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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]

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    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.

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.

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.

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.

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.

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.

Hirokawa F, Hayashi M, Miyamoto Y, et al.
Predictors of poor prognosis by recurrence patterns after curative hepatectomy for hepatocellular carcinoma in Child-Pugh classification A.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):164-8 [PubMed] Related Publications
BACKGROUND/AIMS: The prevention of recurrence is important for improving long-term outcome for HCC. To identify candidates for postoperative adjuvant therapy after curative hepatectomy for HCC in Child-Pugh classification A (Child A).
METHODOLOGY: Of 157 patients who underwent initial hepatectomy for Child A HCC, 93 had recurrence and were divided into 2 groups: group A, ≤2 tumors, each <3 cm in size at the time of intrahepatic recurrence; group B, ≥3 tumors or tumor ≥3 cm in size at the time of intrahepatic recurrence and/or extrahepatic recurrence. Clinicopathological and survival data were analyzed retrospectively in each group to identify poor prognostic factors.
RESULTS: The 1-year recurrence rate was 50%, and the time to recurrence was shorter in group B (10 months) than in group A (20 months) Overall 1-, 3-, and 5-year survival rates were poorer in group B (83%, 52%, and 35% respectively; p < 0.001) than in group A (100%, 96%, and 71% respectively) Cancer spread (vascular invasion and/or intrahepatic metastasis) was significantly affecting the recurrence pattern of Group B (p=0.0238) on multivariate analysis.
CONCLUSIONS: Systemic adjuvant chemotherapy af ter curative hepatectomy for HCC in Child A should be given to patients with microscopic vascular invasion and/or intrahepatic metastasis.

Tsujita E, Maeda T, Kayashima H, et al.
Effect of sustained virological response to interferon therapy for hepatitis C to the hepatectomy for primary hepatocellular carcinoma.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):157-63 [PubMed] Related Publications
BACKGROUND/AIMS: Interferon (IFN) therapy improves the prognosis of the patients with HCV-related hepatocellular carcinoma (HCC). However, the effects of IFN therapy for hepatectomy (Hx) for primary HCC have not been established. Several published reports investigating the effects of IFN therapy on survival and tumor recurrence after curative resection of HCC have been inconclusive.
METHODOLOGY: Subjects included 470 patients who underwent Hx for HCV related primary HCC. One hundred and fifty nine patients received IFN therapy past or postoperatively of the first Hx. Seventy-four of those patients attained a sustained viral response (SVR group). The other 396 patients, including 85 were no responders (NR) and 311 patients who had not received IFN therapy (non-IFN) were classified as the control group.
RESULTS: Overall survival (SVR group vs. control group: 5-yr, 93.2 vs. 61.9%; p<0.0001) and disease-free survival (SVR group vs. control group: 5-yr, 56.0 vs. 27.4%; p<0.0001) rates were significantly different. By multivariate analysis, NR/non-IFN was the independent risk factor for overall survival (p=0.0002) and disease-free survival (p=0.0053) after Hx.
CONCLUSIONS: SVR achieved past or postoperatively to the Hx of HCV-related HCC significantly inhibits recurrence and consequently improves patient survival after Hx for HCC.

Wang XB, Yu QM, Yu PF, et al.
Surgical treatment of huge hepatocarcinoma with invasion or severe adhesion of diaphragm using the technique of orthotopic liver resection.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):153-6 [PubMed] Related Publications
BACKGROUND/AIMS: To explore the clinical application and significance of the technique of orthotopic liver resection.
METHODOLOGY: From January 2004 to December 2011, five patients with huge hepatocellular carcinoma with invasion or severe adhesion of diaphragm were undergone right semi-liver resection using the technique of orthotopic liver resection. The right hemi-liver was isolated from the first liver portal, second liver portal and third liver portal, then isolated from the normal liver, finally the tumor and the invaded diaphragm were resected or removed from the severe adhesion. The approach to hepatic resection involved routine use of Peng's multifunctional operative dissector, selective control of in and out-flow of liver, control of inferior vena cava (IVC) and liver hanging maneuver, anterior approach, etc.
RESULTS: The operations were successfully performed in 5 patients. Operative time was 120, 180, 150, 150 and 160 min, respectively. The amount of blood loss were 350, 350, 400, 450, 600 ml, respectively. Postoperative complications were pleural effusion in 3 cases, and other 2 cases recovered without complications.
CONCLUSIONS: Although the technique of orthotopic liver resection has a high technical requirement for surgeons, it provides a surgical method and operative opportunity for the patients whose tumor has invaded diaphragm or has been severe adhesion with diaphragm and conventional liver resection cannot be performed.

Chen L, Wang K, Chen Z, et al.
High intensity focused ultrasound ablation for patients with inoperable liver cancer.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):140-3 [PubMed] Related Publications
BACKGROUND/AIMS: To analyses the feasibility and efficacy of high intensity focused ultrasound (HIFU) treatment in patients with inoperable liver cancer.
METHODOLOGY: 187 patients were treated with HIFU, of all these patients 116 cases were Primary Liver Cancer (PLC) and 71 cases were Metastatic Liver Cancer (MLC). According to some parameters, such as clinical symptoms, the basis of main organs functional tests, imaging examinations, and progression-free survival (PFS) time to assess the safety and efficacy of HIFU in the treatment of liver cancer.
RESULTS: 55 patients (29.4%) achieved CR and 73 patients (39.0%) achieved PR, 32 patients (17.1%) had responses of SD, and 27 patients (14.4%) were PD, respectively. Response rates were 90.5% (32 CR + 6 PR/42) in left lobe cancer and 64.1% (22 CR + 62 PR/131) in right lobe cancer. The median PFS for those CR case was 7 months, of PLC was 8 months, of MLC was 5 months.
CONCLUSIONS: HIFU is effective and feasible in the treatment of liver cancer. It offer a significant noninvasive therapy for local treatment of liver cancer. For those right lobe liver cancers or with poor ultrasonic window, increasing treatment time or repeated treatment may improve the efficiency of HIFU ablation.

Huang SX, Wu YL, Tang CW, et al.
Prophylactic hepatic artery infusion chemotherapy improved survival after curative resection in patients with hepatocellular carcinoma.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):122-5 [PubMed] Related Publications
BACKGROUND/AIMS: To explore the effect of prophylactic hepatic artery infusion chemotherapy (HAIC) on survival probability after curative resection in patients with hepatocellular carcinoma (HCC).
METHODOLOGY: 85 patients with HCC were randomly assigned to HAIC group (42 cases) and control group (43 patients), all the database of two groups had no significant difference. Patients in HAIC groups underwent hepatic artery infusion chemotherapy (5-FU 1000 mg/m2 on day 1, Oxaliplatin 85 mg/m2 on day 1 and Gemcitabine 1000 mg/m2 on day 1 and 8) starting 3 weeks after operation with intervals of 4 weeks. All patients were followed up for 3 years and intrahepatic recurrence-free survival, disease-free survival rate and overall survival rate were recorded.
RESULTS: Intrahepatic recurrence rate of HAIC group and the control group was respectively 19.05% and 39.53%, P < 0.05. Disease-free survival rate was respectively 57.14% and 44.19%, P < 0.05. Overall survival rate was 66.67% and 46.51%, P < 0.05. All patients in HAIC group tolerated the therapy. No adverse effect above grade 3 was reported in HAIC group.
CONCLUSION: HAIC effectively and safely prevents intrahepatic recurrence and improves the prognosis of patients with HCC after curative resection.

Wang R, Chen XZ, Zhang MG, et al.
Incidence and mortality of liver cancer in mainland China: changes in first decade of 21st century.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):118-21 [PubMed] Related Publications
BACKGROUND/AIMS: To longitudinally analyze changes of primary liver cancer incidence and mortality in mainland China during the first decade of 21st century.
METHODOLOGY: Available data of crude incidence and mortality of primary liver cancer from annual reports of the National Central Cancer Registry in mainland China were retrieved and analyzed.
RESULTS: Either the incidence or mortality of primary liver cancer in mainland China kept increasing and didn't reach peaks during the first decade of the 21st century, particularly among the female population with great incremental rates of incidence (8.76%) and mortality (11.99%) at 2007-2008 and 2009-2010, respectively. The crude incidence increased from 26.18/100,000 persons at 2004 to 29.00/100,000 persons at 2010, while the crude mortality from 25.08/100,000 persons to 28.10/100,000 persons (r=0.857, p=0.014). The incidence and mortality in males kept 2.5-2.9 folds to those in females. The incidence and mortality in rural region were always higher than those in urban regions, but among males both tended to decline in rural region, while in contrast increased in urban region.
CONCLUSIONS: Liver cancer still has high incidence and mortality in mainland China, and further effort is required to prevent and control liver cancer, particularly for male and rural population.

Komeda K, Hayashi M, Inoue Y, et al.
A new strategy with a grading system for liver metastases from colorectal cancer.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):111-7 [PubMed] Related Publications
BACKGROUND/AIMS: The optimal indications, including timing, for resection of liver metastases from colorectal cancer (CRCLM) remain controversial. The Japanese Society of Cancer of the Colon and Rectum has proposed "H-classification" based on the maximum size and number of CRCLM, and has advocated the "CRCLM-grade system", which involves adding the presence of primary lymph node metastasis status to H-classification. We evaluated clinicopathological factors in order to elucidate the optimal indications for and timing of hepatectomy.
METHODOLOGY: Ninety-six patients who underwent initial hepatectomy for CRCLM between August 1995 and May 2009 were retrospectively analyzed with respect to characteristics of primary colorectal metastatic hepatic tumors, operation details and prognosis.
RESULTS: Multivariate analysis identified depth of invasion in primary colorectal cancer (within sub-serosal (non-se) vs. beyond serosal (se)) and CRCLM-grade as independent risk factors. We then performed analyses using the combination of non-se/se and CRCLM-grade. Kaplan-Meier analysis identified significant differences between non-se+gradeA and se+gradeA, between non-se+gradeB and se+gradeB, and between non-se+gradeC and se+gradeC groups.
CONCLUSIONS: We could retrospectively predict survival in CRCLM patients by adopting this new simple classification. This method may allow more precise assessment of operative indications and timing for both operations and perioperative adjuvant treatment.

Engstrand J, Nilsson H, Jansson A, et al.
Fate of necrotic volume after microwave ablation of multiple liver metastases.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):108-10 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of this study was to find the rate of shrinkage of necrosis and time of peak ablation volume after multiple microwave ablations in the treatment of multiple liver metastases of colorectal cancer. These factors are not known and are important in evaluation of treatment and identification of local recurrence, as microwave treatment is becoming more used thanks to improved technology in diagnostics and interventional therapy.
METHODOLOGY: A retrospective analysis of non-cirrhotic patients with multiple liver only metastases of colorectal cancer, not suited for resection for this reason. Patients were selected for palliative microwave treatment at a liver multidisciplinary team conference. 68 ablations were made in six patients. Ablation volume was analysed with repeated imaging and computer analyses.
RESULTS: The ablation volume peeks after 5-7 days where after reduction of the necrosis in the liver occurs logarithmically with a 60% reduction of ablation volume after 100 days and 80% after a year.
DISCUSSION: Liver regeneration after microwave ablations occurs at a constant logarithmic rate after an initial expansion of the ablation volume during the first five days. Evaluation of ablation volume in comparison to tumour volume must take this into account so that follow-up imaging is properly timed.

Sturesson C, Hoekstra L, Andersson R, van Gulik TM
Importance of thrombocytes for the hypertrophy response after portal vein embolization.
Hepatogastroenterology. 2015 Jan-Feb; 62(137):98-101 [PubMed] Related Publications
BACKGROUND/AIMS: Thrombocytes have proved to be important for liver regeneration after liver resection in the experimental setting. The aim of our study is to examine the effects of thrombocytes on liver hypertrophy after portal vein embolization (PVE).
METHODOLOGY: This retrospective cohort study comprised 75 patients with liver metastases from colorectal cancer subjected to PVE in preparation for major liver resection. Patients were divided into 2 groups depending on if chemotherapy was given within 6 weeks before PVE or not.
RESULTS: The chemotherapy group showed lower levels of thrombocytes (p=0.003) and lower degree of hypertrophy (p=0.030) as compared to the group without chemotherapy. No correlation within groups between level of thrombocytes and degree of hypertrophy was found. However, in the chemotherapy group, a positive linear correlation between the degree of hypertrophy and the difference in thrombocytes between the time points of PVE and 2 months preceding PVE was found (p=0.0006).
DISCUSSION: Preprocedural chemotherapy results in decreased hypertrophy of the liver after PVE and lower levels of thrombocytes at the time for PVE. The absolute number of thrombocytes does not influence liver regeneration after PVE. For patients receiving preprocedural chemotherapy, PVE performed at a time when thrombocytes are decreasing is associated with a reduced regeneration.

Goshima S, Kanematsu M, Noda Y, et al.
Diffusion kurtosis imaging to assess response to treatment in hypervascular hepatocellular carcinoma.
AJR Am J Roentgenol. 2015; 204(5):W543-9 [PubMed] Related Publications
OBJECTIVE: The objective of our study was to compare diffusion kurtosis imaging (DKI) with conventional diffusion-weighted imaging (DWI) for assessing the response to treatment in hypervascular hepatocellular carcinoma (HCC).
SUBJECTS AND METHODS: Sixty-two consecutive patients with treated or untreated hypervascular HCC underwent MRI of the liver including DKI (b values of 0, 100, 500, 1000, 1500, and 2000 s/mm(2)). The mean kurtosis (MK) and apparent diffusion coefficient (ADC) values of the hepatic parenchyma and of the HCCs were computed. The detectability of viable HCC based on MK and ADC values was compared. We also assessed the correlation between Child-Pugh grades and MK or ADC values.
RESULTS: For a total of 112 HCC nodules (viable, n = 63; nonviable, n = 49), the MK value was significantly higher for the viable group (mean ± SD, 0.81 ± 0.11) than for the non-viable group (0.57 ± 0.11) (p < 0.001). The mean ADC value was significantly lower for the viable group (1.44 ± 0.42 × 10(-3) mm(2)/s) than for the nonviable group (1.94 ± 0.52 × 10(-3) mm(2)/s) (p < 0.001). The sensitivity, specificity, and AUC of the ROC curve for the assessment of HCC viability were greater (p < 0.001) using MK (85.7%, 98.0%, and 0.95, respectively; cutoff value = 0.710) than using ADC (79.6%, 68.3%, and 0.77, respectively; cutoff value = 1.535 × 10(-3) mm(2)/s). Although the ADC of hepatic parenchyma was lower in patients with Child-Pugh grade B or C disease than in those with grade A disease (p = 0.02), no significant difference in MK (p = 0.45) was found among the Child-Pugh grades.
CONCLUSION: DKI can be a new option for the assessment of posttherapeutic response in HCC.

Granata V, Fusco R, Catalano O, et al.
Percutaneous ablation therapy of hepatocellular carcinoma with irreversible electroporation: MRI findings.
AJR Am J Roentgenol. 2015; 204(5):1000-7 [PubMed] Related Publications
OBJECTIVE: Irreversible electroporation is a new ablation modality. Our purpose was to describe the MRI findings after irreversible electroporation treatment of hepatocellular carcinoma (HCC).
SUBJECTS AND METHODS: In an 18-month period, we treated 24 HCC lesions in 20 patients who were not candidates for surgery. MRI was performed before and 1 month after irreversible electroporation. We used the liver-specific contrast medium gadoxetic acid. We evaluated the size, shape, signal intensity (T1-weighted, T2-weighted, and diffusion-weighted imaging), dynamic contrast enhancement pattern, and signal behavior during the liver-specific phase. Changes in the perilesional parenchyma, perfusion abnormalities, and complications were also recorded.
RESULTS: According to the modified Response Evaluation Criteria in Solid Tumors system, 22 of 24 lesions had a complete response, and two lesions showed a partial response and were retreated. The lesions showed a mean size increase of 10%, with a round or oval shape. On the T1-weighted images, we observed a hyperintense core and a hypointense rim. On the T2-weighted sequences, the signal was heterogeneously hypointense. On diffusion-weighted images, 83% of lesions showed restricted diffusion, with b values of 0-800 s/mm(2), whereas in 17% of the lesions, the signal was not clearly discernible for different b values. The apparent diffusion coefficient values did not show statistically significant differences between the baseline (800-1020 × 10(-3) mm(2)/s) and the reassessment after 1 month (900-1100 × 10(-3) mm(2)/s). The necrotic area did not show a signal increase after contrast material injection. Perfusion abnormalities, such as areas of transient hepatic intensity difference, were present in the tissue adjacent to six treated lesions. In two patients, a reduced or absent concentration of the contrast medium was observed during the liver-specific phase around the ablation zone. One patient had an arteriovenous shunt and another had biliary duct dilatation.
CONCLUSION: MRI detects characteristic morphologic and functional changes after irreversible electroporation treatment.

Hefaiedh R, Sabbegh M, Ennaifer R, et al.
Percutaneous treatment versus hepatic resection for the treatment of small hepatocellular carcinoma.
Tunis Med. 2014; 92(12):711-6 [PubMed] Related Publications
BACKGROUND: Hepatocellular carcinoma is the first liver tumor worldwide. Therefore, it is a matter of debate whether surgical treatment or percutaneous treatment should be preferred for the treatment of patients with small hepatocellular carcinoma. The aim of our study was to compare the long-term outcome and the survival between surgically and percutaneously treated small hepatocellular carcinomas.
METHODS: A retrospective study was performed in the department of hepatology during a period of 2009-2012. The study included all patients carrying small hepatocellular carcinoma which were divided in: group 1 including patients who underwent surgical treatment, and group 2 including patients who underwent percutaneous treatment.
RESULTS: Among the 63 patients who were diagnosed for hepatocellular carcinoma, 28 carried a small hepatocellular carcinoma with a mean age of 63 years and sex-ratio of 0.64. Etiology of cirrhosis was viral in 96% cases. Surgical treatment (hepatic resection) was performed in 53.5% cases while percutaneous treatment was proposed for 46.5%: radiofrequency ablation in 69% and alcoholic injection in 31%. No major complications for both surgical and percutaneous treatment occurred in our study. Overall survival was significantly lower in the surgical resection group. The corresponding 6 months and 1-year overall survival rates for the surgical resection group and the percutaneous treatment group were 100%, 100%, 20%, and 52%, respectively (p=0,04). The disease free survival were not significantly different.
CONCLUSION: Our results showed the efficacy and safety of percutaneous ablation treatments which were better than those of surgical treatment in patients with small hepatocellular carcinoma.

Bonney GK, Coldham C, Adam R, et al.
Role of neoadjuvant chemotherapy in resectable synchronous colorectal liver metastasis; An international multi-center data analysis using LiverMetSurvey.
J Surg Oncol. 2015; 111(6):716-24 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: The use of neo-adjuvant chemotherapy in resectable synchronous liver metastasis is ill defined. The aim of this study was to evaluate neo-adjuvant chemotherapy on outcomes following liver resection for synchronous CLM.
METHODS: An analysis of a multi-centric cohort from the LiverMetSurvey International Registry, who had undergone curative resections for synchronous CLM was undertaken. Patients who received neo-adjuvant chemotherapy prior to liver surgery (group NAS; n = 693) were compared with those treated by surgery alone (group SG; n = 608). Baseline clinicopathological variables were compared. Predictors of overall (OS) and disease free survival (DFS) were subsequently identified.
RESULTS: Clinicopathological comparison of the groups revealed a greater proportion of solitary metastasis in the SG compared to the NAS group (58.8% versus 38.4%; P < 0.001) therefore a separate analysis of solitary versus multi-centric analysis was performed. N-stage (> N1), number of metastasis (> 3), serum CEA (> 5 ng/ml) and no adjuvant chemotherapy independently predicted poorer OS, while N-stage (> N1), serum CEA (> 5 ng/ml) and no adjuvant chemotherapy independently predicted poorer DFS. Neo-adjuvant chemotherapy did not independently affect outcome.
CONCLUSION: We present an analysis of a large multi-center series of the role of neo-adjuvant chemotherapy in resectable CLM and demonstrate no survival advantage in this setting.

Liao W, Mao Y, Ge P, et al.
Value of quantitative and qualitative analyses of circulating cell-free DNA as diagnostic tools for hepatocellular carcinoma: a meta-analysis.
Medicine (Baltimore). 2015; 94(14):e722 [PubMed] Related Publications
Qualitative and quantitative analyses of circulating cell-free DNA (cfDNA) are potential methods for the detection of hepatocellular carcinoma (HCC). Many studies have evaluated these approaches, but the results have been variable. This meta-analysis is the first to synthesize these published results and evaluate the use of circulating cfDNA values for HCC diagnosis. All articles that met our inclusion criteria were assessed using QUADAS guidelines after the literature research. We also investigated 3 subgroups in this meta-analysis: qualitative analysis of abnormal concentrations of circulating cfDNA; qualitative analysis of single-gene methylation alterations; and multiple analyses combined with alpha-fetoprotein (AFP). Statistical analyses were performed using the software Stata 12.0. We synthesized these published results and calculated accuracy measures (pooled sensitivity and specificity, positive/negative likelihood ratios [PLRs/NLRs], diagnostic odds ratios [DORs], and corresponding 95% confidence intervals [95% CIs]). Data were pooled using bivariate generalized linear mixed model. Furthermore, summary receiver operating characteristic curves and area under the curve (AUC) were used to summarize overall test performance. Heterogeneity and publication bias were also examined. A total of 2424 subjects included 1280 HCC patients in 22 studies were recruited in this meta-analysis. Pooled sensitivity and specificity, PLR, NLR, DOR, AUC, and CIs of quantitative analysis were 0.741 (95% CI: 0.610-0.840), 0.851 (95% CI: 0.718-0.927), 4.970 (95% CI: 2.694-9.169), 0.304 (95% CI: 0.205-0.451), 16.347 (95% CI: 8.250-32.388), and 0.86 (95% CI: 0.83-0.89), respectively. For qualitative analysis, the values were 0.538 (95% CI: 0.401-0.669), 0.944 (95% CI: 0.889-0.972), 9.545 (95% CI: 5.298-17.196), 0.490 (95% CI: 0.372-0.646), 19.491 (95% CI: 10.458-36.329), and 0.87 (95% CI: 0.84-0.90), respectively. After combining with AFP assay, the values were 0.818 (95% CI: 0.676-0.906), 0.960 (95% CI: 0.873-0.988), 20.195 (95% CI: 5.973-68.282), 0.190 (95% CI: 0.100-0.359), 106.270 (95% CI: 22.317-506.055), and 0.96 (95% CI: 0.94-0.97), respectively. The results in this meta-analysis suggest that circulating cfDNA have potential value for HCC diagnosis. However, it would not be recommended for using independently, which is based on the nonrobust results. After combining with AFP, the diagnostic performance will be improved. Further investigation with more data is needed.

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