Diffuse Hepatocellular Carcinoma Research Articles

Hepatic infarction occurred after 125I particle stent treatment for hepatocellular carcinoma with portal vein tumor thrombus: A case report

BackgroundHepatic infarction is a rare liver condition. The purpose of this study is to report a case of hepatic infarction caused by thrombus formation following portal vein stent implantation in a patient with hepatocellular carcinoma and portal vein tumor thrombus, and to explore the underlying causes.Case reportThe patient in this study was a 52-year-old male admitted with diffuse hepatocellular carcinoma involving the right lobe and portal vein tumor thrombus. After undergoing portal vein stent implantation and 125I particle strand implantation treatment, the portal vein was patent, and the pressure decreased. However, multiple instances of hepatic artery chemoembolization combined with targeted immunotherapy resulted in gradual reduction in the diameter of the hepatic artery and affecting hepatic arterial blood flow. Two months post-stent implantation, thrombus formation within the stent was noted, and the patient’s condition did not improve with anticoagulant therapy, as evidenced by follow-up CT scans showing an increase in thrombi. Six months later, the patient suffered from gastrointestinal bleeding and, despite emergency esophagogastric variceal ligation and hemostatic treatment, developed hepatic parenchymal infarction and liver function failure.ConclusionsWe reveal the underlying cause is that (1) thrombus formation within the portal vein stent, leading to portal vein embolism and obstructed blood flow due to exacerbate portal hypertension after various treatments; and (2) the effect of hepatic artery chemoembolization, immunotherapy, and targeted therapy on tumor angiogenesis, causing reduced hepatic artery diameter and impaired arterial blood flow. These factors disrupt the liver’s dual blood supply system, ultimately contributing to hepatic infarction. To our knowledge, this is the first report of hepatic infarction as a complication following portal vein stent implantation for hepatocellular carcinoma with portal vein tumor thrombus, and it holds significant reference value for guiding the treatment of hepatocellular carcinoma with concurrent portal vein tumor thrombus in a clinical setting.

Effectiveness and safety of computed tomography-guided high-dose-rate brachytherapy in treating recurrent hepatocellular carcinoma not amenable to repeated resection or radiofrequency ablation

PurposeTo assess the efficacy and safety of computed tomography (CT)-guided high-dose-rate HDR) brachytherapy in treating recurrent hepatocellular carcinoma (HCC) not amenable to repeated resection or radiofrequency ablation. Materials and methodsFrom January 2010 to January 2022, 38 patients (mean age, 70.1 years; SD ± 9.0 years) with 79 nodular and four diffuse intrahepatic HCC recurrences not amenable to repeated resection or radiofrequency ablation underwent CT-guided HDR brachytheapy in our department. Tumor response was evaluated by cross-sectional imaging 6 weeks after CT-guided HDR brachytherapy and every 3 months thereafter. Local tumor control (LTC), progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier curves (KPCs). Severity of procedure-related complications (PRCs) was classified as recommended by the Society of Interventional Radiology (SIR). ResultsPatients were available for MRI evaluation for a mean follow-up of 33.1 months (SD, ±21.6 mm, range 4–86 months; median 29 months). Patients had a mean of 2.3 (SD, ±1.4) intrahepatic tumors. Mean tumor diameter was 43.2 mm (SD, ±19.6 mm). 13 of 38 (34.2%) patients showed local tumor progression after CT-guided HDR brachytherapy. Mean LTC was 29.3 months (SD, ±22.1). Distant tumor progression was seen in 12 patients (31.6%). The mean PFS was 20.8 months (SD, ±22.1). Estimated 1-, 3-, and 5-year PFS rates were 65.1%, 35.1% and 22.5%, respectively. 13 patients died during the follow-up period. Mean OS was 35.4 months (SD, ±21.7). Estimated 1-, 3-, and 5-year OS rates were 91.5%, 77.4% and 58.0%, respectively. SIR grade 1 complications were recorded in 8.6% (5/38) and SIR grade 2 complications in 3.4% (2/58) of interventions. ConclusionCT-guided HDR brachytherapy is a safe and efficient therapeutic option for managing large or critically located HCC recurrences in the remaining liver after prior hepatic resection.

Safety and efficacy of TIPS combined with iodine-125 seed strands in the treatment of patients with hepatocellular carcinoma combined with portal vein tumor thrombosis

Objective: To study the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with iodine-125 (125Ⅰ) seed strands implantation in patients with hepatocellular carcinoma combined with portal vein tumor thrombosis. Methods: 25 cases with diffuse intrahepatic tumor combined with tumor thrombus type Ⅲ/Ⅳ requiring TIPS were simultaneously implanted with 125Ⅰseed strand. Tumor thrombus was controlled with 125I seed implantation brachytherapy to keep the TIPS pathway unobstructed, reduce the portal vein pressure, and observe the changes in the cause of death of the patients. During the same period, 30 cases without TIPS and seed strand implantation were used as controls. Data between groups were compared using t-test, Chi-Squared test or Fisher's exact test. Results: TIPS combined with 125Ⅰ seed strand implantation was safe in patients with diffuse hepatocellular carcinoma combined with type III/IV portal vein tumor thrombus, and 92.0% (23/25) of the patients maintained unobstructed TIPS pathway. Compared with the control group, patients in the treatment group died of fewer lead-related complications, and most died from chronic liver failure (84.0% vs. 56.7%, χ2 = 4.771, P=0.029). The incidence of upper gastrointestinal bleeding was significantly decreased (12.0% vs. 46.7%, χ2 =7.674, P=0.006) and ascites severity was significantly improved (mild 40.0% vs. 16.7%, moderate 52.0% vs. 20.0%, severe 8.0% vs. 46.7%, χ2 =13.246 , P=0.001). Conclusions: TIPS combined with 125Ⅰ seed strand implantation is safe and feasible in patients with diffuse intrahepatic tumor combined with tumor thrombus type Ⅲ/Ⅳ. Moreover, it can effectively keep the shunt patency and reduce portal vein pressure, thereby reducing the incidence of upper gastrointestinal bleeding and improving the degree of ascites. TIPS combined with 125Ⅰ seed strand implantation may be used as a standard treatment modality for patients requiring TIPS therapy combined with tumor thrombus type Ⅲ/Ⅳ.

Primary diffuse hepatocellular carcinoma in a captive polar bear (Ursus maritimus)

Primary diffuse hepatocellular carcinoma in a captive polar bear (<i>Ursus maritimus</i>)

Diffuse hepatocellular carcinoma with extension into the right atrium

Diffuse hepatocellular carcinoma with extension into the right atrium

Metronomic chemotherapy for advanced diffuse hepatocellular carcinoma in a dog

Primary liver tumors represent 0.6% to 1.3% of neoplasms in dogs. Hepatocellular carcinoma (HCC) is the most common liver tumor. It is divided into three morphological groups: massive, nodular and diffuse. The presumptive diagnosis is made through imaging tests, such as ultrasound, although confirmation is made by histopathology. Surgery remains the treatment of choice for massive tumors, but there is no standard treatment for nodular and diffuse forms. This study aimed to report a case of prolonged survival in a dog with diffuse HCC, treated with metronomic chemotherapy and palliative care including non-steroidal anti-inflammatory and low-dose naltrexone.

Sorafenib for the Treatment of Unresectable Hepatocellular Carcinoma: Preliminary Toxicity and Activity Data in Dogs.

Unresectable nodular and diffuse hepatocellular carcinoma (HCC) have a poor prognosis with limited treatment options. Systemic traditional chemotherapy has been only rarely reported, with unsatisfactory results. The aim of this prospective, non-randomized, non-blinded, single center clinical trial was to investigate safety profile, objective response rate, time to progression and overall survival of sorafenib in comparison with metronomic chemotherapy (MC) consisting of thalidomide, piroxicam and cyclophosphamide in dogs with advanced, unresectable HCC. Between December 2011 and June 2017, 13 dogs were enrolled: seven received sorafenib, and six were treated with MC. Median time to progression was 363 days (95% CI, 191–535) in dogs treated with sorafenib versus 27 days (95% CI, 0–68) in dogs treated with MC (p = 0.044). Median overall survival was 361 days (95% CI, 0–909) in dogs receiving sorafenib, while 32 days (95% CI, 0–235) in those receiving MC (p = 0.079). Sorafenib seems to be a good candidate for the treatment of dogs with advanced HCC, due to a benefit in disease control and an acceptable safety profile, offering a good basis on which new randomized prospective clinical trials should be undertaken to compare the efficacy and drawback of sorafenib versus MC or traditional chemotherapy.

3:54 PM Abstract No. 196 Molecularly targeted photothermal ablation enhances the effect of anti-PD1 therapy in a mouse model of hepatocellular carcinoma

Recent clinical studies have shown that immunotherapy approaches to exploit the full potential of the adaptive immune system to control hepatocellular carcinoma (HCC) progression need improvement. Here, we sought to assess the effect of combining immune checkpoint blockade strategies with a novel molecularly targeted photothermal ablation (MTPA) modality for the treatment of HCC using a mouse model. C3H mice were treated via oral gavage with CCl4 (20% vol/vol) for 12 weeks to induce liver cirrhosis. The mice then received implantations of syngeneic HCA-1 cells in the liver (5x106). 12 days after, the animals were randomly assigned to 4 different treatment groups: (1) untreated (n = 2), (2) MTPA only (n = 3), (3) anti-mouse PD1 antibody only (n = 4, 100μg per I.P. injection every 3 days), and (4) MTPA+anti-PD1 (n = 2). MTPA was performed following an I.V. injection of 0.5 mg/kg indocyanine green (ICG), and by illuminating the tumor with a 785nm near infrared laser coupled to a clinical fiberoptic catheter. The mice underwent T2 MRI on POD-13, and tissues were harvested on POD-14. Tumor sections were processed for histology and for characterization of tumor-infiltrating lymphocytes (TILs) through flow cytometry. Masson’s trichrome stain demonstrated extensive liver cirrhosis at the time of tumor implantation. MRI and histology data showed cases of nodular and diffuse infiltrative HCC. Characterization of TILs showed that MTPA increases the CD3+ population and, when used in combination with anti-PD1, together they increase the number of CD8+ cells while reducing the number of CD4+/FoxP3+ cells (Tregs). Our preliminary results indicate that even in the context of impaired liver function, the combination of anti-PD1 therapy with our novel MTPA has a synergistic effect whereby greater numbers of cytotoxic lymphocytes infiltrate the hepatic tumors, while at the same time decreasing the presence of immunosuppressive cells. Longer follow-up should reveal how these changes in the TILs impact disease progression in both nodular and diffuse infiltrative HCC subtypes.

Short article: Management of ruptured hepatocellular carcinoma in a European tertiary care center.

Spontaneous rupture is a rare complication of hepatocellular carcinoma (HCC). Treatment options consist of transcatheter arterial embolization (TAE), hepatic resection, and conservative therapy. The best approach is under debate. This study presents a review of clinical data of patients with a ruptured HCC admitted to a European tertiary care center. Eleven patients were included; six (55%) had underlying cirrhosis. The majority of patients (73%) had no previous history of HCC. Spontaneous HCC rupture was diagnosed using abdominal computed tomography with or without a diagnostic paracentesis. Computed tomography showed one or two tumors in eight (73%) patients; the other patients had multiple tumors or diffuse infiltrative HCC. Seven (64%) patients were initially treated by TAE and one (9%) patient underwent hepatic resection. The remaining three (27%) patients, all of whom had liver cirrhosis, received conservative therapy. Two patients initially treated by TAE underwent a delayed resection and ultimately received systemic therapy. Overall, at the end of the follow-up period, three patients were still alive at 84, 991, and 1026 days after the initial presentation. Eight (73%) patients had died after a median of 88 days (range 7-417). One year after presentation, none of the conservatively treated patients was alive compared with three out of seven (43%) patients treated with TAE with or without delayed resection. Patients with a spontaneously ruptured HCC have a poor prognosis. In selected patients, however, prolonged survival is possible using TAE as initial therapy with or without a delayed resection and systemic therapy.

Bone Metastases of Hepatocellular Carcinoma: Appearance on MRI Using a Standard Abdominal Protocol.

The purpose of this study is to describe the MRI features of hepatocellular carcinoma (HCC) bone metastases. Thirty-three consecutive patients were included. Two radiologists performed qualitative and quantitative analysis. The coordinator searched for clinical and epidemiologic features related to patients and their primary liver tumors. Earlier MRI studies were also reviewed to determine whether bone metastases were already present and prospectively identified. Descriptive statistics and the Lin concordance correlation coefficient were used. Chronic hepatitis C virus infection was the most common cause of liver disease (20/32; 62.5%), and diffuse and multifocal HCC were the most frequent types of liver HCCs (28/33; 84.8%). Most lesions were located at the spine (109/155; 70.3%), with high signal intensity on fat-suppressed T1-weighted (54/62; 87.1%) and T2-weighted (53/62; 85.5%) images. Bone metastases were predominantly nodular (48/62; 77.4%), confined to the vertebral body (40/60; 66.7%), and best visualized at the arterial phase (40/62; 64.5%). The ring pattern of enhancement was present in 23 of 62 lesions, and the remaining lesions showed diffuse enhancement. Thirty-five of 62 (56.4%) bone metastases showed arterial peak of enhancement. In 13 of 33 (39.9%) patients, bone metastases were not prospectively reported. Most patients with bone metastases had chronic hepatitis C virus infection and diffuse or multifocal HCC. Metastases are most commonly appreciated as hypervascular focal moderately intensely enhancing nodular masses on the hepatic arterial dominant phase images, with concomitant moderately high signal intensity on fat-suppressed T1- and T2-weighted images.

C-arm computed tomography parenchymal blood volume measurement in evaluation of hepatocellular carcinoma before transarterial chemoembolization with drug eluting beads.

BackgroundC-arm computed tomography (CT) guided intervention is an increasingly applied technique in transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). The aim of this study was to analyse the value of parenchymal blood volume (PBV) maps acquired during C-arm CT acquisition, for pre-treatment evaluation and planning of TACE in HCC patients.MethodsA total of 64 HCC lesions in 29 patients (median age, 73 years, range, 62–77 years) were included in this retrospective study. All patients received cross-sectional imaging (MRI or CT) prior to TACE and C-arm CT PBV measurement acquisition before performing TACE. Results of cross-sectional imaging regarding the number of HCC lesions and maximum diameter were compared to PBV–maps. Number of lesions and tumour feeding vessels detected in PBV-maps were compared to conventional angiography. Results of PBV were analysed concerning different tumour morphologies (pre-treated, encapsulated and diffuse).ResultsPre-interventional cross-sectional imaging and PBV maps showed an excellent agreement in lesion diameter (p = 0.88, MD = −0.28 mm) and number of detected lesions (κ = 1.0). Compared to conventional angiography, PBV maps showed an increased number of detected lesions (κ = 0.77, p = 0.001) and tumour feeding vessels (κ = 0.71, p < 0.0001). Diffuse HCC lesion revealed a significantly lower PBV compared to encapsulated lesions (p = 0.0001).ConclusionsC-arm CT acquired PBV measurements detect HCC tumours with a lesion detectability comparable to pre-interventional cross-sectional imaging. Furthermore, this technique facilitates TACE, allowing a more precise localization of HCC lesions and tumour feeding vessels compared to conventional angiography. Additionally, calculated PBV values enable a real time quantitative assessment of tumour perfusion.

Preclinical Assessment of the Efficacy of Anti-Angiogenic Therapies in Hepatocellular Carcinoma

Diffuse hepatocellular carcinoma (HCC) is a complex affliction in which comorbidities can bias global outcome of cancer therapy. Better methods are thus warranted to directly assess effects of therapy on tumor angiogenesis and growth. As tumor angiogenesis is invariably associated with changes in local blood flow, we assessed the utility of ultrasound imaging in evaluation of the efficacy of anti-angiogenic therapy in a spontaneous transgenic mouse model of HCC. Blood flow velocities were measured monthly in the celiac trunk before and after administration of sorafenib or bevacizumab at doses corresponding to those currently used in clinical practice. Concordant with clinical experience, sorafenib, but not bevacizumab, reduced microvascular density and suppressed tumor growth relative to controls. Evolution of blood flow velocities correlated with microvascular density and with the evolution of tumor size. Ultrasound imaging thus provides a useful non-invasive tool for preclinical evaluation of new anti-angiogenic therapies for HCC.

An autologous in situ tumor vaccination approach for hepatocellular carcinoma. 2. Tumor-specific immunity and cure after radio-inducible suicide gene therapy and systemic CD40-ligand and Flt3-ligand gene therapy in an orthotopic tumor model.

Diffuse hepatocellular carcinoma (HCC) is a lethal disease that radiation therapy (RT) currently has a limited role in treating because of the potential for developing fatal radiation-induced liver disease. However, recently diffuse HCC, "radio-inducible suicide gene therapy" has been shown to enhance local tumor control and residual microscopic disease within the liver for diffuse HCC, by using a combination of chemoactivation and molecular radiosensitization. We have demonstrated that the addition of recombinant adenovirus-expressing human Flt3 ligand (Adeno-Flt3L) after radio-inducible suicide gene therapy induced a Th1-biased, immune response and enhanced tumor control in an ectopic model of HCC. We hypothesized that sequential administration of recombinant adenovirus-expressing CD40L (Adeno-CD40L) could further potentiate the efficacy of our trimodal therapy with RT + HSV-TK + Adeno-Flt3L. We examined our hypothesis in an orthotopic model of diffuse HCC using BNL1ME A.7R.1 (BNL) cells in Balb/c mice. BNL murine hepatoma cells (5 × 10(4)) transfected with an expression vector of HSV-TK under the control of a radiation-inducible promoter were injected intraportally into BALB/cJ mice. Fourteen days after the HCC injection, mice were treated with a 25 Gy dose of radiation to the whole liver, followed by ganciclovir (GCV) treatment and systemic adenoviral cytokine gene therapy (Flt3L or CD40L or both). Untreated mice died in 27 ± 4 days. Radiation therapy alone had a marginal effect on survival (median = 35 ± 7 days) and the addition of HSV-TK/GCV gene therapy improved the median survival to 47 ± 6 days. However, the addition of Adeno-Flt3L to radiation therapy and HSV-TK/GCV therapy significantly (P = 0.0005) increased survival to a median of 63 ± 20 days with 44% (7/16) of the animals still alive 116 days after tumor implantation. The curative effect of Flt3L was completely abolished when using immunodeficient nude mice or mice depleted for CD4, CD8 and natural killer cells. The addition of Adeno-CD40L further improved the median survival of animals to 80 ± 15 days and this effect was abolished only when using anti-CD8 antibodies. Chromium-51 (51Cr) release assay showed cytotoxic T lymphocyte (CTL) activation, suggesting efficient dendritic cell (DC) activation with CTL activation after the treatment. Furthermore, when surviving mice were rechallenged with BNL-ETK cells on the foot pad, RT + HSV-TK/GCV + Flt3L + CD40L-treated mice developed a small tumor on day 56 but the tumor eventually disappeared after 105 days. Mice treated with RT + HSV-TK/GCV + Flt3L showed a slowed tumor growth curve compared with untreated mice. Therefore, combination therapy using Flt3L to induce DC proliferation and CD40L to enhance DC maturation holds great promise for immunomodulation of radiation therapy to enhance HCC tumor control and prevent progression of disease in patients with diffuse HCC.

Dynamic multidetector computed tomography findings of hepatocellular carcinoma of hepatitis B virus-positive and -negative patients.

BackgroundThe objective of this study was to retrospectively investigate and compare multidetector computed tomography findings of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-positive and -negative patients.MethodsTriphasic (arterial, portal venous, and delayed phases) dynamic multidetector computed tomography (CT) was performed in 83 patients with HCC, 48 of whom were HBV-positive. The diagnosis of HCC was established with typical CT imaging findings (68 patients) or histopathological evaluation (15 patients). Distribution of solitary, multiple, and diffuse HCC, portal/hepatic vein thrombosis, metastasis, and patients with high alpha-fetoprotein levels in the HBV-positive and -negative groups were compared using the Kolmogorov–Smirnov test. Lesion size, alpha-fetoprotein levels, arterial, portal, delayed enhancement, and washout of lesions were compared using the Student’s t-test.ResultsHypervascular tumors were observed in 72 (87%) patients, and hypovascular tumors were found in 11 (13%) patients. The mean alpha-fetoprotein value of HBV-positive patients with HCC was significantly higher than the mean alpha-fetoprotein value of HBV-negative patients (P < 0.05). Portal/hepatic vein thrombosis and metastasis were more frequently observed in HBV-positive patients (P < 0.05). The frequencies of solitary, multiple, and diffuse lesions in HBV-positive and -negative patients were not significantly different (P > 0.05). The mean diameters, arterial, portal, and delayed phase attenuations, and washout of HCC were not significantly different (P > 0.05).ConclusionsMultidetector CT imaging findings of HCC in HBV-positive and -negative patients are alike. Portal/hepatic vein thrombosis and metastasis are more frequently observed in HBV-positive patients. Alpha-fetoprotein levels are higher in HBV-positive patients.

PNPLA3 I148M Polymorphism, Clinical Presentation, and Survival in Patients with Hepatocellular Carcinoma

Background & AimsAim of this study was to evaluate whether the PNPLA3 I148M polymorphism, previously associated with hepatocellular carcinoma (HCC) risk, influences the clinical presentation of HCC and survival.Methodswe considered 460 consecutive HCC patients referred to tertiary care centers in Northern Italy, 353 with follow-up data.ResultsHomozygosity for PNPLA3 148M at risk allele was enriched in HCC patients with alcoholic liver disease or nonalcoholic fatty liver disease (ALD&NAFLD: relative risk 5.9, 95% c.i. 3.5–9.9; other liver diseases: relative risk 1.9, 95% c.i. 1.1–3.4). In ALD&NAFLD patients, the PNPLA3 148M allele was associated with younger age, shorter history of cirrhosis, less advanced (Child A) cirrhosis at HCC diagnosis, and lower HCC differentiation grade (p<0.05). Homozygosity for PNPLA3 148M was associated with reduced survival in the overall series (p = 0.009), and with a higher number of HCC lesions at presentation (p = 0.007) and reduced survival in ALD&NAFLD patients (p = 0.003; median survival 30, 95% c.i. 20–39 vs. 45, 95% c.i. 38–52 months), but not in those with HCC related to other etiologies (p = 0.86; 48, 95% c.i. 32–64 vs. 55, 95% c.i. 43–67 months). At multivariate Cox regression analysis, homozygosity for PNPLA3 148M was the only negative predictor of survival in ALD&NAFLD patients (HR of death 1.57, 95% c.i. 1.12–2.78).ConclusionsPNPLA3 148M is over-represented in ALD&NAFLD HCC patients, and is associated with occurrence at a less advanced stage of liver disease in ALD&NAFLD. In ALD&NAFLD, PNPLA3 148M is associated with more diffuse HCC at presentation, and with reduced survival.

First in-human intraoperative imaging of HCC using the fluorescence goggle system and transarterial delivery of near-infrared fluorescent imaging agent: a pilot study

Surgical resections remain the primary curative interventions for hepatocellular carcinoma (HCC). However, lack of real-time intraoperative image guidance confines surgeons to subjective visual assessment of the surgical bed, leading to poor visualization of small positive nodules and the extension of diffuse HCC. To address this problem, we developed a wearable fluorescence imaging and display system (fluorescence goggle) for intraoperative imaging of HCCs in human patients. In this pilot study, both intravenous (IV) and transarterial hepatic (TAH) delivery of indocyanine green (ICG) were explored to facilitate fluorescence goggle-mediated HCC imaging. The results show that all primary tumors in patients (n = 4) who received TAH delivery of ICG were identified successfully by the fluorescence goggle. In addition, 6 satellite tumors were also detected by the goggle, 5 of which were neither identifiable via preoperative magnetic resonance imaging (MRI) and computed tomography (CT) nor by visual inspection and palpation. In the group (n = 5) that received ICG intravenously, only 2 of 6 tumors visible by preoperative MRI or CT were identified with the fluorescence goggle, demonstrating the limitation of this delivery route for a non-tumor-selective imaging agent. Comparative analysis shows that the HCC-to-liver florescence contrast detected by the goggle was significantly greater in patients that received TAH than IV delivery of ICG (P = 0.013). This pilot study demonstrates the feasibility of using the fluorescence goggle to identify multifocal lesions and small tumor deposits using TAH ICG delivery in HCC patients.

Alleles and genotypes of polymorphisms of IL-18, TNF-α and IFN-γ are associated with a higher risk and severity of hepatocellular carcinoma (HCC) in Brazil

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver. We evaluated the association of alleles and genotypes of polymorphisms of IL-18 (-607C/A and -137G/C), IFN-γ (+874T/A) and TNF-α (-238G/A and -308G/A) with the risk and severity of HCC. One-hundred-and-twelve patients with HCC and 202 healthy controls were studied. Single nucleotide polymorphisms (SNPs) were amplified by PCR with specific primers and the products were submitted to polyacrylamide gel electrophoresis and stained with silver. We evaluated tumor presentation, tumor size and presence of metastasis. Significant higher risk of HCC was associated with: alleles IL-18 -607(*)A (P=0.0235; OR=1.48; 95%CI=1.06-2.08); TNF-α -238(*)A (P=0.0025; OR=2.12; 95%CI=1.32-3.40) and TNF-α -308(*)A (P=0.0351; OR=1.82; 95%CI=1.07-3.08); and genotypes IL-18-607AA (P=0.0048; OR=3.03; 95%CI=1.40-6.55); TNF-α -238GA (P=0.0011; OR=2.44; 95%CI=1.45-4.12); and TNF-α -308GA (P=0.0031; OR=2.51; 95%CI=1.39-4.51). Significant association was found between multinodular HCC and IL-18 -607(*)C allele (P=0.029; OR=2.40, 95%CI: 1.09-5.28), and IL-18 -607CC genotype (P=0.028; OR=3.5, 95%CI: 1.24-9.86). Diffuse HCC was significantly associated with IFN-γ +874TA genotype (P=0.044; OR=3.6, 95%CI: 1.03-12.47). The IL-18 -137(∗)C allele showed a significant association with the presence of metastasis. Thus, IL-18 -607(*)A and TNF-α (-238(*)A and -308(*)A) alleles may confer susceptibility to HCC, while IL-18 -607(*)C and -137(*)C alleles more severe disease.

Aggressive proton beam therapy followed by liver transplantation for a patient with large HCC with portal vein tumor thrombus

We describe the case of a patient with large hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) who was successfully treated with two courses of proton beam therapy (PBT) followed by liver transplantation. The patient was a 69-year-old man with hepatitis C viral infection who was diagnosed with a diffuse HCC, 8 cm in size, and a PVTT that occluded the right portal vein and reached the main trunk of the portal vein. A large tumor in the right lobe and PVTT in the main and right main portal vein were treated by PBT. PVTT in the left main portal vein developed thereafter and was treated with a second course of PBT. Although the tumor was well controlled with two courses of PBT, liver function gradually deteriorated to an irreversible status 20 months after initiation of the first course of PBT. Liver transplantation was successfully performed to maintain liver function. The patient is still alive with no evidence of disease 7 years after the first course of PBT. This case shows that aggressive PBT can be used for treating advanced HCC, with subsequent liver transplantation for hepatic failure that may be caused by PBT.

Management of Diffuse Hepatocellular Carcinoma (≧ 10 Lesions) with Doxorubicin-Loaded DC Beads Is a Safe and Effective Treatment Option

Background: Multinodular hepatocellular carcinoma (HCC; ≧ 10 lesions) has been considered a controversial indication for transarterial chemoembolization (TACE) based on the extent of disease and the belief that no clinical benefit can be achieved. The aim of this study was to assess the safety and efficacy of chemoembolization with doxorubicin-eluting beads (DEBDOX) in the treatment of multinodular HCC. Patients and Methods: A 503-patient prospective multinational DC Bead registry database from 6/2007 to 2/2010 identified 176 patients treated for HCC with DEBDOX. Results: There were 42 patients with multinodular HCC compared to 134 with non-multinodular HCC. After a median follow-up of 12 months, the multinodular group response rate according to modified RECIST criteria was 56% and median overall survival was 7.6 months, compared to 57% and 15 months in the non-multinodular group (p = 0.08). Conclusions: Multinodular HCC represents a more advanced stage of disease; however, DEBDOX treatment is safe and effective when compared to historical controls and current best systemic therapy. Continued hepatic arterial therapy and evaluation is needed in this clinical subset to further confirm these results.

Single‐agent gemcitabine chemotherapy in dogs with hepatocellular carcinomas

The goal of this study was to determine the efficacy and tolerability of gemcitabine in dogs diagnosed with hepatocellular carcinoma (HCC). Eighteen dogs were examined retrospectively (4 massive HCC, 10 nodular HCC and 4 diffuse HCC). All dogs received gemcitabine at 350-400 mg m(-2) weekly for 5 weeks. Toxicity was graded using VCOG-CTCAE guidelines and response was monitored with serial abdominal ultrasounds. Fifteen dogs completed all five cycles. Toxicity was minimal and consisted of grade I/II vomiting, anorexia and diarrhoea and two episodes of grade III neutropenia. Median survival time for all dogs was 983 days. Median progression free interval was 971 days. Based on the results of this study, surgery remains the best treatment for HCC, despite incomplete resection. There was no improvement in the survival of those diagnosed with nonresectable HCC treated with gemcitabine chemotherapy.