Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,sto...Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,stomach,and pancreatic cancers,as well as melanoma,breast cancer,and sarcoma.As an important factor that influences the development of metastatic liver cancer,alternative splicing drives the diversity of RNA transcripts and protein subtypes,which may provide potential to broaden the target space.In particular,the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence,progression,aggressiveness,and drug resistance of cancers caused by the selective splicing of specific genes.This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer.It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes,abnormal splicing,and the contribution of hypoxia to these changes during metastasis.展开更多
AIM To study the angiogenesis induced by liver cancer with different metastatic potentials using corneal micropocket model in nude mice.METHODS Corneal micropockets were created in nude mice. Tumor tissues and liver t...AIM To study the angiogenesis induced by liver cancer with different metastatic potentials using corneal micropocket model in nude mice.METHODS Corneal micropockets were created in nude mice. Tumor tissues and liver tissues were implanted into the corneal micropockets. Angiogenesis was observed using a digital camera under slit-lamp biomicroscope, and compared among different grafts and incision alone. Vascular responses were recorded in regard to the range, number and length of new blood vessels toward the grafts or incisions.RESULTS Vascular responses induced by tumor tissues were greater than those by incision alone and liver tissue grafts. LCI-D20 induced more intensive angiogenesis than LCI-D35.CONCLUSION Highly metastatic liver cancer LCI D20 was more angiogenic than low metastatic cancer LCI D35 and liver tissue. Micropocket was a useful model to study dynamic process of angiogenesis in vivo.展开更多
De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two ...De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population, and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades. Since exposure to immunosuppression is associated with an increased frequency of developing neoplasm, long-term immunosuppression should be therefore minimized. Promising results in the prevention of hepatocellular carcinoma(HCC) recurrence have been reported with the use of m TOR inhibitors including everolimus and sirolimus and the ongoing open-label prospective randomized controlled SILVER. Study will provide more information on whether sirolimus-containing vs m TOR-inhibitorfree immunosuppression is more efficacious in reducing HCC recurrence.展开更多
AIM To study the clinicopathological characteristics of neuroendocrine neoplasms(NEN) on liver samples and apply World Health Organization(WHO) 2010 grading of gastroenteropancreatic(GEP) NEN.METHODS Clinicopathologic...AIM To study the clinicopathological characteristics of neuroendocrine neoplasms(NEN) on liver samples and apply World Health Organization(WHO) 2010 grading of gastroenteropancreatic(GEP) NEN.METHODS Clinicopathological features of 79 cases of NEN of the liver diagnosed between January 2011 to December 2015 were analyzed. WHO 2010 classification of GEP NEN was applied and the tumors were graded as G1, G2 or G3. Two more categories, D1/2(discordant 1/2) and D2/3(discordant 2/3) were also applied. The D1/2 grade tumors had a mitotic count of G1 and Ki-67 index of G2. The D2/3 tumors had a mitotic count of G2 and Ki-67 index of G3. The follow up details which were available till the end of the study period(December 2015) were collected.RESULTS Of the 79 tumors, 16 each were G1 and G2, and 18 were G3 tumors. Of the remaining 29 tumors, 13 were assigned to D1/2 and 16 were D2/3 grade. Male preponderance was noted in all tumors except for G2 neoplasms, which showed a slight female predilection. The median age at presentation was 47 years(range 10-82 years). The most common presentation was abdominal pain(81%). Pancreas(49%) was the most common site of primary followed by gastrointestinal tract(24.4%) and lungs(18%). Radiologically, 87% of the patients had multiple liver lesions. Histopathologically, necrosis was seen in only D2/3 and G3 tumors. Microvascular invasion was seen in all grades. Metastasis occurred in all grades of primary NEN and the grades of the metastatic tumors and their corresponding primary tumors were similar in 67% of the cases. Of the 79 patients, 36 had at least one follow up visit with a median duration of follow up of 8.5 mo(range: 1-50 mo). This study did not show any impact of the grade of tumor on the short term clinical outcome of these patients.CONCLUSION Liver biopsy is an important tool for clinicopathological characterization and grading of NEN, especially when the primary is not identified. Eighty-seven percent of the patients had multifocal liver lesions irrespective of the WHO grade, indicating a higher stage of disease at presentation. Follow up duration was inadequate to derive any meaningful conclusion on long term outcome in our study patients.展开更多
Metastatic colorectal cancer to the liver is associated with a uniform poor prognosis without treatment. Advances in therapy over the past decades have now allowed surgical resections of the liver to occur with a low ...Metastatic colorectal cancer to the liver is associated with a uniform poor prognosis without treatment. Advances in therapy over the past decades have now allowed surgical resections of the liver to occur with a low morbidity and mortality. Improvements in chemotherapy regimes have paralleled technical improvements and now allow a new group of patients to become eligible for surgical resection. This chapter will review the recent advances in surgical and chemotherapeutic regimes in metastatic colorectal cancer to the liver.展开更多
BACKGROUND:Phospholipid scramblase 1(PLSCR1) not only participates in the transbilayer movement of phospholipids,but also plays a role in the pathogenesis and progression of cancers.The present study aimed to evaluate...BACKGROUND:Phospholipid scramblase 1(PLSCR1) not only participates in the transbilayer movement of phospholipids,but also plays a role in the pathogenesis and progression of cancers.The present study aimed to evaluate the effect of silencing PLSCR1 expression by RNA interference in colorectal cancer(CRC) and metastatic liver cancer.METHODS:The expression of PLSCR1 in CRC and metastatic liver cancer samples was assessed by immunohistochemistry.The cultured cells with the highest expression were selected for subsequent experiments.We designed three siRNA oligonucleotide segments targeted at PLSCR1.Successful transfection was confirmed.The biological behavior of the cells in proliferation,adhesion,migration and invasion was determined.RESULTS:PLSCR1 protein expression increased significantly in the majority of CRC and metastatic liver cancer samples compared with normal samples.Lovo cells had the highest expression of PLSCR1.The siRNA-390 oligonucleotide segment had the best silencing effect.After transfection,Lovo cell proliferation was significantly inhibited compared with the controls in the MTT assay.Laminin and fibronectin adhesion assays showed Lovo cell adhesion was also significantly inhibited.In the migration assay,the number of migrating cells in the PLSCR1 siRNA-390 group was 50±12,significantly lower than the number in the siRNA-N group(115±28) and in the control group(118±31).In an invasion test,the number of invading cells in the PLSCR1 siRNA-390 group was 60±18,significantly lower than that in the siRNA-N group(97±26) and the control group(103±24).CONCLUSIONS:PLSCR1 is overexpressed in CRC and metastatic liver cancer.Silencing of PLSCR1 by siRNA inhibits the proliferation,adhesion,migration and invasion of Lovo cells,which suggests that PLSCR1 contributes to the tumorigenesis and tumor progression of CRC.PLSCR1 may be a potential gene therapy target for CRC and associated metastatic liver cancer.展开更多
AIM: To study the role of macrophage inflammatory protein (HIP)-2 in liver resection-induced acceleration of tumor growth in a mouse model of hepatic metastasis. METHODS: After a 50% hepatectomy, 1×10^5 CT26....AIM: To study the role of macrophage inflammatory protein (HIP)-2 in liver resection-induced acceleration of tumor growth in a mouse model of hepatic metastasis. METHODS: After a 50% hepatectomy, 1×10^5 CT26.WT cells were implanted into the left liver lobe of syngeneic balb/c mice (PHx). Additional animals were treated with a monoclonal antibody (HAB452) neutralizing HIP-2 (PHx+mAB). Non-resected and non-mAB-treated mice (Con) served as controls. After 7 d, tumor angiogenesis and microcirculation as well as cell proliferation, tumor growth, and CXCR-2 expression were analyzed using in- travital fluorescence microscopy, histology, immunohisto- chemistry, and flow cytometry. RESULTS: Partial hepatectomy increased (P〈0.05)the expression of the HIP-2 receptor CXCR-2 on tumor cells when compared with non-resected controls, and markedly accelerated (P〈 0.05) angiogenesis and metastatic tumor growth. Neutralization of HIP-2 by HAB452 treatment significantly (P〈 0.05) depressed CXCR-2 expression. Further, the blockade of MIP-2 reduced the angiogenic response (P〈 0.05) and inhibited tumor growth (P〈 0.05). Of interest, liver resection-induced hepatocyte proliferation was not effected by anti-HIP-2 treatment. CONCLUSION: HIP-2 significantly contributes to liver resection-induced acceleration of colorectal CT26.WT hepatic metastasis growth.展开更多
Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratif...Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases.Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model.Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: −0.03-0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78-1.88) and between high and low PLR was 1.47 (95% CI: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44-2.13) and between high and low PLR was 1.05 (95% CI: 0.87-1.24).Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.展开更多
The purpose of this study was to determine the efficacy of using an ultrasound contrast agent(levovist)to enhance the color Doppler imaging of liver neoplasms.Thirty patients with hepatic tu...The purpose of this study was to determine the efficacy of using an ultrasound contrast agent(levovist)to enhance the color Doppler imaging of liver neoplasms.Thirty patients with hepatic tumors were enrolled in this study.After intravenous administration of levovist,the color Doppler signals of normal hepatic vessels were enhanced.In various hepatic tumors,the different patterns of tumor vascularity were observed,which had not been demonstrated in conventional non contrast color Doppler imaging.In 11 of 16 patients with hepatocarcinoma,additional color Doppler signals were observed in the central part of the tumors.On the contrary,3 patients with metastatic liver lesions the enhanced color Doppler signals appear only at the peripheral of tumors.A typical rim like color enhancement was seen in 2 of the 3 cases.In six patients with hepatic hemangiomas contrast enhanced color Doppler imaging demonstrated the blood vessels at the margin of the neoplasms.Contrast enhanced color Doppler imaging improves the visualization of the hepatic neoplasm vascularity.This technique holds great promise for detecting small liver tumors and differentiating hepatic neoplasms.展开更多
Abstract: HCC is the 6th most common cancer in the world. The main risk factors associated with HCC are hepatitis B (HBV) and hepatitis C viral infections and other factors that play a role in HCC development, include...Abstract: HCC is the 6th most common cancer in the world. The main risk factors associated with HCC are hepatitis B (HBV) and hepatitis C viral infections and other factors that play a role in HCC development, include aflatoxin B1 (AFB1) cigarette smoking, and chronic inflammation. The aim of this study is to investigate lipid peroxidation and some antioxidant enzyme activities in patients with primary and metastatic liver cancer. For this purpose, 25 primary and metastatic liver cancer patients and 15 healthy controls were included in the study. In blood samples taken from the patient and control groups, the main product of lipid peroxidation MDA and SOD, GSH, GPx activity levels were examined. In result of study serum MDA level is higher and erythrocyte SOD, GSH, and GPx activities were found to be significantly lower in the patient group compared with the control group (p 0.05). As a result, liver cancer is associated with oxidative stress and antioxidant system weakens, which is an important indicator of oxidative stress, lipid peroxidation levels increased and promotes the tissue damage.展开更多
Cystic hepatic neoplasms are rare tumors,and are classified into two separate entities:mucinous cystic neoplasms(MCNs)and intraductal papillary mucinous neoplasms of the bile duct(IPMN-B).We report the case of a 56-ye...Cystic hepatic neoplasms are rare tumors,and are classified into two separate entities:mucinous cystic neoplasms(MCNs)and intraductal papillary mucinous neoplasms of the bile duct(IPMN-B).We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor.Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B.This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.展开更多
Objective: To assess the value of helical CT in the di- agnosis of liver diseases. Methods: 59 patients with different liver diseases were examined by two-phase or multi-phase dynamic helical CT. Results: Small hepato...Objective: To assess the value of helical CT in the di- agnosis of liver diseases. Methods: 59 patients with different liver diseases were examined by two-phase or multi-phase dynamic helical CT. Results: Small hepatocellular carcinoma showed a higher density in the arterial phase, and a lower den- sity in the portal vein phase. Large hepatic carcino- ma showed a mixed pattern of higher-density in the arterial phase, and a lower density in the portal vein phase. Metastasis carcinoma showed an 'oxeye sign' in the portal vein phase. Hemangioma was not obvi- ously enhanced in the early arterial phase, marginal- ly enhanced in the arterial phase, and equally-densed in the balanced phase. Conclusion: Two-phase helical CT is of value in im- proving the detection rate of or determining the fea- tures of hepatic diseases by two-phase helical dyna- mic scan (2.0-3.0 ml/s speed, and delay time 25- 30 s and 70-85 s).展开更多
Peliosis hepatis(PH) is a rare benign condition characterized by the presence of multiple,randomly distributed,blood filled cystic areas of variable size within the liver parenchyma.PH is difficult to recognize and ma...Peliosis hepatis(PH) is a rare benign condition characterized by the presence of multiple,randomly distributed,blood filled cystic areas of variable size within the liver parenchyma.PH is difficult to recognize and may be mistaken for neoplasm,metastases or multiple abscesses.A 75-year-old female with a previous history of colon cancer was admitted when a liver mass in the right liver lobe was found 11 mo after surgery during the follow-up period.Computed tomography and magnetic resonance imaging scan of the abdomen were performed.The initial possible diagnosis was metastatic hepatocellular carcinoma.The patient underwent excision of the hepatic segment where the nodule was located.The pathological diagnosis of the surgical specimen was PH.PH should be considered in the differential diagnosis of new liver lesions in patients whose clinical settings do not clearly favor metastasization.Clinicians and radiologists must recognize these lesions to minimize the probability of misdiagnosis and inappropriate treatment.展开更多
Aggressive cytoreduction can prolong survival in patients with unresectable liver metastases(LM)from neuroendocrine neoplasms(NEN),and minimally invasive,liver-directed therapies are gaining increasing interest.Cathet...Aggressive cytoreduction can prolong survival in patients with unresectable liver metastases(LM)from neuroendocrine neoplasms(NEN),and minimally invasive,liver-directed therapies are gaining increasing interest.Catheter-based treatments are used in disseminated disease,whereas ablation techniques are usually indicated when the number of LM is limited.Although radiofrequency ablation(RFA)is by far the most used ablative technique,the goal of this opinion review is to explore the potential role of laser ablation(LA)in the treatment of LM from NEN.LA uses thinner needles than RFA,and this is an advantage when the tumors are in at-risk locations.Moreover,the multi-fiber technique enables the use of one to four laser fibers at once,and each fiber provides an almost spherical thermal lesion of 12-15 mm in diameter.Such a characteristic enables to tailor the size of each thermal lesion to the size of each tumor,sparing the liver parenchyma more than any other liver-directed therapy,and allowing for repeated treatments with low risk of liver failure.A recent retrospective study reporting the largest series of LM treated with LA documents both safety and effectiveness of LA,that can play a useful role in the multimodality approach to LM from NEN.展开更多
We report progressive painless jaundice in a 39 year old female with a suspicion of metastatic liver disease on ultrasound and computed tomography scan of the abdomen. Although the most frequent liver lesions are live...We report progressive painless jaundice in a 39 year old female with a suspicion of metastatic liver disease on ultrasound and computed tomography scan of the abdomen. Although the most frequent liver lesions are liver metastasis because of dual blood supply of the liver and the impact of hormones, the index case proved to have acute autoimmune hepatitis (AIH) after liver biopsy was undertaken. AIH, an unresolving inflammation of liver, occurs predominantly among females worldwide. It may present acutely and even fulminant hepatitis has been described. The index case had a dramatic response to steroid treatment with total recovery and complete resolution of liver lesions. She is clinically fine and has been regularly attending our clinic for the last year. To our knowledge from a Medline search, this is the first report where AIH was seen to mimic metastatic liver disease.展开更多
AIM To determine the prevalence,characteristics and clinical course of pancreatic cystic neoplasms(PCNs) in liver transplantation(LT) recipients.METHODS We retrospectively studied consecutive patients who underwent LT...AIM To determine the prevalence,characteristics and clinical course of pancreatic cystic neoplasms(PCNs) in liver transplantation(LT) recipients.METHODS We retrospectively studied consecutive patients who underwent LT between January 1998 to April 2016. Clinical and laboratory data were obtained from patient medical records. Imaging findings on computed tomography and magnetic resonance cholangiopancreatography were reviewed by two radiologists.RESULTS During the study period,872 patients underwent cadaveric LT. Pancreatic cysts were identified in 53/872(6.1%) and 31/53(58.5%) were PCNs [28 intraductal papillary mucinous neoplasm(IPMN),2 mucinous cystic neoplasm(MCN),1 serous cystadenoma]. Patients with PCNs exhibited less male predominance(55% vs 73%,P = 0.03) compared to patients without pancreatic cysts. Thirteen patients(42%) were diagnosed with PCN pre-LT while 18 patients(58%) developed PCN post-LT. The median size of PCNs was 13 mm [interquartile range(IQR) 10-20 mm]. All IPMNs were side-branch type. Most PCNs were found in the head and body of pancreas(37% each),followed by the tail(25%). Five patients underwent further evaluation with endoscopic ultrasound. Progress imaging was performed on 81% of patients. PCNs remained stable in size and number in all but 2 patients. During a median follow up of 39 mo(IQR 26-58 mo),the 2(6%) patients with MCN underwent pancreatectomy. No PCN patient developed pancreatic adenocarcinoma,while 5 died from illnesses unrelated to the PCN. Among patients without PCN,1/841(0.1%) developed pancreatic adenocarcinoma.CONCLUSION The prevalence of PCNs in LT recipients was similar to the general population(3.6%,31/872). Side-branch IPMNs do not appear to have accelerated malignant potential in post-LT patients,indicating the current surveillance guidelines are applicable to this group.展开更多
AIM: To examine the expression of E-cadherin, β-catenin,γ-catenin, VEGF, and p53 in 39 patients with hepatic metastasis from colorectal cancer immunohistochemically.METHODS: The patients were divided into two groups...AIM: To examine the expression of E-cadherin, β-catenin,γ-catenin, VEGF, and p53 in 39 patients with hepatic metastasis from colorectal cancer immunohistochemically.METHODS: The patients were divided into two groups:those (n = 16) who had no chemotherapy for at least 6 mo before the liver resections and those (n = 23)who were treated with chemotherapy before liver resections. A score from 0 to 3 was given for the number of positive cells and from 0 to 3 for the intensity of staining in these cells, in both healthy and metastatic liver parenchyma.RESULTS: No significant differences in the expression of E-cadherin, β- and γ-catenin, VEGF and p53, could be observed between patients who received and did not receive chemotherapy, in both normal and metastatic liver parenchyma.CONCLUSION: Despite the assumption that chemotherapy had an effect on liver metastasis, no influences were noticed immunohistochemically.展开更多
Objective: The aim of our study was to retrospectively analyze 15 patients' clinical materials with laparoscopic resection of liver neoplasms. Methods: From December 2007, a total of 15 patients with liver neoplasm...Objective: The aim of our study was to retrospectively analyze 15 patients' clinical materials with laparoscopic resection of liver neoplasms. Methods: From December 2007, a total of 15 patients with liver neoplasms were performed with laparoscopic hepatectomy, and their clinical materials, perioperative dates, postoperative complications, postoperative recovery and short-term curative effects were analyzed and summarized respectively. Results: Laparoscopic hepatectomy (LH) were performed in 15 patients, including 1 case underwent laparoscopic hepatic left Iobectomy, 1 case of left lateral hepatectomy, 13 cases of partial liver resection. Fourteen cases of total laparoscopic liver resections for liver neoplasms, 1 case of hand-assisted laparoscopic liver resection of the tumor, there was no conversion to open approach. Of the 15 patients with liver neoplasms, 13 cases of hepatic neoplasms with the maximum diameter was 8 cm× 8 cm × 9 cm, 9 cases of the borderline micro hepatocellular carcinoma (MHCC) with the diameter not more than 2 cm, 3 cases of hepatic benign tumor. The mean operation time was (120 ± 30) min, and the intraoperative average hemorrhage was 100 mL, beginning to eat and get out of bed following 1-2 days of operation. The average postoperative hospitalization was 8 days, WBC, ALl', AST, albumin, bilirubin returned to normal after one week of operation. There were no postoperative complications such as hemorrhage, bile leakage or air embolism etc. Twelve patients with HCC were confirmed by postoperative pathology, 1 case of liver smooth muscle lipoma, 2 case of hepatic hemangioma. By one year of followed-up in 12 cases of HCC, the longest survival was 38 months, and no recurrence or death, 1 year survival rate was 100%. Conclusion: Among the choice of cases, the advantages of LH for liver neoplasms compared with open surgery were less trauma, faster recovery and less blood loss. it is safe and effective for choosing a reasonable surgical indication, especially for peripheral micro hepatocellular carcinoma.展开更多
Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment ...Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy.Radioembolization with yttrium-90(^(90)Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy.The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with^(90)Y microspheres,from patient selection to follow up,both technically and clinically,are discussed in this paper.It describes the application and development of^(90)Y microspheres in the treatment of liver cancer.展开更多
Secondary cancers of the liver are more than twenty times more common than primary tumors and are incurable in most cases.While surgical resection and systemic chemotherapy are often the first-line therapy for metasta...Secondary cancers of the liver are more than twenty times more common than primary tumors and are incurable in most cases.While surgical resection and systemic chemotherapy are often the first-line therapy for metastatic liver disease,a majority of patients present with bilobar disease not amenable to curative local resection.Furthermore,by the time metastasis to the liver has developed,many tumors demonstrate a degree of resistance to systemic chemotherapy.Fortunately,catheter-directed and percutaneous locoregional approaches have evolved as major treatment modalities for unresectable metastatic disease.These novel techniques can be used for diverse applications ranging from curative intent for small localized tumors,downstaging of large tumors for resection,or locoregional control and palliation of advanced disease.Their use has been associated with increased tumor response,increased disease-free and overall survival,and decreased morbidity and mortality in a broad range of metastatic disease.This review explores recent advances in liver-directed therapies for metastatic liver disease from primary colorectal,neuroendocrine,breast,and lung cancer,as well as uveal melanoma,cholangiocarcinoma,and sarcoma.Therapies discussed include bland transarterial embolization,chemoembolization,radioembolization,and ablative therapies,with a focus on current treatment approaches,outcomes of locoregional therapy,and future directions in each type of metastatic disease.展开更多
基金Supported by the National Natural Science Foundation of China,No.82002068,No.82272281the Natural Science Foundation of Guangdong Province,No.2021A1515010949.
文摘Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,stomach,and pancreatic cancers,as well as melanoma,breast cancer,and sarcoma.As an important factor that influences the development of metastatic liver cancer,alternative splicing drives the diversity of RNA transcripts and protein subtypes,which may provide potential to broaden the target space.In particular,the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence,progression,aggressiveness,and drug resistance of cancers caused by the selective splicing of specific genes.This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer.It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes,abnormal splicing,and the contribution of hypoxia to these changes during metastasis.
基金Supported by the Fund for Leading Specialty of Shanghai Metropolitan Bureau of Public Health
文摘AIM To study the angiogenesis induced by liver cancer with different metastatic potentials using corneal micropocket model in nude mice.METHODS Corneal micropockets were created in nude mice. Tumor tissues and liver tissues were implanted into the corneal micropockets. Angiogenesis was observed using a digital camera under slit-lamp biomicroscope, and compared among different grafts and incision alone. Vascular responses were recorded in regard to the range, number and length of new blood vessels toward the grafts or incisions.RESULTS Vascular responses induced by tumor tissues were greater than those by incision alone and liver tissue grafts. LCI-D20 induced more intensive angiogenesis than LCI-D35.CONCLUSION Highly metastatic liver cancer LCI D20 was more angiogenic than low metastatic cancer LCI D35 and liver tissue. Micropocket was a useful model to study dynamic process of angiogenesis in vivo.
文摘De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population, and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades. Since exposure to immunosuppression is associated with an increased frequency of developing neoplasm, long-term immunosuppression should be therefore minimized. Promising results in the prevention of hepatocellular carcinoma(HCC) recurrence have been reported with the use of m TOR inhibitors including everolimus and sirolimus and the ongoing open-label prospective randomized controlled SILVER. Study will provide more information on whether sirolimus-containing vs m TOR-inhibitorfree immunosuppression is more efficacious in reducing HCC recurrence.
文摘AIM To study the clinicopathological characteristics of neuroendocrine neoplasms(NEN) on liver samples and apply World Health Organization(WHO) 2010 grading of gastroenteropancreatic(GEP) NEN.METHODS Clinicopathological features of 79 cases of NEN of the liver diagnosed between January 2011 to December 2015 were analyzed. WHO 2010 classification of GEP NEN was applied and the tumors were graded as G1, G2 or G3. Two more categories, D1/2(discordant 1/2) and D2/3(discordant 2/3) were also applied. The D1/2 grade tumors had a mitotic count of G1 and Ki-67 index of G2. The D2/3 tumors had a mitotic count of G2 and Ki-67 index of G3. The follow up details which were available till the end of the study period(December 2015) were collected.RESULTS Of the 79 tumors, 16 each were G1 and G2, and 18 were G3 tumors. Of the remaining 29 tumors, 13 were assigned to D1/2 and 16 were D2/3 grade. Male preponderance was noted in all tumors except for G2 neoplasms, which showed a slight female predilection. The median age at presentation was 47 years(range 10-82 years). The most common presentation was abdominal pain(81%). Pancreas(49%) was the most common site of primary followed by gastrointestinal tract(24.4%) and lungs(18%). Radiologically, 87% of the patients had multiple liver lesions. Histopathologically, necrosis was seen in only D2/3 and G3 tumors. Microvascular invasion was seen in all grades. Metastasis occurred in all grades of primary NEN and the grades of the metastatic tumors and their corresponding primary tumors were similar in 67% of the cases. Of the 79 patients, 36 had at least one follow up visit with a median duration of follow up of 8.5 mo(range: 1-50 mo). This study did not show any impact of the grade of tumor on the short term clinical outcome of these patients.CONCLUSION Liver biopsy is an important tool for clinicopathological characterization and grading of NEN, especially when the primary is not identified. Eighty-seven percent of the patients had multifocal liver lesions irrespective of the WHO grade, indicating a higher stage of disease at presentation. Follow up duration was inadequate to derive any meaningful conclusion on long term outcome in our study patients.
文摘Metastatic colorectal cancer to the liver is associated with a uniform poor prognosis without treatment. Advances in therapy over the past decades have now allowed surgical resections of the liver to occur with a low morbidity and mortality. Improvements in chemotherapy regimes have paralleled technical improvements and now allow a new group of patients to become eligible for surgical resection. This chapter will review the recent advances in surgical and chemotherapeutic regimes in metastatic colorectal cancer to the liver.
基金supported by grants from the National Natural Science Foundation of China (81041025 and 81000189)
文摘BACKGROUND:Phospholipid scramblase 1(PLSCR1) not only participates in the transbilayer movement of phospholipids,but also plays a role in the pathogenesis and progression of cancers.The present study aimed to evaluate the effect of silencing PLSCR1 expression by RNA interference in colorectal cancer(CRC) and metastatic liver cancer.METHODS:The expression of PLSCR1 in CRC and metastatic liver cancer samples was assessed by immunohistochemistry.The cultured cells with the highest expression were selected for subsequent experiments.We designed three siRNA oligonucleotide segments targeted at PLSCR1.Successful transfection was confirmed.The biological behavior of the cells in proliferation,adhesion,migration and invasion was determined.RESULTS:PLSCR1 protein expression increased significantly in the majority of CRC and metastatic liver cancer samples compared with normal samples.Lovo cells had the highest expression of PLSCR1.The siRNA-390 oligonucleotide segment had the best silencing effect.After transfection,Lovo cell proliferation was significantly inhibited compared with the controls in the MTT assay.Laminin and fibronectin adhesion assays showed Lovo cell adhesion was also significantly inhibited.In the migration assay,the number of migrating cells in the PLSCR1 siRNA-390 group was 50±12,significantly lower than the number in the siRNA-N group(115±28) and in the control group(118±31).In an invasion test,the number of invading cells in the PLSCR1 siRNA-390 group was 60±18,significantly lower than that in the siRNA-N group(97±26) and the control group(103±24).CONCLUSIONS:PLSCR1 is overexpressed in CRC and metastatic liver cancer.Silencing of PLSCR1 by siRNA inhibits the proliferation,adhesion,migration and invasion of Lovo cells,which suggests that PLSCR1 contributes to the tumorigenesis and tumor progression of CRC.PLSCR1 may be a potential gene therapy target for CRC and associated metastatic liver cancer.
基金Supported by the grants of the Research Committee the Medical Faculty of the University of Saarland,No.HOMFOR-A/2003/1
文摘AIM: To study the role of macrophage inflammatory protein (HIP)-2 in liver resection-induced acceleration of tumor growth in a mouse model of hepatic metastasis. METHODS: After a 50% hepatectomy, 1×10^5 CT26.WT cells were implanted into the left liver lobe of syngeneic balb/c mice (PHx). Additional animals were treated with a monoclonal antibody (HAB452) neutralizing HIP-2 (PHx+mAB). Non-resected and non-mAB-treated mice (Con) served as controls. After 7 d, tumor angiogenesis and microcirculation as well as cell proliferation, tumor growth, and CXCR-2 expression were analyzed using in- travital fluorescence microscopy, histology, immunohisto- chemistry, and flow cytometry. RESULTS: Partial hepatectomy increased (P〈0.05)the expression of the HIP-2 receptor CXCR-2 on tumor cells when compared with non-resected controls, and markedly accelerated (P〈 0.05) angiogenesis and metastatic tumor growth. Neutralization of HIP-2 by HAB452 treatment significantly (P〈 0.05) depressed CXCR-2 expression. Further, the blockade of MIP-2 reduced the angiogenic response (P〈 0.05) and inhibited tumor growth (P〈 0.05). Of interest, liver resection-induced hepatocyte proliferation was not effected by anti-HIP-2 treatment. CONCLUSION: HIP-2 significantly contributes to liver resection-induced acceleration of colorectal CT26.WT hepatic metastasis growth.
文摘Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases.Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model.Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: −0.03-0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78-1.88) and between high and low PLR was 1.47 (95% CI: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44-2.13) and between high and low PLR was 1.05 (95% CI: 0.87-1.24).Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.
文摘The purpose of this study was to determine the efficacy of using an ultrasound contrast agent(levovist)to enhance the color Doppler imaging of liver neoplasms.Thirty patients with hepatic tumors were enrolled in this study.After intravenous administration of levovist,the color Doppler signals of normal hepatic vessels were enhanced.In various hepatic tumors,the different patterns of tumor vascularity were observed,which had not been demonstrated in conventional non contrast color Doppler imaging.In 11 of 16 patients with hepatocarcinoma,additional color Doppler signals were observed in the central part of the tumors.On the contrary,3 patients with metastatic liver lesions the enhanced color Doppler signals appear only at the peripheral of tumors.A typical rim like color enhancement was seen in 2 of the 3 cases.In six patients with hepatic hemangiomas contrast enhanced color Doppler imaging demonstrated the blood vessels at the margin of the neoplasms.Contrast enhanced color Doppler imaging improves the visualization of the hepatic neoplasm vascularity.This technique holds great promise for detecting small liver tumors and differentiating hepatic neoplasms.
文摘Abstract: HCC is the 6th most common cancer in the world. The main risk factors associated with HCC are hepatitis B (HBV) and hepatitis C viral infections and other factors that play a role in HCC development, include aflatoxin B1 (AFB1) cigarette smoking, and chronic inflammation. The aim of this study is to investigate lipid peroxidation and some antioxidant enzyme activities in patients with primary and metastatic liver cancer. For this purpose, 25 primary and metastatic liver cancer patients and 15 healthy controls were included in the study. In blood samples taken from the patient and control groups, the main product of lipid peroxidation MDA and SOD, GSH, GPx activity levels were examined. In result of study serum MDA level is higher and erythrocyte SOD, GSH, and GPx activities were found to be significantly lower in the patient group compared with the control group (p 0.05). As a result, liver cancer is associated with oxidative stress and antioxidant system weakens, which is an important indicator of oxidative stress, lipid peroxidation levels increased and promotes the tissue damage.
文摘Cystic hepatic neoplasms are rare tumors,and are classified into two separate entities:mucinous cystic neoplasms(MCNs)and intraductal papillary mucinous neoplasms of the bile duct(IPMN-B).We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor.Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B.This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.
文摘Objective: To assess the value of helical CT in the di- agnosis of liver diseases. Methods: 59 patients with different liver diseases were examined by two-phase or multi-phase dynamic helical CT. Results: Small hepatocellular carcinoma showed a higher density in the arterial phase, and a lower den- sity in the portal vein phase. Large hepatic carcino- ma showed a mixed pattern of higher-density in the arterial phase, and a lower density in the portal vein phase. Metastasis carcinoma showed an 'oxeye sign' in the portal vein phase. Hemangioma was not obvi- ously enhanced in the early arterial phase, marginal- ly enhanced in the arterial phase, and equally-densed in the balanced phase. Conclusion: Two-phase helical CT is of value in im- proving the detection rate of or determining the fea- tures of hepatic diseases by two-phase helical dyna- mic scan (2.0-3.0 ml/s speed, and delay time 25- 30 s and 70-85 s).
文摘Peliosis hepatis(PH) is a rare benign condition characterized by the presence of multiple,randomly distributed,blood filled cystic areas of variable size within the liver parenchyma.PH is difficult to recognize and may be mistaken for neoplasm,metastases or multiple abscesses.A 75-year-old female with a previous history of colon cancer was admitted when a liver mass in the right liver lobe was found 11 mo after surgery during the follow-up period.Computed tomography and magnetic resonance imaging scan of the abdomen were performed.The initial possible diagnosis was metastatic hepatocellular carcinoma.The patient underwent excision of the hepatic segment where the nodule was located.The pathological diagnosis of the surgical specimen was PH.PH should be considered in the differential diagnosis of new liver lesions in patients whose clinical settings do not clearly favor metastasization.Clinicians and radiologists must recognize these lesions to minimize the probability of misdiagnosis and inappropriate treatment.
文摘Aggressive cytoreduction can prolong survival in patients with unresectable liver metastases(LM)from neuroendocrine neoplasms(NEN),and minimally invasive,liver-directed therapies are gaining increasing interest.Catheter-based treatments are used in disseminated disease,whereas ablation techniques are usually indicated when the number of LM is limited.Although radiofrequency ablation(RFA)is by far the most used ablative technique,the goal of this opinion review is to explore the potential role of laser ablation(LA)in the treatment of LM from NEN.LA uses thinner needles than RFA,and this is an advantage when the tumors are in at-risk locations.Moreover,the multi-fiber technique enables the use of one to four laser fibers at once,and each fiber provides an almost spherical thermal lesion of 12-15 mm in diameter.Such a characteristic enables to tailor the size of each thermal lesion to the size of each tumor,sparing the liver parenchyma more than any other liver-directed therapy,and allowing for repeated treatments with low risk of liver failure.A recent retrospective study reporting the largest series of LM treated with LA documents both safety and effectiveness of LA,that can play a useful role in the multimodality approach to LM from NEN.
文摘We report progressive painless jaundice in a 39 year old female with a suspicion of metastatic liver disease on ultrasound and computed tomography scan of the abdomen. Although the most frequent liver lesions are liver metastasis because of dual blood supply of the liver and the impact of hormones, the index case proved to have acute autoimmune hepatitis (AIH) after liver biopsy was undertaken. AIH, an unresolving inflammation of liver, occurs predominantly among females worldwide. It may present acutely and even fulminant hepatitis has been described. The index case had a dramatic response to steroid treatment with total recovery and complete resolution of liver lesions. She is clinically fine and has been regularly attending our clinic for the last year. To our knowledge from a Medline search, this is the first report where AIH was seen to mimic metastatic liver disease.
文摘AIM To determine the prevalence,characteristics and clinical course of pancreatic cystic neoplasms(PCNs) in liver transplantation(LT) recipients.METHODS We retrospectively studied consecutive patients who underwent LT between January 1998 to April 2016. Clinical and laboratory data were obtained from patient medical records. Imaging findings on computed tomography and magnetic resonance cholangiopancreatography were reviewed by two radiologists.RESULTS During the study period,872 patients underwent cadaveric LT. Pancreatic cysts were identified in 53/872(6.1%) and 31/53(58.5%) were PCNs [28 intraductal papillary mucinous neoplasm(IPMN),2 mucinous cystic neoplasm(MCN),1 serous cystadenoma]. Patients with PCNs exhibited less male predominance(55% vs 73%,P = 0.03) compared to patients without pancreatic cysts. Thirteen patients(42%) were diagnosed with PCN pre-LT while 18 patients(58%) developed PCN post-LT. The median size of PCNs was 13 mm [interquartile range(IQR) 10-20 mm]. All IPMNs were side-branch type. Most PCNs were found in the head and body of pancreas(37% each),followed by the tail(25%). Five patients underwent further evaluation with endoscopic ultrasound. Progress imaging was performed on 81% of patients. PCNs remained stable in size and number in all but 2 patients. During a median follow up of 39 mo(IQR 26-58 mo),the 2(6%) patients with MCN underwent pancreatectomy. No PCN patient developed pancreatic adenocarcinoma,while 5 died from illnesses unrelated to the PCN. Among patients without PCN,1/841(0.1%) developed pancreatic adenocarcinoma.CONCLUSION The prevalence of PCNs in LT recipients was similar to the general population(3.6%,31/872). Side-branch IPMNs do not appear to have accelerated malignant potential in post-LT patients,indicating the current surveillance guidelines are applicable to this group.
文摘AIM: To examine the expression of E-cadherin, β-catenin,γ-catenin, VEGF, and p53 in 39 patients with hepatic metastasis from colorectal cancer immunohistochemically.METHODS: The patients were divided into two groups:those (n = 16) who had no chemotherapy for at least 6 mo before the liver resections and those (n = 23)who were treated with chemotherapy before liver resections. A score from 0 to 3 was given for the number of positive cells and from 0 to 3 for the intensity of staining in these cells, in both healthy and metastatic liver parenchyma.RESULTS: No significant differences in the expression of E-cadherin, β- and γ-catenin, VEGF and p53, could be observed between patients who received and did not receive chemotherapy, in both normal and metastatic liver parenchyma.CONCLUSION: Despite the assumption that chemotherapy had an effect on liver metastasis, no influences were noticed immunohistochemically.
文摘Objective: The aim of our study was to retrospectively analyze 15 patients' clinical materials with laparoscopic resection of liver neoplasms. Methods: From December 2007, a total of 15 patients with liver neoplasms were performed with laparoscopic hepatectomy, and their clinical materials, perioperative dates, postoperative complications, postoperative recovery and short-term curative effects were analyzed and summarized respectively. Results: Laparoscopic hepatectomy (LH) were performed in 15 patients, including 1 case underwent laparoscopic hepatic left Iobectomy, 1 case of left lateral hepatectomy, 13 cases of partial liver resection. Fourteen cases of total laparoscopic liver resections for liver neoplasms, 1 case of hand-assisted laparoscopic liver resection of the tumor, there was no conversion to open approach. Of the 15 patients with liver neoplasms, 13 cases of hepatic neoplasms with the maximum diameter was 8 cm× 8 cm × 9 cm, 9 cases of the borderline micro hepatocellular carcinoma (MHCC) with the diameter not more than 2 cm, 3 cases of hepatic benign tumor. The mean operation time was (120 ± 30) min, and the intraoperative average hemorrhage was 100 mL, beginning to eat and get out of bed following 1-2 days of operation. The average postoperative hospitalization was 8 days, WBC, ALl', AST, albumin, bilirubin returned to normal after one week of operation. There were no postoperative complications such as hemorrhage, bile leakage or air embolism etc. Twelve patients with HCC were confirmed by postoperative pathology, 1 case of liver smooth muscle lipoma, 2 case of hepatic hemangioma. By one year of followed-up in 12 cases of HCC, the longest survival was 38 months, and no recurrence or death, 1 year survival rate was 100%. Conclusion: Among the choice of cases, the advantages of LH for liver neoplasms compared with open surgery were less trauma, faster recovery and less blood loss. it is safe and effective for choosing a reasonable surgical indication, especially for peripheral micro hepatocellular carcinoma.
文摘Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy.Radioembolization with yttrium-90(^(90)Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy.The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with^(90)Y microspheres,from patient selection to follow up,both technically and clinically,are discussed in this paper.It describes the application and development of^(90)Y microspheres in the treatment of liver cancer.
文摘Secondary cancers of the liver are more than twenty times more common than primary tumors and are incurable in most cases.While surgical resection and systemic chemotherapy are often the first-line therapy for metastatic liver disease,a majority of patients present with bilobar disease not amenable to curative local resection.Furthermore,by the time metastasis to the liver has developed,many tumors demonstrate a degree of resistance to systemic chemotherapy.Fortunately,catheter-directed and percutaneous locoregional approaches have evolved as major treatment modalities for unresectable metastatic disease.These novel techniques can be used for diverse applications ranging from curative intent for small localized tumors,downstaging of large tumors for resection,or locoregional control and palliation of advanced disease.Their use has been associated with increased tumor response,increased disease-free and overall survival,and decreased morbidity and mortality in a broad range of metastatic disease.This review explores recent advances in liver-directed therapies for metastatic liver disease from primary colorectal,neuroendocrine,breast,and lung cancer,as well as uveal melanoma,cholangiocarcinoma,and sarcoma.Therapies discussed include bland transarterial embolization,chemoembolization,radioembolization,and ablative therapies,with a focus on current treatment approaches,outcomes of locoregional therapy,and future directions in each type of metastatic disease.