Abstract:

Objective: To investigate the indication and value of surgical treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Methods: The clinicopathologic and follow-up data of 335 patients with HCC and PVTT were retrospectively analyzed. Of the patients, 273 cases underwent surgical treatment that included anatomic or non-anatomic liver resection (HR) plus PVTT removal (HR group), and 62 cases were subjected to transcatheter arterial chemoembolization (TACE) treatment (TACE group). The post-treatment survival between the two groups of patients was compared. Results: The median survival time for HR group and TACE group was 4.46 and 5.65 months, respectively, which had no significant difference (P=0.455); the 6- and 12-month survival rate for HR group was 30.7% and 12.1%, for TACE group was 38.7% and 19.2% respectively, which also showed no significant difference (both P>0.05). Conclusion: Concomitant PVTT in HCC is not a surgical contraindication, for which HR is safe and feasible, but offers no obvious survival advantage, so the option of surgical treatment should be considered cautiously according to the individualized assessments. The overall therapeutic effectiveness on this condition can be improved by the development of multi-disciplinary team (MDT) and precise medicine model in HCC treatment.

Abstract:

Objective: To investigate the surgical treatment for patients with hepatocellular carcinoma (HCC) and concomitant portal vein tumor thrombus (PVTT) and the efficacy. Methods: The clinical data of 68 HCC patients with PVTT treated from January 2010 to January 2013 were retrospectively analyzed. Of the patients, 50 cases underwent surgical treatment (regular hemihepatectomy plus involved portal vein resection, or irregular liver resection and PVTT removal) followed by transcatheter arterial chemoembolization (TACE) (combination treatment group), and 18 cases received treatment of oral sorafenib only (sorafenib treatment group). PVTT involved the second- or lower-order portal vein branches in 11 cases, and involved the first-order portal vein branches in 39 cases in combination treatment group, and all cases in sorafenib treatment group had PVTT in the first-order portal vein branches. The 0.5-, 1-, 2-, and 3-year survival rate, overall survival (OS) and time to tumor progression (TTP) of the patients were analyzed. Results: In combination treatment group, the 0.5-, 1-, 2-, and 3-year survival rate for patients with the second- or lower-order portal vein branch involvement was 100%, 90.9%, 18.2% and 9.1%, and for patients with the first-order portal vein branch involvement was 87.2%, 51.3%, 15.4% and 5.1%, which for patients in sorafenib treatment group was 83.3%, 33.3%, 0% and 0%, respectively. In combination treatment group, the median OS and TTP for patients with the second- or lower-order portal vein branch involvement was 16 and 7 months, and for patients with the first-order portal vein branch involvement was 12 and 5 months, which for patients in sorafenib treatment group was 9 and 4 months, respectively. Statistical analysis showed that both median OS and TTP for patients either with the second- or lower-order portal vein branch involvement, or the first-order portal vein branch involvement were significantly longer than those for patients in sorafenib treatment group (all P<0.05). Conclusion: Surgical resection followed with TACE treatment can be performed in patients with advanced HCC and PVTT involving the first- or lower-order portal branches, which may offer better efficacy than lone sorafenib administration.

Abstract:

Objective: To investigate the efficacy of anatomic right trisegmentectomy for huge or multifocal right hepatic hepatocellular carcinoma (HCC). Methods: Twelve patients with huge or multifocal right hepatic HCC tumors underwent anatomic right trisegmentectomy with preservation of segment V or VIII, in whom the preoperative CT-based liver volumetry suggested that the percentage of future liver remnant volume (%FLRV) would be insufficient for them after right hemihepatectomy, which could be increased by an average of 14.3% by right trisegmentectomy instead. During operation, the segment V or VIII was identified by use of selective hepatic inflow occlusion, and then a “┏┛” or “┕┓”shaped resection line was marked on the diaphragmatic surface of the liver; right hemihepatic or total hepatic inflow occlusion was used according to different resection plane to avoid ischemia/reperfusion injury during parenchymal transection. Results: Anatomic right trisegmentectomy was successfully completed in all patients, with an average operative time of 285 min and intraoperative blood loss of 720 mL. The tumors in all patients were completely resected, the inflow and outflow of segment V or VIII remained intact, no perioperative death occurred, and AFP level in all patients returned to normal range within 2 months after operation. Of the whole group of 12 patients, 10 cases were alive so far with a longest tumor-free survival for 3 years in one case; one case died of obstructive suppurative cholangitis, and one case died of multiple intrahepatic metastases and liver failure, while one case with left hepatic recurrence and 2 cases with lung metastases lived with tumor under comprehensive therapy, but in the remaining cases, no tumor recurrence or metastasis occurred, and liver function parameters and AFP level were in normal ranges. Conclusion: Anatomic right trisegmentectomy guarantees the maximum preservation of remnant functional liver tissue, so it can be a conventional operation for patients with huge or multifocal right hepatic HCC without segment V or VIII involvement, and thereby improves the overall resection rate of HCC.

Abstract:

Objective: To evaluate the efficacy of percutaneous thermal ablation in treatment of very early stage hepatocellular carcinoma (HCC) and the prognostic factors. Methods: The clinical data of 139 patients with very early stage HCC undergoing ultrasound-guided percutaneous thermal ablation from January 2007 to January 2010 were reviewed. The complete ablation rate, overall survival rate and disease-free survival rate were determined and the influential prognost0ic factors were analyzed. Results: In whole group of patients, the complete ablation rate was 97.84%; the average survival time was (70.10±28.87) months, and the 1-, 3-, and 5-year overall survival rates was 94.90%, 87.70% and 73.10%, respectively; the average disease-free survival time was (44.70±24.21) months, and the 1-, 3-, and 5-year disease-free survival rate was 90.60%, 61.90% and 43.20%, respectively. The results of univariate and multivariate analysis showed that age more than 60 years, disease-free survival time less than 2 years and extrahepatic metastases were independent risk factors for overall survival (all P<0.05); hepatitis C infection and preoperative high AFP level were unfavorable factors for disease-free survival (all P<0.05). Conclusion: Percutaneous thermal ablation is a safe and effective treatment modality for very early stage HCC. However, patients with an old age, short-term recurrence after operation, extrahepatic metastases, high preoperative AFP level and hepatitis C infection may face poor outcomes.

Abstract:Objective: To establish a predictive index (PI) model for estimation of postoperative survival in patients with hepatitis B-related hepatocellular carcinoma (HCC). Methods: The clinical data of 102 patients with hepatitis B-related HCC undergoing hepatectomy in the First Affiliated Hospital of Xinjiang Medical University during October 2007 to October 2009 were collected. The variables affecting the postoperative 5-year survival of the patients were determined by using COX proportional hazard regression method, then, based on the results from above analyses, the PI model was established and finally the accuracy of the established PI model was verified. Results: Multivariate COX regression analysis showed that the neutrophil-to-lymphocyte ratio (NLR), microvascular invasion (MVI), the maximum size of tumor (MST), the amount of tumor (AT), postoperative transarterial chemoembolization (TACE) treatment were independent variables affecting the prognosis in these patients (all P<0.05). The PI model was established according to the above variables and was expressed as PI=0.317×NLR+0.958×MVI (Yes=1, No=0) +0.700×MST (<5 cm=0, ≥5 cm=1) +0.945×AT (multiple=1, single=0) –1.168×TACE (Yes=1, No=0). The verification results demonstrated that and the AUC of this model for predicting the 5-year survival of the patients reached 0.795, with the cut-off value of 1.46 and accuracy of 75.49%, respectively. Conclusion: The PI model for predicting the postoperative 5-year survival of patients with hepatitis B-related HCC is established successfully,which may be of help to estimate the prognosis and choose a proper treatment plan for these patients in clinical practice.

Abstract:Objective: To investigate the influence of sorafenib on growth and expressions of tumor-related genes in human hepatocellular carcinoma (HCC) cells in vitro. Methods: Human HCC cells (Hep3B2.1-7) were exposed to different concentrations (0, 5, 10, and 20 μmol/L) of sorafenib for 24 h, and then, the cell proliferation was analyzed by CCK-8 assay, and the mRNA and protein expressions of p53, PTEN and TGF-β1 in the HCC cells were determined by real-time PCR and Western blot, respectively. Results: Compared with the group of cells with 0 μmol/L sorafenib treatment (control group), in the other groups of cells with sorafenib treatment, the cell proliferation rates were all significantly decreased (all P<0.05); the mRNA and protein expressions of p53 and PTEN were significantly increased, while the mRNA and protein expressions of TGF-β1 were significantly decreased (all P<0.05). All these effects of sorafenib showed a certain concentration-dependent manner. Conclusion: Sorafenib can inhibit the growth of human HCC cells in vitro, and the mechanism may be attributed to its regulating the expressions of tumor-related genes.

Abstract:Objective: To investigate the influence of miR-101 on the biological behavior of hepatocellular carcinoma (HCC) cells. Methods: The HCC HepG2 and SMMC-7721 cells were transfected with miR-101 mimics or miRNA negative control sequences, using the two types of cells cultured without any treatment as corresponding blank control, and then the effect of miR-101 on proliferation, colony formation ability, apoptosis and cell cycle, as well as the migration and invasion ability of the two types of cells were observed. Results: Compared with corresponding blank control, in either HepG2 or SMMC-7721 cells after transfection with miR-101 minics, the proliferative ability was decreased, colony formation was reduced, G0/G1 phase cell ratio was increased, apoptosis rate was increased, and the ability of migration and invasion was reduced markedly (all P<0.05); transfection of miRNA negative control sequences exerted no obvious effect on above parameters for the two types of cells (all P>0.05). Conclusion: miR-101 possibly plays a role as cancer suppressor gene in HCC cells, and upregulating its expression may suppress the malignant activity of HCC.

Abstract:Objective: To establish a stable 30% reduced-size liver transplantation model in rats. Methods: Using male SD rats of similar weight, the reduced-size grafts were obtained by resecting the hepatic left and medial lobe in vivo, with preservation of the caudate, right and triangle lobe of the liver, and liver implantation was performed by two-cuff technique, respectively. The wet weight ratio of graft to the entire liver was determined, and the 2- and 7-d post-implantation survival rates were observed. Results: A total of 80 reduced-size liver transplantation rat models were created. The wet weight of graft and entire liver was (4.02±0.64) g and (11.84±1.36) g respectively, and the wet weight ratio graft to entire liver was 33.81%, with the 95% confident interval of 33.22% to 34.40%. The 2- and 7-d post-implantation survival rate of the recipient was 84% and 66% respectively, and the main causes of death included abdominal hemorrhage, bile leakage, abdominal infection, chronic liver graft dysfunction, and pulmonary infection. Conclusion: The method of resecting left and middle lobe can maximally reduce the non-functional remnant liver, with weight ratio of remnant liver to entire liver approximating to 30%, by which the stable reduced-size liver transplantation model can be established.

Abstract:Objective: To investigate the function of cholic acid (CA) in liver regeneration of obstructive jaundice (OJ) following partial hepatectomy in mice and the mechanism. Methods: One hundred and eighty healthy male mice were equally randomized into 6 groups, and underwent sham operation (control group), common bile duct ligation (OJ group), common bile duct ligation followed by external drainage (ED)7 d later (ED group), common bile duct ligation plus 0.2%CA gavage followed by ED 7 d later (ED+0.2%CA group), common bile duct ligation plus 1%CA gavage followed by ED 7 d later (ED+1%CA group), and common bile duct ligation followed by internal drainage (ID) 7 d later (ID group), respectively. In the 14th day of experiment, partial (70%) liver resection was performed in each group of mice, and ID conversion was made in each group of mice with ED treatment. On different time points after hepatecomy, the liver regeneration rate and expression of proliferation-associated nuclear antigen Ki-67, mRNA expression of forkhead box M1b (Foxm1b), and protein expression of fibroblast growth factor receptor 4 (FGFR4) in the liver tissue were determined, and in situ apoptosis of hepatic cells was also observed in some of the groups. Results: Excluding the control group, the liver regeneration rate, Ki-67 positive expression rate, and Foxm1b mRNA as well as FGFR4 protein expression levels in the remaining groups were all presented in a decreasing order as follows: ID group>ED+0.2%CA group>ED group>OJ group>ED+1%CA group, and all inter-group differences had statistical significance (all P<0.05); there was no significant difference in any of the above parameters between ID group and control group (all P>0.05). The apoptosis rate of hepatic cells showed a decreasing order as follows: ED+1%CA group>ED group>ED+0.2%CA group>control group, and all inter-group differences had statistical significance (all P<0.05). Conclusion: ID is beneficial to liver regeneration after liver resection through reducing endogenous CA loss; low concentration of exogenous CA supplement can improve the liver regeneration retardation caused by ED, which may be associated with its up-regulating Foxm1b and FGFR4 expressions, and thereby promote liver regeneration.

Abstract:Objective: To investigate the expressions and clinical significance of high mobility group protein box l (HMGBl) and NF-κB in tissues of hepatolithiasis-associated intrahepatic cholangiocarcinoma. Methods: The expressions of HMGB1 and NF-κB in tumor tissues from 40 cases of hepatolithiasis-associated intrahepatic cholangiocarcinoma (tumor group), inflammatory bile duct tissues from 40 cases of simple hepatolithiasis (inflammatory group) and normal bile duct tissues form 30 cases undergoing surgical resection for hepatic hemangioma or liver injury (normal group) were determined by immunohistochemical staining. The difference in expressions of the two proteins among the tissues was compared and their relations with clinicopathologic factors and prognosis of the patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma were analyzed. Results: Both expression intensities of HMGB1 and NF-κB among the different tissues were statistically different, which were increased in the order of normal group, inflammatory group, and tumor group,respectively (all P<0.05); there was a positive correlation between the expressions of HMGB1 and NF-κB in cholangiocarcinoma tissue (χ2=13.713, r=0.586, P<0.05). The HMGB1 expression was significantly associated with the degree of tumor differentiation, the depth of tumor invasion and the lymph node metastasis in patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma (all P<0.05), while the NF-κB expression showed no significant relation with any of the selected factors (all P>0.05). In patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma, the survival rate in cases with positive HMGB1 expression was significantly lower than those with negative HMGB1 expression (P<0.05), however, the NF-κB expression exerted no impact on survival (P>0.05). Conclusion: The HMGB1/NF-κB pathway probably participate in the process of occurrence and development of hepatolithiasis-associated intrahepatic cholangiocarcinoma, and HMGB1 expression may exert a decisive impact on degree of malignancy of the tumor and prognosis of the patients.

Abstract:Objective: To investigate the protective effect of tauroursodeoxycholic acid (TUDCA) against hepatic ischemia reperfusion injury (HIRI) in rat and the mechanism. Methods: Twenty male SD rats were equally randomized into sham operation group, TUDCA group, HIRI group and TUDCA plus HIRI group, and underwent sham operation, TUDCA treatment plus sham operation, HIRI model induction, and TUDCA treatment plus HIRI model induction, respectively. TUDCA (250 mg/kg) was administered by gavage 1 h before operation, and HIRI rat model was induced by Pringle maneuver (60-min hepatic ischemia followed by 12-h reperfusion). Rats in each group were sacrificed after 12-h reperfusion and the hepatic samples were collected; the pathological changes in liver tissues were observed, serum alanine aminotransferase (ALT) level was measured, apoptosis of hepatic cells was determined by TUNEL staining, and the proteins associated with endoplasmic reticulum (ER) stress which included glucose regulate protein 78(GRP78), p-eukaryotic translation initiation factor-2α (p-eIF2α) and C-EBP response element binding protein (CHOP) were determined by Western blot analysis. Results: Except in sham operation group and TUDCA group, the liver tissues in either HIRI group or TUDCA plus HIRI group presented the evident pathological changes associated with liver injury, but the degree of injury in TUDCA plus HIRI group was milder than that in HIRI group. Compared with sham operation group, the serum ALT levels, hepatic cell apoptosis and the protein expression levels of GRP78, p-eIF2a and CHOP in liver tissues were significantly increased in both HIRI group and TUDCA plus HIRI group (all P<0.05), but the increasing amplitudes of all these parameters in TUDCA plus HIRI group were significantly less than those in HIRI group (all P<0.05); all the parameters in TUDCA showed no significant alteration (all P>0.05). Conclusion: TUDCA has protective effect against HIRI in rats, and the mechanism may probably be associated with its suppression of ER stress response.

Abstract:Objective: To assess the clinical efficacy of laparoscopic microwave ablation for symptomatic hepatic hemangioma less than 10 cm in diameter. Methods: The clinical data of 145 patients with hepatic hemangioma admitted to Tongji Hospital of Huazhong University of Science and Technology from January 2011 to January 2014 were analyzed. Of the patients, 58 patients underwent laparoscopic microwave ablation (laparoscopic microwave ablation group), while the other 87 patients underwent surgical resection (surgical resection group). The short-term and long-term outcomes of the two methods of treatment for hepatic hemangioma were evaluated. Results: The preoperative data of the two groups of patients were comparable. In laparoscopic microwave ablation group, the variables that included operative time, intraoperative blood loss, number of cases requiring blood transfusion, incidence of postoperative complications, and length of postoperative hospital stay were all superior to those in surgical resection group (all P<0.05), while the symptom- eliminating efficacy was similar to that in surgical resection group. All patients were followed up, and no recurrence was noted. Conclusion: Laparoscopic microwave ablation has proven efficacy in treatment of symptomatic hepatic hemangioma with diameter less than 10 cm, with advantages of being safe, minimal invasiveness, and less complications.

Abstract:Objective: To determine the application value of preoperative dual-source CT (DSCT) hepatic angiography with 3-D reconstruction plus intraoperative regional blood flow occlusion and persistent methylene blue dyeing in precise liver resection. Methods: Thirty-seven liver cancer patients underwent DSCT hepatic tumor angiography with 3-D reconstruction, followed by the surgical procedure that in order included dissection of the first hepatic hilum, exposure of each vessel enveloped by the sheath of Glisson’s capsule into the lobe or segments to be resected, methylene blue injection through the tributaries of the portal vein (or through the bile duct in cases with portal vein tumor thrombus) to the lobe or segments to be resected, and then occlusion of blood flow of the liver to be resected, and lobectomy or segmentectomy according to the boundary of methylene blue dyeing. These 37 patients (observational group) were compared with 32 liver cancer patients undergoing conventional liver resection (control group) during the same period. Results: In the 37 cases of observational group undergoing precise liver resection, the results of preoperative hepatic angiography were consistent with the views of intraoperative liver staining. Compared with control group, in observational group, the operative time was prolonged, but the blood loss during liver resection was reduced, the changes in liver function parameters were mild with quicker recovery, the incidence of postoperative complications was decreased and the length of hospital stay was shortened (all P<0.05). Conclusion: Using preoperative hepatic angiography and 3-D reconstruction plus persistent methylene blue dyeing and regional blood flow occlusion in precise liver resection can reduce bleeding, avoid injury of the vessels of Glisson’s system of the preserved liver tissue, and reduce the damage of liver function and surgical complications.

Abstract:Objective: To review the clinicopathologic features of the infantile hepatic hemangioendothelioma (IHHE) in adults, so as to improve the diagnosis and treatment for this disease. Methods: The clinical data of 7 adult patients (age ranged from 32 to 63 years) with pathological confirmation of IHHE, who underwent surgical treatment from January 2003 to December 2013 in Eastern Hepatobiliary Surgery Hospital, were retrospectively analyzed. Results: Of the 7 patients, 5 cases had no obvious clinical symptoms before operation, and the other cases had intermittent pain in the right upper abdomen and anorexia, respectively. The routine blood tests and liver function parameters showed no obvious abnormality, tumor markers and hepatitis virus indexes were all negative, and results of the CD34 immunohistochemical staining were all positive. All cases had a solitary lesion, and diagnosis was not confirmed by preoperative imaging examination. All patients were followed up regularly after operation, and no tumor recurrence was noted, as of August 2014. Conclusion: IHHE in adults is an extremely rare condition, and in cases without a history of hepatitis or positive result of tumor markers, and after exclusion of cavernous hemangioma by CT and MRI findings, this condition should be considered.

Abstract:Objective: To determine the application value of quantitative analysis of contrast-enhanced ultrasonography (CEUS) in evaluation of early response of colorectal cancer liver metastasis to bevacizumab plus cytotoxic chemotherapy or cytotoxic chemotherapy alone. Methods: Twenty-eight patients with colorectal cancer liver metastasis were designated to bevacizumab plus mFOLFOX6 treatment group and mFOLFOX6 alone treatment group, with 14 cases in each group. Conventional ultrasound and CEUS were performed 1d prior to the first four administrations of chemotherapy, and quantitative parameters of liver metastases were recorded by using contrast dynamic software. Based on the final results assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), the differences in percentage change of the quantitative parameters of the liver lesions between 1d prior to first-course chemotherapy and 1d prior to second-course chemotherapy were compared between responders and non-responders of the two groups, respectively. Results: The percentage change of lesion quantitative parameter peak intensity (PI) was statistically different (P=0.03), but that of all other parameters showed no statistical difference between responders and non-responders in bevacizumab plus mFOLFOX6 treatment group (all P>0.05); no statistical difference was noted in percentage change of lesion quantitative parameters between responders and non-responders in mFOLFOX6 alone treatment group (all P>0.05). Conclusion: CEUS quantitative parameter PI has certain application value in evaluation of early response of colorectal cancer liver metastasis to bevacizumab plus cytotoxic chemotherapy.

Abstract:Primary liver cancer is a malignant tumor caused by abnormal cellular proliferation and differentiation of the hepatic cells or bile duct cells. The formation of tumor thrombus is one of the most important factors for the poor prognosis of primary liver cancer, so a better understanding of tumor thrombus (including portal vein tumor thrombus and bile duct tumor thrombus) has great importance for clinical management and estimation of prognosis. This paper addresses the research progress in the study of primary liver cancer complicated with tumor thrombus.

Abstract:

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. At present, immunotherapy has become the fourth treatment for HCC following surgery, radiotherapy and chemotherapy. Many studies have proven that immunotherapy can improve the systemic immunological function to reduce the recurrence and metastasis of HCC and prolong the survival time for HCC patients. Dendritic cells (DC) are the most powerful antigen-presenting cells in vivo and play an important role in anti-tumor immune response. The DC-based immunotherapy including DC anti-tumor vaccine, DC-cytokine induced killer cells immunotherapy and DC immunotherapy combined with transcatheter arterial chemoembolization or photodynamic therapy has become the research focus in immunotherapy of HCC and also shown a promising direction. This review concentrates on the research progress of DC-based immunotherapy for HCC in recent years.

Abstract:Tumor suppressor miRNA-7 (miR-7) is found down-regulated in cancer tissues, but the underlying mechanism remains elusive. Recent studies demonstrated that circular RNA-7 (ciRS-7) acts as a sponge for miR-7 and thus can inhibit the miRNA-7 activity. This finding provided a new perspective for revealing the mechanisms of decreased expression of miR-7 in tumors. It is now believed that the ciRS-7/miR-7 axis not only has important biological functions, but participates in the occurrence and development of a range of diseases. Here, the authors present the research progress in ciRS-7/miR-7 axis regulating tumor growth and metastasis.

Abstract:

With the development and improvement in technology of diagnosis and therapy, the detection rate of liver fibrosis has been greatly improved and its reversibility has also been recognized by relevant studies. Here, the authors, based on the literature review and extraction, present the current advances in diagnosis and treatment of liver fibrosis.

Abstract:Liver fibrosis characterized by excessive deposition of collagenous tissue in the liver, is the consequence of chronic liver injury of different etiologies, and may even progress to cirrhosis and liver cancer. Activation of the hepatic stellate cells (HSC) resulting in an imbalance between production and degeneration of the extracellular matrix (ECM) is an important part in the occurrence and development of liver fibrosis. Oxidative stress response as one of the important mechanisms participating in the HSC activation and ECM deposition is closely related to liver fibrosis, so using antioxidant agents for management of liver fibrosis have become the focus of interest. In this article, the authors address the recent development in antioxidant therapy for liver fibrosis.