perform the statistical analysis. Results In total, 43 articles with 5,758 cases and 14,741 controls were selected. Compared with the control group, a significantly increased risk of NAFLD was observed for the C282Y polymorphism in the Caucasian population under all genetic models and for the H63D polymorphism under the allele, heterozygote and dominant models (all OR>1, PassociationHFE C282Y and H63D (all Passociation>0.05). In addition, we found that HFE C282Y was statistically associated with increased HCC susceptibility in the overall population, while H63D increased the odds of developing non-cirrhotic HCC in the African population (all OR>1, PassociationHFE C282Y and H63D polymorphisms confer increased genetic susceptibility to NAFLD and HCC but not liver cirrhosis. Additional well-powered studies are required to confirm our conclusion. PMID:27657935

FBX8 Acts as an Invasion and Metastasis Suppressor and Correlates with Poor Survival in Hepatocellular Carcinoma.

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Feifei Wang

Full Text Available F-box only protein 8 (FBX8, a novel component of F-box proteins, is lost in several cancers and has been associated with invasiveness of cancer cells. However, its expression pattern and role in the progression of hepatocellular carcinoma remain unclear. This study investigated the prognostic significance of FBX8 in hepatocellular carcinoma samples and analyzed FBX8 function in hepatocellular carcinoma cells by gene manipulation.The expression of FBX8 was detected in 120 cases of clinical paraffin-embedded hepatocellular carcinoma tissues, 20 matched pairs of fresh tissues and five hepatocellular carcinoma cell lines by immunohistochemistry with clinicopathological analyses, real-time RT-PCR or Western blot. The correlation of FBX8 expression with cell proliferation and invasion in five HCC cell lines was analyzed. Moreover, loss of function and gain of function assays were performed to evaluate the effect of FBX8 on cell proliferation, motility, invasion in vitro and metastasis in vivo.We found that FBX8 was obviously down-regulated in HCC tissues and cell lines (P<0.05. The FBX8 down-regulation correlated significantly with poor prognosis, and FBX8 status was identified as an independent significant prognostic factor. Over-expression of FBX8 decreased proliferation, migration and invasion in HepG2 and 97H cells, while knock-down of FBX8 in 7721 cells showed the opposite effect. FBX8 negatively correlated with cell proliferation and invasion in 7701, M3, HepG2 and 97H cell lines. In vivo functional assays showed FBX8 suppressed tumor growth and pulmonary metastatic potential in mice. Our results indicate that down-regulation of FBX8 significantly correlates with invasion, metastasis and poor survival in hepatocellular carcinoma patients. It may be a useful biomarker for therapeutic strategy and control in hepatocellular carcinoma treatment.

Building the multidisciplinary team for management of patients with hepatocellular carcinoma.

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Naugler, Willscott E; Alsina, Angel E; Frenette, Catherine T; Rossaro, Lorenzo; Sellers, Marty T

2015-05-01

Optimal care of the patient with hepatocellular carcinoma (HCC) necessitates the involvement of multiple providers. Because the patient with HCC often carries 2 conditions with competing mortality risks (cancer and underlying cirrhosis), no single provider is equipped to deal with all of these patients' needs adequately. Multidisciplinary teams (MDTs) have evolved to facilitate care coordination, reassessments of clinical course, and nimble changes in treatment plans required for this complex group of patients. Providers or sites that elect to manage patients with HCC thus are increasingly aware of the need to build their own MDT or communicate with an established one. The availability of new communication technologies, such as teleconferencing or teleconsultation, offers the possibility of MDT expansion into underserved or rural areas, as well as areas such as correctional facilities. Although the availability of resources for HCC patient care varies from site to site, construction of an MDT is possible in a wide spectrum of clinical practices, and this article suggests a blueprint for assembly of such collaboration. Research strategies are needed to explain how MDTs improve clinical outcomes so that MDTs themselves can be improved. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Serum Golgi protein 73 is a prognostic rather than diagnostic marker in hepatocellular carcinoma.

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Dong, Min; Chen, Zhan-Hong; Li, Xing; Li, Xiao-Yun; Wen, Jing-Yun; Lin, Qu; Ma, Xiao-Kun; Wei, Li; Chen, Jie; Ruan, Dan-Yun; Lin, Ze-Xiao; Wang, Tian-Tian; Wu, Dong-Hao; Wu, Xiang-Yuan

2017-11-01

Serum Golgi protein 73 (sGP73) is a candidate diagnostic biomarker for hepatocellular carcinoma (HCC). However, current evidence of its diagnostic value is conflicting, primarily due to the small sample sizes of previous studies, and its prognostic role in HCC also remains unclear. In the present study, sGP73 levels in 462 patients with HCC, 186 patients with liver cirrhosis, and 83 healthy controls were evaluated using ELISA, and it was identified that the median sGP73 levels were significantly higher in the HCC (18.7 ng/ml) and liver cirrhosis (18.5 ng/ml) patients than in the healthy controls (0 ng/ml; both P<0.001); however, the levels did not significantly differ between the HCC and liver cirrhosis groups (P=0.632). sGP73 had an inferior sensitivity and specificity for HCC diagnosis (27.79 and 77.96%, respectively) compared with α-fetoprotein (57.36 and 90.96%, respectively; P<0.001). In the HCC group, a high level of sGP73 was associated with aggressive clinicopathological features and independently predicted poor overall survival (OS) time (P<0.001). Additionally, in patients with resectable HCC, a high level of sGP73 was associated with significantly decreased disease-free survival (P<0.001) and OS (P=0.039) times compared with a low level of sGP73. This study demonstrated that sGP73 is unsuitable as a diagnostic marker for the early detection of HCC; however, it is an independent negative prognostic marker, providing a novel risk stratification factor and a potential therapeutic molecular target for HCC.

Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C.

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Virlogeux, Victor; Pradat, Pierre; Hartig-Lavie, Kerstin; Bailly, François; Maynard, Marianne; Ouziel, Guillaume; Poinsot, Domitille; Lebossé, Fanny; Ecochard, Marie; Radenne, Sylvie; Benmakhlouf, Samir; Koffi, Joseph; Lack, Philippe; Scholtes, Caroline; Uhres, Anne-Claire; Ducerf, Christian; Mabrut, Jean-Yves; Rode, Agnès; Levrero, Massimo; Combet, Christophe; Merle, Philippe; Zoulim, Fabien

2017-08-01

Arrival of direct-acting antiviral agents against hepatitis C virus with high-sustained virological response rates and very few side effects has drastically changed the management of hepatitis C virus infection. The impact of direct-acting antiviral exposure on hepatocellular carcinoma recurrence after a first remission in patients with advanced fibrosis remains to be clarified. 68 consecutive hepatitis C virus patients with a first hepatocellular carcinoma diagnosis and under remission, subsequently treated or not with a direct-acting antiviral combination, were included. Clinical, biological and virological data were collected at first hepatocellular carcinoma diagnosis, at remission and during the surveillance period. All patients were cirrhotic. Median age was 62 years and 76% of patients were male. Twenty-three patients (34%) were treated with direct-acting antivirals and 96% of them achieved sustained virological response. Median time between hepatocellular carcinoma remission and direct-acting antivirals initiation was 7.2 months (IQR: 3.6-13.5; range: 0.3-71.4) and median time between direct-acting antivirals start and hepatocellular carcinoma recurrence was 13.0 months (IQR: 9.2-19.6; range: 3.0-24.7). Recurrence rate was 1.7/100 person-months among treated patients vs 4.2/100 person-months among untreated patients (P=.008). In multivariate survival analysis, the hazard ratio for hepatocellular carcinoma recurrence after direct-acting antivirals exposure was 0.24 (95% confidence interval: 0.10-0.55; PHepatocellular carcinoma recurrence rate was significantly lower among patients treated with direct-acting antivirals compared with untreated patients. Given the potential impact of our observation, large-scale prospective cohort studies are needed to confirm these results. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association between the HFE C282Y, H63D Polymorphisms and the Risks of Non-Alcoholic Fatty Liver Disease, Liver Cirrhosis and Hepatocellular Carcinoma: An Updated Systematic Review and Meta-Analysis of 5,758 Cases and 14,741 Controls.

Directory of Open Access Journals (Sweden)

Qing Ye

Full Text Available Conflicting results have been obtained for the association between two common polymorphisms (C282Y, H63D of human HFE (hereditary hemochromatosis gene and the risks of the liver diseases, including non-alcoholic fatty liver disease (NAFLD, liver cirrhosis and hepatocellular carcinoma (HCC.An updated systematic review and meta-analysis was conducted to evaluate the potential role of HFE polymorphisms in the susceptibility to NAFLD, liver cirrhosis and HCC. After retrieving articles from online databases, eligible studies were enrolled according to the selection criteria. Stata/SE 12.0 software was utilized to perform the statistical analysis.In total, 43 articles with 5,758 cases and 14,741 controls were selected. Compared with the control group, a significantly increased risk of NAFLD was observed for the C282Y polymorphism in the Caucasian population under all genetic models and for the H63D polymorphism under the allele, heterozygote and dominant models (all OR>1, Passociation0.05. In addition, we found that HFE C282Y was statistically associated with increased HCC susceptibility in the overall population, while H63D increased the odds of developing non-cirrhotic HCC in the African population (all OR>1, Passociation<0.05. Moreover, a positive association between compound heterozygosity for C282Y/H63D and the risk of NAFLD and HCC, but not liver cirrhosis, was observed.Our meta-analysis provides evidence that the HFE C282Y and H63D polymorphisms confer increased genetic susceptibility to NAFLD and HCC but not liver cirrhosis. Additional well-powered studies are required to confirm our conclusion.

Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

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Chaisaingmongkol, Jittiporn; Budhu, Anuradha; Dang, Hien

2017-01-01

Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We identified common molecular subtypes linked to similar prognosis among 199 Thai ICC and HCC patients through systems integratio...

Assessment of the correlation between serum prolidase and alpha-fetoprotein levels in patients with hepatocellular carcinoma.

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Ilikhan, Sevil Uygun; Bilici, Muammer; Sahin, Hatice; Akca, Ayşe Semra Demir; Can, Murat; Oz, Ibrahim Ilker; Guven, Berrak; Buyukuysal, M Cagatay; Ustundag, Yucel

2015-06-14

To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma (HCC). Sixty-eight patients with HCC (mean age of 69.1 ± 10.1), 31 cirrhosis patients (mean age of 59.3 ± 6.3) and 33 healthy volunteers (mean age of 51.4 ± 12.6) were enrolled in this study. Univariate and multivariate analysis were used to evaluate the association of serum α-fetoprotein (AFP) values with HCC clinicopathological features, such as tumor size, number and presence of vascular and macrovascular invasion. The patients with HCC were divided into groups according to tumor size, number and presence of vascular invasion (diameters; ≤ 3 cm, 3-5 cm and ≥ 5 cm, number; 1, 2 and ≥ 3, macrovascular invasion; yes/no). Barcelona-clinic liver cancer (BCLC) criteria were used to stage HCC patients. Serum samples for measurement of prolidase and alpha-fetoprotein levels were kept at -80 °C until use. Prolidase levels were measured spectrophotometrically and AFP concentrations were determined by a chemiluminescence immunometric commercial diagnostic assay. In patients with HCC, prolidase and AFP values were evaluated according to tumor size, number, presence of macrovascular invasion and BCLC staging classification. Prolidase values were significantly higher in patients with HCC compared with controls (P < 0.001). Prolidase levels were significantly associated with tumor size and number (P < 0.001, P = 0.002, respectively). Prolidase levels also differed in patients in terms of BCLC staging classification (P < 0.001). Furthermore the prolidase levels in HCC patients showed a significant difference compared with patients with cirrhosis (P < 0.001). In HCC patients grouped according to tumor size, number and BCLC staging classification, AFP values differed separately (P = 0.032, P = 0.038, P = 0.015, respectively). In patients with HCC, there was a significant correlation (r = 0.616; P < 0.001) between

Use of transient elastography to predict de novo recurrence after radiofrequency ablation for hepatocellular carcinoma

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Lee SH

2015-02-01

Full Text Available Sang Hoon Lee,1 Seung Up Kim,1–3 Jeong Won Jang,4 Si Hyun Bae,4 Sanghun Lee,1,3 Beom Kyung Kim,1–3 Jun Yong Park,1–3 Do Young Kim,1–3 Sang Hoon Ahn,1–3 Kwang–Hyub Han1–31Department of Internal Medicine, 2Institute of Gastroenterology, Yonsei University College of Medicine, 3Liver Cirrhosis Clinical Research Center, 4Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, KoreaBackground/purpose: Liver stiffness (LS measurement using transient elastography can accurately assess the degree of liver fibrosis, which is associated with the risk of the development of hepatocellular carcinoma (HCC. We investigated whether LS values could predict HCC de novo recurrence after radiofrequency ablation (RFA.Methods: This retrospective, multicenter study analyzed 111 patients with HCC who underwent RFA and LS measurement using transient elastography between May 2005 and April 2011. All patients were followed until March 2013 to monitor for HCC recurrence.Results: This study included 76 men and 35 women with a mean age of 62.4 years, and the mean LS value was 21.2 kPa. During the follow-up period (median 22.4 months, 47 (42.3% patients experienced HCC de novo recurrence, and 18 (16.2% died. Patients with recurrence had significantly more frequent liver cirrhosis, more frequent history of previous treatment for HCC, higher total bilirubin, larger spleen size, larger total tumor size, higher tumor number, higher LS values, and lower platelet counts than those without recurrence (all P<0.05. On multivariate analysis, together with previous anti-HCC treatment history, patients with LS values >13.0 kPa were at significantly greater risk for recurrence after RFA, with a hazard ratio (HR of 3.115 (95% confidence interval [CI], 1.238–7.842, P<0.05. Moreover, LS values independently predicted the mortality after RFA, with a HR of 9.834 (95% CI, 1.148–84.211, P<0.05, together with total bilirubin.Conclusions: Our

Dynamic contrast enhanced MR imaging for evaluation of angiogenesis of hepatocellular nodules in liver cirrhosis in N-nitrosodiethylamine induced rat model

Energy Technology Data Exchange (ETDEWEB)

Zhang, Wei; Chen, Hui Juan; Huang, Wei; Zhang, Long Jiang [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Wang, Zhen J. [University of California, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

2017-05-15

To investigate whether dynamic contrast -enhanced MRI (DCE-MRI) can distinguish the type of liver nodules in a rat model with N-nitrosodiethylamine- induced cirrhosis. Liver nodules in cirrhosis were induced in 60 male Wistar rats via 0.01 % N-nitrosodiethylamine in the drinking water for 35-100 days. The nodules were divided into three groups: regenerative nodule (RN), dysplastic nodule (DN), and hepatocellular carcinoma (HCC). DCE-MRI was performed, and parameters including transfer constant (K{sup trans}), rate constant (K{sub ep}), extravascular extracellular space volume fraction (V{sub e}), and initial area under the contrast concentration versus time curve (iAUC) were measured and compared. The highest K{sup trans} and iAUC values were seen in HCC, followed by DN and RN (all P < 0.05). The area under the receiver operating characteristic curve (AUROC) for DN and HCC were 0.738 and 0.728 for K{sup trans} and iAUC, respectively. The AUROC for HCC were 0.850 and 0.840 for K{sup trans} and iAUC, respectively. Ordinal logistic regression analysis showed that K{sup trans} had a high goodness of fit (0.970, 95 % confidence interval, 13.751-24.958). DCE-MRI is a promising method to differentiate of liver nodules. Elevated K{sup trans} suggested that the nodules may be transformed into HCC. (orig.)

Peritoneal carcinomatosis: an unusual presentation of fibrolamellar hepatocellular carcinoma; Carcinomatosis peritoneal como forma de presentacion infrecuente del hepatocarcinoma fibrolamelar

Energy Technology Data Exchange (ETDEWEB)

Vicente, R; Garcia-Gutierrez, J A; Fernandez, A; Santalla, F [Hospital Comarcal de la Axarquia. Malaga (Spain)

2001-07-01

Fibrolamellar hepatocellular carcinoma is an uncommon malignant tumor with characteristic clinical, radiological and histopahtological features that is usually associated with a more favorable natural course and greater survival than more common variants of hepatocellular carcinoma. We describe an atypical case of a fibrolamellar hepatocellular carcinomas sowing aggressive behaviour in a 20-year-old woman. The lesion presented with massive ascites, and imaging studies revealed extensive peritoneal metastatic spread. (Author) 8 refs.

Emerging role of microRNAs in the treatment of hepatocellular carcinoma

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Callegari E

2015-05-01

Full Text Available Elisa Callegari,1 Marco Domenicali,2 Laura Gramantieri,3 Massimo Negrini,1 Silvia Sabbioni4 1Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, 2Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 3Center for Applied Biomedical Research, S Orsola-Malpighi University Hospital, Bologna, 4Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy Abstract: Hepatocellular carcinoma is the third leading cause of cancer deaths worldwide. Currently available curative options, such as surgery and transplantation, are not available to patients with advanced stages of disease. Among the potential new treatments being investigated are microRNA (miRNA-based therapies. A number of preclinical studies have reported antitumor activities of miRNA mimics or anti-miRNA molecules. Optimal in vivo delivery of miRNA molecules is crucial to their action. To this end, significant progress has been made in the development of nanoparticles for in vivo delivery of miRNA molecules. Delivery of these molecules, alone or in combination with other drugs, promises to open new possibilities for therapeutic approaches to hepatocellular carcinoma. Keywords: hepatocellular carcinoma, microRNA, nanocarriers, therapy 

Preclinical evaluation of transcriptional targeting strategy for human hepatocellular carcinoma in an orthotopic xenograft mouse model.

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Sia, Kian Chuan; Huynh, Hung; Chung, Alexander Yaw Fui; Ooi, London Lucien Peng Jin; Lim, Kiat Hon; Hui, Kam Man; Lam, Paula Yeng Po

2013-08-01

Gene regulation of many key cell-cycle players in S-, G(2) phase, and mitosis results from transcriptional repression in their respective promoter regions during the G(0) and G(1) phases of cell cycle. Within these promoter regions are phylogenetically conserved sequences known as the cell-cycle-dependent element (CDE) and cell-cycle genes homology regions (CHR) sites. Thus, we hypothesize that transcriptional regulation of cell-cycle regulation via the CDE/CHR region together with liver-specific apolipoprotein E (apoE)-hAAT promoter could bring about a selective transgene expression in proliferating human hepatocellular carcinoma. We show that the newly generated vector AH-6CC-L2C could mediate hepatocyte-targeted luciferase gene expression in tumor cells and freshly isolated short-term hepatocellular carcinoma cultures from patient biopsy. In contrast, normal murine and human hepatocytes infected with AH-6CC-L2C expressed minimal or low luciferase activities. In the presence of prodrug 5-fluorocytosine (5-FC), AH-6CC-L2C effectively suppressed the growth of orthotopic hepatocellular carcinoma patient-derived xenograft mouse model via the expression of yeast cytosine deaminase (yCD) that converts 5-FC to anticancer metabolite 5-fluoruracil. More importantly, we show that combination treatment of AH-6CC-L2C with an EZH2 inhibitor, DZNep, that targets EpCAM-positive hepatocellular carcinoma, can bring about a greater therapeutic efficacy compared with a single treatment of virus or inhibitor. Our study showed that targeting proliferating human hepatocellular carcinoma cells through the transcriptional control of therapeutic gene could represent a feasible approach against hepatocellular carcinoma.

Mutant woodchuck hepatitis virus genomes from virions resemble rearranged hepadnaviral integrants in hepatocellular carcinoma.

OpenAIRE

Kew, M C; Miller, R H; Chen, H S; Tennant, B C; Purcell, R H

1993-01-01

Although hepadnaviruses are implicated in the etiology of hepatocellular carcinoma, the pathogenic mechanisms involved remain uncertain. Clonally propagated integrations of hepadnaviral DNA into cellular DNA can be demonstrated in most virally induced hepatocellular carcinomas. Integration occurs at random sites in cellular DNA, but the highly preferred sites in viral DNA are adjacent to the directly repeated sequence DR1, less often DR2, or in the cohesive overlap region. Integrants invariab...

Hepatocellular carcinoma (HCC) and diagnostic significance of alpha-fetoprotein (AFP)

International Nuclear Information System (INIS)

Baig, J.A.; Alam, J.M.; Baig, M.; Mahmood, S.R.; Shaheen, R.; Waheed, A.

2009-01-01

Alpha-fetoprotein (alpha-fetoprotein, AFP) is a Glycoprotein, belonging to the intriguing class of onco-development protein. Generally designated as tumour marker, AFP is recognized as an important blood component, having specific diagnostic utilities Elevation of its level up to pathological range in adults correlate with the appearance of several malignant and chronic conditions, such as hepatocellular carcinoma (HCC) and chronic liver disease, respectively. To evaluate the diagnostic significance of AFP in HCC, a study was carried out for a period of two years (Jan. 2004 to Dec. 2005) A brief history of Patients was taken with clinical symptoms and signs and initial diagnosis. Patients admitted in wards or visiting OPDs with diagnosis or suspicions of HCC and additional conditions of Chronic Liver disease (CLDs), hepatitis C (HCV) and hepatitis B viral (HBV) infections, were selected and classified according to gender. When confirmed, their HCC status was evaluated and classified according to clinical condition. In 1012 adults including, males 762 (75.3%) and females 250 (24.7%) patients suspected of or diagnosed with HCC and presence of HBV and HCV infections. Out of 480 males, who depicted elevated AFP levels, 39 (8.13%) were diagnosed with HCC. Similarly, 7 (5.34%) females out of 131 with elevated levels of AFP were diagnosed with HCC. Mean elevated AFP levels in all HCC patients were, 421+-59 mu g/ml (range 157-4019 mu g/ml) in males and 163+-32 mu g/ml (range 101-2341 mu g/ml) in females. In males, the overall estimated mean AFP elevated values were analyzed to be 514 mu g/ml (range 67-4019+-59 mu g/ml), whereas in females it was 396+-42 mu g/ml (range 21-2341 mu g/ml). It was also noted that 43 (8.96%) males and 7 (5.34%) female patients, exhibited elevated levels of AFP, however, found negative for HCV and HBV infections. It is concluded that AFP is a significant markers for Hepatocellular carcinoma, helpful in assessing problems in management of HCC and

Venom from Cuban Blue Scorpion has tumor activating effect in hepatocellular carcinoma.

Science.gov (United States)

Giovannini, Catia; Baglioni, Michele; Baron Toaldo, Marco; Cescon, Matteo; Bolondi, Luigi; Gramantieri, Laura

2017-03-21

Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. We found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. Our results suggest that the concentration of Vidatox used in the present study has not anti-neoplastic effects and care must be taken in hiring Vidatox in patients with HCC.