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Hypoxia and hypoxia-driven angiogenesis play an important role on the recurrence of hepatocellular carcinoma after insufficient radiofrequency ablation. The hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor-A (VEGFA) pathway plays an important part in this process. Sorafenib is a multikinase inhibitor with activity against several receptor tyrosine kinases. However, it is unclear whether sorafenib can affect the HIF-1α/VEGFA pathway. Here, we explore whether sorafenib affects HIF-1α and the change of invasion ability in this process. In this experiment, the control group, cobalt chloride (CoCl2)-treated group, sorafenib-treated group, and cobalt chloride combined with sorafenib-treated group were adopted. Western blot and PCR were performed to detect the protein and mRNA expression of HIF-1α and VEGFA in different groups. Transwell assay was used to test the changes of invasion ability. Flow cytometry was adopted to detect the apoptotic role of sorafenib on hepatoma cells. Cobalt chloride upregulated the expression of HIF-1α protein, and the upregulation effect was more obvious when the concentration was increased gradually. Sorafenib inhibited cobalt-induced HIF-1α and VEGFA expression in hepatoma cells. Sorafenib decreased the tumor cell invasiveness induced by cobalt chloride in vitro. Sorafenib inhibited cell proliferation and induced apoptosis in hepatoma cells. These results showed that sorafenib was an effective inhibitor of the HIF-1α/VEGFA pathway, which can provide new insight into the mechanism of its anticancer activity. [ABSTRACT FROM AUTHOR]

Objective: To explore the technical success rate, efficacy, overall survival, recurrence-free survival and prognostic factors of transcatheter arterial chemoembolization (TACE) plus thermal ablations of radiofrequency ablation (RFA) and microwave ablation (MWA) in the patients with large hepatocellular carcinoma (HCC)., Methods: Forty-five cases with Child-pugh class A, B cirrhosis and large HCC with a maximum tumor between 5.0 cm to 10.0 cm underwent TACE and thermal ablation. Twenty-five patients received TACE plus RFA while the other 20 patients underwent TACE plus MWA. Their efficacy, long-term survival and prognostic factors were statistically analyzed., Results: TACE plus thermal ablation were performed in 84 tumors with a successful rate of 100% (86/86) and a complete ablation rate of 94.0% (79/84). The major complication rate was 6.7% (3/45). Local and distant recurrence rates were 66.7% (30/45) and 71.1% (32/45) respectively. The 1 and 2-year recurrence-free survival rates were 26.7% (12/45) and 13.3% (6/45). And the 1, 2 and 3-year survival rates were 80.0% (36/45), 33.3% (15/45) and 6.7% (3/45) respectively. Univariate and Cox regression analyses indicated that tumor size > 7.0 cm, multi-nodularity, incomplete necrosis and pretherapy α-fetoprotein (AFP) ≥ 200 µg/L were 4 unfavorable prognostic factors for the long-term survival., Conclusion: The combined procedures of TACE and percutaneous thermal ablation are both safe and effective for the unresectable large HCC (> 5.0 cm). It represents an alleviate treatment for those patients with tumor size > 7.0 cm. Tumor size, tumor number, completeness of necrosis and AFP level are all significant prognostic factors.

Objective: To compare the outcomes between anterior versus conventional approach right hepatectomy for large hepatocellular carcinoma (HCC)., Methods: A total of 188 consecutive patients with large HCC ( > or =5 cm) undergoing right hepatectomy were reviewed retrospectively. Among them, 92 patients received anterior approach right hepatectomy (anterior group) while the other conventional right hepatectomy (conventional group). Their clinicopathologic data and survivals were compared., Results: There were five surgical deaths (2.7%), two in the anterior group and three in the conventional group. The biochemical and tumor pathological data (except for tumor size) of these two groups were comparable. The mean intraoperative blood loss, the number of patients with massive hemorrhage ( >3000 ml) and the volume of blood transfusion of the anterior group were markedly less than those of conventional group. The 1-, 3-year disease-free survival rates of the anterior group were significantly better than those of the conventional group (56.2%, 30.9% vs. 39.1%, 13.0%, P = 0.043). The 1- & 3-year cumulative survival rates of the anterior group were also markedly higher than those of conventional group. The Cox regression model indicated that tumor size [P = 0.014, odd ratio (OD) = 1.074] and surgical procedure (P = 0.009, OD = 0. 468) were independent risk factors correlated with disease-free survival. And the surgical procedure (P = 0.003, OD = 0.369) was the only independent risk factor for postoperative cumulative survival., Conclusion: Anterior approach right hepatectomy can significantly decrease intraoperative blood loss. The postoperative survivals of large HCC patients are significantly improved by anterior approach right hepatectomy.

Objective: To investigate the safety and efficacy of hepatic resection combined with intraoperative ablation to treat multifocal hepatocellular carcinoma., Methods: Clinical data of patients diagnosed with multifocal hepatocellular carcinoma and treated with hepatic resection combined with intraoperative ablation from March 1998 to September 2007 were retrospectively reviewed. Treatment response, postoperative complications and survival data were analyzed., Results: Combined treatment modalities were well tolerated except one patient dying of postoperative hepatic functional failure. The postoperative complication rate was 23.5% with a mortality rate of 6.7%. Postoperative complication included wound infection (1 case), bile leakage (1 case), subphrenic and pleural effusion (1 case), ablation-associated liver abscess (1 case), all of which were treated with non-surgical methods. The median survival time was 25.9 months. The 1, 3, 5 year survival rates were 70.6% (12/17), 23.5% (4/17), 17.6% (3/17), respectively. Three patients survived more than 5 years after surgery. Up to April 2008, 4 patients were still alive., Conclusion: Hepatectomy combined with intraoperative thermal ablation provides a treatment modality for patients with multifocal hepatocellular carcinoma and may improve the prognosis.

Objective: To evaluate the clinical value of high frequency ultrasound in diagnosing peripheral nerve diseases (PNDs)., Methods: From January 2003 to December 2006, 64 cases of PNDs were analyzed retrospectively. The ultrasound diagnosis was compared with the operative and pathological diagnosis., Results: Based on the operative and histopathological results, in 38 patients with trauma or entrapment, 38 among 45 traumatic nerves were rightly diagnosed by ultrasound. The coincidence rate was 84.4%. In 26 patients with original peripheral nerve tumors (PNTs), including 20 neurilemmomas, 4 neurofibromas and 2 malignant neurilemmomas, 16 cases were diagnosed by ultrasound with a coincidence rate of 61.5%. The coincidence rates in limbs and trunk were 86.7% (13/15) and 27.3% (3/11) respectively., Conclusions: The study suggests that high frequency ultrasound can locate peripheral nerve trauma precisely, assess the impair degree correctly and provide useful information for clinic diagnosis. The high frequency ultrasound brings better diagnosis outcome in limbs nerve tumors than in trunk.

Objective: To investigate the value of contrast-enhanced ultrasound in the differential diagnosis of solid focal lesions of pancreas (s-FLPs)., Methods: We retrospectively analyzed the clinical data of 56 s-FLPs examined with contrast agent combined with low mechanical indicators contrast-enhanced ultrasound., Results: The surrounding pancreas parenchyma enhancement time, lesion enhancement time, and peak enhancement time between different groups of s-FLPs had no significant differences (P > 0.05), while the beginning to peak enhancement time showed significant difference (P < 0.05). When using the enhancement speed as a diagnostic indicator to differentiate pancreatic carcinoma from tumor-like pancreatitis, the sensitivity, specificity, and accuracy were 90.5%, 71.4%, and 85.7% for pancreatic carcinoma and 75.0%, 91.7%, and 89.3% for tumor-like pancreatitis. When using the enhancement pattern as a diagnosis indicator to differentiate pancreatic carcinoma from tumor-like pancreatitis, the sensitivity, specificity, and accuracy were 85.7%, 78.6%, and 83.9% for pancreatic carcinoma and 75.0%, 100%, and 94.6% for tumor-like pancreatitis. When different indicators were combined, enhancement pattern and enhancement speed showed the best diagnostic results; however, the Youden index was not improved., Conclusions: Different s-FLPs show different enhancement findings on contrast-enhanced ultrasound. The enhancement pattern and enhancement speed are the most useful diagnostic indicators.

Objective: To evaluate the optimal timing of hepatectomy for intrahepatic lithiasis complicated with acute cholangitis., Methods: One hundred and twenty-six patients with hepatolithiasis who had a history of acute cholangitis and underwent hepatectomy were reviewed retrospectively. According to the period between the surgery and last attack of acute cholangitis, 126 patients were divided into 3 groups: > 3 months (group A, n = 73), 1 approximately 3 months (group B, n = 28), < 1 month (group C, n = 25). The operation time, blood loss, hospital stay, postoperative complications and stone residual rate were compared among the groups., Results: The intraoperative blood loss of C group was (644.0 +/- 625.7) ml, which was significantly higher than those of A and B group [(409.2 +/- 250.7) ml and (423.2 +/- 237.1) ml, respectively]. The numbers of patients who needed transfusion and the amount of blood transfusion in group C were also higher than those of group A and B. The incidence rate of complications, residual stone in group C were all markedly higher than those of group A and B. The period of hospital stay in group C was much longer than that in group A and B., Conclusions: The optimal timing of hepatectomy for hepatolithiasis complicated with acute cholangitis is at least one month after subsidence of cholangitis.

Objective: To summarize the experience of surgical resection of 103 hilar cholangiocarcinoma., Methods: One hundred and three consecutive cases of hilar cholangiocarcinoma who underwent surgical resection at our hospital over the past ten years were reviewed retrospectively. The clinical data and long-term outcome were analyzed., Results: Out of 103 cases, 43 patients underwent radical resection (41.7%), and 60 patients underwent palliative resection. There were 34 patients developed postoperative complications and 8 patients died in hospital. For the radical resection group, the median survival time was 29.9 months and 1-year, 3-year, 5-year survival rate was 69.6%, 42.0%, 20.9%, respectively, which was significant greater than 34.1%, 10.2%, 0 of the palliative resection group (P < 0.05). Over the past five years, 42 cases underwent pre-operative drainage of bile and the rate of combined liver resection reached 53.8%. The tumor radical resection rate has increased to 45.7%, the median survival time have reached 24.7 months (P < 0.05)., Conclusions: Improvement of pre-operative management, intraoperative pathology for resection margin, and combined liver resection may help in increasing the radical resection rate. Radical resection can improve postoperative survival, and produce a satisfactory outcome for patient with hepatic hilar cholangiocarcinoma.

Objective: To compare the clinical results of surgical resection (SR) and percutaneous thermal ablation (PTA) for early-stage hepatocellular carcinoma (HCC) (single tumor nodule

Objective: To evaluate the clinical performance of an innovative contrast-enhanced ultrasound (CEUS) technique in characterization of focal liver lesions (FLL)., Methods: CEUS was performed in 505 patients with FLLs. A sulfur hexafluoride-filled microbubble ultrasound contrast agent and a continuous real-time imaging technique of contrast pulse sequencing were used. The observation items included initial nodule enhancement time, enhancement level and pattern, and dynamic evolution of enhancement along with the CEUS phases., Results: There were similar findings for both malignant and benign FLLs in initial enhancement time and enhancement level on CEUS. The dynamic evolution of enhancement along with enhancement phase was the most significant parameter for characterization of FLLs. Most malignant lesions showed enhancement at arterial phase and hypo-enhancing at late phase, whereas the benign lesions presented enhancement at arterial phase and persistent hyper- or iso-enhancing until late phase. Using these characteristics as a diagnostic criteria, the sensitivity, specificity, positive predicative value, negative predicative value and accuracy of CEUS in identifying malignant FLLs were 95.7% (313/327), 86.0% (153/178), 92.6% (313/338), 91.6% (153/167) and 92.3% (466/505), respectively., Conclusions: Characterization of FLLs by using the innovative CEUS technique is recommendable due to its safety, facility and high accuracy.

Objective: To evaluate the effects of autologous tumor vaccines in preventing recurrences of hepatocellular carcinoma (HCC)., Methods: From March 1999 to June 2003, 80 patients with HCC undergoing resections were randomly assigned into a tumor vaccine group (n=40) and a control group (n=40). Tumor vaccines, consisting of formalin-fixed HCC tissue fragments, biodegradable sustained-releasers of granulocyte-macrophage-colony stimulating factor, interleukin-2, and an adjuvant, were developed. Every vaccine group patient received 3 vaccinations at a 2-week interval and the control group just received the adjuvant. Delayed-type-hypersensitivity (DTH) test and recurrent rates were analyzed., Results: Eight patients of the vaccine group and five patients of the control group were lost in the follow-up. Thirty-two patients completed the tumor vaccine procedure and no essential adverse effects occurred. 23/32 patients developed DTH responses against the fragments of HCC. The follow-up averaged 34.3 months (from 15 to 55 months). 1-, 2-, 3-year recurrence rates of the vaccine group were 12.6%, 35.9% and 54.0%, respectively; 1-, 2-, 3-year recurrence rates of the control group were 31.6%, 61.3% and 72.1%, respectively. The recurrent rate was significantly better in the tumor vaccine group than in the control group (P = 0.037)., Conclusions: Autologous tumor vaccine is a promising adjunctive modality to prevent recurrence of human HCC.

Aim: To evaluate the therapeutic efficacy of systemic chemo-immunotherapy for advanced hepatocellular carcinoma (HCC)., Methods: Twenty-six patients with advanced HCC were treated by using systemic chemo-immunotherapy (PIAF regimen), which consisted of cisplatin (20 mg/m2) intravenously daily for 4 consecutive day, doxorubicin (40 mg/m2) intravenously on day 1, 5-fluorouracil (400 mg/m2) intravenously daily for 4 consecutive day, and human recombinant alpha-interferon-2a (5 MU/m2) subcutaneous injection daily for 4 consecutive day. The treatment was repeated every 3 wk, with a maximum of six cycles., Results: A total of 90 cycles of PIAF treatment were administered, with a mean number of 3.9 cycles per patient. Eight patients received six cycles of treatment (group A), and the remaining 18 were subjected to two to five cycles (group B). There were 0 complete responses, 4 partial responses, 9 static diseases and 13 progressive diseases, with a disease control rate of 50% (13/26). The 1-year survival rate was 24.3%, with a median survival time of 6.0 mo. Group A had a remarkably better survival as compared with group B, the 1- and 2-year survival rates were 62.5% vs 6.1% and 32.3% vs 0%, and a median survival time was 12.5 mo vs 5.0 mo (P = 0.001)., Conclusion: Systemic chemo-immunotherapy using PIAF regimen represented an effective treatment and could improve the survival rate and prolong the survival time in selected patients with advanced HCC.

Aim: To study the changes of quantitative expression, adhering activity and genomic density polymorphism of complement types in erythrocytes (CR1) of patients with gallbladder carcinoma and the related clinical significance., Methods: Polymerase chain reaction (PCR), Hind III restriction enzyme digestion, quantitative assay of CR1 and adhering activity assay of CR1 in erythrocytes were used., Results: The number and adhering activity of CR1 in patients with gallbladder carcinoma (0.738+/-0.23, 45.9+/-5.7) were significantly lower than those in chronic cholecystitis and cholecystolithiasis (1.078+/-0.21, 55.1+/-5.9) and healthy controls (1.252+/-0.31, 64.2+/-7.4) (P<0.01). The number and adhering activity of CR1 in patients with chronic cholecystitis and cholecystolithiasis (1.078+/-0.21, 55.1+/-5.9) were significantly lower than those in healthy controls (1.252+/-0.31, 64.2+/-7.4) (P<0.05). There was a positive correlation between quantitative expression and adhering activity of CR1 (r = 0.79, P<0.01). Compared with those on preoperative day (0.738+/-0.23, 45.4+/-4.9), the number and adhering activity of CR1 in patients with gallbladder carcinoma decreased greatly on the third postoperative day (0.310+/-0.25, 31.8+/-5.1) (P<0.01), and on the first postoperative week (0.480+/-0.25, 38.9+/-5.2) (P<0.01), but they were increased slightly than those on the preoperative day (P>0.05). The number and adhering activity of CR1 recovered in the second postoperative week(0.740+/-0.24, 46.8+/-5.9) (P<0.01) and increased greatly in the third postoperative week (0.858+/-0.35, 52.7+/-5.8) (P<0.01) in comparison with those on the preoperative day and in the first postoperative week. The number and adhering activity of CR1 of gallbladder carcinoma patients with infiltrating, adjacent lymphogenous and distant organ metastases were significantly lower than those of gallbladder carcinoma patients without them (P<0.01). No difference was observed between the patients with gallbladder carcinoma and healthy individuals in the spot mutation rate of CR1 density gene (chi(2) = 0.521, P>0.05). The distribution of expression was 67.8% in high expression genomic type, 24.8% in moderate expression genomic type, and 7.4% in low expression genomic type. The number and adhering activity of CR1 high expression genomic type gallbladder carcinomas (0.749+/-0.22, 42.1+/-6.2) were significantly lower than those of healthy individuals (1.240+/-0.29, 63.9+/-7.2), and were also significantly lower than those of healthy individuals (0.921+/-0.23, 54.8+/-7.1), but no difference was observed between the number and adhering activity of CR1 lower expression genomic type gallbladder carcinomas (0.582+/-0.18, 44.3+/-5.5) and those of healthy individuals (0.610+/-0.20, 45.8+/-5.7) (P>0.05)., Conclusion: Defective expression of CR1 in gallbladder carcinoma is mostly acquired through central peripheral mechanisms. The changes in CR1 quantitative expression and adhering activity are consanguineously related to the development and metastasis in gallbladder carcinoma.

Objective: To evaluate the clinical values of ultrasound-guided percutaneous composite thermal ablation technique in the treatment of medium and large hepatocellular carcinoma (HCC)., Methods: By the composite technique of multiple-needle insertion and multi-point energy application, ultrasound-guided percutaneous radiofrequency ablation (RFA) or microwave ablation (MWA) were employed to treat 68 patients of HCC with tumor nodule > or = 3.1 cm in diameter. There was a total number of 73 tumor nodules, with a mean diameter of (4.5 +/- 1.7) cm (3.1-13.0 cm). Sixty-three patients had single tumor nodule, and the remaining 5 had 2 nodules. With a follow-up time of 1.9 - 67.6 months [(16.0 +/- 14.8) months], the local and long-term efficacy was analyzed., Results: Hepatic subcapsular hematoma were found in 1 patient. And skin burning in 1 patient 1. Complete ablation rate was 78.1% (57/73), local tumor progression was presented in 24.6% tumor nodules (14/57) and distant recurrence developed in 56.7% patients (38/67). The 1-, 3-, 5-years survival rate was 62.3%, 29.6% and 21.6%, respectively, with a median survival time of 18.6 months, (95% confidence interval: 10.9 months, 26.3 months). There were no remarkable differences in complete ablation rate, local tumor progression, distant recurrence rate and survival rate between RFA and MWA., Conclusions: By the composite ablation technique, ultrasound-guided percutaneous thermal ablation was effective in treating medium and large unresectable HCC. And the advantage is minimal invasiveness. RFA and MWA had no marked differences in terms of therapeutic efficacy.

Objective: To investigate the therapeutic efficacy and its influencing factors of ultrasound-guided percutaneous radiofrequency ablation (PRFA) in the treatment of liver carcinoma., Methods: With a temperature-controlled multi-electrode needle, ultrasound-guided PRFA was employed to treat forty-seven patients with 67 tumor nodules, with a diameter of 2.6 +/- 1.1 cm (1.0 - 5.5 cm)., Results: A complete ablation (CA) rate of 80.6% was achieved in the present series, with a CA rate of 91.7% in the tumors < or = 3 cm in diameter, 75.0% in tumors from 3.1 to 4.0 cm, and 14.3% in tumors > 4 cm. The CA rate was significantly greater in tumors with a temperature rising up to 70 degrees C within the initial 2 minutes at ablation as compared with that longer than 2 minutes (P < 0.05). A markedly higher CA rate was obtained in tumors with an ablation-maintaining temperature of over 80 degrees C than that between 70 degrees C and 80 degrees C (P < 0.01). All patients were followed up with a mean time of 11.3 months. The local recurrence rate was 9.3% (5/54), and 1-year survival rate was 82.1%. Eighteen patients (38.3%) had a distant recurrence., Conclusions: The tumor size, temperature-rising time and ablation-maintaining temperature represented the important factors affecting the therapeutic efficacy of PRFA.