Lingjun Liu

Antitumor effects of ginsenoside Rg3 on human hepatocellular carcinoma cells

The antitumor effects of ginsenoside Rg3 have been reported in several kinds of human malignant tumors. The purpose of this study was to investigate whether ginsenoside Rg3 can inhibit the growth of human hepatocellular carcinoma cell lines and to discuss the possible molecular mechanism(s). We cultured the human hepatocellular carcinoma cell lines, SMMC-7721 and HepG2. The cells were treated with different concentrations of ginsenoside Rg3 (0, 25, 50, 75 and 100 µg/ml), and the cell proliferation was detected by MTT assay at the 12, 24, 36 and 48 h time-points. Flow cytometry experiments were carried out to investigate the effect of Rg3 on cell apoptosis after the cells had been treated with Rg3 (50 and 100 µg/ml) for 24 and 48 h. The expression levels of caspase-3, bax and bcl-2 in Rg3-treated cells (100 µg/ml, 48 h), as well as normal cells were detected through real-time PCR experiments. MTT assay showed that the inhibition rate of cell proliferation in the Rg3 groups was significantly higher compared to the control groups in both the SMMC-7721 and HepG2 cell lines, and the inhibition rate increased with increasing Rg3 concentrations and duration of treatment. Flow cytometry analysis demonstrated that the Rg3 groups had a significantly higher cell apoptotic rate compared to the control groups in both the SMMC-7721 and HepG2 cell lines, and that the effect of Rg3 on cell apoptosis occurred in a concentration- and time-dependent manner, as was also shown by the MTT assay. Real-time PCR analysis showed that the gene expression levels of caspase-3 and bax were significantly enhanced in the Rg3 groups compared to the control groups in both the SMMC-7721 and HepG2 cell lines, but the gene expression level of bcl-2 was significantly inhibited. These results indicate that ginsenoside Rg3 can effectively inhibit the growth of human hepatocellular carcinoma cell lines by inhibiting cancer cell proliferation and promoting cancer cell apoptosis, and it may promote cancer cell apoptosis via the endogenous mitochondrial-mediated caspase-dependent apoptotic pathway.

Stent-grafts for the treatment of TIPS dysfunction: Fluency stent vs Wallgraft stent

AIM To evaluate the clinical efficacy of an expanded polytetrafluoro-ethylene-covered Fluency stent compared with that of a polyethylene terephthalate-covered Wallgraft stent for the management of transjugular intrahepatic portosystemic shunt (TIPS) dysfunction. METHODS A retrospective review of patients who underwent TIPS revision with stent-grafts between May 2007 and June 2011 was conducted. The patients were divided into two groups according to the stent-grafts implanted: the Fluency stent (Bard Incorporated, Karlsruhe, Germany) and the Wallgraft stent (Boston Scientific, Galway, Ireland). The primary patency rates were calculated and compared using the Kaplan-Meier method. RESULTS A total of 73 patients were evaluated in this study: 33 with Fluency stents and 40 with Wallgraft stents. The primary patency rates at 12 and 24 mo were 91% and 85%, respectively, in the Fluency stent group and 78% and 63%, respectively, in the Wallgraft stent group. The primary shunt patency rates after TIPS revision were significantly better with the Fluency stent than with the Wallgraft stent (P = 0.033). CONCLUSION TIPS revision with the Fluency stent has higher medium-term patency rates than that with the Wallgraft stent.

Hepatic arterial administration of ginsenoside Rg3 and transcatheter arterial embolization for the treatment of VX2 liver carcinomas

Ginsenoside Rg3 has been demonstrated to inhibit tumor cell proliferation and angiogenesis. However, its effect on liver tumors when administered via the hepatic artery has not been investigated. The purpose of this study was to evaluate the therapeutic effect of hepatic artery administration of Rg3 combined with transcatheter arterial embolization (TAE) in the treatment of liver tumors. A total of 48 rabbits with VX2 liver tumors were randomly divided into four groups: Group 1, Rg3; Group 2, TAE; Group 3, Rg3 and TAE; and Group 4, control. Abdominal contrast computed tomography (CT) scans were performed 2 weeks before and after intervention to assess tumor growth. Immunohistochemical staining was used to detect the expression of the angiogenesis biomarkers CD31 and VEGF, and the cell apoptosis marker caspase-3. Semi-quantitative RT-PCR and western blotting were employed to detect the expression of the caspase-3, Bax and Bcl-2 apoptosis-related genes and proteins. In addition, HepG2 cells were treated with Rg3 at different concentrations (0, 25, 50, 75 and 100 mg/l) in vitro. An MTT assay and western blot analysis were used to analyze the cell proliferation and VEGF expression. Compared with the other experimental groups, the Rg3 and TAE group expressed significantly lower levels of CD31 and VEGF (P<0.05), significantly increased levels of the pro-apoptotic genes caspase-3 and Bax (P<0.05), and significantly reduced levels of anti-apoptotic Bcl-2 at the mRNA and protein levels (P<0.05). In vitro, Rg3 inhibited HepG2 cell proliferation and downregulated VEGF expression significantly. These results indicated that ginsenoside Rg3 combined with TAE may effectively inhibit tumor growth by inhibiting tumor angiogenesis and inducing cancer cell apoptosis.

Hepatobiliary and Pancreatic: Hepatocellular carcinoma supplied by portal blood after repeated transcatheter arterial chemoembolization

Hepatocellular carcinoma is the fifth most common cancer worldwide and the most common malignant tumor of the liver. Transarterial chemoembolization (TACE) is widely used in the treatment of liver tumors and has become the preferred treatment for patients with hepatocellular cancer who are not suitable for surgical or ablative therapies. The technique is based on the observation that most hepatocellular carcinomas are very vascular tumors with a blood supply that is largely or solely derived from the hepatic artery. The procedure permits the local administration of relatively high concentrations of chemotherapeutic drugs and, in addition, impairs the viability of the tumor by reducing its blood supply. Although TACE can decrease the size of the tumor in up to 70% of patients, there is debate as to the optimal chemotherapeutic drug, the method of embolization and the use of newer products such as drug-eluting beads. Although TACE can be repeated on a number of occasions, a potential issue is that occlusion of the arterial blood supply may lead to nourishment of the tumor by portal blood. An example of this phenomenon is illustrated below. A male, aged 69, was admitted to our hospital because of refractory ascites. He was known to have hepatitis B and had been diagnosed with hepatocellular carcinoma 4 years previously. At the time of diagnosis, hepatic arteriography showed that the tumor was supplied by a branch of the right hepatic artery (Figure 1). He was subsequently treated by TACE and had repeat procedures on five occasions. Prior to admission, ascites had increased in severity with a poor response to diuretics and salt restriction. Blood tests revealed a hemoglobin of 76 g/l with minor changes in liver function tests and a normal serum level of alpha fetoprotein. Peritoneal fluid was a transudate (serum-fluid albumin gradient >1.1 g/dl; 11 g/l) and was repeatedly negative for malignant cells. Arterial portography using a computed tomography scan showed signs of portal hypertension and blood flow to the tumor that contained iodized oil (Figure 2 left). Subsequently, the patient had hepatic arteriography and was treated with a transjugular intrahepatic portosystemic shunt (TIPS). Hepatic angiography was entirely normal but direct portal venography prior to insertion of the shunt revealed tumor staining and a prominent gastric coronary vein (Figure 2 right). The TIPS procedure was associated with improvement in ascites.

Education and Imaging. Hepatobiliary and pancreatic: spontaneous intrahepatic portosystemic shunt associated with cirrhosis.

A 36-year-old woman was under regular review because of biopsyproven cirrhosis secondary to autoimmune hepatitis. A recent symptom was that of spontaneous episodes of bleeding from her nose. A blood count revealed a low white cell count (3.16 ¥ 10/l) and a low platelet count (16 ¥ 10/l). An upper abdominal ultrasound study showed an enlarged nodular liver along with an enlarged spleen. Because of bleeding with a low platelet count, she was referred for partial splenic embolization. A contrast-enhanced computed tomography (CT) scan prior to the procedure showed that contrast in the portal vein (Figure 1, left) passed into a dilated right hepatic vein (Figure 1, right). The appearance was typical of an intrahepatic portosystemic shunt. The shunt was thought to be spontaneous as there was no history of trauma and the shunt had not been present on a CT scan performed 8 months previously. Direct portography was performed by passage of a catheter from the femoral vein into the hepatic vein and then into the portal vein (Figure 2, left). Blood flow was in the direction of the hepatic vein (Figure 2, right). The pressure gradient between the main portal vein and the inferior vena cava was elevated at 27.8 mmHg. Hepatic arteriography excluded the possibility that blood flow from the hepatic artery contributed to the shunt. Partial splenic embolization was then performed (approximately 50% of the spleen) after which the white cell count and platelet count returned to normal. Spontaneous nose bleeds also ceased. Spontaneous intrahepatic portosystemic shunts are rare anatomic anomalies that may be congenital or acquired. Acquired shunts have mostly been associated with portal hypertension or hepatic trauma. Those associated with portal hypertension have usually been relatively small and have sometimes been diffusely located throughout the liver. Large shunts that dominate the portal flow are extremely rare and have sometimes been associated with refractory hepatic encephalopathy. In the above case, the shunt appeared to be relatively large but was still associated with significant portal hypertension. An additional feature in the above case was the correction of hematologic abnormalities caused by hypersplenism using partial splenic embolization.

Education and Imaging. Hepatobiliary and pancreatic: hepatocellular carcinoma supplied by portal blood after repeated transcatheter arterial chemoembolization.

Hepatocellular carcinoma is the fifth most common cancer worldwide and the most common malignant tumor of the liver. Transarterial chemoembolization (TACE) is widely used in the treatment of liver tumors and has become the preferred treatment for patients with hepatocellular cancer who are not suitable for surgical or ablative therapies. The technique is based on the observation that most hepatocellular carcinomas are very vascular tumors with a blood supply that is largely or solely derived from the hepatic artery. The procedure permits the local administration of relatively high concentrations of chemotherapeutic drugs and, in addition, impairs the viability of the tumor by reducing its blood supply. Although TACE can decrease the size of the tumor in up to 70% of patients, there is debate as to the optimal chemotherapeutic drug, the method of embolization and the use of newer products such as drug-eluting beads. Although TACE can be repeated on a number of occasions, a potential issue is that occlusion of the arterial blood supply may lead to nourishment of the tumor by portal blood. An example of this phenomenon is illustrated below. A male, aged 69, was admitted to our hospital because of refractory ascites. He was known to have hepatitis B and had been diagnosed with hepatocellular carcinoma 4 years previously. At the time of diagnosis, hepatic arteriography showed that the tumor was supplied by a branch of the right hepatic artery (Figure 1). He was subsequently treated by TACE and had repeat procedures on five occasions. Prior to admission, ascites had increased in severity with a poor response to diuretics and salt restriction. Blood tests revealed a hemoglobin of 76 g/l with minor changes in liver function tests and a normal serum level of alpha fetoprotein. Peritoneal fluid was a transudate (serum-fluid albumin gradient >1.1 g/dl; 11 g/l) and was repeatedly negative for malignant cells. Arterial portography using a computed tomography scan showed signs of portal hypertension and blood flow to the tumor that contained iodized oil (Figure 2 left). Subsequently, the patient had hepatic arteriography and was treated with a transjugular intrahepatic portosystemic shunt (TIPS). Hepatic angiography was entirely normal but direct portal venography prior to insertion of the shunt revealed tumor staining and a prominent gastric coronary vein (Figure 2 right). The TIPS procedure was associated with improvement in ascites.

Management of Superior Mesenteric Arteriovenous Fistula after Small Bowel Resection 20 Years Previously: Endovascular Treatment

A 59-year-old man was admitted to the West China Hospital (Sichuan, China) with recurrent abdominal pain and diarrhea. The patient had undergone a resection of the small bowel due to small intestinal bleeding caused by an ulcer 20 years previously and had no history of trauma. Physical examination revealed stable vital signs, but there was tenderness in the area of the epigastrium radiating to the back without muscle tension and rebound pain. Laboratory tests revealed hemoglobin, white blood cell, total bilirubin, prothrombin time, albumin and creatinine levels of 97 g/L, 18.65×109/L, 53 umol/L, 12.0 s, 34.1 g/L, 112 μmol/L, respectively. Computed tomography (CT) angiography of the abdomen and pelvis revealed marked enhancement of the superior mesenteric vein (3.1 cm in diameter) in the arterial phase, the fistula of the neck between the superior mesenteric artery and the superior mesenteric vein (0.9 cm in diameter), the engorgement of the intestinal walls and mesentery, and abdominal ascites (Figure 1). Endovascular treatment was implemented in the hybrid operating room. If unsuccessful, open surgery would immediately follow. Superior mesenteric angiography demonstrated a superior mesenteric arteriovenous fistula (SMAVF) in accord with CT (Figure 2). Embolization of the fistula was performed with multiple 8 mm, 10 mm and 12 mm coils deployed at the neck of the SMAVF, respectively. An additional angiogram showed no opacification of the SMAVF (Figure 3). After the procedure, the patient was monitored carefully for any evidence of bowel ischemia. During the next several days, the patient’s abdominal pain disappeared and the initial watery diarrhea gradually resolved. Confirmation of these findings was obtained by ultrasound with no evidence of portal hypertension. At the three-month follow-up, the patient was in satisfactory condition and had no symptoms of bowel ischemia.

Hepatobiliary and pancreatic: transient hepatic ischemia caused by acute portal vein thrombosis.

A 79-year-old man was investigated because of a 10-day history of pain in the right upper quadrant of his abdomen. There was no preceding history of liver disease. Blood tests revealed a mild elevation of bilirubin (66 μmol/l), alanine aminotransferase (168 U/L) and aspartate aminotransferase (78 U/L). The international normalized ratio (INR) was mildly elevated (1.6). A contrast-enhanced computed tomography (CT) scan showed extensive thrombosis in the intrahepatic and extrahepatic portal vein (Figure 1 left). In addition, there were diffuse low-density liver lesions that were best shown in the portal venous phase (Figure 1 right). Subsequently, he was treated with anticoagulants to maintain the INR between 2 and 3. After 2 weeks, his pain resolved and liver function tests returned to normal. A repeat CT scan showed that the portal vein thrombosis was less prominent than previously (Figure 2 left) and that the low-density liver lesions had resolved. He was discharged from hospital on oral anticoagulants and had a further CT scan after 3 months. The scan showed cavernous transformation of the portal vein (Figure 2 right). The portal vein normally supplies approximately two-thirds of the blood supply to the liver. The remainder is provided by the hepatic artery. Although portal vein thrombosis is relatively common in cirrhosis and hepatic tumors, it appears to develop slowly in most patients and is usually asymptomatic without significant changes in liver enzymes. Presumably, the compensation for reduced portal flow is enhanced arterial flow as well as portal to portal collaterals. However, if portal vein thrombosis is acute, at least some patients have abdominal pain as well as changes in liver function tests. Fortunately, death due to hepatic ischemia is very rare. In the above patient, the appearance of low-density ischemic lesions was similar to that of multiple hepatic neoplasms. However, most neoplasms are best visualized in the arterial phase whereas ischemic lesions are more prominent in the portal venous phase. The interval between portal vein thrombosis and imaging features of cavernous transformation is somewhat variable but is usually between 2 and 12 months. In the patient described above, the cause of portal vein thrombosis remained unclear as various investigations for hypercoagulable states were unhelpful.

Hepatobiliary and Pancreatic: Spontaneous intrahepatic portosystemic shunt associated with cirrhosis

A 36-year-old woman was under regular review because of biopsyproven cirrhosis secondary to autoimmune hepatitis. A recent symptom was that of spontaneous episodes of bleeding from her nose. A blood count revealed a low white cell count (3.16 ¥ 10/l) and a low platelet count (16 ¥ 10/l). An upper abdominal ultrasound study showed an enlarged nodular liver along with an enlarged spleen. Because of bleeding with a low platelet count, she was referred for partial splenic embolization. A contrast-enhanced computed tomography (CT) scan prior to the procedure showed that contrast in the portal vein (Figure 1, left) passed into a dilated right hepatic vein (Figure 1, right). The appearance was typical of an intrahepatic portosystemic shunt. The shunt was thought to be spontaneous as there was no history of trauma and the shunt had not been present on a CT scan performed 8 months previously. Direct portography was performed by passage of a catheter from the femoral vein into the hepatic vein and then into the portal vein (Figure 2, left). Blood flow was in the direction of the hepatic vein (Figure 2, right). The pressure gradient between the main portal vein and the inferior vena cava was elevated at 27.8 mmHg. Hepatic arteriography excluded the possibility that blood flow from the hepatic artery contributed to the shunt. Partial splenic embolization was then performed (approximately 50% of the spleen) after which the white cell count and platelet count returned to normal. Spontaneous nose bleeds also ceased. Spontaneous intrahepatic portosystemic shunts are rare anatomic anomalies that may be congenital or acquired. Acquired shunts have mostly been associated with portal hypertension or hepatic trauma. Those associated with portal hypertension have usually been relatively small and have sometimes been diffusely located throughout the liver. Large shunts that dominate the portal flow are extremely rare and have sometimes been associated with refractory hepatic encephalopathy. In the above case, the shunt appeared to be relatively large but was still associated with significant portal hypertension. An additional feature in the above case was the correction of hematologic abnormalities caused by hypersplenism using partial splenic embolization.

Hepatobiliary and Pancreatic: Spontaneous intrahepatic portosystemic shunt associated with cirrhosis: Education and Imaging

A 36-year-old woman was under regular review because of biopsyproven cirrhosis secondary to autoimmune hepatitis. A recent symptom was that of spontaneous episodes of bleeding from her nose. A blood count revealed a low white cell count (3.16 ¥ 10/l) and a low platelet count (16 ¥ 10/l). An upper abdominal ultrasound study showed an enlarged nodular liver along with an enlarged spleen. Because of bleeding with a low platelet count, she was referred for partial splenic embolization. A contrast-enhanced computed tomography (CT) scan prior to the procedure showed that contrast in the portal vein (Figure 1, left) passed into a dilated right hepatic vein (Figure 1, right). The appearance was typical of an intrahepatic portosystemic shunt. The shunt was thought to be spontaneous as there was no history of trauma and the shunt had not been present on a CT scan performed 8 months previously. Direct portography was performed by passage of a catheter from the femoral vein into the hepatic vein and then into the portal vein (Figure 2, left). Blood flow was in the direction of the hepatic vein (Figure 2, right). The pressure gradient between the main portal vein and the inferior vena cava was elevated at 27.8 mmHg. Hepatic arteriography excluded the possibility that blood flow from the hepatic artery contributed to the shunt. Partial splenic embolization was then performed (approximately 50% of the spleen) after which the white cell count and platelet count returned to normal. Spontaneous nose bleeds also ceased. Spontaneous intrahepatic portosystemic shunts are rare anatomic anomalies that may be congenital or acquired. Acquired shunts have mostly been associated with portal hypertension or hepatic trauma. Those associated with portal hypertension have usually been relatively small and have sometimes been diffusely located throughout the liver. Large shunts that dominate the portal flow are extremely rare and have sometimes been associated with refractory hepatic encephalopathy. In the above case, the shunt appeared to be relatively large but was still associated with significant portal hypertension. An additional feature in the above case was the correction of hematologic abnormalities caused by hypersplenism using partial splenic embolization.