Primary liver cell carcinoma (PLCC) or Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor in Nigeria. It is a difficult problem in surgery for the diagnosis and therapy of spontaneous live...Primary liver cell carcinoma (PLCC) or Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor in Nigeria. It is a difficult problem in surgery for the diagnosis and therapy of spontaneous liver rupture. The clinical presentation can be varied owing to its clinical signs being usually not specific; therefore, correct diagnosis and management are very important. Without any treatment, the outcome is poor and survival rate is only 10%. Surgeons operate on those patients who present with ruptured PLCC; consisting of packing, hepatic artery ligation and hepatectomy. However, it is often associated with a high mortality rate; as high as 70%, even for the less invasive procedures like packing, argon beam coagulation or hepatic artery ligation. We present a 24-year old lady who had ligation of hepatic artery at an emergency laparotomy for ruptured primary liver cell carcinoma.展开更多
AIM: To investigate the selective tropism of liver stem cells to hepatocellular carcinoma (HCC) in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC. METHODS: WB-...AIM: To investigate the selective tropism of liver stem cells to hepatocellular carcinoma (HCC) in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC. METHODS: WB-F344, a kind of rat liver stem cell, was infected with recombinant virus to establish a cell line with stable, high-level expressing enhanced green fluorescent protein (EGFP). An animal model of HCC in Wistar rats was established by implanting HCC cells (CBRH7919) combined with an immunosuppressive drug. EGFP labeled liver stem cells were injected into caudal veins of the animals and distribution was observed at different time points after injection. SDF-1 and c-kit expression in non-tumor liver and tumor tissue were analysed by immunohistochemistry for the relationshiop between the expression and migration of liver stem cells. Furthermore, hepatic stem cells were injected via the portal vein, hepatic artery, caudal vein, or directly into the pericancerous liver tissue, respectively, and effects on migration, localization, and proliferation of the hepatic stem cells within the tumor tissue were observed and analyzed. RESULTS: Recombinant adenovirus could deliver the EGFP gene to hepatic stem cells. A new stem cell line, named WB-EGFP, was established that stably expressed EGFP. WB-EGFP cells still showed selective tropism towards HCC and EGFP expression was stable in vivo. According to immunohistochemistry results, SDF-1 may not be related to the mechanisms of tropism of hepatic stem cells. Different application sites affected the distribution of liver stem cells. Injection via the portalvein was superior with regard to selective migration, localization, and proliferation of the hepatic stem cells within the tumor tissue. CONCLUSION: Liver stem cells have the biological behavior of selective migration to HCC in vivo and they could localize and proliferate within HCC tissue stably expressing the target gene. Liver stem cells are a potential tool for a targeted gene therapy of HCC.展开更多
Primary squamous cell carcinoma (SCC) of the liveris rare. Totally nine such cases have been reportedin the literature. Primary SCC of the liver has beenreported to be associated with hepatic teratoma,hepatic cyst, or...Primary squamous cell carcinoma (SCC) of the liveris rare. Totally nine such cases have been reportedin the literature. Primary SCC of the liver has beenreported to be associated with hepatic teratoma,hepatic cyst, or hepatolithiasis. Complete remission ofpoorly differentiated SCC of the liver could be achievedby systemic chemotherapy followed by surgery orremarkably respond to hepatic arterial injection of lowdose chemotherapeutic drugs. Here we report the fi rstcase of primary SCC of the liver presenting as a solidtumor and receiving successful hepatic resection with9-mo disease free survival.展开更多
A 36-year-old woman was admitted to our department for close examination of a liver tumor that was found during a medical checkup. Abdominal US, CT and MRI showed a tumor in segment 7 (S7) of the liver. Although imagi...A 36-year-old woman was admitted to our department for close examination of a liver tumor that was found during a medical checkup. Abdominal US, CT and MRI showed a tumor in segment 7 (S7) of the liver. Although imaging suggested hepatocellular carcinoma, laboratory tests showed no abnormality in liver function, hepatitis virus markers were negative, and tumor markers including protein induced by vitamin K absence or antagonist Ⅱ (PIVKA-Ⅱ), α-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) were all within normal ranges. Upon aspiration biopsy of the liver, the histopathological diagnosis was moderately differentiated hepatocellular carcinoma. Therefore, right hepatectomy was performed. Although a part of the tumor was necrotic, about 60% of the viable part showed a clear-cell variant. Consequently, it was diagnosed as clear-cell hepatocellular carcinoma. It was noted that the background liver tissue was normal. This case is worthy of reporting because development of clear-cell hepatocellular carcinoma in the normal liver of a middle-aged woman is rarely seen.展开更多
A case of intraductal papillary neoplasm of the bile duct (IPNB) arising in a patient with hepatitis B-related liver cirrhosis with hepatocellular carcinoma (HCC) is reported. A 76-year-old man was admitted to our hos...A case of intraductal papillary neoplasm of the bile duct (IPNB) arising in a patient with hepatitis B-related liver cirrhosis with hepatocellular carcinoma (HCC) is reported. A 76-year-old man was admitted to our hospital with recurrent HCC. Laboratory data showed that levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were elevated. He died of progressive hepatic failure. At autopsy,in addition to HCCs,an intraductal papillary proliferation of malignant cholangiocytes with fibrovascular cores was found in the dilated large bile ducts in the left lobe,and this papillary carcinoma was associated with an invasive mucinous carcinoma (invasive IPNB). Interestingly,extensive intraductal spread of the cholangiocarcinoma was found from the reactive bile ductular level to the interlobular bile ducts and septal bile ducts and to the large bile ducts in the left lobe. Neural cell adhesion molecule,a hepatic progenitor cell marker,was detected in IPNB cells. It seems possible in this case that hepatic progenitor cells located in reactive bile ductules in liver cirrhosis may have been responsible for the development of the cholangiocarcinoma and HCC,and that the former could have spread in the intrahepatic bile ducts and eventually formed grossly visible IPNB.展开更多
Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely ...Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely described in physiologic conditions and in relation to metastasis during the past 30 years. This paper provides an 'overview' of how these cells function in health and in diseases such as liver metastasis.展开更多
AIM: To analyze outcomes in patients who underwent liver transplantation(LT) for hepatocellular carcinoma(HCC) and received autologous intraoperative blood salvage(IBS). METHODS: Consecutive HCC patients who underwent...AIM: To analyze outcomes in patients who underwent liver transplantation(LT) for hepatocellular carcinoma(HCC) and received autologous intraoperative blood salvage(IBS). METHODS: Consecutive HCC patients who underwent LT were studied retrospectively and analyzed according to the use of IBS or not. Demographic and surgical data were collected from a departmental prospective maintained database. Statistical analyses were performed using the Fisher's exact test and the Wilcoxon rank sum test to examine covariate differences between patients who underwent IBS and those who did not. Univariate and multivariate Cox regression models were developed to evaluate recurrence and death,and survival probabilities were estimated using the Kaplan-Meier method and compared by the log-rank test.RESULTS: Between 2002 and 2012,158 consecutive patients who underwent LT in the same medical center and by the same surgical team were identified. Among these patients,122(77.2%) were in the IBS group and 36(22.8%) in the non-IBS group. The overall survival(OS) and recurrence free survival(RFS) at 5 years were 59.7% and 83.3%,respectively. No differences in OS(P=0.51) or RFS(P=0.953) were detected between the IBS and non-IBS groups. On multivariate analysis for OS,degree of tumor differentiation remained as the only independent predictor. Regarding patients who received IBS,no differences were detected in OS or RFS(P=0.055 and P=0.512,respectively) according to the volume infused,even when outcomes at 90 d or longer were analyzed separately(P=0.518 for both outcomes).CONCLUSION: No differences in RFS or OS were detected according to IBS use. Trials addressing this question are justified and should be designed to detect small differences in long-term outcomes.展开更多
An 80-year-old woman presenting with chest pain was found to have a large,lobulated soft tissue mass in the liver and nearby tissues on abdominal computed tomography(CT).The tumor had invaded the common hepatic artery...An 80-year-old woman presenting with chest pain was found to have a large,lobulated soft tissue mass in the liver and nearby tissues on abdominal computed tomography(CT).The tumor had invaded the common hepatic artery and main portal vein.Jaundice developed 4 wk later,at which point,a pancreas and biliary CT scan revealed a large mass in the right lobe of the liver and a hilar duct obstruction,which was found to be a small cell carcinoma.Despite its rarity,liver and bile duct small cell carcinoma should be considered in the differential diagnosis of atypical chest pain without jaundice.展开更多
A recombinant plasmid containing a full length human epidermal growth factor receptor (EGFR) cDNA sequence in antisense orientation was transferred into cells of a human liver carcinoma cell line BEL-7404. Compared wi...A recombinant plasmid containing a full length human epidermal growth factor receptor (EGFR) cDNA sequence in antisense orientation was transferred into cells of a human liver carcinoma cell line BEL-7404. Compared with the control cell clone JX-0 transferred with the vector plasmid and the parent BEL-7404 cells, the antisense EGFR transferred cell clone JX-1 showed a decreased EGFR gene expression and reduced significantly the growth potential either in anchorage-dependent or anchorage-independent growth. Furthermore. JX-1 cells appeared to be distinctly dependent on serum concentration for monolayer growth. The results suggested that antisense EGFR could partly block the EGFR gene ex-pression and reverse the malignant growth properties of human liver carcinoma cells in vitro.展开更多
BACKGROUND Polycystic liver disease(PCLD) with a large cystic volume deteriorates the quality of life of patients through substantial effects on the adjacent organs,recurrent cyst infections, cyst rupture, and hemorrh...BACKGROUND Polycystic liver disease(PCLD) with a large cystic volume deteriorates the quality of life of patients through substantial effects on the adjacent organs,recurrent cyst infections, cyst rupture, and hemorrhage. Surgical or radiological intervention is usually needed to alleviate these symptoms. We report a rare case of the cystic metastasis of renal cell carcinoma(RCC), which was misdiagnosed as PCLD, as a result of the clinical and radiological similarity between these disorders.CASE SUMMARY A 74-year-old female who had undergone nephrectomy for papillary-type RCC(PRCC) was suffering from abdominal pain and the recurrent intracystic hemorrhage of multiple cysts in the liver. Imaging studies and aspiration cytology of the cysts showed no evidence of malignancy. With a diagnosis of autosomal dominant polycystic liver disease, the patient received hepatectomy for the purpose of mass reduction and infectious cyst removal. Surgery was performed without complications, and the patient was discharged on postoperative day 14. Postoperatively, the pathology revealed a diagnosis of recurrent PRCC with cystic formation.CONCLUSION This case demonstrates the importance of excluding the cystic metastasis of a cancer when liver cysts are observed.展开更多
Hepatocellular carcinoma(HCC) represents a unique challenge for physicians and patients.There is no definitively curative treatment.Rather,many treatment and management modalities exist with differing advantages and d...Hepatocellular carcinoma(HCC) represents a unique challenge for physicians and patients.There is no definitively curative treatment.Rather,many treatment and management modalities exist with differing advantages and disadvantages.Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC.In addition,quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies.Thus,considering all the options and their various pros and cons can quickly become complex for both clinicians and patients.In this review,we systematically discuss the current treatment modalities available for HCC,detailing relevant clinical data,risks and rewards and overall outcomes for each approach.Surgical options discussed include resection,transplantation and ablation.We also discuss the radiation modalities:conformal radiotherapy,yttrium 90 microspheres and proton and heavy ion radiotherapy.The biologic agent Sorafenib is discussed as a promising new approach,and recent clinical trials are reviewed.We then detail currently described molecular pathways implicated in the initiation and progression of HCC,and we explore the potential of each pathway as an avenue for drug exploitation.We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease.展开更多
Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to th...Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs) as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC) transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.展开更多
In recent years, the results of several studies suggest that human liver tumors can be derived from hepatic progenitor cells rather than from mature cell types. The available data indeed strongly suggest that most com...In recent years, the results of several studies suggest that human liver tumors can be derived from hepatic progenitor cells rather than from mature cell types. The available data indeed strongly suggest that most combined hepatocellular-cholangiocarcinomas arise from hepatic progenitor cells that retained their potential to differentiate into the hepatocytic and biliary lineages. Hepatic progenitor cells could also be the basis for some hepatocellular carcinomas and hepatocellular adenomas, although it is very difficult to determine the origin of an individual hepatocellular carcinoma. There is currently not enough data to make statements regarding a hepatic progenitor cell origin of cholangiocarcinoma. The presence of hepatic progenitor cell markers and the presence and extent of the cholangiocellular component are factors that are related to the prognosis of hepatocellular carcinomas and combined hepatocellular- cholangiocarcinomas, respectively.展开更多
The prognosis of patients diagnosed with hepatocellular carcinoma (HCC) is often dismal, mainly due to late presentation, high recurrence rate, and frequent resistance to chemotherapy and radiotherapy. Accumulating ev...The prognosis of patients diagnosed with hepatocellular carcinoma (HCC) is often dismal, mainly due to late presentation, high recurrence rate, and frequent resistance to chemotherapy and radiotherapy. Accumulating evidence on the differential microRNA (miRNA) expression patterns between non-tumor and HCC tissues or between liver cancer stem cells (CSCs) and non-CSC subsets and the significant clinical implications of these differences suggest that miRNAs are a promising, non-invasive marker for the prognosis and diagnosis of the disease. This perspective article summarizes the current knowledge of miRNAs in liver CSCs and highlights the need for further investigations of the role of miRNAs in regulating liver CSC subsets for possible future clinical applications.展开更多
Liver transplant(LT) is the primary treatment for patients with end-stage liver disease. About 25000 LTs are performed annually in the world. The potential for intraoperative bleeding is quite variable. However, massi...Liver transplant(LT) is the primary treatment for patients with end-stage liver disease. About 25000 LTs are performed annually in the world. The potential for intraoperative bleeding is quite variable. However, massive bleeding is common and requires blood transfusion. Allogeneic blood transfusion has an immunosuppressive effect and an impact on recipient survival, in addition to the risk of transmission of viral infections and transfusion errors, among others.Techniques to prevent excessive bleeding or to use autologous blood have been proposed to minimize the negative effects of allogeneic blood transfusion.Intraoperative reinfusion of autologous blood is possible through previous selfdonation or blood collected during the operation. However, LT does not normally allow autologous transfusion by prior self-donation. Hence, using autologous blood collected intraoperatively is the most feasible option. The use of intraoperative blood salvage autotransfusion(IBSA) minimizes the perioperative use of allogeneic blood, preventing negative transfusion effects without negatively impacting other clinical outcomes. The use of IBSA in patients with cancer is still a matter of debate due to the theoretical risk of reinfusion of tumor cells. However, studies have demonstrated the safety of IBSA in several surgical procedures, including LT for hepatocellular carcinoma. Considering the literature available to date, we can state that IBSA should be routinely used in LT, both in patients with cancer and in patients with benign diseases.展开更多
Liver cancer is a common malignancy and surgery is the main treatment strategy. However, the prognosis is still poor because of high frequencies of postoperative recurrence and metastasis. In recent years, cancer stem...Liver cancer is a common malignancy and surgery is the main treatment strategy. However, the prognosis is still poor because of high frequencies of postoperative recurrence and metastasis. In recent years, cancer stem cell(CSC) theory has evolved with the concept of stem cells, and has been applied to oncological research. According to cancer stem cell theory, liver cancer can be radically cured only by eradication of liver cancer stem cells(LCSCs). This notion has lead to the isolation and identification of LCSCs, which has become a highly researched area. Analysis of LCSC markers is considered to be the primary method for identification of LCSCs. Here, we provide an overview of the current research progress and prospects of surface markers for LCSCs.展开更多
OBJECTIVE It has been reported that heating can enhance sensitivity of rabbit VX2 cells to adriamycin and increase the intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effe...OBJECTIVE It has been reported that heating can enhance sensitivity of rabbit VX2 cells to adriamycin and increase the intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effect of interventional hyperthermia and interventional thermochemotherapy on VX2 carcinoma in rabbit liver. METHODS VX2 carcinoma cells were surgically implanted into the right liver lobe of 60 male New Zealand white rabbits, which were randomly divided into 4 groups (15 per group). The 4 groups (designated as 1, 2, 3, 4 respectively) were injected with 10 ml of the following via the hepatic artery: physiological saline (37℃); adriamycin (37℃); physiological saline (60℃); adriamycin (60℃). One week later, the tumor volume, serum level of aspartate transaminase (AST) and the survival of the rabbits bearing VX2 were observed and compared among the different treated groups. RESULTS The tumor growth rate in group 4 (ADM 60℃) (0.53±0.21)% was significantly lower than that in group 1 (3.48±1.17)%, in group 2 (1.09±0.26)% and group 3 (3.32±1.28)% (P<0.05, P<0.05, P<0.01, respectively). The days of survival days for group 4 (87.0±2.0) were significantly more than that in group 1 (40.0±3.0). Group 4 showed a significantly higher increase in serum AST compared to group 1 (P<0.05), but without significant differences compared to the other groups (P>0.05). CONCLUSION Adriamycin treatment at 60℃ significantly deceased the tumor growth, prolonged the survival period and resulted in reversible liver damage.展开更多
A 56-year-old man was found to have a pancreatic tail tumor. His blood chemistry showed no infection with hepatitis B or C virus and no elevations of tumor markers or pancreatic hormones. Abdominal ultrasound showed a...A 56-year-old man was found to have a pancreatic tail tumor. His blood chemistry showed no infection with hepatitis B or C virus and no elevations of tumor markers or pancreatic hormones. Abdominal ultrasound showed an encapsulated, rather heterogeneous, hypoechoic tumor, 6.5 cm in maximum diameter, with a beak sign. Helical dynamic CT revealed an irregularly enhanced tumor with pooling of contrast medium in the delayed phase. Abdominal angiography showed a hypervascular tumor. With a tentative diagnosis of non-functional islet-cell tumor, the patient underwent resection of the pancreatic body and tail with splenectomy. The contour of the liver and its surface were normal. In microscopic examination, tumor cells arranged in a trabecular pattern with focal bile pigment resembling hepatocellular carcinoma (HCC). Immunohistochemically, these tumor cells were positivefor HEPPAR-1, CAM5.2, cytokeratin 18 and COX-2, but negative for MUC-1, and cytokeratins 7, 20 and 8. These results supported a diagnosis of HCC without any adenocarcinoma component. The patient is currently doing well without any signs of recurrence in either the remaining pancreas or liver three years after surgery. We report the rare case with ectopic HCC in the pancreas with a review of the literature.展开更多
AIM: To evaluate the relationship between hepatocellular carcinoma(HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation recurrence.METHODS: This retrospect...AIM: To evaluate the relationship between hepatocellular carcinoma(HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation recurrence.METHODS: This retrospective study included 165 patients(143 men, 22 women; median age 56.8 years, range 28-70.4 years) transplanted for HCC who had a follow-up period longer than 2 mo. Pre-transplantation dynamic computed tomography or magnetic resonance examinations were retrospectively reviewed, classifying HCC imaging enhancement pattern into hypervascular and hypovascular based on presence of wash-in during arterial phase. All pathologic reports of the explanted livers were reviewed, collecting data about HCC differentiation degree. The association between imaging vascular pattern and pathological grade was estimated using the Fisher exact test. All follow-up clinical and imaging data were reviewed for evidence of recurrence. Recurrence rate was calculated and imaging features of recurrent tumor were collected, classifying early and late recurrences based on timing(< or ≥ 2 years after transplantation) and intrahepatic, extrahepatic and both intrahepatic and extrahepatic recurrences based onlocation. All intrahepatic recurrences were classified as hypervascular or hypovascular and the differentiation degree was collected where available. The presence of variations in imaging enhancement pattern and pathological grade between the primary tumor and the intrahepatic recurrence was evaluated and the association between imaging and histopatholgical variations was estimated by using the χ2 test. RESULTS: Of the 163 patients with imaging evidence of viable tumor, 156(95.7%) had hypervascular and 7(4.3%) hypovascular HCC. Among the 125 patients with evidence of viable tumor in the explanted liver, 19(15.2%) had grade 1, 56(44.8%) grade 2, 40(32%) grade 3 and 4(3.2%) grade 4 HCC, while the differentiation degree was not assessable for 6 patients(4.8%). A significant association was found between imaging vascularity and pathological grade(P = 0.035). Post-transplantation recurrence rate was 14.55%(24/165). All recurrences occurred in patients who had a hypervascular primary tumor. Three patients(12.5%) experienced late recurrence; the location of the first recurrence was extrahepatic in 14 patients(58.3%), intrahepatic in 7 patients(29.2%) and both intrahepatic and extrahepatic in 3 patients(12.5%). Two patients had a variation in imaging characteristics between the primary HCC(hypervascular) and the intrahepatic recurrent HCC(hypovascular), while 1 patient had a variation of histopathological characteristics(from moderate to poor differentiation), however no association was found between imaging and histopathological variations.CONCLUSION: A correlation was found between HCC grade and vascularity; some degree of variability may exist between the primary and the recurrence imaging/histopathological characteristics, apparently not correlated.展开更多
文摘Primary liver cell carcinoma (PLCC) or Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor in Nigeria. It is a difficult problem in surgery for the diagnosis and therapy of spontaneous liver rupture. The clinical presentation can be varied owing to its clinical signs being usually not specific; therefore, correct diagnosis and management are very important. Without any treatment, the outcome is poor and survival rate is only 10%. Surgeons operate on those patients who present with ruptured PLCC; consisting of packing, hepatic artery ligation and hepatectomy. However, it is often associated with a high mortality rate; as high as 70%, even for the less invasive procedures like packing, argon beam coagulation or hepatic artery ligation. We present a 24-year old lady who had ligation of hepatic artery at an emergency laparotomy for ruptured primary liver cell carcinoma.
文摘AIM: To investigate the selective tropism of liver stem cells to hepatocellular carcinoma (HCC) in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC. METHODS: WB-F344, a kind of rat liver stem cell, was infected with recombinant virus to establish a cell line with stable, high-level expressing enhanced green fluorescent protein (EGFP). An animal model of HCC in Wistar rats was established by implanting HCC cells (CBRH7919) combined with an immunosuppressive drug. EGFP labeled liver stem cells were injected into caudal veins of the animals and distribution was observed at different time points after injection. SDF-1 and c-kit expression in non-tumor liver and tumor tissue were analysed by immunohistochemistry for the relationshiop between the expression and migration of liver stem cells. Furthermore, hepatic stem cells were injected via the portal vein, hepatic artery, caudal vein, or directly into the pericancerous liver tissue, respectively, and effects on migration, localization, and proliferation of the hepatic stem cells within the tumor tissue were observed and analyzed. RESULTS: Recombinant adenovirus could deliver the EGFP gene to hepatic stem cells. A new stem cell line, named WB-EGFP, was established that stably expressed EGFP. WB-EGFP cells still showed selective tropism towards HCC and EGFP expression was stable in vivo. According to immunohistochemistry results, SDF-1 may not be related to the mechanisms of tropism of hepatic stem cells. Different application sites affected the distribution of liver stem cells. Injection via the portalvein was superior with regard to selective migration, localization, and proliferation of the hepatic stem cells within the tumor tissue. CONCLUSION: Liver stem cells have the biological behavior of selective migration to HCC in vivo and they could localize and proliferate within HCC tissue stably expressing the target gene. Liver stem cells are a potential tool for a targeted gene therapy of HCC.
文摘Primary squamous cell carcinoma (SCC) of the liveris rare. Totally nine such cases have been reportedin the literature. Primary SCC of the liver has beenreported to be associated with hepatic teratoma,hepatic cyst, or hepatolithiasis. Complete remission ofpoorly differentiated SCC of the liver could be achievedby systemic chemotherapy followed by surgery orremarkably respond to hepatic arterial injection of lowdose chemotherapeutic drugs. Here we report the fi rstcase of primary SCC of the liver presenting as a solidtumor and receiving successful hepatic resection with9-mo disease free survival.
文摘A 36-year-old woman was admitted to our department for close examination of a liver tumor that was found during a medical checkup. Abdominal US, CT and MRI showed a tumor in segment 7 (S7) of the liver. Although imaging suggested hepatocellular carcinoma, laboratory tests showed no abnormality in liver function, hepatitis virus markers were negative, and tumor markers including protein induced by vitamin K absence or antagonist Ⅱ (PIVKA-Ⅱ), α-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) were all within normal ranges. Upon aspiration biopsy of the liver, the histopathological diagnosis was moderately differentiated hepatocellular carcinoma. Therefore, right hepatectomy was performed. Although a part of the tumor was necrotic, about 60% of the viable part showed a clear-cell variant. Consequently, it was diagnosed as clear-cell hepatocellular carcinoma. It was noted that the background liver tissue was normal. This case is worthy of reporting because development of clear-cell hepatocellular carcinoma in the normal liver of a middle-aged woman is rarely seen.
文摘A case of intraductal papillary neoplasm of the bile duct (IPNB) arising in a patient with hepatitis B-related liver cirrhosis with hepatocellular carcinoma (HCC) is reported. A 76-year-old man was admitted to our hospital with recurrent HCC. Laboratory data showed that levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were elevated. He died of progressive hepatic failure. At autopsy,in addition to HCCs,an intraductal papillary proliferation of malignant cholangiocytes with fibrovascular cores was found in the dilated large bile ducts in the left lobe,and this papillary carcinoma was associated with an invasive mucinous carcinoma (invasive IPNB). Interestingly,extensive intraductal spread of the cholangiocarcinoma was found from the reactive bile ductular level to the interlobular bile ducts and septal bile ducts and to the large bile ducts in the left lobe. Neural cell adhesion molecule,a hepatic progenitor cell marker,was detected in IPNB cells. It seems possible in this case that hepatic progenitor cells located in reactive bile ductules in liver cirrhosis may have been responsible for the development of the cholangiocarcinoma and HCC,and that the former could have spread in the intrahepatic bile ducts and eventually formed grossly visible IPNB.
基金Supported by the Fund for Scientific Research-Flanders, No. 1.5.001.04N[F.B.]
文摘Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely described in physiologic conditions and in relation to metastasis during the past 30 years. This paper provides an 'overview' of how these cells function in health and in diseases such as liver metastasis.
文摘AIM: To analyze outcomes in patients who underwent liver transplantation(LT) for hepatocellular carcinoma(HCC) and received autologous intraoperative blood salvage(IBS). METHODS: Consecutive HCC patients who underwent LT were studied retrospectively and analyzed according to the use of IBS or not. Demographic and surgical data were collected from a departmental prospective maintained database. Statistical analyses were performed using the Fisher's exact test and the Wilcoxon rank sum test to examine covariate differences between patients who underwent IBS and those who did not. Univariate and multivariate Cox regression models were developed to evaluate recurrence and death,and survival probabilities were estimated using the Kaplan-Meier method and compared by the log-rank test.RESULTS: Between 2002 and 2012,158 consecutive patients who underwent LT in the same medical center and by the same surgical team were identified. Among these patients,122(77.2%) were in the IBS group and 36(22.8%) in the non-IBS group. The overall survival(OS) and recurrence free survival(RFS) at 5 years were 59.7% and 83.3%,respectively. No differences in OS(P=0.51) or RFS(P=0.953) were detected between the IBS and non-IBS groups. On multivariate analysis for OS,degree of tumor differentiation remained as the only independent predictor. Regarding patients who received IBS,no differences were detected in OS or RFS(P=0.055 and P=0.512,respectively) according to the volume infused,even when outcomes at 90 d or longer were analyzed separately(P=0.518 for both outcomes).CONCLUSION: No differences in RFS or OS were detected according to IBS use. Trials addressing this question are justified and should be designed to detect small differences in long-term outcomes.
文摘An 80-year-old woman presenting with chest pain was found to have a large,lobulated soft tissue mass in the liver and nearby tissues on abdominal computed tomography(CT).The tumor had invaded the common hepatic artery and main portal vein.Jaundice developed 4 wk later,at which point,a pancreas and biliary CT scan revealed a large mass in the right lobe of the liver and a hilar duct obstruction,which was found to be a small cell carcinoma.Despite its rarity,liver and bile duct small cell carcinoma should be considered in the differential diagnosis of atypical chest pain without jaundice.
文摘A recombinant plasmid containing a full length human epidermal growth factor receptor (EGFR) cDNA sequence in antisense orientation was transferred into cells of a human liver carcinoma cell line BEL-7404. Compared with the control cell clone JX-0 transferred with the vector plasmid and the parent BEL-7404 cells, the antisense EGFR transferred cell clone JX-1 showed a decreased EGFR gene expression and reduced significantly the growth potential either in anchorage-dependent or anchorage-independent growth. Furthermore. JX-1 cells appeared to be distinctly dependent on serum concentration for monolayer growth. The results suggested that antisense EGFR could partly block the EGFR gene ex-pression and reverse the malignant growth properties of human liver carcinoma cells in vitro.
文摘BACKGROUND Polycystic liver disease(PCLD) with a large cystic volume deteriorates the quality of life of patients through substantial effects on the adjacent organs,recurrent cyst infections, cyst rupture, and hemorrhage. Surgical or radiological intervention is usually needed to alleviate these symptoms. We report a rare case of the cystic metastasis of renal cell carcinoma(RCC), which was misdiagnosed as PCLD, as a result of the clinical and radiological similarity between these disorders.CASE SUMMARY A 74-year-old female who had undergone nephrectomy for papillary-type RCC(PRCC) was suffering from abdominal pain and the recurrent intracystic hemorrhage of multiple cysts in the liver. Imaging studies and aspiration cytology of the cysts showed no evidence of malignancy. With a diagnosis of autosomal dominant polycystic liver disease, the patient received hepatectomy for the purpose of mass reduction and infectious cyst removal. Surgery was performed without complications, and the patient was discharged on postoperative day 14. Postoperatively, the pathology revealed a diagnosis of recurrent PRCC with cystic formation.CONCLUSION This case demonstrates the importance of excluding the cystic metastasis of a cancer when liver cysts are observed.
文摘Hepatocellular carcinoma(HCC) represents a unique challenge for physicians and patients.There is no definitively curative treatment.Rather,many treatment and management modalities exist with differing advantages and disadvantages.Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC.In addition,quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies.Thus,considering all the options and their various pros and cons can quickly become complex for both clinicians and patients.In this review,we systematically discuss the current treatment modalities available for HCC,detailing relevant clinical data,risks and rewards and overall outcomes for each approach.Surgical options discussed include resection,transplantation and ablation.We also discuss the radiation modalities:conformal radiotherapy,yttrium 90 microspheres and proton and heavy ion radiotherapy.The biologic agent Sorafenib is discussed as a promising new approach,and recent clinical trials are reviewed.We then detail currently described molecular pathways implicated in the initiation and progression of HCC,and we explore the potential of each pathway as an avenue for drug exploitation.We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease.
基金Supported by a Grant from the Italian Liver Foundation
文摘Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs) as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC) transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.
文摘In recent years, the results of several studies suggest that human liver tumors can be derived from hepatic progenitor cells rather than from mature cell types. The available data indeed strongly suggest that most combined hepatocellular-cholangiocarcinomas arise from hepatic progenitor cells that retained their potential to differentiate into the hepatocytic and biliary lineages. Hepatic progenitor cells could also be the basis for some hepatocellular carcinomas and hepatocellular adenomas, although it is very difficult to determine the origin of an individual hepatocellular carcinoma. There is currently not enough data to make statements regarding a hepatic progenitor cell origin of cholangiocarcinoma. The presence of hepatic progenitor cell markers and the presence and extent of the cholangiocellular component are factors that are related to the prognosis of hepatocellular carcinomas and combined hepatocellular- cholangiocarcinomas, respectively.
基金supported by grants from the Research Grant Council-General Research Fund (HKU 760911M and HKU 773412M)Research Grant Council-Collaborative Research Fund (CUHK8/CRF/11R, HKU3/ CRF/11R and HKU7/CRF/09)the University of Hong Kong Strategic Research Theme in Cancer
文摘The prognosis of patients diagnosed with hepatocellular carcinoma (HCC) is often dismal, mainly due to late presentation, high recurrence rate, and frequent resistance to chemotherapy and radiotherapy. Accumulating evidence on the differential microRNA (miRNA) expression patterns between non-tumor and HCC tissues or between liver cancer stem cells (CSCs) and non-CSC subsets and the significant clinical implications of these differences suggest that miRNAs are a promising, non-invasive marker for the prognosis and diagnosis of the disease. This perspective article summarizes the current knowledge of miRNAs in liver CSCs and highlights the need for further investigations of the role of miRNAs in regulating liver CSC subsets for possible future clinical applications.
文摘Liver transplant(LT) is the primary treatment for patients with end-stage liver disease. About 25000 LTs are performed annually in the world. The potential for intraoperative bleeding is quite variable. However, massive bleeding is common and requires blood transfusion. Allogeneic blood transfusion has an immunosuppressive effect and an impact on recipient survival, in addition to the risk of transmission of viral infections and transfusion errors, among others.Techniques to prevent excessive bleeding or to use autologous blood have been proposed to minimize the negative effects of allogeneic blood transfusion.Intraoperative reinfusion of autologous blood is possible through previous selfdonation or blood collected during the operation. However, LT does not normally allow autologous transfusion by prior self-donation. Hence, using autologous blood collected intraoperatively is the most feasible option. The use of intraoperative blood salvage autotransfusion(IBSA) minimizes the perioperative use of allogeneic blood, preventing negative transfusion effects without negatively impacting other clinical outcomes. The use of IBSA in patients with cancer is still a matter of debate due to the theoretical risk of reinfusion of tumor cells. However, studies have demonstrated the safety of IBSA in several surgical procedures, including LT for hepatocellular carcinoma. Considering the literature available to date, we can state that IBSA should be routinely used in LT, both in patients with cancer and in patients with benign diseases.
基金Supported by International Science and Technology Cooperation Projects,No.2015DFA30650 and No.2010DFB33720Capital Special Research Project for Health Development,No.2014-2-4012+1 种基金Capital Research Project for Characteristics Clinical Application,No.Z151100004015170Program for New Century Excellent Talents in University,No.NCET-11-0288
文摘Liver cancer is a common malignancy and surgery is the main treatment strategy. However, the prognosis is still poor because of high frequencies of postoperative recurrence and metastasis. In recent years, cancer stem cell(CSC) theory has evolved with the concept of stem cells, and has been applied to oncological research. According to cancer stem cell theory, liver cancer can be radically cured only by eradication of liver cancer stem cells(LCSCs). This notion has lead to the isolation and identification of LCSCs, which has become a highly researched area. Analysis of LCSC markers is considered to be the primary method for identification of LCSCs. Here, we provide an overview of the current research progress and prospects of surface markers for LCSCs.
文摘OBJECTIVE It has been reported that heating can enhance sensitivity of rabbit VX2 cells to adriamycin and increase the intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effect of interventional hyperthermia and interventional thermochemotherapy on VX2 carcinoma in rabbit liver. METHODS VX2 carcinoma cells were surgically implanted into the right liver lobe of 60 male New Zealand white rabbits, which were randomly divided into 4 groups (15 per group). The 4 groups (designated as 1, 2, 3, 4 respectively) were injected with 10 ml of the following via the hepatic artery: physiological saline (37℃); adriamycin (37℃); physiological saline (60℃); adriamycin (60℃). One week later, the tumor volume, serum level of aspartate transaminase (AST) and the survival of the rabbits bearing VX2 were observed and compared among the different treated groups. RESULTS The tumor growth rate in group 4 (ADM 60℃) (0.53±0.21)% was significantly lower than that in group 1 (3.48±1.17)%, in group 2 (1.09±0.26)% and group 3 (3.32±1.28)% (P<0.05, P<0.05, P<0.01, respectively). The days of survival days for group 4 (87.0±2.0) were significantly more than that in group 1 (40.0±3.0). Group 4 showed a significantly higher increase in serum AST compared to group 1 (P<0.05), but without significant differences compared to the other groups (P>0.05). CONCLUSION Adriamycin treatment at 60℃ significantly deceased the tumor growth, prolonged the survival period and resulted in reversible liver damage.
文摘A 56-year-old man was found to have a pancreatic tail tumor. His blood chemistry showed no infection with hepatitis B or C virus and no elevations of tumor markers or pancreatic hormones. Abdominal ultrasound showed an encapsulated, rather heterogeneous, hypoechoic tumor, 6.5 cm in maximum diameter, with a beak sign. Helical dynamic CT revealed an irregularly enhanced tumor with pooling of contrast medium in the delayed phase. Abdominal angiography showed a hypervascular tumor. With a tentative diagnosis of non-functional islet-cell tumor, the patient underwent resection of the pancreatic body and tail with splenectomy. The contour of the liver and its surface were normal. In microscopic examination, tumor cells arranged in a trabecular pattern with focal bile pigment resembling hepatocellular carcinoma (HCC). Immunohistochemically, these tumor cells were positivefor HEPPAR-1, CAM5.2, cytokeratin 18 and COX-2, but negative for MUC-1, and cytokeratins 7, 20 and 8. These results supported a diagnosis of HCC without any adenocarcinoma component. The patient is currently doing well without any signs of recurrence in either the remaining pancreas or liver three years after surgery. We report the rare case with ectopic HCC in the pancreas with a review of the literature.
文摘AIM: To evaluate the relationship between hepatocellular carcinoma(HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation recurrence.METHODS: This retrospective study included 165 patients(143 men, 22 women; median age 56.8 years, range 28-70.4 years) transplanted for HCC who had a follow-up period longer than 2 mo. Pre-transplantation dynamic computed tomography or magnetic resonance examinations were retrospectively reviewed, classifying HCC imaging enhancement pattern into hypervascular and hypovascular based on presence of wash-in during arterial phase. All pathologic reports of the explanted livers were reviewed, collecting data about HCC differentiation degree. The association between imaging vascular pattern and pathological grade was estimated using the Fisher exact test. All follow-up clinical and imaging data were reviewed for evidence of recurrence. Recurrence rate was calculated and imaging features of recurrent tumor were collected, classifying early and late recurrences based on timing(< or ≥ 2 years after transplantation) and intrahepatic, extrahepatic and both intrahepatic and extrahepatic recurrences based onlocation. All intrahepatic recurrences were classified as hypervascular or hypovascular and the differentiation degree was collected where available. The presence of variations in imaging enhancement pattern and pathological grade between the primary tumor and the intrahepatic recurrence was evaluated and the association between imaging and histopatholgical variations was estimated by using the χ2 test. RESULTS: Of the 163 patients with imaging evidence of viable tumor, 156(95.7%) had hypervascular and 7(4.3%) hypovascular HCC. Among the 125 patients with evidence of viable tumor in the explanted liver, 19(15.2%) had grade 1, 56(44.8%) grade 2, 40(32%) grade 3 and 4(3.2%) grade 4 HCC, while the differentiation degree was not assessable for 6 patients(4.8%). A significant association was found between imaging vascularity and pathological grade(P = 0.035). Post-transplantation recurrence rate was 14.55%(24/165). All recurrences occurred in patients who had a hypervascular primary tumor. Three patients(12.5%) experienced late recurrence; the location of the first recurrence was extrahepatic in 14 patients(58.3%), intrahepatic in 7 patients(29.2%) and both intrahepatic and extrahepatic in 3 patients(12.5%). Two patients had a variation in imaging characteristics between the primary HCC(hypervascular) and the intrahepatic recurrent HCC(hypovascular), while 1 patient had a variation of histopathological characteristics(from moderate to poor differentiation), however no association was found between imaging and histopathological variations.CONCLUSION: A correlation was found between HCC grade and vascularity; some degree of variability may exist between the primary and the recurrence imaging/histopathological characteristics, apparently not correlated.