Liver Cancer
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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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Information for Patients and the Public
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Latest Research Publications
Childhood Liver Cancer

Information Patients and the Public (12 links)

Information for Health Professionals / Researchers (13 links)

Latest Research Publications

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

Limaiem F, Bouslama S, Bouraoui S, Mzabi S
Primary hepatic vascular tumours. A clinicopathologic study of 10 cases.
Acta Gastroenterol Belg. 2014; 77(3):347-52 [PubMed] Related Publications
BACKGROUND: Primary hepatic vascular neoplasms constitute a heterogeneous group of neoplasms with characteristic histology and variable tumour biology.
AIM: To provide an updated overview on clinicopathological features, treatment and outcome of primary hepatic vascular tumours.
PATIENTS AND METHODS: In our retrospective study, we reviewed 10 cases of primary hepatic vascular tumours that were diagnosed at the pathology department of Mongi Slim hospital over a thirteen-year period (2000-2012). Relevant clinical information and microscopic slides were available in all cases and were retrospec- tively reviewed.
RESULTS: Our study group included 4 men and 6 women (sex ra- tio M/F = 0.66) aged between 23 and 78 years (mean = 55.5 years). Based on imaging studies, preoperative diagnosis of hemangioma was accurately made in only three cases. Three cases were misdiagnosed preoperatively as having hydatid cyst and four cases of hemangiomas were misdiagnosed preoperatively as liver metastases. All our patients underwent surgical resection of the tumour. Histopathological examination of the surgical specimen established the diagnosis of angiosarcoma in one case, cavernous hemangioma in 8 cases and sclerosing hemangioma in one case.
CONCLUSION: Hepatic tumours are increasingly detected incidentally due to widespread use of modern abdominal imaging techniques. Therefore, reliable noninvasive characterization and differentiation of such liver tumours is of major importance for clinical practice. Definitive diagnosis is based on histopathologic examination.

Suenaga M, Fujii T, Kanda M, et al.
Pattern of first recurrent lesions in pancreatic cancer: hepatic relapse is associated with dismal prognosis and portal vein invasion.
Hepatogastroenterology. 2014; 61(134):1756-61 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of this study was to evaluate patterns of the initial recurrence after pancreatectomy for pancreatic cancer and risk factors in each pattern.
METHODOLOGY: This study included 209 pancreatic cancer patients who underwent pancreatectomy and of whom the detailed information on the first recurrent lesions detected by imaging during postoperative followup were available. Relapse patterns were classified into 4 groups: liver, peritoneal, local and extra-abdominal recurrences. We evaluated their associations with prognosis and various clinicopathological factors to identify relevant risk factors.
RESULTS: Cumulative numbers of patients with liver, peritoneal, local, and extra-abdominal recurrences were 81, 70, 98 and 22, respectively, for the first recurrences. Hepatic relapse was associated with significantly shorter overall survival than other sites (p<0.001) and was an independent prognostic factor in multivariate analysis (p<0.001). Pathological portal vein invasion was the only independent risk factor for hepatic relapse (p=0.045). There was no significant correlation between the depth of invasion and prevalence of hepatic relapse.
CONCLUSIONS: Hepatic relapse was associated with a dismal prognosis and with pathological portal vein invasion. Novel therapeutic strategies are therefore required to reduce the incidence of hepatic relapse, especially in patients with portal vein invasion.

Fu C, Liu N, Deng Q, et al.
Radiofrequency ablation vs. surgical resection on the treatment of patients with small hepatocellular carcinoma: a system review and meta-analysis of five randomized controlled trials.
Hepatogastroenterology. 2014; 61(134):1722-9 [PubMed] Related Publications
BACKGROUND/AIMS: To investigate the meta-analysis of randomized controlled trials(RCTs) of the efficacy and safety between radiofrequency ablation (RFA ) and surgical resection (SR) in treating small hepatocellular carcinoma (SHCC).
METHODOLOGY: RCTs comparing RFA with SR for SHCC were collected from PubMed/Medline, Cochrane Library, EMBASE and CNKI data base. Odds ratios and 95% confidence intervals were calculated.
RESULTS: Five RCTs with a total of 776 patients were included in this analysis. The 1-, 3-year overall survival rate and 1-year recurrence-free survival rate were of no difference between the RFA and SR . However, SR was shown to be superior to the RFA with the analysis of 5-year overall rate and 3-, 5-year recurrence-free survival rate. The 1-year recurrence rate was similar between the SR and RFA . However, the 2-, 3-year recurrence rate of RFA is significantly higher than SR . In addition, the SR presented a high complication rate.
CONCLUSIONS: SR treatment led to a higher long-term survival rate and a lower long-term recurrence rate, while RFA led to a lower complication rate than SR. However, Further research was needed to investigate the efficacy of RFA because of the inadequate research data and the heterogeneity among the included studies.

De Carlis L, Sguinzi R, De Carlis R, et al.
Residual right portal branch flow after first-step ALPPS: artifact or homeostatic response?
Hepatogastroenterology. 2014; 61(134):1712-6 [PubMed] Related Publications
BACKGROUND/AIMS: Mutual interactions between portal vein and hepatic artery can be documented during hepatobiliary surgery. Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) is a recently introduced surgical technique which can also represent a unique living human model to investigate intrahepatic blood circulation. We report three consecutive cases in which a residual right portal branch flow was clearly detectable after first-step ALPPS, and try to further investigate this unexpected finding with intraoperative clamping tests.
METHODOLOGY: Every patient was evaluated with CT scan 7 days after first-step ALPPS and Intraoperative Doppler Ultrasonography (IOUS) at both steps of the procedure.
RESULTS: In every patient, CT scan and second-step IOUS demonstrated a clear hepatopetal flow distally to the divided right portal branch. The flow was present after right biliary duct clamping and stopped after right total hilar clamping as well as after right hepatic artery occlusion.
CONCLUSIONS: Neither cross-portal circulation between the two hemilivers nor trans-sinusoidal backflow from the hepatic veins can explain these findings, which are rather consistent with a refilling of the occluded portal branch through the opening of intrahepatic arterioportal shunts (APS). APS could represent the simplest homeostatic mechanism that regulate intrahepatic blood flow.

Related: Extra-Hepatic Bile duct cancer (cholangiocarcinoma)

Zhou L, Rui JA, Wang SB, et al.
Risk factors of microvascular invasion, portal vein tumor thrombosis and poor post-resectional survival in HBV-related hepatocellular carcinoma.
Hepatogastroenterology. 2014; 61(134):1696-703 [PubMed] Related Publications
BACKGROUND/AIMS: Microvascular invasion (MVI) and portal vein tumor thrombosis (PVTT) associated factors in hepatocellular carcinoma (HCC) were previously shown. However, those for HBV-related HCC remain unknown. This study aimed to investigate the risk factors of MVI, PVTT and poor prognosis in this type of HCC.
METHODOLOGY: Consecutive 130 patients with HBV-related HCC were enrolled. The impact of variables on MVI, PVTT and post-resectional survival was determined by uni- and multi-variate analyses.
RESULTS: By Chi-square analysis, Edmondson-Steiner grade and tumor size were related to MVI, whereas Edmondson-Steiner grade and MVI were associated with PVTT. Logistic regression identified Edmondson-Steiner grade as the sole independent determinant of MVI, but none is significant for PVTT. Tumor size carried high sensitivity and negative predictive value in prediction of MVI. Survival estimation revealed that Edmondson-Steiner grade, tumor size, PVTT, MVI, satellite nodule, TNM stage and AFP level were prognostic for overall and disease-free survival, but only Edmondson-Steiner grade was of independent implication for both. Besides, tumor size independently predicted overall survival.
CONCLUSIONS: In HBV-related HCC, differentiation degree might play an important role in vascular involvement, tumor size might be helpful in primary screening of MVI, differentiation and tumor size might be particularly significant as prognostic markers.

EI-Emshaty HM, Gadelhak SA, Abdelaziz MM, et al.
Serum P53 Abs in HCC patients with viral hepatitis - type C.
Hepatogastroenterology. 2014; 61(134):1688-95 [PubMed] Related Publications
BACKGROUND/AIMS: P53 gene mutations have a higher malignant potential and often leads to the production of p53 Abs. This study was conducted to evaluate the clinical implications of p53Abs in HCV-related HCC and its diagnostic capacity as a new biomarker in HCC.
METHODOLOGY: 83 patients with HCV-chronic liver disease (25 with LC and 58 with HCC) were enrolled in this study. Ten healthy individuals (HI) served as control group. The studied group was subjected to clinical examination, imaging radiology, laboratory investigation and liver biopsy. Serum p53 Abs was assessed by (ELISA).
RESULTS: Serum p53 Abs in HCC (0.5567±0.227) was significantly elevated (p<0.0001) than LC (0.252±0.0099) and HI (0.214±0.068) (p=0.001). Serum P53 Abs was significantly (p=0.01) increased with the progression of child score but there was no significant difference with regard to age, sex, tumor size or serum liver profile. However, serum p53 Abs showed no significant positive correlation with AFP in HCV-related HCC (r=0.09, p value= 0.6) but serum p53 Abs in combination with AFP showed higher diagnostic sensitivity (82.2%) of HCC than either alone.
CONCLUSIONS: P53 Abs could be regarded as a specific biomarker for cancer process and its use in combination with AFP may increase the diagnostic sensitivity of HCC.

Related: TP53 AFP

Ohkawa K, Imanaka K, Sakakibara M, et al.
Factors related to shift from hepatic borderline lesion to overt HCC diagnosed by CT.
Hepatogastroenterology. 2014; 61(134):1680-7 [PubMed] Related Publications
BACKGROUND/AIMS: Factors contributing to the shift from the hepatic borderline lesion to overt hepatocellular carcinoma (HCC) were investigated.
METHODOLOGY: Ninety-five borderline nodules from 69 patients were followed-up for 6-55 (median 24) months. The borderline lesion was diagnosed when the CT image demonstrated low density in the portal phase and lacked enhancement in the arterial phase.
RESULTS: The shift to overt HCC was seen in 32 nodules from 27 patients. Using multivariate analysis, only size was a significant factor contributing to the shift to overt HCC (p = 0.009). The cumulative incidence of the shift to overt HCC was higher in nodules of ≥13 mm in size than in those of < 13 mm (p = 0.034). Among nodules of ≥13 mm, nodules showing iso density in the arterial phase and low density in the portal phase had a higher cumulative incidence of the shift to overt HCC than those showing low density in the arterial and portal phases on CT (p=0.007).
CONCLUSIONS: In hepatic borderline nodules diagnosed by CT, greater size, and iso density in the arterial phase and low density in the portal phase may be risk factors associated with the shift to overt HCC.

Lin CC, Lin KH, Hung YJ, Chen YL
A novel technique for resection of huge right lobe hepatocellular carcinoma extending to the right atrium: in-situ cold perfusion of liver.
Hepatogastroenterology. 2014; 61(134):1677-9 [PubMed] Related Publications
BACKGROUND/AIMS: Surgery for advanced hepatocellular carcinoma with inferior vena cava or right atrium extension represents challenging procedures for hepatobiliary surgeons. Regardless of the surgical approach chosen, the liver parenchyma inevitably has to suffer from ischemia during the total hepatic vascular exclusion period.
METHODOLOGY: We report our novel technique for resection of a huge hepatocellular carcinoma extending to the right atrium. During the total hepatic vascular exclusion period, in-situ cold perfusion of the liver was performed in order to minimize the ischemic insults.
RESULTS: The 53-year-old male patient with chronic hepatitis B was diagnosed to have a huge right lobe hepatocellular carcinoma, besides which the tumor had invaded the right hepatic vein and right atrium. With the help of cardio-pulmonary bypass and in-situ cold perfusion of the liver, the tumor was removed en-bloc. The operating time was 458 minutes. The cold ischemia time of the liver was 53 minutes 30 seconds. The cardio-pulmonary bypass time was 61 minutes. The estimated blood loss was about 7000 ml. The patient was discharged under stable condition on postoperative day 35.
CONCLUSIONS: In selected patients, when the expected tumor resection time is long, the in-situ cold perfusion of the liver could be considered an option.

Kim JM, Kwon CH, Joh JW, et al.
The effect of hepatocellular carcinoma bile duct tumor thrombi in liver transplantation.
Hepatogastroenterology. 2014; 61(134):1673-6 [PubMed] Related Publications
BACKGROUND/AIMS: The presence of bile duct tumor thrombi (BDTT) of hepatocellular carcinoma (HCC) in explant liver is considered to be a poor prognostic factor. However, studies about HCC BDTT in liver transplant recipients are rare. We compared the characteristics of liver transplant recipients with HCC BDTT in their pathology with those of recipients who had portal vein tumor thrombi (PVTT) of HCC in their pathology.
METHODOLOGY: The medical records of patients who underwent liver transplantation from 2002 to 2008 at Samsung Medical Center were reviewed. HCC recurrence was considered as an end-point.
RESULTS: Eight patients were identified as having HCC BDTT in explant liver. The disease-free survival rates at 1-year and 5-year were 37.5% and 25.0%, respectively. Patients whose HCC did not recur had lower alpha-fetoprotein (AFP) levels than others (P=0.046). Patients with HCC BDTT were compared with recipients who had PVTT in their pathology, and there was no statistically significant difference between the two groups (P=0.750).
CONCLUSIONS: HCC BDTT of explant liver has been considered to be a poor prognostic factor, like PVTT of HCC. However, we found that patients with low AFP levels before transplantation could be expected to have a longer disease-free survival.

Related: AFP

Nakanishi M, Kuriu Y, Murayama Y, et al.
Efficacy of perioperative chemotherapy in patients with colorectal cancer undergoing hepatectomy for resectable synchronous liver metastasis.
Hepatogastroenterology. 2014; 61(134):1582-7 [PubMed] Related Publications
BACKGROUND/AIMS: Although aggressive resection is recommended for the treatment of resectable liver metastasis of colorectal cancer, recurrences often develop in the remaining liver. In our department, perioperative chemotherapy was introduced for the treatment of colorectal cancer associated with resectable synchronous liver metastasis. The results of this treatment are reported herein. The study population was 20 patients (9 men, 11 women) with colorectal cancer associated with resectable synchronous liver metastasis whose data were collected between April 2009 and September 2012.
METHODOLOGY: The patients received chemotherapy (mFOLFOX6 or XELOX + bevacizumab) for 3 months each before and after hepatectomy following resection of the primary lesion.
RESULTS: Preoperative chemotherapy yielded a response rate of 66.7%, and no serious postoperative complications were noted. Although recurrence was found in 9 patients after treatment, 4 have so far remained cancer-free after re-resection. Thus, re-resection of the recurrent lesion resulted in patients maintaining cancer-free status for a prolonged period.
CONCLUSIONS: The use of perioperative chemotherapy in patients with colorectal cancer associated with resectable synchronous liver metastasis may improve outcomes after hepatectomy.

Related: Colorectal (Bowel) Cancer

Wang Y, Duan B, Shen C, et al.
Treatment and multivariate analysis of colorectal cancer with liver metastasis.
Hepatogastroenterology. 2014; 61(134):1568-73 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of this study was to identify the influencing factors related to outcome of patients of colorectal cancer with liver metastasis.
METHODOLOGY: From January 1999 to January 2009, 293 cases of colorectal cancer with liver metastasis undergoing surgery were analysised retrospectively. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate analysis. Results: The 1-, 3- and 5-year survival rates of patients after resection were 58.3%, 26.4%, and 11.3%, respectively. Univariate analysis showed that preoperative CEA level, degree of primary tumor differentiation, resection margin, number of liver metastases, resection of liver metastases were prognostic impacts. The difference was statistically significant (p<0.05). Cox multivariate analysis showed that preoperative CEA level, number of liver metastases, and resection of liver metastases are three separate prognostic factors.
CONCLUSIONS: Racical resection is the key to improve the long-term survival rate of colorectal cancer with liver metastasis. Important predictive factors related to poor survival are preoperative CEA level and number of liver metastases.

Related: Colorectal (Bowel) Cancer

Gunduz S, Ozgur O, Bozcuk H, et al.
Yttrium-90 radioembolization in patients with unresectable liver metastases: determining the factors that lead to treatment efficacy.
Hepatogastroenterology. 2014; 61(134):1529-34 [PubMed] Related Publications
INTRODUCTION: Locoregional treatments, such as radioembolization, can be used to treat patients with unresectable liver metastases. We aimed to determine the progression-free survival and factors that predict survival of patients with liver metastases whose response to selective internal radiation therapy (SIRT) with Y-90 was assessed by positron emission tomography-computed tomography (PET-CT).
PATIENTS: Our study included 78 liver cancer patients who were treated with Y-90 radioembolization.
RESULTS: The post-treatment response rates were as follows: 7 patients (9%) had stable disease (SD), 26 patients (33.3%) had a partial response (PR), 4 patients (5.1%) had a complete response (CR). The median hepatic progression-free survival (HPFS) was 4.4 months while median overall survival was 10.1 months. Univariate analysis revealed that HPFS is significantly affected by international normalized ratio (INR) levels and age (Hazard Ratio(HR)=0.54 (95%CI:0.30-096), P=0.034, HR=1.03(95%CI:1.00-1.05), P=0.051). However, only INR levels retained significance with multivariate analysis (HR=0.53 (95%CI:0.30-0.93), P=0.028), while age had limited significance (HR =1.02 (95% CI:1.00-1.05), P=0.051).
CONCLUSIONS: We determined that Y-90 radioembolization is effective as a salvage therapy in patients with predominant liver metastases. For the first time, we showed that age and INR values reflecting the functional hepatic reserve can be used as positive predictive factors for HPFS.

Gao PJ, Gao J, Li Z, et al.
Hepatocellular carcinoma recurrence is an independent risk factor for HB recurrence after liver transplantation.
Hepatogastroenterology. 2014; 61(134):1523-8 [PubMed] Related Publications
BACKGROUND/AIMS: To confirm the relationship between hepatitis B recurrence and Hepatocellular carcinoma recurrence.
METHODOLOGY: Data from 340 patients undergoing liver transplantation for HBV-related liver disease were retrospectively evaluated. Clinically relevant variables were analyzed using univariate models. Significant variables were subjected to multivariate logistic regression analysis to identify the independent predictors for HBV recurrence. Fifteen samples removed from HCC recurrence patients were stained for HBsAg and HBcAg.
RESULTS: The analyzed population included 283 male and 57 female patients. The mean age was 48.5±9.33 years and median follow-up was 47 months. Hepatitis B relapsed in 16 patients (4.7%). Univariate analysis indicated that HCC (P=0.022) and HCC recurrence (P=0.000) were associated to post transplantation HB. Multivariate analysis identified HCC recurrence as an independent risk factor for HB recurrence (hazard ratio: 23.262 (95% CI: 3.752, 144.216); P <0.001). Three of 15 metastatic lesions were positive for HBsAg and 1 lesion was positive for HBcAg. Conclusion: HCC recurrence is an independent risk factor for post transplantation recurrence of hepatitis.

Aizawa M, Nashimoto A, Yabusaki H, et al.
Clinical benefit of surgical management for gastric cancer with synchronous liver metastasis.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1439-45 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of this study was to evaluate the benefit of resection for liver metastasis from gastric cancer.
METHODOLOGY: Consecutive 74 patients of gastric cancer who undergone the gastrectomy for primary gastric cancer and simultaneous hepatic resection for synchronous liver metastasis were enrolled. The clinicopathological factors were retrospectively compared to the prognosis.
RESULTS: The median survival time and 5-year overall survival rate in 53 patients who accomplished microscopically negative margin resection was 27.4 months and 18.6%, respectively. In the multivariate survival analysis, the number of liver metastasis was identified as an independent prognostic factor (HR;2.232, 95%CI;1.036-4.808, p=0.04). When the patients undergone curative resection were subdivided into solitary and multiple liver metastasis, the median survival time and 5-year overall survival rate in a subgroup with solitary liver metastasis was 24.2 months and 27.2%, which was superior to the corresponding values of 12.6 months and 5.5% in another group with multiple liver metastasis (p=0.02).
CONCLUSIONS: The resection for liver metastasis might offer a chance for long-term survival in a carefully selected group of patients. The number of liver metastasis was a reliable criterion to discriminate the subgroup of patients who are most likely to benefit from hepatic resection.

Related: Stomach Cancer Gastric Cancer

Zheng YY, Tang CW, Xu YQ, et al.
Hepatic arterial infusion chemotherapy reduced hepatic metastases from pancreatic cancer after pancreatectomy.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1415-20 [PubMed] Related Publications
BACKGROUND/AIMS: This study aims to investigate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases from pancreatic cancer after pancreatectomy.
METHODOLOGY: We randomly assigned 106 patients with pancreatic cancer after pancreatectomy between 2005 and 2010 to receive 2 cycles of HAIC plus 4 cycles of systemic chemotherapy (Combined Therapy) or 6 cycles of systemic chemotherapy alone (Monotherapy). Both the HAIC and systemic chemotherapy regimen consisted of a 5-hour infusion of 5-fluorouracil 1000 mg/m2 on day 1 followed by gemcitabine 800 mg/m2 as an over 30-min infusion on day 1 and day 8. The treatment was started on an average of 21.2 days after surgery and repeated every 4 weeks. The disease-free survival, overall survival and liver metastases-free survival were compared.
RESULTS: There was no significant difference in adverse effects between two groups. Significant differences were found in 3-year overall survival (Combined Therapy, 23.08 %; Monotherapy, 14.81%; P=0.0473) and liver metastases-free survival (Combined Therapy, 80.77%; Monotherapy, 55.56%; P=0.0014).
CONCLUSIONS: HAIC effectively and safely prevents liver metastases and improves the prognosis of patients with pancreatic cancer after pancreatectomy.

Related: Fluorouracil Cancer of the Pancreas Pancreatic Cancer Gemcitabine

Obiekwe SR, Quintaine L, Khannaz A, et al.
To Pringle or not to pringle: is Pedicle clamping a necessity in liver resection?
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1402-14 [PubMed] Related Publications
A single center prospective study was done to evaluate the role of hepatic portal pedicle clamping (PC) during right hepatectomy (RH) in patients with primary and secondary liver tumors. Cirrhotics were excluded. Two groups were compared for preoperative demographics including diagnosis, tumor size, portal vein embolization and liver enzymes, pre and postoperative hemoglobin levels, percentage of residual liver mass, morbidity and mortality, pedicle clamp time, intensive care unit stay, length of hospital stay and blood loss. We observed no significant difference in the analysis of the post-operative hemoglobin, liver enzymes, residual liver size, size of tumor resected, need for postoperative monitoring in ICU stay, length of hospital stay and blood loss. Mortality and morbidity were the same. None of the patients were transfused during surgery. Our findings show that pedicle clamping was beneficial 15% of the time when uncontrolled intra-operative bleeding was encountered or in a subset of patients with peliosis, steatohepatitis, Jehovah Witness patient, and post-chemotherapy patients. However, its advantage has to be weighed against the disadvantages.

Related: France

EI-Emshaty HM, Saad EA, Toson EA, et al.
Apoptosis and cell proliferation: correlation with BCL-2 and P53 oncoprotein expression in human hepatocellular carcinoma.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1393-401 [PubMed] Related Publications
BACKGROUND/AIM: Occurrence and biological characteristics of tumors are related not only to over-proliferation of carcinoma cells but also to decrease of apoptosis. The present study was suggested to evaluate the correlation between P53 and Bcl-2 oncoprotein expression with apoptosis and cell proliferative activity in HCC patients.
METHODOLOGY: P53 and Bcl-2 protein expression were estimated in the sera and in liver tissues of 45 HCC cases using ELISA and immunohistochemistry. Apoptosis was estimated as apoptotic index (AI) and cell proliferative activity was detected using AgNORs.
RESULTS: Serum p53 antigen in HCC patients (0.46±0.331ng/ml) showed significant elevation than healthy individuals (0.24±0.11ng/ml, p<0.05). P53 protein was immunostained in 41% of HCC; 37.5% of these positive cases were in diffuse pattern representing the mutant p53. Serum Bcl-2 was elevated in HCC cases (50.28±25.83u/ ml) than healthy individuals (26.65±8.63u/ml, p<0.05). Bcl-2 was immunohistochemically localized in 35.9% of HCC and the positivity was inversely proportional with the histological grade (47.4%, 25%, 25% in grade I,II,III respectively). Bcl-2 showed a positive linear correlation with p53 in the sera of carcinoma patients (p<0.05).
CONCLUSION: Bcl-2 may play a role in hepatocarcinogenesis as an inhibitor of apoptosis. However, a positive linear correlation was found between bcl-2 and p53 suggesting that bcl-2/p53 co-expression pattern may be of value in the development of more effective medical therapies in HCC.

Related: Apoptosis TP53

Yamagami T, Yoshimatsu R, Ishikawa M, et al.
Transcatheter arterial chemoembolization with an interventional-CT system for recurrent hepatocellular carcinoma after living donor liver transplantation.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1387-92 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of this retrospective study was to evaluate the feasibility and treatment effects of transcatheter arterial chemoembolization (TACE) for recurrent intrahepatic hepatocellular carcinoma (HCC) after liver transplantation.
METHODOLOGY: Between March 2007 and December 2012, we treated 8 patients (6 men and 2 women; mean age, 54 years) with recurrent HCC after living donor liver transplantation by TACE using an interventional-CT system. We retrospectively investigated treatment outcomes, complications, and the prognosis in these patients.
RESULTS: Overall, 17 sessions of TACE were performed. A single TACE session was performed in 4 patients while multiple TACE sessions were performed in 4 patients. Anticancer drugs and embolic agents were selectively infused from the right hepatic artery (n=7), left hepatic artery (n=1), A3 (n=1), A5 (n=1), A6 (n=1), A7 (n=2), anterior branch (n=1), posterior branch (n=3), intercostal artery (n=1), and right inferior phrenic artery (n=5). There were no procedure-related complications. Response rate was 50%. The median overall survival from the initial TACE for recurrence of HCC was 12.9 months (95% confidence interval, 5 to 21). The 1-year survival rate was 42.9%.
CONCLUSION: TACE with an interventional-CT system could play an important role in the treatment of recurrent HCC after liver transplantation.

Shi R, Zhang YM, Zhu ZJ, et al.
Synchronous splenectomy and hepatectomy in patients with hepatocellular carcinoma, hypersplenism and liver cirrhosis.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1363-7 [PubMed] Related Publications
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) mainly arises from underlying liver disease. Complicated liver cirrhosis and secondary hypersplenism are the most risk factors preventing surgical treatment of patients with HCC. The present study aimed at investigating the safety and long term outcome of patients with HCC and liver cirrhosis undergoing synchronous hepatectomy and splenectomy.
METHODOLOGY: The clinical data of 306 cases of patients with HCC and liver cirrhosis undergoing curative hepatectomy were reviewed. 18 cases underwent synchronous hepatectomy and splenectomy. The rest 288 cases of HCC with hepatectomy only were compared in aspects of clinicopathological and surgical variables and surgical outcomes.
RESULTS: Preoperative hemoglobin and platelet count were significantly lower in splenectomy than non-splenectomy group (p<0.01, respectively). Patients undergoing combined splenectomy and hepatectomy needed longer surgery time and hospital stay time, and transfused much more blood intraoperatively (p=0.07, 0.03, and 0.02), and also experienced more portal vein thrombosis (p<0.01). The level of hemoglobin and platelet increased after splenectomy and finally to normal level one month postoperatively. There was no statistical difference of overall and disease-free survival of patients in splenectomy and non-splenectomy groups (p>0.05).
CONCLUSIONS: With strict selection, patients with HCC and hypersplenism could undergo combined splenectomy and hepatectomy safely.

Kobayashi T, Kawakamil M, Hara Y, et al.
Combined evaluation of the Glasgow prognostic score and carcinoembryonic antigen concentration prior to hepatectomy predicts postoperative outcomes in patients with liver metastasis from colorectal cancer.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1359-62 [PubMed] Related Publications
BACKGROUND/AIMS: Little is known about the ability of the inflammation-based Glasgow prognostic score (GPS).
METHODOLOGY: 106 patients who underwent curative resection for colorectal liver metastasis (CRLM) were analyzed. Patients with an elevated Creactive protein concentration (>10 mg/L) and hypoalbuminemia (<35 g/L) at admission were assigned a GPS 2, those with only 1 of these biochemical abnormalities were assigned a GPS 1, and those without either abnormality were assigned a GPS 0.
RESULTS: Multivariate analysis showed that 2 variables, carcinoembryonic antigen (CEA) concentration > 30 ng/mL and a GPS 1 or 2, were independently prognostic of survival. Patients were classified into 3 groups on the basis of these 2 variables. Patients with GPS 1 or 2 and CEA concentration > 30 ng/mL were assigned a new score of 2, those with either 1 factor were assigned a new score of 1, and those with neither factors were assigned a new score of 0. The 5-year overall survival rates of new scores of 0, 1, 2 were 71.5%, 31.6%, and 0%, respectively (P < 0.0001).
CONCLUSIONS: This simple staging system may be able to identify a subgroup of patients who are eligible for curative resection but show poor prognosis.

Related: Colorectal (Bowel) Cancer

Choi WJ, Jeong WK, Kim Y, et al.
Assessment of treatment success and short-term effectiveness using C-arm CT immediately after hepatic chemoembolization of HCC.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1353-8 [PubMed] Related Publications
BACKGROUND/AIMS: To investigate semiquantitative analyses based on amount and morphology of iodized oil uptake about non-enhanced C-arm cone-beam CT(C-arm CT) immediately following hepatic chemoembolization of HCC.
METHODOLOGY: We retrospectively reviewed 40 C-arm CT images taken immediately following chemoembolization in 29 consecutive patients who underwent hepatic chemoembolization for HCC lesions(n=97). Two radiologists scored iodized oil uptake in the index tumours from Grade 0(complete) to 4(invisible). To describe the morphologic characteristics of uptake, the lesions scored as Grade 1 to 3 were subclassified as ‘defective’ and ‘not-defective’ with respect to uptake. To evaluate the performance of this modality, we performed a receiver operating characteristic curve analysis.
RESULTS: All treated lesions were classified into ‘complete treatment’(n=50) and 'viable HCC'(n=47). Thirty-one lesions were evaluated as Grade 0, two as Grade 4, and the rest (n=64) as between Grades 1 and 3, and the lesions of Grade 3 or 4 were all viable. Of the defective uptake lesions(n=35), 28 lesions were also viable. The areas under the curves of the lesions were 0.827 to 0.860.
CONCLUSIONS: The analysis of C-arm CT based on the amount and morphologic characteristics of iodized oil uptake may be useful to predict the effectiveness of the hepatic chemoembolization of HCC.

Govil S
Central hepatic resection under hypothermic total vascular exclusion using ante-situm techniques while maintaining liver blood supply.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1350-2 [PubMed] Related Publications
Ante-situm liver resection under hypothermic total vascular exclusion is used to resect large tumours that involve the hepatic veins close to the vena cava or the cava itself. This procedure traditionally requires venovenous bypass when it is necessary to clamp the cava, or portocaval shunt when caval continuity is maintained by piggyback dissection of the liver. We present a technique of ante-situm liver resection, operating on one side of the liver at a time while maintaining prograde portal flow through the opposite side of the liver, thereby avoiding venovenous bypass, portacaval shunt and portal vein reconstruction.

Hammond JS, Franko J, Holloway SE, et al.
Gemcitabine transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1339-43 [PubMed] Related Publications
BACKGROUND/AIMS: Transcatheter arterial chemoembolization (TACE) has been shown to increase survival in patients with unresectable hepatocellular carcinoma (HCC), however toxicity from commonly used agents limits its use in unresectable disease. Gemcitabine is a well tolerated chemotherapeutic agent with a high first pass clearance. In this study we evaluated a cohort of patients with unresectable HCC treated with gemcitabine-TACE alone.
METHODOLOGY: A review of all patients that underwent gemcitabine-TACE for unresectable HCC from 2002 to 2006 was performed. No patients were eligible for resection, liver transplantation or ablation. All patients received gemcitabine-TACE alone. The primary outcome measure was survival from first treatment. Secondary outcome measures included radiological response and toxicity.
RESULTS: 55 patients underwent a total of 172 gemcitabine-TACE treatments for unresectable HCC. Median age was 64.7 years. All patients had Barcelona-Clinic Liver Cancer (BCLC) stage B (44%) or C (56%) disease. Median survival following gemcitabine-TACE was 8.8 months. 22% demonstrated a partial response and 61% had stable disease. 6% experienced grade 3/4 adverse events. There was 1 treatment related death.
CONCLUSIONS: Gemcitabine-TACE is well tolerated and appears to provide an alternative agent for patients with unresectable HCC undergoing chemoembolization.

Related: Gemcitabine

Wang B, Tao X, Huang CZ, et al.
Decreased expression of liver-type fatty acid-binding protein is associated with poor prognosis in hepatocellular carcinoma.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1321-6 [PubMed] Related Publications
BACKGROUND/AIMS: The purpose of this study was to assess liver-type fatty acid-binding protein (L-FABP) expression and its association with clinicopathological features in hepatocellular carcinoma (HCC).
METHODOLOGY: L-FABP mRNA expression in 57 samples of HCC and corresponding adjacent liver tissue and 8 normal liver tissue samples were examined by real-time reverse transcriptase (RT)–PCR analyses. Tissue microarray technique and immunohistochemistry (IHC) were used to detect the expression of L-FABP in 163 HCCs. The association between L-FABP expression and the clinicopathological factors and prognosis was analyzed.
RESULTS: The average expression of L-FABP mRNA was 0.233 in the HCC tissues, 1.407 in the peri-carcinoma tissues, and 1.0 in the normal liver tissues. IHC analysis showed that there were 47% (76/163) HCCs exhibited weak or even no immunoreactivity of L-FABP. The L-FABP expression in HCC showed significant associations with preoperative levels of AFP (p=0.039), tumor size (p=0.026), histological grade (p=0.000), differential degree (p=0.000), vascular invasion (p=0.016), capsular invasion (p=0.029) and recurrence (p=0.004). Patients with L-FABP high-expression showed better prognosis than patients with L-FABP low-expression (p=0.008).
CONCLUSIONS: L-FABP was downregulated in HCC and could be served as a promising prognostic marker for HCC patients.

Riediger C, Bachmann J, Hapfelmeier A, et al.
Low postoperative platelet count is associated with negative outcome after liver resection for hepatocellular carcinoma.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1313-20 [PubMed] Related Publications
BACKGROUND/AIMS: Hepatocellular carcinoma is one of the most common malignancies worldwide. The only curative treatment is surgery. As hepatocellular carcinoma is often associated with liver cirrhosis, patients are at risk for postoperative liver failure. In the recent years, platelets are thought to play an important role in liver regeneration.The aim of this study was to discover the relevance of postoperative platelet counts after liver resection for hepatocellular carcinoma.
METHODOLOGY: Data of 68 patients who underwent liver resection for hepatocellular carcinoma between July 2007 and July 2012 in a single centre were analysed. Postoperative morbidity and mortality were evaluated in regard to postoperative platelet counts. Comparative analysis between patients with platelet counts ≤100 2x109/ l and >100 x109/ l at d1 was performed in regard to postoperative outcome.
RESULTS: Within this cohort, 43 patients (63%) suffered from histologically proven liver cirrhosis. Postoperative mortality was statistically significant associated with postoperative reduced platelet counts. Comparative analysis showed significantly elevated postoperative bilirubin levels and lower prothrombin time in patients with platelet counts ≤ 100 1x109/ l at d1.
CONCLUSIONS: Postoperative low platelet counts are associated with poor outcome after hepatic resection for hepatocellular carcinoma.

Yunqiao L, Vanke H, Jun X, Tangmeng G
MicroRNA-206, down-regulated in hepatocellular carcinoma, suppresses cell proliferation and promotes apoptosis.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1302-7 [PubMed] Related Publications
BACKGROUND/AIMS: MicroRNA-206 has been proven down-regulated in many human malignancies and correlated with tumor progression. However, the expression and functions of miR-206 in hepatocellular carcinoma (HCC) are still unclear. The aim of this study was to explore the effects of miR-206 in HCC tumorigenesis and development.
METHODOLOGY: The expression levels of miR-206 were quantified by qRT-PCR in 147 surgically resected HCC and matched adjacent non-cancerous tissues, and correlated with clinicopathological factors. MTT, flow cytometric assay, and Transwell invasion and migration assays were used to test the proliferation, apoptosis, invasion, and migration of HepG2 HCC cells transfected with miR-206 mimics or negative control (NC) RNA-oligonucleotides.
RESULTS: MiR-206 expression was significantly downregulated in HCC compared with matched non-cancerous liver tissues. Low level of miR-206 was associated with poor tumor differentiation, multiple tumor nodes, lymph node metastasis, and advanced TNM stage. In addition, transfection of miR-206 mimics in HepG2 cells was able to reduce cell proliferation, invasion, and migration, and promote cell apoptosis.
CONCLUSIONS: These findings demonstrate that miRNA-206 could not only be useful as a novel biomarker but also serve as a potential target for gene therapy of HCC.

Related: Apoptosis MicroRNAs

Ulas M, Ozer I, Bostancil EB, et al.
Giant hemangiomas: effects of size and type of surgical procedure on postoperative outcome.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1297-301 [PubMed] Related Publications
BACKGROUND/AIMS: Controversies still exist regarding the management of giant hemangiomas. The purpose of this study was to evaluate in a retrospective manner the effects of size and type of surgical procedures on early postoperative results.
METHODOLOGY: Between January 2000 and January 2011, a total of 82 patients underwent surgery. Patients were divided into 2 groups; according to size (Group 1 >10cm and Group 2 ≤10cm) and the selected operative procedure.
RESULTS: When the patients were compared according to size of the lesions, the operation time was significantly longer (p=0.01) and the amount of blood loss was significantly higher (p=0.04) in hemangiomas >10cm. If the patients were compared according to type of the surgical procedure, hepatic resection was more frequently preferred in bilobar and left lobe localized lesions, whereas enucleation was significantly more chosen in lesions localized to the right lobe (p=0.01).
CONCLUSIONS: Size of the hemangioma did not alter selection of the surgical procedure in this series. Larger hemangiomas are associated with longer operation time and more blood loss. Surgical results after enucleation and resection are similar. Although enucleation seems preferable, it is not an easy procedure, and may result in severe bleeding.

Tan YN, Li XF, Li JJ, et al.
The accuracy of computed tomography in the pretreatment staging of colorectal cancer.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1207-12 [PubMed] Related Publications
Colorectal cancer (CRC) is one of the most frequent cancers around the world. Multimodality therapies are used for CRC including surgery, chemotherapy, radiotherapy and targeted therapy. Correct treatment plan depends greatly on the accurate pretreatment staging. Computed tomography (CT) is a widely used detection and staging modality for CRC patients in clinical practice. The role of CT in assessing the patients with CRC has been well established, but the accuracy of pretreatment staging by CT varies in different reports. With the development of CT techniques, some reformations such as multi-detector CT (MDCT), CT with water enema or air insufflations, multiple planner reconstruction (MPR) help to give us higher resolution images in shorter time. The accuracy of CT for N staging was still not so ideal, but CT played an important role in chest and liver staging. Magnetic resonance imaging (MRI) and endorectal ultrasound (ERUS) may provide more precise images and evaluation of local T and N staging for rectal cancer. And positron emission tomography (PET) or PET/CT is recommended as a complement of CT, only for cases suspected of residual or recurrent colorectal carcinoma or before metastasectomy, not for routine use.

Herrigel DJ, Moss RA
Diabetes mellitus as a novel risk factor for gastrointestinal malignancies.
Postgrad Med. 2014; 126(6):106-18 [PubMed] Related Publications
Evidence of an emerging etiologic link between diabetes mellitus and several gastrointestinal malignancies is presented. Although a correlation between pancreatic cancer and diabetes mellitus has long been suspected, the potential role diabetes mellitus plays in the pathogenicity of both hepatocellular carcinoma and colon cancer is becoming increasingly well defined. Further supporting the prospect of etiologic linkage, the association of diabetes mellitus with colon cancer is consistently demonstrated to be independent of obesity. An increasing incidence of diabetes and obesity in the United States has led to a recent surge in incidence of hepatocellular cancer on the background of nonalcoholic fatty liver disease, and this disease is expected to commensurately grow in incidence. Widespread recognition of this emerging risk factor may lead to a change in screening practices. Although the mechanisms underlying the correlation are still under investigation, the role of insulin, the insulin-like growth factor-I, and related binding and signaling pathways as regulators of cell growth and cell proliferation are implicated in carcinogenesis and tumor growth. The potential role of metformin and other medications for diabetes mellitus in the chemoprevention, carcinogenesis, and treatment of gastrointestinal malignancies is also presented.

Related: Colorectal (Bowel) Cancer Cancer of the Pancreas Pancreatic Cancer

Pocha C, Knott A, Rector TS, Dieperink E
Are selective serotonin reuptake inhibitors associated with hepatocellular carcinoma in patients with hepatitis C?
J Clin Psychiatry. 2014; 75(10):e1122-6 [PubMed] Related Publications
BACKGROUND AND AIMS: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for patients with chronic hepatitis C virus (HCV) infection. Research suggests that serotonin promotes the development and growth of hepatocellular carcinoma (HCC). We tested the hypothesis whether exposure to SSRIs is associated with an increased risk of HCC in HCV patients.
METHOD: Patients who entered the United States Veterans Affairs (VA) Hepatitis C Clinical Case Registry in 2000 to 2009 were analyzed. During the 8 years of follow-up, 36,192 patients filled at least 1 SSRI prescription. Cases of HCC were identified by diagnosis codes (ICD-9 155.0). Multivariable Cox regression analyses estimated adjusted HCC hazard ratios (HRs) for SSRI-exposed versus SSRI-unexposed subjects and categories of average SSRI doses.
RESULTS: The annual incidence of HCC in the VA registry cohort of 109,736 patients was 0.5% and significantly greater in the 8% with cirrhosis at baseline (HR = 5.2; 95% CI, 4.7-5.7). There was no evidence for significant interactions between the effect of SSRI-exposure and cirrhosis. Baseline characteristics of the exposed (n = 36,192) and unexposed (n = 73,544) subjects were similar. The median (interquartile range [IQR]) follow-up period after SSRI-exposure began was 44 (20-74) months with 18 (3-49) months between the first and last prescription. The median average SSRI dose during follow-up expressed as a fraction of initial recommended doses for depression was 0.94 (IQR, 0.5 to 1.3). The risk of HCC was not significantly increased after SSRI exposure (HR = 0.96; 95% CI, 0.87-1.05) or with increasing SSRI doses.
CONCLUSIONS: Analysis of a large cohort of HCV patients did not support the hypothesis that SSRIs increase the risk of developing HCC.

Related: USA

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