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Liver Cancer

Primary liver cancer is a disease in which the cells of liver become cancerous (malignant). Primary liver cancer is different from cancer that has spread from another place in the body to the liver. The liver is found in the upper right side of the abdomen. It is an an important organ which is involved in digesting food and converting it to energy and it also filters and stores blood. Liver cancer is relatively rare, known risk factors for liver cancer are prior hepatitis B or C infections or cirrhosis of the liver. There are two main types of liver cancer in adults: hepatocellular carcinoma and cholangiocarcinoma. Hepatoblastoma is another type of liver cancer which mostly occurs in children. Some types of liver cancer produce abnormaly high levels of alpha-fetoprotein (AFP) which can aid diagnosis.

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Childhood Liver Cancer

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  • PubMed search for publications about Liver Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Liver Cancer
    MeSH term: Liver Neoplasms
    International US National Library of Medicine
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Millar AJ
Liver tumours in children: current surgical management and role of transplantation.
S Afr Med J. 2014; 104(11 Pt 2):813-5 [PubMed] Related Publications
This article reviews the current surgical management of liver tumours in children in the light of improved chemotherapy, surgical techniques and outcomes from transplantation. It is a principle of management that complete removal of a tumour must be achieved for cure. Neoadjuvant chemotherapy may downstage advanced local disease to enable safe curative tumour resection. When this is not achievable, transplant is indicated. Conventional indications for transplant are unresectable stages 3 and 4 tumours confined to the liver. With the realisation that lifelong immunosuppressive therapy has considerable adverse consequences, there has been a recent trend towards extreme and 'acrobatic' liver resection to avoid transplantation, but still obtain a cure. The current literature is reviewed in the light of these trends and our own experience.

Ibrahim AA, Abdel Aleem MH, Abdella HM, Helmy A
Study of the role of insulin resistance as a risk factor in HCV related hepatocellular carcinoma.
J Egypt Soc Parasitol. 2015; 45(1):107-13 [PubMed] Related Publications
Chronic HCV infection causes hepatic cirrhosis and approximately 10%-20% of cirrhotic patients may develop hepatocellular carcinoma within 5 years. Diabetes mellitus is associated with a 2-4-fold increase in the risk of HCC. Insulin resistance (IR) emerged as a risk factor for a variety of cancers, including endometrial and breast and various gastrointestinal cancers The role of IR in the development of HCC associated with chronic HCV infection has not, been established. This study elucidated the role of insulin resistance assessed by the homeostasis model (HOMA-IR) in development of hepatocellular carcinoma associated with chronic hepatitis C infection. The study included 3 groups: GI: 100 newly diagnosed cases of HCV related hepatocellular carcinoma GII: 60 patients with HCV related chronic liver disease. Forty healthy persons as a control group (GIII). All groups were subjected to full history taking, physical examination, laboratory investigations abdominal ultrasonography and Triphasic C.T examination. In addition to Calculation of Body mass Index, Measurement of fasting blood insulin and glucose, Calculation of insulin resistance using HOMA-IR. The results showed that fasting insulin and HOMA-IR were significantly higher among HCC group than HCV group & control group. Also, fasting insulin and HOMA-IR were significantly higher in HCV group than control group. HOMA-IR above 3.7, insulin above 9μU/L & DM were considered independent predictors of HCC.

Uygun Ilikhan S, Bilici M, Sahin H, et al.
The influence of cisplatin, doxorubicin, pegylated doxorubicin, oxaliplatin and gemcitabine on mahlavu cell line.
J BUON. 2015 Mar-Apr; 20(2):608-13 [PubMed] Related Publications
PURPOSE: Hepatocellar carcinoma (HCC) remains a major health problem being the third leading cause of deaths due to cancer worldwide. Because HCC is known to be highly resistant to conventional systemic therapies, single-agent or combination of systemic therapies have been investigated. Today, sorafenib, a multikinase inhibitor, is the only approved systemic agent for the first line treatment of advanced HCC. In this study, we aimed to investigate the influence of different concentrations of cisplatin, doxorubicin, pegylated doxorubicin (PLD), oxaliplatin and gemcitabine by applying these agents either single or in combinations on mahlavu cell line.
METHODS: HCC mahlavu cell line was used for the experiments. Cell death was measured by flow cytometry at 48 hrs after incubation with various concentrations (0.1 μg/ml, 1.0 μg/ml and 10 μg/ml) of the drugs.
RESULTS: Cell death due to gemcitabine was found to be significantly higher than cell deaths caused by the other single agents including cisplatin, oxaliplatin, doxorubicin and PLD (p<0.001, p<0.001, p<0.001 and p=0.0049, respectively). There was no significant difference between gemcitabine and both the gemcitabine combination with doxorubicin and PLD (p=0.992 and p=0.441, respectively).
CONCLUSION: This is a preliminary analysis evaluating the effect of the conventional chemotherapeutic agents on mahlavu cell line in vitro. The findings of this study suggest that gemcitabine-based therapies keep on being the prefered therapeutic approach for the treatment of HCC.

Yurtcu E, Darcansoy Iseri O, Iffet Sahin F
Effects of silymarin and silymarin-doxorubicin applications on telomerase activity of human hepatocellular carcinoma cell line HepG2.
J BUON. 2015 Mar-Apr; 20(2):555-61 [PubMed] Related Publications
PURPOSE: Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapeutics such as doxorubicin. Milk thistle extract, or its active constituent silymarin has been used by cancer patients as an alternative and complementary agent. Telomerase activation is one of the initial events of HCC. In this study, we applied doxorubicin and silymarin for 72 hrs in order to test individual and combined effect of the agents on telomerase activity.
METHODS: The effects of doxorubicin, silymarin, and their combination on the proliferation of HepG2 cell line were tested by MTT assay, and Checkerboard micro plate method was applied to define the nature of doxorubicin and silymarin interactions on the cells. Lipid peroxidations were assessed by thiobarbituric acid reactive substance (TBARS) level. Telomerase activity was determined according to the telomeric repeat amplification protocol (TRAP). Untreated cells were used as control group.
RESULTS: Doxorubicin-silymarin combination had indifferent antiproliferative effects on HepG2 cells. Telomerase activity of the cells incubated with IC50 of doxorubicin and silymarin decreased to 72% (p<0.05). IC50 combinations of doxorubicin and silymarin caused 70% (p<0.05) reduction. All treatments except for the 1/2IC50 of silymarin caused significant increase in lipid peroxidation levels when compared to controls. TBARS levels did not significantly increase when doxorubicin and silymarin were applied in combination, which is in concordance with the indifferent drug interaction.
CONCLUSION: IC50 of both doxorubicin and silymarin alone and in combination inhibited telomerase activity. Mechanism of inhibition may be elucidated by further molecular studies.

Bu X, Ge Z, Ma J, et al.
Long-term efficacy of radiofrequency ablation compared to surgical resection for the treatment of small hepatocellular carcinoma.
J BUON. 2015 Mar-Apr; 20(2):548-54 [PubMed] Related Publications
PURPOSE: To compare the clinical efficacy of surgical resection (SR) and radiofrequency ablation (RFA) for the treatment of small hepatocellular carcinoma (SHC; ≥ 5 cm in diameter).
METHODS: The clinical and follow-up data for 88 patients with SHC, including 42 cases of SR and 46 cases of RFA, were analyzed.
RESULTS: The mean follow-up time was 34.36 ± 16.93 (range 6-72) months. The 1-, 3- and 5-year tumor-free survival rates were 85.4, 40.9, and 29.2% for the SR group and 82.6, 27.7, and 16.4% for the RFA group (p=0.51). The mean tumor-free survival for the SR and RFA groups was 32.78 and 29.39 months (p=0.51), respectively. The cumulative survival rates were 100. 63.7, and 50.4% for the SR group and 100, 66.3 and 37.4% for the RFA group (p=0.67). The average survival time was 50.78 and 47.62 months (p=0.67) for the SR and RFA groups, respectively. We divided the tumors into a ≤ 3 cm diameter group and a 3-5 cm diameter group and found that the data for both groups were not statistically different. Cox multivariate analysis indicated that the number of tumors significantly affected overall survival (p=0.02) after the effects of various factors were excluded. The overall tumor-free survival and overall survival of the SR and RFA groups were not statistically different.
CONCLUSIONS: RFA is safe and effective for the treatment of SHC, with a long-term efficacy similar to that achieved by SR. Therefore, RFA is a preferred treatment method for SHC.

Muresan M, Zaharie F, Bojan A, et al.
MicroRNAs in liver malignancies. Basic science applied in surgery.
J BUON. 2015 Mar-Apr; 20(2):361-75 [PubMed] Related Publications
Liver malignancies represent one of the major public health problems worldwide because of late diagnosis and failure of current treatments to offer a curative option for many of the patients. MicroRNAs (miRs) are small non-coding RNA molecules that are known to regulate the gene expression at a post-transcriptional level through complementary base pairing with thousands of messenger (m)RNAs. Recent data has shown the involvement of miRs in the pathogenesis of many human cancers, including those of the liver, with huge possible impact in the clinic, mainly due to the identification of non-coding RNAs as biomarkers that can often be detected in the systemic circulation. In the current review, we present the importance of miRs in liver cancers by discussing their role in the pathobiology of these diseases, apart from their role as diagnostic and prognostic markers for liver malignancies.

Wang X, Wang N, Cheung F, et al.
Chinese medicines for prevention and treatment of human hepatocellular carcinoma: current progress on pharmacological actions and mechanisms.
J Integr Med. 2015; 13(3):142-64 [PubMed] Related Publications
Hepatocellular carcinoma (HCC) is one of leading causes of death in the world. Although various treatments have been developed, the therapeutic side effects are far from desirable. Chinese medicines (CMs, including plants, animal parts and minerals) have drawn a great deal of attention in recent years for their potential in the treatment of HCC. Most studies have shown that CMs may be able to retard HCC progression with multiple actions, either alone or in combination with other conventional therapies to improve quality of life in HCC patients. Additionally, CMs are used for preventing HCC occurrence. The aim of this study is to review the potential prophylactic and curative effects of CMs on human HCC and the possible mechanisms that underlie these pharmacological actions. Publications were collected and reviewed from PubMed and China National Knowledge Infrastructure from 2000 to 2014. Keywords for literature searches include "Chinese medicine", "Chinese herb", "traditional Chinese Medicine", "hepatocellular carcinoma" and "liver cancer". CMs in forms of pure compounds, isolated fractions, and composite formulas are included. Combination therapies are also considered. Both in vitro and in vivo efficacies of CMs are being discussed and the translational potential to bedside is to be discussed with clinical cases, which show the actions of CMs on HCC may include tumor growth inhibition, antimetastatic activities, anti-inflammation, anti-liver cancer stem cells, reversal on multi-drug resistance and induction/reduction of oxidative stress. Multiple types of molecules are found to contribute in the above actions. The review paper indicated that CMs might have potential to both prevent HCC occurrence and retard HCC progression with several molecular targets involved.

Wang Y, Song D, Costanza F, et al.
Targeted delivery of tanshinone IIA-conjugated mPEG-PLGA-PLL-cRGD nanoparticles to hepatocellular carcinoma.
J Biomed Nanotechnol. 2014; 10(11):3244-52 [PubMed] Related Publications
Tanshinone IIA (TSIIA) is an active constituent of the traditional Chinese medicinal plant Salvia miltiorrhiza that is known to have anti-tumor properties. In order to increase the selectivity of TSIIA's anti-tumor activity, the current study evaluated the tumor-targeting efficacy of TSIIA incorporated into nanoparticles (NPs). TSIIA was loaded into mPEG-PLGA-PLL-cRGD (methoxy polyethylene glycol, polylactic-co-glycolic acid, poly-L-lysine, cyclic arginine-glycine-aspartic acid) nanoparticles (TNPs) and used to treat hepatocellular carcinoma in vitro and in vivo. Our data demonstrate that TNPs were stable and had an even size distribution as well as an extended TSIIA releasing time, and improved tumor-targeting activity. As a novel drug carrier system, TNPs significantly inhibited the development of liver cancer both in vitro and in vivo, proving to be a novel promising targeted treatment for liver cancer.

Felker ER, Lee-Felker SA, Ajwichai K, et al.
Intraductal Cooling via a Nasobiliary Tube During Radiofrequency Ablation of Central Liver Tumors Reduces Biliary Injuries.
AJR Am J Roentgenol. 2015; 204(6):1329-35 [PubMed] Related Publications
OBJECTIVE: The objective of our study was to determine the safety and efficacy of intraductal perfusion of chilled 5% dextrose in water (D5W) via an endoscopic nasobiliary tube (NBT) for the prevention of thermal bile duct injury in patients undergoing percutaneous radiofrequency ablation (RFA) of central liver tumors.
MATERIALS AND METHODS: We performed a retrospective study comparing outcomes of 32 consecutive patients who underwent percutaneous RFA of central liver tumors without intraductal perfusion of chilled D5W (control cohort) and 14 consecutive patients who underwent temporary intraductal perfusion of chilled D5W at 2 mL/s via endoscopic NBT placement before RFA (endoscopic NBT cohort). The primary and secondary outcomes were the rate of biliary complications and local tumor progression, respectively.
RESULTS: All patients tolerated the procedures well. There was a significantly lower rate of biliary complications in the endoscopic NBT cohort (0/14 patients, 0%) than in the control cohort (10/32 patients, 31%) (p < 0.03) with a trend toward improved preservation of liver function in the endoscopic NBT cohort (12/14 patients, 86%) compared with the control cohort (20/32 patients, 62%) (p = 0.05). There was no difference in the rate of local tumor progression between the endoscopic NBT cohort (4/19 tumors, 21%) and the control cohort (9/39 tumors, 23%) (p = 1.0).
CONCLUSION: Perfusion of chilled water through an endoscopic NBT helps prevent thermal biliary injury during RFA of central liver tumors without increasing rates of local tumor progression.

Zu QQ, Liu S, Zhou CG, et al.
Chemoembolization of recurrent hepatoma after curative resection: prognostic factors.
AJR Am J Roentgenol. 2015; 204(6):1322-8 [PubMed] Related Publications
OBJECTIVE: The long-term prognosis after hepatic resection for the treatment of hepatocellular carcinoma (HCC) has been disappointing because of the high recurrence rates in the remnant liver, which constitutes the major cause of death. The purpose of this study was to identify the prognostic factors for overall survival after transarterial chemoembolization (TACE) in recurrent HCC after the initial curative surgical resection.
MATERIALS AND METHODS: From January 2003 through October 2012, 362 patients who developed recurrent HCC after initial surgical resection and underwent TACE as the first-line therapy were retrospectively studied at a single institution in our hospital. Patients who met our inclusion criteria were followed until December 2012. Prognostic factors for overall survival were analyzed.
RESULTS: In total, 287 patients were enrolled. The median overall survival period was 747 days. The 1-, 2-, and 3-year overall survival rates after TACE were 72.9%, 51.8%, and 31.8%, respectively. Multivariate analysis indicated that the number of resected HCCs (≥ 2, p < 0.001), the number (≥ 2, p < 0.001) and size (> 5 cm, p = 0.022) of the recurrent HCCs, and the number of TACE sessions (≤ 3, p < 0.001) are independent risk factors for poor survival after TACE for recurrent HCC after HCC resection.
CONCLUSION: TACE appears to be an effective treatment of patients who experienced a recurrence after curative HCC resection. An initial solitary HCC, a solitary recurrence, and recurrent tumor mass 5 cm or smaller are statistically significant independent prognostic factors for survival.

Lv Y, Liang R, Hu X, et al.
Combination of oxaliplatin and S-1 versus sorafenib alone in patients with advanced hepatocellular carcinoma.
Pharmazie. 2014; 69(10):759-63 [PubMed] Related Publications
Sorafenib and conventional systemic cytotoxicity chemotherapy are currently being used in parallel for the patients with advanced hepatocellular carcinoma (HCC). While sorafenib has been proven to improve the prognosis in patients with this malignant disease, however, the outcome of other newly developed systemic chemotherapeutic regimens remains controversial. We evaluated the outcome and safety of patients treated with the SOX regimen (oxaliplatin + S-1) and those treated with sorafenib in a single-center cohort. This retrospective study involved a total of 46 patients with advanced HCC, 22 of which were treated with SOX regimen (oxaliplatin [130 mg/m2] on day 1 and S-1 [80 mg/m2/day] on day 1-14, every 3 weeks), and 24 were daily treated with sorafenib (400 mg, b.i.d.). The median progression-free survival was 3.6 months (95% confidence interval [CI], 1.7 to 5.6) with SOX and 1.7 months (95% CI, 1.5 to 1.9) with sorafenib, respectively (P = 0.444). The median overall survival in SOX and sorafenib group was 7.6 months (95% CI, 4.3 to 10.9) and 4.7 months (95% CI, 2.7 to 7.3), respectively (P = 0.246). Response rate was 22.2% with SOX and 5.6% with sorafenib, respectively (P = 0.154). The frequent side effects in SOX-treated patients were thrombocytopenia, elevation of transaminase levels and neuropathy, whereas hand-foot syndrome, diarrhea and pruritus were common in sorafenib-treated patients. These preliminary results suggest that the SOX regimen may serve as an effective treatment for patients with advanced HCC, and the treatment-related toxicities were generally well-tolerated.

Chou R, Cuevas C, Fu R, et al.
Imaging Techniques for the Diagnosis of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.
Ann Intern Med. 2015; 162(10):697-711 [PubMed] Related Publications
BACKGROUND: Several imaging modalities are available for diagnosis of hepatocellular carcinoma (HCC).
PURPOSE: To evaluate the test performance of imaging modalities for HCC.
DATA SOURCES: MEDLINE (1998 to December 2014), the Cochrane Library Database, Scopus, and reference lists.
STUDY SELECTION: Studies on test performance of ultrasonography, computed tomography (CT), or magnetic resonance imaging (MRI).
DATA EXTRACTION: One investigator abstracted data, and a second investigator confirmed them; 2 investigators independently assessed study quality and strength of evidence.
DATA SYNTHESIS: Few studies have evaluated imaging for HCC in surveillance settings. In nonsurveillance settings, sensitivity for detection of HCC lesions was lower for ultrasonography without contrast than for CT or MRI (pooled difference based on direct comparisons, 0.11 to 0.22), and MRI was associated with higher sensitivity than CT (pooled difference, 0.09 [95% CI, 0.07 to 12]). For evaluation of focal liver lesions, there were no clear differences in sensitivity among ultrasonography with contrast, CT, and MRI. Specificity was generally 0.85 or higher across imaging modalities, but this item was not reported in many studies. Factors associated with lower sensitivity included use of an explanted liver reference standard, and smaller or more well-differentiated HCC lesions. For MRI, sensitivity was slightly higher for hepatic-specific than nonspecific contrast agents.
LIMITATIONS: Only English-language articles were included, there was statistical heterogeneity in pooled analyses, and costs were not assessed. Most studies were conducted in Asia and had methodological limitations.
CONCLUSION: CT and MRI are associated with higher sensitivity than ultrasonography without contrast for detection of HCC; sensitivity was higher for MRI than CT. For evaluation of focal liver lesions, the sensitivities of ultrasonography with contrast, CT, and MRI for HCC are similar.
PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (
PROSPERO: CRD42014007016).

Chaouki W, Meddah B, Hmamouchi M
Antiproliferative and apoptotic potential of Daphne gnidium L. root extract on lung cancer and hepatoma cells.
Pharmazie. 2015; 70(3):205-10 [PubMed] Related Publications
Daphne gnidium L. (Thymeleacees) is a famous Moroccan plant with cancer-related ethnobotanical use. Previously, we demonstrated that ethyl acetate extract of D. gnidium had antiproliferative and pro-apoptotic potential on human breast tumor MCF-7 cells. The purpose of this study was to investigate if the antiproliferative effect of this extract was similar for different human cancer cell lines such as A549 lung cancer and SMMC-7721 hepatoma cells. Moreover, this work essentially focused on the intrinsic apoptotic signaling pathway. Antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide on A549 and SMMC-7721 cells. The characterization of the mechanisms involved in this effect was determined by lactate dehydrogenase test, apoptosis assays and western blot analyses. Our present study has shown that this extract strongly inhibited proliferation of A549 (IC50: 213 ± 15 μg/ml) and SMMC-7721 (IC50: 170 ± 13 μLg/ml) cells. The characterization of antiproliferative effect demonstrated that this extract was an apoptosis inducer in both cell lines tested. The results of western blot analyses have shown in SMMC-7721 cells that this extract activated caspase signaling triggered by the modulation of Bcl-2 family proteins. These findings suggest that this natural extract-induced effects may have novel therapeutic applications for the treatment of different cancer types.

Jarraya H, Borde P, Mirabel X, et al.
Lobulated enhancement evaluation in the follow-up of liver metastases treated by stereotactic body radiation therapy.
Int J Radiat Oncol Biol Phys. 2015; 92(2):292-8 [PubMed] Related Publications
OBJECTIVE: The Response Evaluation Criteria in Solid Tumors (RECIST) can have limitations when used to evaluate local treatments for cancer, especially for liver malignancies treated by stereotactic body radiation therapy (SBRT). The aim of this study was to validate the relationship between the occurrence of lobulated enhancement (LE) and local relapse and to evaluate the utility of this relationship for predicting local progression.
PATIENTS AND METHODS: Imaging data of 59 lesions in 46 patients, including 281 computed tomographic (CT) scans, were retrospectively and blindly reviewed by 3 radiologists. One radiologist measured the lesion size, for each CT and overall, to classify responses using RECIST threshold criteria. The second studied LE occurrence. A third radiologist was later included and studied LE occurrence to evaluate the interobserver consistency for LE evaluation.
RESULTS: The mean duration of follow-up was 13.6 months. LE was observed in 16 of 18 progressive lesions, occurring before size-based progression in 50% of cases, and the median delay of LE detection was 3.2 months. The sensitivity of LE to predict progression was 89%, and its specificity was 100%. The positive predictive value was 100%, the negative predictive value was 95.3%, and the overall accuracy was 97%. The probability of local progression-free survival at 12 months was significantly higher for lesions without LE compared with all lesions: 0.80 (CI 95%: 0.65-0.89) versus 0.69 (CI 95%: 0.54-0.80), respectively. The overall concordance rate between the 2 readers of LE was 97.9%.
CONCLUSION: Response assessment of liver metastases treated by SBRT can be improved by including LE. This study demonstrates the diagnostic and predictive utility of LE for assessing local progression at a size still eligible for local salvage treatment.

Techathuvanan K, Srisajjakul S, Pongpaibul A, et al.
Comparison between disease free survival of hepatocellular carcinoma after hepatic resection in chronic hepatitis B patients with or without cirrhosis.
J Med Assoc Thai. 2015; 98(4):334-42 [PubMed] Related Publications
BACKGROUND: Hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients can develop in those with cirrhotic and non-cirrhotic liver Not only impairment of liver status, but also the extension of tumor and difference of pathogenesis may also affect characteristics of patient and tumor including survival and recurrence.
OBJECTIVE: To evaluate the disease free survival, prognostic factors and features of HCC after hepatic resection in CHB patients with and without cirrhosis.
MATERIAL AND METHOD: Two hundred fifteen HBV-related HCC patients underwent hepatic resection and were analyzed. Cirrhotic and non-cirrhotic groups were compared for differences inpatient and tumor characteristics, disease-free survival including prognostic factors.
RESULTS: In comparison with cirrhotic patients, non-cirrhotic patients had more family history of HCC, more preserved liver function, were less HBeAg positive, and had lower HBV viral load. HCC characteristics in non-cirrhotic groups showed significantly larger (5.8 ± 3.7 vs. 4.9 ± 3.9 cm, p = 0.036) and operative data revealed that non-cirrhotic patients underwent more major surgery (50.7 vs. 18.3%, p < 0.001), and had shorter hospital stay (10.8 ± 8.9 vs. 8.1 ± 4.3 days, p = 0.006) than cirrhotic ones. Operative time, blood loss and requirement of PRC transfusion were similar in both groups. Pathological profiles of HCC and liver parenchyma were comparable in both cirrhotic and non-cirrhotic patients. The disease-free survival of non-cirrhotic patients was longer than cirrhotic patients (Median disease free survival were 21 and 11 months respectively, p = 0.022). The independent predictive factor of lower disease-free survival of non-cirrhotic CHB patients who underwent hepatic resection was lymph node involvement (Hazard ratio (HR), 4.598. 95% confidence interval (CI), 1.1-19.212; p = 0.037) while of cirrhotic patients, factors were age > 50 years old (HR, 2.998; 95% CI, 1.298-6.925; p = 0.01), multifocal tumor (HR, 5.835; 95% CI, 1.122-30.342; p = 0.036) andportal vein involvement (HR, 3.722; 95% CI, 1.121-12.353; p = 0.032). HBV treatment after HCC diagnosis was a significant predictor in the cirrhotic group by univariate analysis (p = 0.04).
CONCLUSION: Imaging and histological findings of HCC in cirrhotic and non-cirrhotic CHB patients were not different, except for larger tumor size in non-cirrhotic patients. Lymph node involvement is the predictor of HCC recurrence in non- cirrhotic CHB patients. Age > 50 year old and multifocal tumor and portal vein involvement are the predictors of HCC recurrence in cirrhotic CHB patients. These groups may need surveillance that is more intensive after hepatic resection. Antiviral therapy may lower the risk of HCC recurrence among CHB cirrhotic patients.

Li J, Lei B, Nie X, et al.
A comprehensive method for predicting fatal liver failure of patients with liver cancer resection.
Medicine (Baltimore). 2015; 94(17):e784 [PubMed] Related Publications
There are many methods to assess liver function, but none of them has been verified as fully effective. The purpose of this study is to establish a comprehensive method evaluating perioperative liver reserve function (LRF) in patients with primary liver cancer (PLC).In this study, 310 PLC patients who underwent liver resection were included. The cohort was divided into a training set (n = 235) and a validation set (n = 75). The factors affecting postoperative liver dysfunction (POLD) during preoperative, intraoperative, and postoperative periods were confirmed by logistic regression analysis. The equation for calculating the preoperative liver functional evaluation index (PLFEI) was established; the cutoff value of PLFEI determined through analysis by receiver-operating characteristic curve was used to predict postoperative liver function.The data showed that body mass index, international normalized ratio, indocyanine green (ICG) retention rate at 15 minutes (ICGR15), ICG elimination rate, standard remnant liver volume (SRLV), operative bleeding volume (OBV), blood transfusion volume, and operative time were statistically different (all P < 0.05) between 2 groups of patients with and without POLD. The relationship among PLFEI, ICGR15, OBV, and SRLV is expressed as an equation of "PLFEI = 0.181 × ICGR15 + 0.001 × OBV - 0.008 × SRLV." The cutoff value of PLFEI to predict POLD was -2.16 whose sensitivity and specificity were 90.3% and 73.5%, respectively. However, when predicting fatal liver failure (FLF), the cutoff value of PLFEI was switched to -1.97 whose sensitivity and specificity were 100% and 68.8%, respectively.PLFEI will be a more comprehensive, sensitive, and accurate index assessing perioperative LRF in liver cancer patients who receive liver resection. And keeping PLFEI <-1.97 is a safety margin for preventing FLF in PLC patients who underwent liver resection.

Kato T, Uehara K, Maeda A, et al.
Phase II multicenter study of adjuvant S-1 for colorectal liver metastasis: survival analysis of N-SOG 01 trial.
Cancer Chemother Pharmacol. 2015; 75(6):1281-8 [PubMed] Related Publications
PURPOSE: We previously showed that S-1 after curative resection of colorectal liver metastasis had acceptable toxicity and a high rate of completion of therapy in a prospective phase II trial. We here reported the primary endpoint of disease-free survival (DFS).
METHODS: Between October 2008 and August 2010, 60 patients were eligible for this study and received S-1 for 28 days followed by a 2-week rest period. Treatment was started within 8 weeks after surgery and repeated for eight cycles.
RESULTS: Median follow-up was 41 months. Among 60 patients, 45 had solitary metastasis, and the median maximum tumor diameter was 2.6 cm. The 3-year DFS and overall survival were 47.4 and 80.0 %, respectively. Recurrences developed in 31 patients, with the remnant liver the most common site (19 patients). Multivariate analysis showed that positive lymph node metastasis around the primary site (p = 0.013) and early liver metastasis (synchronous disease or metachronous disease within 12 months) (p = 0.041) were independent poor prognostic factors for DFS. Patients having both risk factors had a significantly worse DFS than those without these risk factors (p < 0.001). Early liver metastasis was an independent indicator of early recurrence within 1 year.
CONCLUSIONS: S-1 after curative liver resection yielded promising survival in patients with a low tumor burden. Outcome in patients having both positive lymph node metastasis around the primary site and early liver metastasis was much worse than in patients without these conditions; therefore, they might warrant more aggressive therapy.

Nabet BY, Minn AJ
Linking primary and metastatic tumour re-initiation.
Nat Cell Biol. 2015; 17(5):542-3 [PubMed] Related Publications
Whether the cancer cells responsible for the growth of primary tumours are also able to re-initiate tumour growth after seeding to distant organs is unclear. The characterization of breast cancer cells with both of these attributes now identifies the functional and molecular determinants necessary to mediate primary tumour formation and re-initiation at the secondary site.

Amankwatia EB, Chakravarty P, Carey FA, et al.
MicroRNA-224 is associated with colorectal cancer progression and response to 5-fluorouracil-based chemotherapy by KRAS-dependent and -independent mechanisms.
Br J Cancer. 2015; 112(9):1480-90 [PubMed] Article available free on PMC after 28/04/2016 Related Publications
BACKGROUND: Colorectal cancers arise from benign adenomas, although not all adenomas progress to cancer and there are marked interpatient differences in disease progression. We have previously associated KRAS mutations with disease progression and reduced survival in colorectal cancer patients.
METHODS: We used TaqMan low-density array (TLDA) qRT-PCR analysis to identify miRNAs differentially expressed in normal colorectal mucosa, adenomas and cancers and in isogeneic KRAS WT and mutant HCT116 cells, and used a variety of phenotypic assays to assess the influence of miRNA expression on KRAS activity, chemosensitivity, proliferation and invasion.
RESULTS: MicroRNA-224 was differentially expressed in dysplastic colorectal disease and in isogeneic KRAS WT and mutant HCT116 cells. Antagomir-mediated miR-224 silencing in HCT116 KRAS WT cells phenocopied KRAS mutation, increased KRAS activity and ERK and AKT phosphorylation. 5-FU chemosensitivity was significantly increased in miR-224 knockdown cells, and in NIH3T3 cells expressing KRAS and BRAF mutant proteins. Bioinformatics analysis of predicted miR-224 target genes predicted altered cell proliferation, invasion and epithelial-mesenchymal transition (EMT) phenotypes that were experimentally confirmed in miR-224 knockdown cells.
CONCLUSIONS: We describe a novel mechanism of KRAS regulation, and highlight the clinical utility of colorectal cancer-specific miRNAs as disease progression or clinical response biomarkers.

Kim JM, Kwon CH, Joh JW, et al.
Intrahepatic metastasis is more risky than multiple occurrence in hepatocellular carcinoma patients after curative liver resection.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):399-404 [PubMed] Related Publications
BACKGROUND/AIMS: The characteristics of multiple nudules in hepatocellular carcinomas (HCCs) after curative liver resection remain obscure. We compare the clinicopathologic characteristics and prognoses between patients with hepatic lesions with multicentric occurrence (MO) and intrahepatic metastasis (IM) at the time of surgical resection.
METHODOLOGY: The histopathologic features of multiple tumors from 198 patients of HCC were analyzed and divided into MO group (n = 51, 25.8%) for multicentric HCCs and an IM group (n = 147, 74.2%) in cases with intrahepatic metastases. Overall survival rate, disease-free survival and clinicopathologic differences were compared between the two groups.
RESULTS: Microvascular invasion and increased tumor size were the most important factors discriminating the IM group from the MO group (P < 0.001 and P = 0.027, respectively). Kaplan-Meier and log rank tests revealed that disease-free survival and overall survival rates in the MO group were significantly higher than those for the IM group (P < 0.001 and P < 0.001, respectively). A multivariate analysis of Cox's proportional hazards model showed that increased alpha-fetoprotein (AFP) and protein induced by vitamin K antagonist-II (PIVKA-II) levels, portal vein invasion and intrahepatic metastases were the most important prognostic factors.
CONCLUSIONS: Among HCCs, the prognosis of patients with MO is significantly better than that of patients with IM.

Yamada N, Amano R, Kimura K, et al.
Two-surgeon technique for liver transection using precoagulation by a soft-coagulation system and ultrasonic dissection.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):389-92 [PubMed] Related Publications
BACKGROUND/AIMS: A soft-coagulation system (SCS) was introduced as an effective device to reduce blood loss in hepatectomy. Here we evaluated the efficacy of a two-surgeon technique using precoagulation by an SCS and the Cavitron Ultrasonic Surgical Aspirator (CUSA) for liver transection.
METHODOLOGY: The 163 patients with liver tumors were divided into two groups (conventional group and two-surgeon group). Liver transection was conducted using saline-coupled bipolar electrocautery and CUSA in 102 patients (conventional group). In 61 patients (the two-surgeon group), a two-surgeon technique using precoagulation by an SCS and CUSA for liver resection was performed.
RESULTS: The median blood loss was significantly less in the two-surgeon group compared to the conventional group (354.8 mL vs. 557.8 mL, respec tively: p = 0.0011). The postoperative hospital stay was significantly shorter in the two-surgeon group compared to the conventional group (12.7 days vs. 15.5 days, p = 0.0035).
CONCLUSIONS: The two-surgeon technique using precoagulation by an SCS and CUSA was significantly reduced blood loss during liver transection, and associated with low morbidity and mortality. This technique may be useful for many hepatobiliary surgeons.

Baek YH, Lee SW, Jeong YJ, et al.
Tumor-to-muscle ratio of 8F-FDG PET for predicting histologic features and recurrence of HCC.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):383-8 [PubMed] Related Publications
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) recurrence is observed in up to 70-80% of patients despite a curative treatment. Microvascular invasion (MVI) and poor differentiation are strong risk factors for recurrence, but these cannot be known preoperatively. The aim of this study was to investigate the correlation of 18F-FDG PET with MVI and differentiation, and predictive role of tumor-to-background ratio of PET for recurrence in HCC.
METHODOLOGY: Fifty-four patients had 18F-FDG PET/CT study before surgical resection as a first treatment of HCC between December 2008 and December 2012. We analyzed the predictive role of metabolic parameters of PET for recurrence of HCC. Maximal standardized uptake value, tumor-to-nontumor ratio, tumor-to-muscle ratio (TMR) and tumor-to-blood ratio were tested as metabolic index of 18F-FDG PET.
RESULTS: Twenty-seven patients had increased uptake in preoperative PET and 14 (51.9%) of them experienced the recurrence. Increased uptake in PET and TMR were associated with MVI (p = 0.04, p = 0.005) and histologic differentiation (p = 0.018, p = 0.002). MVI was the only predictive factor for re- currence in multivariate analysis although TMR ≥ 6.36 showed a favorable result despite no statistical significance (p = 0.061).
CONCLUSIONS: Increased 18F-FDG uptake of HCC, especially high TMR might be correlated with MVI and poor differentiation, and tends to have a risk for recurrence in HCC.

Wang D, Tan J, Xu Y, et al.
Identification of MicroRNAs and target genes involvement in hepatocellular carcinoma with microarray data.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):378-82 [PubMed] Related Publications
The aim of the study is to identify the differentially expressed microRNAs (miRNAs) between hepatocellular carcinoma (HCC) samples and controls and provide new diagnostic potential miRNAs for HCC. The miRNAs expression profile data GSE20077 included 7 HCC samples, 1 HeLa sample and 3 controls. Differentially expressed miRNAs (DE-miRNAs) were identified by t-test and wilcox test. The miRNA with significantly differential expression was chosen for further analysis. Target genes for this miRNA were selected using TargetScan and miRbase database. STRING software was applied to construct the target genes interaction network and topology analysis was carried out to identify the hub gene in the network. And we identified the mechanism for affecting miRNA function. A total of 54 differentially expressed miRNAs were identified, in which there were 13 miRNAs published to be related to HCC. The differentially expressed hsa-miR-106b was chosen for further analysis and PTPRT (Receptor-type tyrosine-protein phosphatase T) was its potential target gene. The target genes interaction network was constructed among 33 genes, in which PTPRT was the hub gene. We got the conclusion that the differentially expressed hsa-miR-106b may play an important role in the development of HCC by regulating the expression of its potential target gene PT-PRT.

Bai H, Huangz X, Jing L, et al.
The effect of radiofrequency ablation vs. liver resection on survival outcome of colorectal liver metastases (CRLM): a meta-analysis.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):373-7 [PubMed] Related Publications
BACKGROUND/AIMS: For patients with solitary colorectal liver metastasis (CRLM), it is still controversial whether radiofrequency ablation (RFA) has the same effect as liver resection (LR). This study aims to pool available evidence and to analyze the effect of RFA versus LR for resectable solitary CRLM in sur- vival indicators.
METHODOLOGY: Relevant studies were searched among databases and a meta-analysis was performed to pool the hazard ratio (HR) of RFA versus LR in overall survival (OS) and disease free survival (DFS).
RESULTS: A total of 10 studies were included in this meta-analysis. Pooled results showed poorer OS (HR: 1.85, 95% CI: 1.48 to 2.32, p < 0.00001) and DFS (HR: 1.68, 95% CI: 1.14 to 2.48, p = 0.009) among the patient received RFA compared those received LR. Sensitivity analysis confirmed high robustness of the findings.
CONCLUSION: In patients with resectable CRLM, LR is superior to RFA in survival outcomes. RFA should be reserved for patients who are not optimal candidates for resection until new supportive evidence is obtained from large RCTs.

Yamamoto T, Yagi S, Kita R, et al.
Comparison between anatomical subsegmentectomy and nonanatomical partial resection for hepatocellular carcinoma located within a single subsegment: a single-center retrospective analysis.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):363-7 [PubMed] Related Publications
BACKGROUND/AIMS: For hepatocellular carcinoma (HCC) within a single subsegment, the superiority of anatomical subsegmentectomy over non-anatomical partial resection is still controversial. In this study, we assessed the potential benefit of subsegmentectomy.
METHODOLOGY: We selected 44 patients with a single HCC lesion within one subsegment who had undergone anatomical subsegmentectomy or non-anatomical partial resection from among 173 patients who underwent hepatectomy in our hospital from August 2003 to May 2013. We compared the results following anatomical subsegmentectomy (Group A; n = 16) and non-anatomical partial resection (Group N; n = 28).
RESULTS: One- and two-year survival rates were 92.5% and 89.3%, respectively; 1- and 2-year recurrence-free survival (RFS) rates were 88.9% and 69.1%, respectively. There was no significant difference in overall survival or RFS between the groups. However, among HBV-positive patients, RFS was significantly better for Group A than Group N (p = 0.008).
CONCLUSIONS: For HBV-positive HCC within a single subsegment, we recommend subsegmentectomy.

Bacalbaşa N, Popescu I
Ovarian cancer liver metastases--should we apply the principle of optimal cytoreduction to the liver? A review.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):355-7 [PubMed] Related Publications
Advanced stage ovarian cancer is a common situation at presentation and current medical practice lacks efficient methods of prevention and early diagnosis. Primary maximal cytoreductive surgery followed by adjuvant chemotherapy is currently a generally accepted principle; most patients however undergo recurrence and common therapeutical attitude is secondary cytoreduction based approximately on the same principles as the primary one. Due to the success of liver resections in colorectal metastases and the development of liver surgery in general, different centers worldwide analyzed in the last 20 years liver resections' utility for other primaries, including ovarian tumors.

Sinn DH, Yi J, Choi MS, et al.
Serum alpha-fetoprotein may have a significant role in the surveillance of hepatocellular carcinoma in hepatitis B endemic areas.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):327-32 [PubMed] Related Publications
BACKGROUND/AIMS: The role of serum alpha-fetoprotein (AFP) determination in hepatocellular carcinoma (HCC) surveillance is controversial.
METHODS: We reviewed a total of 132 patients (mean age 57.8 ± 9.6, males = 101 (76%); HBsAg positive = 109 (82.6%); cirrhosis = 94 (71.2%)) who were diagnosed with HCC during regular surveillance test with ultrasound (US) and AFP.
RESULTS: The primary mode of tumor detection was US only in 51.5%, US and AFP in 22.0%, AFP only in 19.7%, and incidental in 6.8% of patients. US detected 68.5% of tumor diagnosed at early stage, which was significantly lower than tumor beyond-early stage (85.0%, p = 0.048). AFP doubling (an increase in AFP level more than double from a prior surveillance) was more frequently observed in HBV-related HCC (47.7%) than HCV-related HCC (11.8%, p = 0.009). The AFP increased sensitivity by 19.7% for all patients; 28.0% for HBV-related early stage HCC patients.
CONCLUSIONS: This result suggest that serum AFP measurements may have a significant role in increasing sensitivity in HCC surveillance, especially for detecting early stage HBV-related HCC.

Katayose Y, Yamamoto K, Nakagawal K, et al.
Feasibility Assessment of Modified FOLFOX-6 as adjuvant treatment after resection of liver metastases from colorectal cancer: analyses of a multicenter phase II clinical trial (Miyagi-HBPCOG Trial-001).
Hepatogastroenterology. 2015 Mar-Apr; 62(138):303-8 [PubMed] Related Publications
BACKGROUND/AIMS: This multicenter and single arm phase II clinical trial was performed to examine the safety and efficacy of modified FOLFOX6 (mFOLFOX6) as adjuvant treatment after resection of liver metastases from colorectal cancer.
METHODOLOGY: Patients who had undergone R0-1 resection of liver metastases were assigned to 12 cycles of mFOLFOX6. The primary end point was disease-free survival (DFS).
RESULTS: We enrolled 49 cases and analyzed adverse events in 48 cases, since in one patient cancer recurred before starting treatment. As to the relative dose intensity, 5-FU was 78.8%, and oxaliplatin was 75.9%. Adverse events of Grade 3 and above includ- ed 18 cases of neutropenia (37.5%), 4 cases of sensory neuropathy (8.3%), 4 cases of thrombocytopenia (8.3%) and 4 cases of allergy (8.3%), and there were no cases of fatality caused by adverse events. The most difference of adverse event compared with MOSAIC trial (Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer) was thrombocytopenia. The 2-year DFS was 59.2% (95% CI: 36.7-78.4) in the 49 enrolled cases.
CONCLUSION: mFOLFOX6 after hepatectomy was tolerable. And mFOLFOX6 also seemed to improve DFS. mFOLFOX is one of the options for such patients and appears promising as an adjuvant treatment.

de Stefano G, Farella N, Scognamiglio U, et al.
Sorafenib after RFA in HCC patients: a pilot study.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):261-3 [PubMed] Related Publications
BACKGROUND/AIMS: To investigate the effectiveness and safety of sorafenib after radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC).
METHODOLOGY: 44 intermediate or advanced HCC patients received sorafenib treatment after debulking with RFA therapy. Time to progression (TTP), response rate (RR), duration of sorafenib treatment and adverse effects were evaluated. An explorative comparison was performed with patients treated with sorafenib only.
RESULTS: At 12 months, TTP was 10.3 months (range: 1-32). RR was 61% with 2 complete responses, and duration of sorafenib therapy was 10.9 months (1-32). No new safety concerns were report-ed. With sorafenib only, TTP was 7.2 months (range: 0-38) and RR was 40%, with one complete response; duration of therapy was 7.3 months (0-38).
CONCLUSIONS: The sequence of RFA and sorafenib appears effective and safe in HCC patients. These findings could support the use of a sequential treatment with RFA and sorafenib in HCC patients.

Ma N, Chen F, Shen SL, et al.
MicroRNA-129-5p inhibits hepatocellular carcinoma cell metastasis and invasion via targeting ETS1.
Biochem Biophys Res Commun. 2015; 461(4):618-23 [PubMed] Related Publications
MiR-129-5p is deregulated in various human cancers and has been associated with hepatocellular carcinoma (HCC) progression. However, the underlying mechanisms of miR-129-5p involvement in the development and progression of HCC and the effects of miR-129-5p deregulation on the clinical characteristics observed in HCC patients remain poorly understood. We therefore investigated the correlation between low miR-129-5p expression and vascular invasion, intrahepatic metastasis, and poor patient survival. Ectopic restoration of miR-129-5p expression in HCC cells suppressed cellular migration and invasion and the expression of v-ets erythroblastosis virus E26 oncogene homolog 1 (ETS1), while inhibition of endogenous miR-129-5p caused an increase in these parameters. We identified the ETS1 gene as a novel direct target of miR-129-5p. SiRNA-mediated ETS1 knockdown rescued the effects of anti-miR-129-5p inhibitor in HCC cell lines, while the effects of miR-129-5p overexpression were partially phenocopied in the knockdown model. In addition, miR-129-5p levels inversely correlated with those of ETS1 in HCC cells and tissues. Taken together, our findings indicate an important role for miR-129-5p in the molecular etiology of invasive HCC and suggest that miR-129-5p could have potential therapeutic applications in HCC.

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