Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure.

OBJECTIVE: Shortage of organ donors, a critical challenge for treatment of end-stage organ failure, has motivated the development of alternative strategies to generate organs in vitro. Here, we aim to describe the hepatorganoids, which is a liver tissue model generated by three-dimensional (3D) bioprinting of HepaRG cells and investigate its liver functions in vitro and in vivo. DESIGN: 3D bioprinted hepatorganoids (3DP-HOs) were constructed using HepaRG cells and bioink, according to specific 3D printing procedures. Liver functions of 3DP-HOs were detected after 7 days of differentiation in vitro, which were later transplanted into Fah-deficient mice. The in vivo liver functions of 3DP-HOs were evaluated by survival time and liver damage of mice, human liver function markers and human-specific debrisoquine metabolite production. RESULTS: 3DP-HOs broadly acquired liver functions, such as ALBUMIN secretion, drug metabolism and glycogen storage after 7 days of differentiation. After transplantation into abdominal cavity of Fah-/-Rag2-/- mouse model of liver injury, 3DP-HOs further matured and displayed increased synthesis of liver-specific proteins. Particularly, the mice acquired human-specific drug metabolism activities. Functional vascular systems were also formed in transplanted 3DP-HOs, further enhancing the material transport and liver functions of 3DP-HOs. Most importantly, transplantation of 3DP-HOs significantly improved the survival of mice. CONCLUSIONS: Our results demonstrated a comprehensive proof of principle, which indicated that 3DP-HO model of liver tissues possessed in vivo hepatic functions and alleviated liver failure after transplantation, suggesting that 3D bioprinting could be used to generate human liver tissues as the alternative transplantation donors for treatment of liver diseases.

Unique TP53 neoantigen and the immune microenvironment in long-term survivors of Hepatocellular carcinoma.

Neoantigens are T-cell antigens derived from protein-coding mutations in tumor cells. Although neoantigens have recently been linked to anti-tumor immunity in long-term survivors of cancers such as melanoma, their prognostic and immune-modulatory role in many cancer types remain unexplored. We investigate neoantigens in hepatocellular carcinoma (HCC) through a combination of whole exome sequencing (WES), RNA sequencing (RNA-seq), computational bioinformation, and immunohistochemistry. Our analysis reveals that patients carried with TP53 neoantigen have a longer overall survival than others (p = 0.0371) and they showed higher Immune score (p = 0.0441), higher cytotoxic lymphocytes infiltration (p = 0.0428), and higher CYT score (p = 0.0388). In contrast, the prognosis is not associated with TMB and neoantigen load. Our study draws a preliminary conclusion that it is not TMB or neoantigen load but the TP53 specific neoantigen is related to overall survival of HCC patients. We suggest that the TP53 neoantigen may affect prognosis by regulating anti-tumor immunity and that the TP53 neoantigen may be harnessed as potential targets for immunotherapies of HCC.

Comprehensive analysis of coagulation indices for predicting survival in patients with biliary tract cancer.

BACKGROUND: Abnormal activation of the coagulation system has been reported in patients with malignancies, but its prognostic significance in biliary tract cancer (BTC) remains unclear. This study aims to analyze and compare the prognostic value of coagulation indices in patients with BTC. METHODS: The medical records of 450 patients with BTC who underwent surgical resection at our hospital between 2003 and 2017 were retrospectively analyzed. Time-dependent receiver operating characteristic curves were plotted to compare the predictive accuracy of coagulation indices. A predictive nomogram for overall survival (OS) was established based on the Cox regression analysis and validated in both the training and validation cohorts. A novel stratification model was created according to the total points of the nomogram. RESULTS: Fibrinogen and international normalized ratio (INR) had the best predictive accuracy among the coagulation indices considered and were also the independent prognostic factors for OS. The nomogram and the novel stratification model had satisfactory performance and outperformed TNM staging. CONCLUSIONS: The study demonstrated that coagulation indices are valuable in predicting OS in BTC, with fibrinogen and INR having the best predictive ability. The nomogram and the novel stratification model could be applied to predict survival for patients with BTC.

Integrated analysis of serum lipid profile for predicting clinical outcomes of patients with malignant biliary tumor.

BACKGROUND: Serum lipids were reported to be the prognostic factors of various cancers, but their prognostic value in malignant biliary tumor (MBT) patients remains unclear. Thus we aim to assess and compare prognosis values of different serum lipids, and construct a novel prognostic nomogram based on serum lipids. METHODS: Patients with a confirmed diagnosis of MBT at our institute from 2003 to 2017 were retrospectively reviewed. Prognosis-related factors were identified via univariate and multivariate Cox regression analyses. Then the novel prognostic nomogram and a 3-tier staging system were constructed based on these factors and further compared to the TNM staging system. RESULTS: A total of 368 patients were included in this study. Seven optimal survival-related factors-TC/HDL >  10.08, apolipoprotein B >  0.9 g/L, lipoprotein> 72 mg/L, lymph node metastasis, radical cure, CA199 > 37 U/mL, and tumor differentiation -were included to construct the prognostic nomogram. The C-indexes in training and validation sets were 0.738 and 0.721, respectively. Besides, ROC curves, calibration plots, and decision curve analysis all suggested favorable discrimination and predictive ability. The nomogram also performed better predictive ability than the TNM system and nomogram without lipid parameters. And the staging system based on nomogram also presented better discriminative ability than TNM system (P < 0.001). CONCLUSIONS: The promising prognostic nomogram based on lipid parameters provided an intuitive method for performing survival prediction and facilitating individualized treatment and was a great complement to the TNM staging system in predicting overall survival.

Alteration in gut microbiota caused by time-restricted feeding alleviate hepatic ischaemia reperfusion injury in mice.

Time-restricted feeding (TRF), that is, no caloric intake for 14-16 hours each day leads to favourable nutritional outcomes. This study is the first to investigate TRF through a surgical perspective verifying its efficacy against liver ischaemia reperfusion (I/R) injury. We randomly assigned 100 10-week-old wild-type male C57BL/6 mice into two feeding regimens: TRF and ad libitum access to food. Main outcomes were evaluated at 6, 12 and 24 hours post-I/R surgery after 12 weeks of intervention. TRF group demonstrated minor liver injury via histological study; lower serum levels of liver enzymes, glucose and lipids; higher concentrations of free fatty acid and ß-hydroxybutyrate; decreased oxidative stress and inflammatory biomarkers; as well as less severe cell apoptosis and proliferation. Further exploration indicated better gut microenvironment and intestinal epithelial tight junction function. TRF employed its positive influence on a wide spectrum of biochemical pathways and ultimately revealed protective effect against hepatic I/R injury possibly through adjusting the gut microbiota. The results referred to a strong indication of adopting better feeding pattern for surgical patients.

Time-restricted feeding causes irreversible metabolic disorders and gut microbiota shift in pediatric mice.

BACKGROUND: Time-restricted feeding regimen (TRF), that is, no food consumption for 14-16 h during the light phase per day, attenuates the fattening traits and metabolic disorders in adults. This study aims to further investigate whether TRF would be protective against similar nutritional challenges in juvenile mice. METHODS: Mice in the experimental group were treated with TRF during the first 4 weeks (considered to be the childhood phase of mice) before switching to ad libitum (AD) feeding pattern as adults; the control group with all subjects sticks to AD mode. Body weight was monitored, and serum biochemistry, sexual maturity, immune function, and gut microbiota were assessed at a certain timing. RESULTS: Mice treated with TRF during the childhood period (from weaning age) but went through AD feeding pattern as adults demonstrated the tendency of higher body weight, higher levels of serum glucose, shrunken Langerhans islets, fatty liver disease, thickening of aortic walls, delayed sexual development, increased proportion of T regulatory cells, and unhealthy gut microbiota. CONCLUSION: Childhood TRF causes pleiotropic adverse effects, including severe irreversible metabolic disorders, depressed immune function, and retarded puberty. Microbiota set the stage for TRF to employ downstream reactions on the above changes.

Differential Diagnosis of Immunoglobulin G4-associated Cholangitis From Cholangiocarcinoma.

BACKGROUND AND AIM: Immunoglobulin G4-associated cholangitis (IAC) shares many similar symptoms with cholangiocarcinoma (CCA). However, the treatment and the prognosis are substantially different. This study aimed to identify the important markers for the differential diagnosis of these 2 diseases. METHODS: Thirty IAC patients and 275 CCA patients were reviewed retrospectively for their clinical symptoms, serological tests, and imaging characteristics. Posttreatment responses were also studied. RESULTS: IgG4 had 100% specificity for IAC at a cutoff of 6 times the upper normal limit. IAC patients had a significantly higher incidence of weight loss (P=0.025) and a higher level of weight loss (P=0.008) than CCA patients. The positive rates of biological markers CA199, CA242, and CEA in CCA and IAC were 81.5% versus 42.9%, 45.5% versus 4.5%, and 29.2% versus 7.1%, respectively. Levels of these tumor markers in CCA were significantly higher than in IAC (P<0.05). The thickened wall [17/18 (94.4%) vs. 3/10 (30%), P=0.001] and the occupying lesion on the bile duct [1/18 (5.6%) vs. 8/10 (80%), P<0.001] were found to be significantly different in IAC and CCA, respectively, by endoscopic ultrasonography. Autoimmune pancreatitis was the most frequently observed comorbidity of IAC (25/30). All IAC patients respond positively to steroid treatment. CONCLUSIONS: Increased tumor markers, 6-fold higher levels of serum IgG4, and other organs' involvement could be the reference factors for a differential diagnosis of IAC and CCA. Endoscopic ultrasonography might be an effective imaging tool for diagnosis, although clinical signs and symptoms of IAC and CCA are similar. Experimental steroid treatment can be useful in the diagnosis for certain difficult cases.

Voluntary organ donation system adapted to Chinese cultural values and social reality.

Organ donation and transplant systems have unique characteristics based on the local culture and socioeconomic context. China's transplant and organ donation systems developed without regulatory oversight until 2006 when regulation and policy were developed and then implemented over the next several years. Most recently, the pilot project of establishing a voluntary citizen-based deceased donor program was established. The pilot program addressed the legal, financial, and cultural barriers to organ donation in China. The pilot program has evolved into a national program. Significantly, it established a uniquely Chinese donor classification system. The Chinese donor classification system recognizes donation after brain death (category I), donation after circulatory death (category II), and donation after brain death followed by circulatory death (category III). Through August 2014, the system has identified 2326 donors and provided 6416 organs that have been allocated though a transparent organ allocation system. The estimated number of donors in 2014 is 1147. As China's attitudes toward organ donation have matured and evolved and as China, as a nation, is taking its place on the world stage, it is recognizing that its past practice of using organs from executed prisoners is not sustainable. It is time to recognize that the efforts to regulate transplantation and provide voluntary citizen-based deceased organ donation have been successful and that China should use this system to provide organs for all transplants in every province and hospital in China. At the national organ transplant congress on October 30, 2014, the Chairman of the China's national organ donation and transplantation committee, Jeifu Huang required all hospitals to stop using organs from executed prisoners immediately and the civilian organ donation will be sole source for organ transplant in China starting January 2015.

Using Dynamic 99mT c-GSA SPECT/CT fusion images for hepatectomy planning and postoperative liver failure prediction.

BACKGROUND: Available tools in liver surgery planning rely on the future remnant liver (FRL) volume. Inappropriate decision might be made since the same FRL volume might represent different liver functions depending on the severity of underlying liver damage. This study developed an alternative system to estimate FRL function and to predict the risk of postoperative liver failure. METHODS: Current study recruited 71 prehepatectomy patients and 71 healthy volunteers. A technetium-99-labelled asialoglycoproteins was given to participants and SPECT was used to capture the intensity of the signal, represented by uptake index (UI). The agreement between preoperative UI values, liver function tests, and Child scores were evaluated. Linear regression was used to evaluate the agreement between predicted UI for FRL and postoperative UI values. Area under the receiver operating characteristic (AUC) curve was used to evaluate the discriminative performance of UI in differentiating patient with high risk of liver failure. RESULTS: Preoperative UIs are highly correlated with Child score (P < 0.0001), especially to identify patients with ascites and elevated bilirubin. The predicted UIs were in close agreement with the actual postoperative UI values (r = 0.95 P < 0.001). The AUC analysis indicated that UI values had a high accuracy in predicting the risk of liver failure (AUC = 0.95, P < 0.0001). The best cut-off point was 0.9 and the corresponding sensitivity was 100 % and specificity was 92 %. CONCLUSIONS: The new methodology reliably estimates FRL function and predicts the risk of liver failure. It provides a visual aid for liver surgeon in surgery planning and risk assessment.

Retrospective and comparative study of inflammatory myofibroblastic tumor of the liver.

BACKGROUND AND AIM: Inflammatory myofibroblastic tumor of the liver (IMTL) is a very rare benign disease with a good prognosis. The study aims to determine the clinical, radiological, and pathological characteristics of IMTL. The diagnosis and treatment strategies were discussed. METHODS: A total of 11 patients with pathologically confirmed IMTL receiving treatment over a 15-year period were reviewed retrospectively. The analysis included demographics information and pertinent clinical data. Results obtained from patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHCC), and metastatic liver cancer (MLC) receiving surgical resection were compared. RESULTS: In comparison to HCC, IHCC, and MLC, IMTL has an earlier onset (P < 0.001). IMTL patients had significantly lower aspartate aminotransferase (P = 0.003) and higher alkaline phosphatase (P = 0.034) than HCC patients, and higher gamma-glutamyl transpeptidase (P = 0.010) than MLC patients. Increased serum α-fetoprotein level was detected in only one patient. Serum α-fetoprotein was significantly lower in patients with IMTL (P = 0.000) than in those with HCC but not IHCC (P = 0.558) or MLC (P = 0.514). In contrast to elevated serum CA19-9 in patients with HCC/IHCC/MLC, the serum CA19-9 in IMTL cases was generally normal (vs HCC P = 0.008; vs IHCC P = 0.000; vs MLC P = 0.022). In nine IMTL patients, the tumor appeared as a hypoechogenic solid mass on the ultrasonography. In contrast, most patients with HCC, IHCC, or MLC showed hybrid echo. In contrast computed tomography and magnetic resonance imaging, the lesion of IMTL and MLC appeared as peripheral enhancement. CONCLUSION: Lab tests, imaging features, and patient history are helpful in the differential diagnosis of IMTL from HCC/IHCC/MLC. Surgical resection is curative for IMTL.

The response of Golgi protein 73 to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma may relate to the influence of certain chemotherapeutics.

BACKGROUND: Golgi protein 73 (GP73) is a promising biomarker of hepatocellular carcinoma (HCC). It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoembolization (TACE) have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients after TACE treatment, and the possible underlying mechanisms in the cell cultures. METHODS: Blood samples were collected from 72 HCC patients, before TACE, at day 1 and day 30 after TACE. GP73 levels were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents (5-FU and pirarubicin) on GP73 expression were tested in three HCC cell lines (HepG2, HCCLM3 and MHCC97H). RESULTS: The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure (P<0.05). There was no statistical difference between the two time points after TACE, nor correlation between GP73 levels and clinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, significantly increased GP73 expression in three cell lines. CONCLUSIONS: Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.

Identification of prognostic biomarkers in hepatitis B virus-related hepatocellular carcinoma and stratification by integrative multi-omics analysis.

BACKGROUND & AIMS: The differentiation of distinct multifocal hepatocellular carcinoma (HCC): multicentric disease vs. intrahepatic metastases, in which the management and prognosis varies substantively, remains problematic. We aim to stratify multifocal HCC and identify novel diagnostic and prognostic biomarkers by performing whole genome and transcriptome sequencing, as part of a multi-omics strategy. METHODS: A complete collection of tumour and somatic specimens (intrahepatic HCC lesions, matched non-cancerous liver tissue and blood) were obtained from representative patients with multifocal HCC exhibiting two distinct postsurgical courses. Whole-genome and transcriptome sequencing with genotyping were performed for each tissue specimen to contrast genomic alterations, including hepatitis B virus integrations, somatic mutations, copy number variations, and structural variations. We then constructed a phylogenetic tree to visualise individual tumour evolution and performed functional enrichment analyses on select differentially expressed genes to elucidate biological processes involved in multifocal HCC development. Multi-omics data were integrated with detailed clinicopathological information to identify HCC biomarkers, which were further validated using a large cohort of HCC patients (n = 174). RESULTS: The multi-omics profiling and tumour biomarkers could successfully distinguish the two multifocal HCC types, while accurately predicting clonality and aggressiveness. The dual-specificity protein kinase TTK, which is a key mitotic checkpoint regulator with links to p53 signaling, was further shown to be a promising overall prognostic marker for HCC in the large patient cohort. CONCLUSIONS: Comprehensive multi-omics characterisation of multifocal tumour evolution may improve clinical decision-making, facilitate personalised medicine, and expedite identification of novel biomarkers and therapeutic targets in HCC.

Golgi protein 73, not Glypican-3, may be a tumor marker complementary to α-Fetoprotein for hepatocellular carcinoma diagnosis.

BACKGROUND AND AIM: This study aimed to evaluate the effectiveness of serum Golgi protein 73 (GP73) and Glypican-3 (GPC-3) as tumor markers for diagnosis of hepatocellular carcinoma (HCC). METHODS: A total of 257 subjects were enrolled and consisted of 61 healthy controls, 32 hepatitis B virus carriers, 80 cirrhosis patients, and 84 HCC patients. Diagnosis was performed based on established clinical procedure. Serum GP73, GPC-3, and α-fetoprotein were measured. Receiving operating characteristic (ROC) curves were plotted to determine the sensitivity and specificity of each serum marker and their combinations. RESULT: Serum GP73 levels were significantly increased in HCC patients. No significant differences were observed between GP73 and α-fetoprotein (AFP) as markers for HCC diagnosis. However, GP73 was more sensitive than AFP in the diagnosis of small HCC. A combination of GP73 and AFP tests increased the sensitivity and specificity for HCC diagnosis. The area under the ROC curve (AUC) of combined test was 0.93 compared with 0.88 for GP73 and 0.90 for AFP alone. GPC-3 tests were negative in all 84 HCC patients. The AUC for GPC-3 is 0.43, indicating that serum GPC-3 was not an effective tumor marker for HCC diagnosis. CONCLUSION: Serum GP73 is a potential tumor marker for HCC diagnosis, especially for differential diagnosis of small HCC and cirrhosis. The combination of GP73 and AFP is more sensitive than AFP alone. Serum GPC-3 does not appear to be an effective tumor marker for HCC diagnosis.

A pilot programme of organ donation after cardiac death in China.

China's aims are to develop an ethical and sustainable organ transplantation system for the Chinese people and to be accepted as a responsible member of the international transplantation community. In 2007, China implemented the Regulation on Human Organ Transplantation, which was the first step towards the establishment of a voluntary organ donation system. Although progress has been made, several ethical and legal issues associated with transplantation in China remain, including the use of organs from executed prisoners, organ scarcity, the illegal organ trade, and transplantation tourism. In this Health Policy article we outline the standards used to define cardiac death in China and a legal and procedural framework for an organ donation system based on voluntary donation after cardiac death that adheres to both China's social and cultural principles and international transplantation standards.

Clinical diagnosis and treatment of alpha-fetoprotein-negative small hepatic lesions.

OBJECTIVE: We examined 103 cases over the last five years and discussed diagnosis and treatment of alpha-fetoprotein (AFP)-negative small hepatic lesions. BACKGROUND: Small hepatic lesions (less than 2 cm in diameter) usually have no typical imaging characteristics and therefore are difficult to diagnose, especially when AFP tests provide a negative result. METHODS: A total of 103 patients with AFP-negative small hepatic lesions from January 2003 to December 2008 were retrospectively reviewed. Differential diagnosis was performed by digital subtraction angiography (DSA), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), contrast-enhanced ultrasound (CEUS), or positron emission tomography-computed tomography (PET-CT) based on the multiplicity of lesions. Ninety-four patients with suspected cancers underwent partial hepatectomy. Clinical data were collected from hospital records and follow-up questionnaires. RESULTS: Hepatocellular carcinoma (HCC) diagnostic sensitivity of DSA, DCE-MRI, CEUS and PET-CT was 88.2%, 93.9%, 88.9% and 88.9%, respectively. The surgery-related complication rate was 6.4%. Prognosis was good, with 1- and 3-year survival rates of 98.8% and 76.1%, respectively. CONCLUSIONS: DSA, DCE-MRI, CEUS and PET-CT are valuable for diagnosis of small hepatic lesions. Partial hepatectomy is a preferred surgical procedure. Surgery for small liver cancers usually has little risk and good prognosis, therefore it can be actively applied in suspected HCC cases.

Primary liver cancer presenting as pyogenic liver abscess: characteristics, diagnosis, and management.

BACKGROUND AND OBJECTIVES: Primary liver cancer (PLC) presenting as pyogenic liver abscess (PLA) is potentially life-threatening, but has been occasionally reported, especially for cholangiocarcinoma. METHODS: Medical records of nine patients who presented as PLA, but were eventually confirmed as hepatocellular carcinoma (HCC; n = 5) or intrahepatic cholangiocarcinoma (IHCC; n = 4), from September 1997 through April 2011, were retrospectively reviewed. RESULTS: Presenting symptoms included fever, chills, right-upper-quadrant abdominal pain, nausea, vomiting, weight loss, and diarrhea. Physical signs included tenderness in the right-upper-quadrant abdomen, jaundice, and ascites. With the exception of elevated alpha-fetoprotein (AFP) in HCC patients and elevated carbohydrate antigen 19-9 (CA19-9) in IHCC patients, lab results were not significantly different between these nine patients and PLA patients. All the nine patients underwent invasive treatment in addition to antibiotics. CONCLUSIONS: Elevated AFP and CA19-9 could suggest HCC and IHCC in patients with symptoms/signs typical of PLA. Contrast-enhanced computed tomography could be helpful in patients with normal AFP and CA19-9. Making an accurate and early diagnosis and seizing the opportunity of surgery are essential to improve the management strategies of patients with PLC mimicking PLA.

Hepatobiliary cystadenomas and cystadenocarcinomas: a report of 33 cases.

BACKGROUND: Hepatobiliary cystadenomas and cystadenocarcinomas are rare and often misdiagnosed. AIMS: We report our experience with 33 cases over 20 years to discuss an algorithm for these diseases. METHODS: Patients presenting with a diagnosis of hepatobiliary cystadenomas and cystadenocarcinomas were retrospectively reviewed from January 1991 to October 2010. Clinical data were collected by examining hospital records and by follow-up questionnaire interviews. RESULTS: Thirty-three patients had pathologically diagnosed hepatobiliary cystadenomas (19/33, 17 females and two males) or cystadenocarcinomas (14/33, five females and nine males). Symptoms of cystadenomas at hospitalization were abdominal bloating or pain (9/19). Nine patients had an elevated level of carbohydrate antigen (CA) 19-9. The surgical procedures, i.e. cyst enucleation, segmentectomy, sectionectomy and hemihepatectomy, were performed with satisfactory outcomes. Symptoms of cystadenocarcinomas included abdominal bloating or pain (8/14) and fever (3/14). Seven patients had elevated CA19-9. The imaging characteristics of cystadenocarcinomas were similar to those of cystadenomas. The clinical outcomes for cystadenocarcinomas were mostly poor after either surgical or conservative treatment. CONCLUSIONS: Clinical symptoms are unreliable for these diagnoses and their differential diagnosis. Imaging evaluations and CA19-9 are of value for the recognition of cystadenoma and cystadenocarcinoma, but not for their differential diagnosis. Any recurrence of liver cyst after surgery or other treatments should lead one to suspect one of these diseases. Invasive examination and percutaneous fine-needle aspiration cytology are not recommended. Complete excision or careful enucleation should be the first treatment choice for a better prognosis.

Increased Golgi protein 73 expression in hepatocellular carcinoma tissue correlates with tumor aggression but not survival.

BACKGROUND AND AIM: Serum Golgi protein 73 (sGP73) is a novel and promising biomarker for hepatocellular carcinoma (HCC). However, there are few reports on the pattern of GP73 expression in HCC and the relationship of this expression to clinicopathologic features of patients. This study aimed to investigate the expression of GP73 and it correlation with clinical parameters. METHODS: We examined GP73 expression in HCC and adjacent paracarcinomatous liver (PCL) tissue in 36 HCC patients, and took 14 normal liver (NL) samples from hepatic hemangioma patients. Western blot analysis and quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) were used for analyses. RESULTS: GP73 expression in HCC was significantly higher than in the corresponding PCL and NL samples at both protein and mRNA levels (P < 0.001). The elevated level of GP73 protein was strongly associated with tumor size, vein invasion, and tumor differentiation, suggesting augmented tumor invasion and metastasis. However, there was no association between GP73 expression and patient survival. CONCLUSION: Significant overexpression of GP73 at both protein and mRNA levels along with overexpression of GP73 protein is associated with aggressive behavior of HCC, but not overall patient survival. Further research is needed to determine the potential of GP73 as a therapeutic target.

[Diagnosis and treatment of primary hepatic angiosarcoma: a report of 7 cases with a literature review].

OBJECTIVE: To explore the clinical features, diagnosis, treatment and prognosis of primary hepatic angiosarcoma (PHA). METHODS: The clinical data of 7 PHA patients admitted to our hospital from December 2004 to December 2010 were retrospectively analyzed and the relevant literatures reviewed. RESULTS: Seven cases (5 males and 2 females) were diagnosed as PHA among 1027 (0.68%) patients with primary hepatic malignant tumors. Their mean age was 43.3 years old (range: 33 - 74). Four cases were of solitary lesion and three of multiple lesions. No specific clinical features were observed. The PHA lesions were easily misdiagnosed as benign or hepatic metastatic tumors. Contrast enhanced ultrasound (CEUS) showed the lesions with characteristic manifestations. And the positron emission tomography (PET-CT) could confirm the hepatic lesions as malignant tumors. The survival time for two untreated cases was 3 & 5 months, for two cases with liver transplantation (LTx) 3 & 8 months and for two cases treated with surgical resection & targeted therapy was 14 & 19 months respectively. One case was lost to follow-up at 6 months after hepatic resection. CONCLUSION: PHA is a clinically rare and highly malignant tumor with a rapid progression and a poor prognosis. Both CEUS and PET-CT are helpful for its differential and confirmative diagnosis. LTx should be considered as a contraindication for PHA. Hepatic resection has proven to be beneficial for PHA patients with solitary lesion. Surgical resection plus targeted medicines may improve their survival.

Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma.

BACKGROUND AND AIMS: Golgi protein 73 (GP73) as a potential serum marker for hepatocellular carcinoma (HCC) has not been validated in large cohort studies. Furthermore, its significance in the assessment of tumour recurrence after HCC resection remains unknown. The aim of this study was to determine the value of serum GP73 in the diagnosis of HCC. METHODS: Serum GP73 and alpha-fetoprotein (AFP) were compared in a total of 4217 human subjects in this multicentre study, including 1690 healthy adults, 337 hepatitis B virus (HBV) carriers, 512 patients with cirrhosis, 789 patients with HCC, 61 patients with other malignant liver lesions, 206 patients with benign liver lesions and 622 patients with 14 different kinds of non-liver cancers. The main outcome measures were the specificity and sensitivity of GP73 in patients at risk for the development of HCC. RESULTS: Using 8.5 relative units as a cut-off value, the sensitivity and specificity of serum GP73 for HCC were 74.6% (95% CI 71.5% to 77.6%) and 97.4% (95% CI 96.8 to 98.3%), compared with 58.2% (95% CI 55.2% to 62.1%) and 85.3% (95% CI 83.4% to 88.1%) for AFP (p<0.001) using 35 ng/ml as a cut-off value. The GP73 level was significantly increased in patients with HCC compared with healthy controls (14.7 vs 1.2, p<0.001). Although GP73 levels in HBV carriers (2.9) and patients with cirrhosis (4.7) were somewhat elevated, they were much lower than that in patients with HCC (p<0.001). GP73 decreased following surgical resection of HCC lesions and increased with tumour recurrence. Fourteen types of non-liver cancers were analysed; all the benign and other malignant liver lesions had moderate elevations of GP73, albeit at a much lower level than in HCC. CONCLUSIONS: GP73 is an accurate serum marker for the detection of HCC and its recurrence after surgery, with higher sensitivity and specificity than AFP. Clinical implementation of serum GP73 measurement as a standard test for HCC is recommended.