BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem worldwide. It is the fifth most common cancer in the world, and the third most common cause of cancer-related death. Without specific treatment, the prognosis is very poor. The  goal  of  management is "cancer control"—a reduction in its incidence and mortality as well as an improvement in the quality of life of patients with HCC and their families. This article aims to review the current management of HCC and its recent advances.
DATA SOURCES: A MEDLINE database search was performed to identify relevant article using the keywords "hepatocellular carcinoma", "hepatectomy", "liver transplantation", and "local ablative therapy". Additional papers and book chapters were identified by a manual search of the references from the key articles.
RESULTS: Liver resection and liver transplantation remain the options that give the best chance of a cure. Recent evidence suggests that local ablative therapy may offer comparable survival results in patients with small HCC, and preserved liver function. Transarterial chemoembolization (TACE) is the most promising palliative modality for unresectable HCC, but other techniques, such as transarterial radioembolization (TARE), and local ablative therapy, have also shown comparable results.
CONCLUSIONS: Early diagnosis of HCC remains a key goal in improving the prognosis of patients. During the last two decades, operative mortality and surgical outcome of liver resection and liver transplantation for HCC have improved. Progress also has been made in multi-modality therapy which can increase the chance of survival and improve the quality of life for patients with advanced HCC.

BACKGROUND: Blockade interaction between CD28 and B7 with CTLA4Ig has been shown to induce experimental transplantation tolerance. In order to prolong the inhibitory effect of CTLA4Ig, a recombinant adeno-associated virus vector pSNAV expressing CTLA4Ig was constructed, and its effects on transplanted liver allografts were investigated.
METHODS: The pSNAV-CTLA4Ig construct was infused into partial liver allografts of rats via the portal vein during transplantation. CTLA4Ig expression in the transplanted livers was detected with reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Furthermore, real-time quantita-tive PCR was used to measure the expression of IL-2, IFN-γ, IL-4 and IL-10 in the allografts.
RESULTS: The expression of CTLA4Ig in the partial allograft was detected successfully and pSNAV-CTLA4Ig improved the survival rate of rats after liver transplantation. Agarose gel analysis of RT-PCR products indicated the presence of CTLA4Ig in the pSNAV-CTLA4Ig treatment group. Cytokines expressed in allografts on day 7 after orthotopic liver transplantation showed that IL-2, IFN-γ, IL-4 and IL-10 mRNA levels decreased in transplant recipients treated with pSNAV-CTLA4Ig compared with those treated with pSNAV-LacZ (1.62±0.09, 1.52±0.11, 1.50±0.07 and 1.43±0.07 versus 1.29±0.09, 1.32±0.07, 1.34±0.06 and 1.35±0.04, respectively).
CONCLUSIONS: pSNAV-CTLA4Ig effectively expressed CTLA4Ig in liver allografts. CTLA4Ig improved the pathological findings after liver transplantation. CTLA4Ig induced immune tolerance of liver transplantation, and the mechanism involved induced alteration of Th1 and Th2 cytokine transcripts. The adeno-associated virus vector encoding CTLA4Ig may be useful in the clinical study of transplantation tolerance.

BACKGROUND: Bone marrow cells can differentiate into hepatocytes in a suitable microenvironment. This study was undertaken to investigate the effects of transplanted bone marrow stromal cells (BMSCs) on liver fibrosis in mice.
METHODS: BMSCs were harvested and cultured from male BALB/c mice, then transplanted into female syngenic BALB/c mice via the portal vein. After partial hepatectomy, diethylnitrosamine (DEN) was administered to induce liver fibrosis. Controls received BMSCs and non-supplemented drinking water, the model group received DEN with their water, and the experimental group received BMSCs and DEN. Mice were killed after 3 months, and ALT, AST, hyaluronic acid (HA), and laminin (LN) in serum and hydroxyproline (Hyp) in the liver were assessed. Alpha-smooth muscle actin (α-SMA) in the liver was assessed by immunohistochemistry. Bone marrow-derived hepatocytes were identified by fluorescent in situ hybridization (FISH) in liver sections.
RESULTS: BMSCs were shown to differentiate into hepatocyte-like phenotypes after hepatocyte growth factor treatment in vitro. Serum ALT, AST, HA, and LN were markedly reduced by transplanted BMSCs. Liver Hyp content and α-SMA staining in mice receiving BMSCs were lower than in the model group, consistent with altered liver pathology. FISH analysis revealed the presence of donor-derived hepatocytes in the injured liver after cross-gender mouse BMSC transplantation. After three months, about 10% of cells in the injured liver were bone marrow-derived.
CONCLUSION: BMSCs transplanted via the portal vein can convert into hepatocytes to repair liver injury induced by DEN, restore liver function, and reduce liver fibrosis.

BACKGROUND: There are significant variations in the geographical distribution of hepatitis B virus (HBV) genotypes throughout the world, and some genotypes are associated with different clinical outcomes. Eight genotypes of human HBV (designated A-H) have been reported. The present study was designed to examine the distribution of HBV genotypes among patients at various stages of chronic type B liver disease in Yunnan Province, China, and to explore its significance and the relationship of HBV genotype with gender and age, clinical spectrum of chronic HBV infection, and viral replicative activity.
METHODS: Serum samples from 126 patients with chronic HBV infection from Yunnan Province, including 26 chronic asymptomatic HBV carriers (ASC), 61 patients with chronic hepatitis B (CHB) (21 mild, 30 moderate and 10 severe), 20 patients with chronic fulminant hepatic failure (CFHF), 12 patients with HBV-related liver cirrhosis (LC) and 7 patients with HBV-related hepatocellular carcinoma (HCC) were analyzed using reverse dot blot (RDB) methodology, which is based on the reverse hybridization principle for HBV genotyping. The relations of HBV genotype with gender and age, clinical patterns, and serological data of the patients were analyzed.
RESULTS: In this series, genotypes A, B, C, and D were found. 38.1% patients (48/126) belonged to B, 54.8% (69/126) to C, 0.8% (1/126) to D, 1.6% (2/126) to a mixture of B and C, and 1.6% (2/126) to a mixture of A and C. 3.2% patients (4/126) had unknown genotypes. No other genotypes (E, F, G, and H) were found. Genotypes B and C were predominant. There was a statistically significant difference in the distributions of genotypes C and B (χ2=7.04, P=0.008), and C was the dominant genotype in all patient categories. The rate of genotype B in the mild CHB group was significantly higher than that in the moderate and severe groups (χ2=12.16, P=0.0001; χ2=11.98, P=0.001, respectively), the ASC group (χ2=5.46, P=0.02), the CFHF group (χ2=5.53, P=0.019), and the LC/HCC group (χ2=12.13, P=0.001). The rate of genotype C in the LC/HCC group and the severe CHB group were significantly higher than that in the mild group (χ2=9.95, P=0.002; χ2=8.78, P=0.003, respectively). HBV DNA positivity and HBeAg positivity were higher in genotype C than in genotype B (χ2=9.81, P=0.002; χ2=3.85, P=0.05, respectively). The prevalence of genotype C showed an increasing trend in lowest-, middle- and highest-level groups of HBV replication (25.0%, 70.0%, and 55.6%, respectively); in contrast, the prevalence of genotype B showed an opposite trend in the same order (62.5%, 30.0%, and 37.0%, respectively). The rate of genotype C in the highest-level group of HBV replication was higher than genotype B (χ2=7.45, P=0.006). The rate of genotype C in the over-30 age group was higher than that in the below-30 age group (χ2=3.7, P=0.05). There was no difference between the sexes (P>0.05). More severe liver damage was found in genotype C than in genotype B (P<0.05).
CONCLUSIONS: The predominant HBV genotypes in chronic HBV-infected patients are B and C, and C is the most prevalent genotype in Yunnan Province, China. HBV genotype C is associated with the development of more severe liver disease and a higher level of HBV viral replication, and genotype B has a relatively good progress.

BACKGROUND: Effective measures are lacking to treat long-term poorly closed incisions after hepatobiliary surgery, including chronic sinus tract and keloid. This study aimed to introduce the treatment experiences with the abdominal wall and costal margin complications after hepatobiliary surgery, and to investigate the method for prevention of this kind of complication.
METHODS: We retrospectively studied 26 patients with complications of abdominal wall and costal margin after hepatobiliary surgery, who had been admitted to our hospital since 1998. The 26 patients were classified according to complications into 3 groups: chronic ulcer with costal chondritis (5 patients), single chronic ulcer (3), and keloid (18). According to the symptoms of patients, treatments given included focal removal regional flap transfer restoration and focal removal dermatoplasty combined with glucocorticoid injection, anti-scar medication, external application of silicone gel film, and pressure therapy after surgery to inhibit recurrence.
RESULTS: Satisfactory results were observed in the 26 patients after the treatments. Focal and regional ache and itching disappeared, and 2-3-year follow-up revealed no recurrence.
CONCLUSIONS: Attention should be paid to patients with complications of abdominal wall and costal margin after hepatobiliary surgery. Combined treatment or mainly operations produce satisfactory result.

BACKGROUND: Hepatic angiomyolipoma (HAML) is a rare hepatic mesenchymal tumor. This study was designed to explore its clinical features.
METHODS: Clinical data from 26 patients who had been pathologically confirmed with HAML and had received surgical resection at our hospital were analyzed retrospectively.
RESULTS: HAML was seen more frequently in females (18/26) in this series, and most of the patients presented no significant symptoms except for one who had a spontaneous rupture hemorrhage. Serum alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were negative in all patients. Imaging presentations were diverse. Pre-operative diagnosis was made in only 3 patients. Pathological study showed that the tumor was composed of adipose tissue, smooth muscle and blood vessels in different proportions. One patient showed hepatic vessel invasion. HMB-45 immunohistochemical staining was positive in all tumors. All patients underwent surgical resection without significant complications. Except for one patient who died 14 months after operation because of recurrent disease, no tumor recurrence was observed in the remaining 25 patients during a 2-3 years follow-up.
CONCLUSIONS: Pre-operative diagnosis of HAML is difficult. There are potential risks of spontaneous rupture and malignant transformation. Surgical resection is the treatment of choice for HAML.

BACKGROUND: Transforming growth factor-β (TGF-β) plays an important role in the regulation of cell growth and differentiation, angiogenesis, extracellular matrix formation, immunosuppression and cancer development. In this study, we investigated the levels of TGF-β1 and TGF-β1 mRNA expression, their relationship with HBV replication, and their diagnostic value for hepatocellular carcinoma (HCC).
METHODS: Total RNAs were extracted from HCC samples and matched non-tumor tissues, and from peripheral blood mononuclear cells in HCC patients. TGF-β1 mRNA was amplified by RT-PCR and confirmed by DNA sequencing. The distribution of TGF-β1 expression was assessed by immunohistochemistry. The clinical characteristics were analyzed between TGF-β1 and HBV replication. The diagnostic value of circulating TGF-β1 and TGF-β1 mRNA levels were investigated in HCC patients.
RESULTS: The incidence of hepatic TGF-β1 expression was 83.3% in HCC samples, 43.3% in the surrounding tissues, 94.7% in the HBV DNA-positive group, and 63.6% in the HBV DNA-negative group. Liver TGF-β1 expression was associated with the degree of HCC differentiation and the status of HBV replication, but not with the size or number of tumors. Circulating TGF-β1 level and incidence of TGF-β1 mRNA were significantly higher in the HCC group than in any group of patients with benign liver disease, with a higher sensitivity of 89.5% and a specificity of 94.0% for HCC diagnosis when circulating TGF-β1 levels were >1.2 µg/L. No significant correlation was found between TGF-β1 expression and AFP level or tumor size. Combining TGF-β1 level and serum AFP raised the detection rate to 97.4%.
CONCLUSIONS: Abnormal expression of hepatic TGF-β1 is associated with the degree of HCC differentiation and HBV replication. Both circulating TGF-β1 and TGF-β1 mRNA can be used as sensitive biomarkers for the diagnosis and prognosis of HBV-induced HCC.

BACKGROUND: With the development of hepatic surgery, especially liver transplantation, the pathophysiological processes of hepatic ischemia-reperfusion (I/R) injury have gained special attention. Controlling I/R injury has become one of the most important factors for successful liver transplantation. This study aimed to investigate the effects of tumor necrosis factor-alpha (TNF-α) in rats with hepatic I/R injury and promote the recognition of I/R injury in the liver.
METHODS: Thirty-two Sprague-Dawley rats were randomly divided into 2 groups. Rats in the sham-operated (SO) group served as controls. Rats in the hepatic ischemia-reperfusion (I/R) group underwent reperfusion after 30 minutes of liver ischemia. Rats were sacrificed at 1, 6 and 12 hours. The expression of TNF-α mRNA in the liver was measured by RT-PCR. Histological changes in the liver were assessed. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were measured.
RESULTS: The expression of TNF-α mRNA in the SO group was decreased compared with that in the I/R group (P<0.05). TNF-α mRNA expression progressively increased in the I/R group. The serum levels of ALT and AST in the I/R group were higher than those in the SO group (P<0.01). The histological changes were in accord with hepatic I/R injury.
CONCLUSION: ALT and AST in serum are closely related to hepatic I/R injury and inflammatory reaction. TNF-α production in the liver triggers hepatic I/R injury through a cascade.

BACKGROUND: Biliary cast syndrome (BCS) is an unusual complication of orthotopic liver transplantation (OLTx), and its management is difficult. Limited success using endoscopic retrograde cholangiopancreatography (ERCP) or open exploration to clear casts has been reported, but failure usually results in re-transplantation. We aimed to review our experience with BCS and highlight a novel combined percutaneous and endoscopic approach for duct clearance. A brief review of the literature is given.
METHODS: We retrospectively reviewed our experience of managing BCS using case notes review. Details were also gathered from radiology, where interventional procedures were carried out.
RESULTS: We had a total of three cases of BCS reported between 2002 and 2005. Multiple attempts were made to remove these casts. All three were treated in a variety of ways. Management is discussed along with highlighting a novel combined percutaneous and endoscopic approach for duct clearance.
CONCLUSIONS: BCS is a potential complication of OLTx. Surgical and endoscopic methods of removing casts are used. However, in circumstances where these methods are technically difficult, a percutaneous endoscopic approach with serial dilatation of the cutaneous port and surgical removal of casts can be done.

BACKGROUND: Choledocholithiasis is the most common cause of obstructive jaundice and cholangitis and occurs in about 10% of patients with symptomatic gallstone. The aim of this study was to find preoperative and non-invasive tests for predicting common bile duct stones (CBDs).
METHODS: Findings of clinical examination, history, laboratory tests and ultrasound (US) in 60 patients with CBDs were compared retrospectively, with 60 patients with gallstones. The data were collected from medical charts. The sensitivity, specificity and positive predictive value (PPV) were determined.
RESULTS: The comparison between the two groups showed significant differences in anorexia, itching, dark urine, subicterus (slightly elevated serum bilirubin without clinical evidence of jaundice) and jaundice appearance, increased bilirubin level, aspartate aminotransferase (AST) and alanine aminotranferase (ALT), CBD diameter >6 mm and stone observation under US (P<0.05). The highest specificity (100%) and PPV (100%) were found in dark urine and pale colored stool, history of cholangitis, and icterus. Among paraclinical tests, alkaline phosphatase (ALP) had the highest specificity (72.1%) and PPV (12.5%). Under US, stone observation in CBD was the most important factor with a sensitivity of 94.5%, a specificity of 100% and a PPV of 100%.
CONCLUSIONS: The most important factors for predicting CBDs are history of cholangitis and pancreatitis, presence of icterus, dark urine, pale colored stool, elevation of ALP, and sonographic evidence of chledocholithiasis.

BACKGROUND: Around 60% to 80% of patients with periampullary carcinoma are unresectable either due to distant metastasis or local vascular invasion. With the advancement of endoscopic interventional procedures, the role of surgical bypass has diminished. However, surgical bypass is still appropriate in patients with unresectable disease discovered at the time of surgery. This study was conducted to assess the results of palliative surgical bypass for patients with unresectable periampullary carcinoma at our hospital, a tertiary referral center of Northern India.
METHOD: The study group comprised 204 patients who had undergone surgical bypass for advanced periampullary carcinoma over the last 15 years.
RESULTS: Between January 1990 and December 2004, 204 patients (128 males, 76 females) consisting of 179 patients with carcinoma of head of the pancreas, 14 patients with ampullary carcinoma, 8 patients with lower end cholangiocarcinoma and 3 patients with duodenal carcinoma underwent surgical bypass. Their average age was 51 years (range 20-78 years). Both biliary and gastric bypasses were done in 158 (77.45%), biliary bypass alone in 37 (18.13%), and gastric bypass alone in 9 (4.32%). Biliary bypass was done by Roux-en-Y hepaticojejunostomy, and gastric bypass by retrocolic gastrojejunostomy. The overall postoperative mortality and morbidity were 0.98% and 26.9%, respectively. The patients who died had undergone previously endoscopic intervention. Complications included wound infection in 12.25% of the patients, bile leak in 5.12%, delayed gastric emptying in 5.38%, ascitic leak from drains in 8.8%, and upper gastrointestinal bleeding in 1.96%. The incidences of wound infection and bile leak both were significantly higher in patients who had had preoperative biliary stenting. None of the patients who had undergone Roux-en-Y hepati-cojejunostomy+retrocolic gastrojejunostomy required any intervention later in their life.
CONCLUSIONS: Surgical bypass is a safe procedure with negligible mortality and minimal morbidity. It has not lost its relevance and is an appropriate treatment in patients deemed unresectable on peroperative assessment.

BACKGROUND: Pancreatic cancer is a devastating disease with abnormal genetic changes. The pituitary tumor-derived transforming gene (PTTG) is considered to be implicated in the tumorigenesis of cancers when the gene is epigenetically transformed. In this study, we investigated the relationships between aberrant expression and epigenetic changes of the PTTG1 gene in pancreatic cancer.
METHODS: We chose 4 cell lines (PANC-1, Colo357, T3M-4 and PancTuⅠ) and pancreatic ductal adenocarcinoma (PDAC) tissues. After using restriction isoschizomer endonucleases (MspⅠ/HpaⅡ) to digest the DNA sequence (5'-CCGG-3'), we performed PCR reaction to amplify the product. And RT-PCR was applied to determine the gene expression.
RESULTS: The mRNA expression of the PTTG1 gene was higher in pancreatic tumor than in normal tissue. The gene was also expressed in the 4 PDAC cell lines. The methylation states of the upstream regions of the PTTG1 gene were almost identical in normal, tumor pancreatic tissues and the 4 PDAC cell lines. Some (5'-CCGG-3') areas in the upstream region of PTTG1 were methylated, while some others were unmethylated.
CONCLUSIONS: The oncogene PTTG1 was overexpressed in pancreatic tumor tissues and verified by RT-PCR detection. The methylation status of DNA in promoter areas was involved in the gene expression with the help of other factors in pancreatic cancer.

BACKGROUND: Since conventional methods are difficult to deal with pancreatic tumors close to the portal veins, we investigated the feasibility and norms for retrograde distal pancreatectomy by cutting the neck of the pancreas first.
METHOD: The clinical data and surgical procedures of retrograde distal pancreatectomy given to 11 patients from July 2001 to June 2007 were analyzed.
RESULTS: All 11 operations were completed successfully. The mean time of the operation was 143±71 minutes. The mean volume of hemorrhage was 239 ml. The mean time of hospitalization was 12±4.2 days. No blood transfusion was needed during the operation, and all patients had a good postoperative recovery. No neopathy of diabetes mellitus, pancreatic fistula or other complications occurred after the operation. The follow-up of all patients (4-60 months) showed that 3 patients survived for 14, 16 and 33 months, respectively, and the other patients are still alive.
CONCLUSIONS: Retrograde distal pancreatectomy is useful for exposing the portal and superior mesenteric veins while avoiding operative injury. Interception of the blood supply of the spleen helps to reduce the volume of hemorrhage, while making the operation easier and the operative time short. It is advantageous for tumor resection of the body of the pancreas near the portal veins.

BACKGROUND: Extensive portal vein thrombosis (PVT) in the recipient of liver transplantation increases postoperative morbidity and mortality. Cavoportal hemitransposition (CPHT) has been described as a salvage technique in the presence of extensive portal and superior mesenteric venous thrombosis.
METHODS: We report three patients who underwent this procedure, review the literature, and discuss the postoperative complications of CPHT.
RESULTS: Fifty-six patients with extensive PVT who underwent CPHT have been reported. Seventeen patients have died to date. The common complications of CPHT were ascites (55.4%), renal insufficiency (48.2%), variceal bleeding (30.4%), or thrombosis of cavoportal anastomosis or portal branch (14.3%).
CONCLUSION: CPHT is a salvage measure to maintain the patency of portal inflow to the liver graft in the presence of extensive PVT.

BACKGROUND: Percutaneous radiologically-guided liver biopsy is used routinely worldwide in all secondary-level hospital centers. While it has an undoubted role in the investigation and management of acute and chronic inflammatory conditions of the liver, its role in hepatic oncology is doubtful and probably dangerous.
METHOD: We report on two patients who underwent preoperative biopsy of potentially resectable liver tumors.
RESULTS: At the time of surgery, there was evidence of seeding at the biopsy site in both cases. In case 1, potentially curative liver resection was rendered incurable because of gross peritoneal carcinomatosis lying adjacent to the site of liver biopsy. In case 2, the patient underwent curative liver resection, but there was histopathological evidence of peritoneal disease beyond the liver capsule along the falciform ligament at the site of the previous biopsy.
CONCLUSIONS: No patient with a suspicious liver tumor which is thought to be malignant and has any possibility of being a potential candidate for liver surgery, should be subjected to pre-operative diagnostic biopsy in a non-specialist center.

BACKGROUND: Tuberculosis rarely involves the liver and spleen and when it does so, it is usually associated with disseminated disease.
METHOD: We report a patient with isolated tuberculosis of the liver and spleen.
RESULTS: A 50-year-old man presented with weakness and loss of weight for two months. CT scan of the abdomen showed multiple small hypodense lesions in the liver and spleen. Image-guided biopsy of liver lesion was inconclusive as it showed normal hepatocytes with interspersed lymphocytes. On laparotomy, the liver and spleen were studded with multiple small nodules. A 5-cm wedge of the liver was resected. Histopathological examination confirmed the diagnosis of tubercular hepatitis. A detailed work-up failed to identify any other focus of tuberculosis.
CONCLUSION: Although rare, tuberculosis should also be considered in the differential diagnosis for multiple nodules in the liver and spleen, along with lymphoproliferative diseases and metastatic lesions.

BACKGROUND: Chronic pancreatitis shows alterations in the trypsinogen gene (protease serine 1, PRSS1) in some individuals. The conversion of trypsinogen to trypsin in the pancreas is believed to be one of the causes of pancreatitis. This study was to identify the mutation of the PRSS1 gene in a Chinese patient with chronic pancreatitis and to analyze the clinical features of the disease.
METHODS: In 6 patients with chronic pancreatitis and 120 normal controls, PRSS1 genes were amplified by the polymerase chain reaction and the products were analyzed by sequencing.
RESULTS: Multisite mutations of PRSS1 were found in a patient with chronic pancreatitis. C to A mutation occurred in exon 3 of PRSS1, and T to A mutation in the same exon. These mutations were not found in normal controls or the patients with chronic pancreatitis.
CONCLUSION: These are novel mutations in PRSS1.