BACKGROUND In hepatocellular carcinoma(HCC),detection and treatment prior to growth beyond 2 cm are important as a larger tumor size is more frequently associated with microvascular invasion and/or satellites.In the s...BACKGROUND In hepatocellular carcinoma(HCC),detection and treatment prior to growth beyond 2 cm are important as a larger tumor size is more frequently associated with microvascular invasion and/or satellites.In the surveillance of very small HCC nodules(≤2 cm in maximum diameter,Barcelona clinical stage 0),we demonstrated that the tumor markers alpha-fetoprotein and PIVKA-Ⅱare not so useful.Therefore,we must survey with imaging modalities.The superiority of magnetic resonance imaging(MRI)over ultrasound(US)to detect HCC was confirmed in many studies.Although enhanced MRI is now performed to accurately diagnose HCC,in conventional clinical practice for HCC surveillance in liver diseases,unenhanced MRI is widely performed throughout the world.While,MRI has made marked improvements in recent years.AIM To make a comparison of unenhanced MRI and US in detecting very small HCC that was examined in the last ten years in patients in whom MRI and US examinations were performed nearly simultaneously.METHODS In 394 patients with very small HCC nodules,those who underwent MRI and US at nearly the same time(on the same day whenever possible or at least within 14 days of one another)at the first diagnosis of HCC were selected.The detection rate of HCC with unenhanced MRI was investigated and compared with that of unenhanced US.RESULTS The sensitivity of unenhanced MRI for detecting very small HCC was 95.1%(97/102,95%confidence interval:90.9-99.3)and that of unenhanced US was 69.6%(71/102,95%confidence interval:60.7-78.5).The sensitivity of unenhanced MRI for detecting very small HCC was significantly higher than that of unenhanced US(P<0.001).Regarding the location of HCC in the liver in patients in whom detection by US was unsuccessful,S7-8 was identified in 51.7%.CONCLUSION Currently,unenhanced MRI is a very useful tool for the surveillance of very small HCC in conventional clinical follow-up practice.展开更多
AIM:To investigate the clinicopathologic features of bile duct tumor thrombus(BDTT) occurrence after treatment of primary small hepatocellular carcinoma(sHCC) .METHODS:A total of 423 patients with primary sHCC admitte...AIM:To investigate the clinicopathologic features of bile duct tumor thrombus(BDTT) occurrence after treatment of primary small hepatocellular carcinoma(sHCC) .METHODS:A total of 423 patients with primary sHCC admitted to our hospital underwent surgical resection or local ablation.During follow-up,only six patients were hospitalized due to obstructive jaundice,which occurred 5-76 mo after initial treatment.The clinicopathologic features of these six patients were reviewed.RESULTS:Six patients underwent hepatic resection(n=5) or radio-frequency ablation(n=1) due to primary sHCC.Five cases had an R1 resection margin,and one case had an ablative margin less than 5.0 mm.No vascular infiltration,microsatellites or bile duct/canaliculus affection was noted in the initial resected specimens.During the follow-up,imaging studies revealed a macroscopic BDTT extending to the common bile duct in all six patients.Four patients had a concomitant intrahepatic recurrent tumor.Surgical re-resection of intrahepatic recurrent tumors and removal of BDTTs(n=4) ,BDTT removal through choledochotomy(n= 1) ,and conservative treatment(n=1) was performed.Microscopic portal vein invasion was noted in three of the four resected specimens.All six patients died,with a mean survival of 11 mo after BDTT removal or conservative treatment.CONCLUSION:BDTT occurrence is a rare,special recurrent pattern of primary sHCC.Patients with BDTTs extending to the common bile duct usually have an unfavorable prognosis even following aggressive surgery.Insufficient resection or ablative margins against primary sHCC may be a risk factor for BDTT development.展开更多
Background: More than two decades have gone bysince the early report of resection for small hepatocel-lular carcinoma (HCC), which resulted in improvedprognosis of HCC.Objective: To review the past and recent data, an...Background: More than two decades have gone bysince the early report of resection for small hepatocel-lular carcinoma (HCC), which resulted in improvedprognosis of HCC.Objective: To review the past and recent data, andprospect the future in this field.Data sources: Literature and recent data from theLiver Cancer Institute of Fudan University, Shang-hai, China.Data synthesis: 1232 patients with small HCC fromthe institute were analyzed between 1960-1984 (n=107) and 1985-1999 (n=1125). The increase of li-mited resection rate from 69.5 % to 82.5 % contribu-ted in part to the increase of resectability from76.6 % to 95.5 %, decrease of operative mortalityfrom 2.4 % to 1.2 %, and improvement of 5-year sur-vival after resection (from 53.1% to 64.0%). The5-year survival was higher after limited resectionthan after lobectomy, being 64.4 % versus 55.9%.The 5-year survival after resection was superior tothat after cryosurgery and other regional cancertherapies (32.8 %). However, molecular studiesfound that biological characteristics were only slightlybetter in small HCC than in large HCC.Conclusions: Resection remains the treatment choicefor small HCC with compensated liver function,while regional cancer therapies and liver transplanta-tion are alternatives for patients with incompensatedliver function. Biological characteristics remain theleading factor influencing prognosis of small HCC.展开更多
Background: Small hepatocellular carcinoma(sHCC) is a unique variant of HCC that is characterized by small tumor size(maximum tumor diameter predic≤3 cm) and favorable long?term outcomes. The present study aimed to d...Background: Small hepatocellular carcinoma(sHCC) is a unique variant of HCC that is characterized by small tumor size(maximum tumor diameter predic≤3 cm) and favorable long?term outcomes. The present study aimed to define clin?icopathologic factors that t survival in patients with s HCC.Methods: The study population consisted of 335 patients who underwent hepatectomy for solitary s HCC between December 1998 and 2010. Prognostic factors were evaluated using Kaplan–Meier curves and Cox proportional hazard models.Results: The 5?year overall survival(OS) and recurrence?free survival(RFS) rates were 77.7% and 59.9%, respectively. Kaplan–Meier curves showed that tumor size and vascular invasion had prognostic significance within this relatively selected cohort(P < 0.05). Multivariate analysis confirmed that increased tumor size and vascular invasion were independent prognostic factors for short OS(hazard ratio [HR] = 2.367, 95% confidence interval [CI] 1.406–3.985; HR = 2.954, 95% CI 1.781–4.900) and RFS(HR = 1.779, 95% CI 1.259–2.514; HR < 0.05). Importantly, a proposed prognostic scoring model was deri= 1.699, 95% CI 1.165–2.477) in s HCC patients(Pved according to the two variables; tumor size and extent of vascular invasion were significantly associated with OS and RFS in patients with s HCC(P < 0.001).Conclusions: Tumor size and vascular invasion are feasible and useful prognostic factors for s HCC. The proposed prognostic model, based on tumor size and vascular invasion, is informative in predicting survival in s HCC patients undergoing hepatectomy.展开更多
Early resection of hepatocellular carcinoma is a key measure to prolong the survival of patients. This study was designed to summarize our experience in surgical resection of small hepatocellular carcinoma (HCC), and ...Early resection of hepatocellular carcinoma is a key measure to prolong the survival of patients. This study was designed to summarize our experience in surgical resection of small hepatocellular carcinoma (HCC), and to analyze the factors influencing the postoperative survival of patients. METHODS:The clinicopathologic data of 105 patients with small HCC after resection from 1986 through 2003 were analyzed ; the patients had been followed up for more than half a year (median 33 months). Nine clinicopathologic factors, preoperative α-fetoprotein (AFP) level, liver cirrhosis, Child-Pugh score, tumor size (】2cm vs.≤2 cm) and number (single vs. multiple), capsule formation, portal vein tumor thrombi (PVTT), Edmondson tumor grade and surgical method, were analyzed by the log-rank test and the Cox proportional harzards model analysis. RESULTS:The cumulative 1-,3- and 5-year survival rates after the operation were 86.5%, 70.3% and 55.2%, respectively, and the 1-, 3- and 5-year disease-free survival rates were 78%, 58. 9% and 45. 6%, respectively. One patient died from esophagogastric varices hemorrhage in 2 weeks after reoperation. Thirty-six patients had intrahepatic recurrence or metastasis postoperatively and 34 patients died. The Kaplan-Meier method and the Cox proportional harzards model analysis indicated that poor Child-Pugh score, tumor more than 2 cm in diameter, PVTT and multiple lesions (including satellitic lesions) were adverse factors affecting postoperative survival. The Cox proportional harzards model analysis indicated that tumor size, PVTT and multiple lesions were the factors influencing postoperative disease-free survival. CONCLUSIONS:Limited hepatectomy with a margin more than 1 cm is an appropriate surgical approach. Adverse preoperative Child-Pugh score and postoperative intrahepatic recurrences are the main factors leading to the death of patients with small HCC.展开更多
AIM:To clarify the effect of a high des-gamma-carboxy prothrombin (DCP) level on the invasiveness and prognosis of small hepatocellular carcinoma. METHODS: Among 142 consecutive patients with known DCP levels, who und...AIM:To clarify the effect of a high des-gamma-carboxy prothrombin (DCP) level on the invasiveness and prognosis of small hepatocellular carcinoma. METHODS: Among 142 consecutive patients with known DCP levels, who underwent hepatectomy because of hepatocellular carcinoma, 85 patients met the criteria for small hepatocellular carcinoma, i.e. one ≤ 5 cm sized single tumor or no more than three ≤ 3 cm sized tumors. RESULTS: The overall survival rate of the 142 patients was 92.1% for 1 year, 69.6% for 3 years, and 56.9% for 5 years. Multivariate analysis showed that microscopic vascular invasion (P = 0.03) and serum DCP ≥ 400 mAU/mL (P = 0.02) were independent prognostic factors. In the group of patients who met the criteria for small hepatocellular carcinoma, DCP ≥ 400 mAU/mL was found to be an independent prognostic factor for recurrence-free (P = 0.02) and overall survival (P = 0.0005). In patients who did not meet the criteria, the presence of vascular invasion was an independent factor for recurrence-free (P = 0.02) and overall survivals (P = 0.01). In 75% of patients with small hepatocellular carcinoma and high DCP levels, recurrence occurred extrahepatically. CONCLUSION: For small hepatocellular carcinoma, a high preoperative DCP level appears indicative fortumor recurrence. Because many patients with a high preoperative DCP level develop extrahepatic recurrence, it is necessary to screen the whole body.展开更多
BACKGROUND Vessels encapsulating tumor clusters(VETC)represent a recently discovered vascular pattern associated with novel metastasis mechanisms in hepatocellular carcinoma(HCC).However,it seems that no one have focu...BACKGROUND Vessels encapsulating tumor clusters(VETC)represent a recently discovered vascular pattern associated with novel metastasis mechanisms in hepatocellular carcinoma(HCC).However,it seems that no one have focused on predicting VETC status in small HCC(sHCC).This study aimed to develop a new nomogram for predicting VETC positivity using preoperative clinical data and image features in sHCC(≤3 cm)patients.AIM To construct a nomogram that combines preoperative clinical parameters and image features to predict patterns of VETC and evaluate the prognosis of sHCC patients.METHODS A total of 309 patients with sHCC,who underwent segmental resection and had their VETC status confirmed,were included in the study.These patients were recruited from three different hospitals:Hospital 1 contributed 177 patients for the training set,Hospital 2 provided 78 patients for the test set,and Hospital 3 provided 54 patients for the validation set.Independent predictors of VETC were identified through univariate and multivariate logistic analyses.These independent predictors were then used to construct a VETC prediction model for sHCC.The model’s performance was evaluated using the area under the curve(AUC),calibration curve,and clinical decision curve.Additionally,Kaplan-Meier survival analysis was performed to confirm whether the predicted VETC status by the model is associated with early recurrence,just as it is with the actual VETC status and early recurrence.RESULTS Alpha-fetoprotein_lg10,carbohydrate antigen 199,irregular shape,non-smooth margin,and arterial peritumoral enhancement were identified as independent predictors of VETC.The model incorporating these predictors demonstrated strong predictive performance.The AUC was 0.811 for the training set,0.800 for the test set,and 0.791 for the validation set.The calibration curve indicated that the predicted probability was consistent with the actual VETC status in all three sets.Furthermore,the decision curve analysis demonstrated the clinical benefits of our model for patients with sHCC.Finally,early recurrence was more likely to occur in the VETC-positive group compared to the VETC-negative group,regardless of whether considering the actual or predicted VETC status.CONCLUSION Our novel prediction model demonstrates strong performance in predicting VETC positivity in sHCC(≤3 cm)patients,and it holds potential for predicting early recurrence.This model equips clinicians with valuable information to make informed clinical treatment decisions.展开更多
Surgical resection or radiofrequency ablation(RFA)is considered first-choice treatment for small hepatocellular carcinomas(HCCs).When a patient has a small HCC that is inoperable or unsuitable for RFA,what are alterna...Surgical resection or radiofrequency ablation(RFA)is considered first-choice treatment for small hepatocellular carcinomas(HCCs).When a patient has a small HCC that is inoperable or unsuitable for RFA,what are alternative treatments?Some oncologists recommend transarterial chemoembolization(TACE),chemotherapy,molecular-targeted therapy,or immunotherapy.However,these treatments have minimally beneficial effects in small HCCs.Stereotactic body radiation therapy(SBRT)is a liver-directed radical therapy for small HCCs,with treatment outcomes similar to those for surgical resection or RFA,but many oncologists do not comprehend its efficacy or accept this therapy.We herein discuss 11 typical patients who received SBRT for various indications:refusal to undergo resection or RFA;surgical resection or RFA considered difficult or unfeasible;residual cancer after surgical resection or RFA or incomplete iodized oil retention after TACE;or tumor recurrence after resection or RFA.We describe each case,including the radiation field,tumor radiation dose,and response to SBRT in both the tumor and liver parenchyma.These clinical data should help readers understand this new therapeutic technique.We also conducted a literature review and found evidence to support survival benefit with SBRT,including good three-and five-year overall survival rates.The purpose of this article is to encourage readers to accept the concept that SBRT is a low-toxicity and effective therapeutic option for patients with small HCCs,which offers substantial local control and improved overall survival,especially for patients with a tumor that is unresectable or unsuitable for RFA,residual tumor after local therapy,or intrahepatic recurrent tumor.展开更多
Hepatocellular carcinoma(HCC) is the predominant form of primary liver cancer and represents the third leading cause of cancer-related death worldwide. Current available therapeutic approaches are poorly effective,esp...Hepatocellular carcinoma(HCC) is the predominant form of primary liver cancer and represents the third leading cause of cancer-related death worldwide. Current available therapeutic approaches are poorly effective,especially for the advanced forms of the disease. In the last year,short double stranded RNA molecules termed small interfering RNAs(si RNAs) and micro interfering RNAs(mi RNA),emerged as interesting molecules with potential therapeutic value for HCC. The practical use of these molecules is however limited by the identification of optimal molecular targets and especially by the lack of effective and targeted HCC delivery systems. Here we focus our discussion on the most recent advances in the identification of si RNAs/mi RNAs molecular targets and on the development of suitable si RNA/mi RNAs delivery systems.展开更多
BACKGROUND:Primary sclerosing cholangitis(PSC)is a chronic progressive cholestatic liver disease,which usually affects young adults and is diagnosed by cholangiography.On a few occasions,the disease either starts in o...BACKGROUND:Primary sclerosing cholangitis(PSC)is a chronic progressive cholestatic liver disease,which usually affects young adults and is diagnosed by cholangiography.On a few occasions,the disease either starts in or exclusively involves the small intrahepatic bile ducts,referred to as small-duct PSC. METHODS:A 31-year-old man presented with severe hematemesis secondary to liver cirrhosis.Over a course of 8 years,his liver decompensated and required an orthotopic liver transplantation. In this report we discuss his disease presentation,course of management,and the post-transplantation course of manage- ment,and review the morphologic diagnosis,and differential diagnosis of the disease with large-duct type and other diseases that involve small intrahepatic bile ducts. RESULTS:The patient's explanted liver showed changes of PSC affecting only the small-and medium-sized bile ducts in addition to three incidental nodules of hepatocellular carcinoma. CONCLUSIONS:Small-duct PSC has a substantially better prognosis than the large-duct type,with less chance of developing cirrhosis and an equal risk for developing hepato- cellular carcinoma,but no increased risk for developing cholangiocarcinoma.Treatment seems to help relieve the symptoms but not necessarily improve survival.Liver transplantation remains the ultimate cure.展开更多
BACKGROUND: Early recurrence(ER) after hepatic resection(HR) is a poor prognostic factor for patients with hepatocellular carcinoma(HCC). This study aimed to identify the clinicopathological features, outcomes, and ri...BACKGROUND: Early recurrence(ER) after hepatic resection(HR) is a poor prognostic factor for patients with hepatocellular carcinoma(HCC). This study aimed to identify the clinicopathological features, outcomes, and risk factors for ER after HR for small HCC in order to clarify the reasons why ER is a worse recurrence pattern.METHODS: We retrospectively examined 130 patients who underwent HR for small HCC(≤30 mm). Recurrence was classified into ER(<2 years) and late recurrence(LR)(≥2 years). The clinicopathological features, outcomes, and risk factors for ER were analyzed by multivariate analysis.RESULTS: ER was observed in 39 patients(30.0%). The survival rate of the ER group was significantly lower than that of the LR group(P<0.005), and ER was an independent prognostic factor for poor survival(P=0.0001). The ER group had a significantly higher frequency(P=0.0039) and shorter interval(P=0.027) of development to carcinoma beyond the Milan criteria(DBMC) compared with the LR group, and ER was an independent risk factor for DBMC(P<0.0001). Multi-nodularity, non-simple nodular type, and microvascular invasion were independent predictors for ER(P=0.012, 0.010, and 0.019, respectively).CONCLUSIONS: ER was a highly malignant recurrence pattern associated with DBMC and subsequent poor survival after HR for small HCC. Multi-nodularity, non-simple nodular type, and microvascular invasion predict ER, and taking these factors into consideration may be useful for the decision of the treatment strategy for small HCC after HR.展开更多
AIM:To evaluate the long-term results of radiofrequency ablation(RFA)compared to left lateral sectionectomy(LLS)in patients with Child-Pugh class A disease for the treatment of single and small hepatocellular carcinom...AIM:To evaluate the long-term results of radiofrequency ablation(RFA)compared to left lateral sectionectomy(LLS)in patients with Child-Pugh class A disease for the treatment of single and small hepatocellular carcinoma(HCC)in the left lateral segments.METHODS:We retrospectively reviewed the data of133 patients with single HCC(≤3 cm)in their left lateral segments who underwent curative LLS(n=66)or RFA(n=67)between 2006 and 2010.RESULTS:The median follow-up period was 33.5mo in the LLS group and 29 mo in the RFA group(P=0.060).Most patients had hepatitis B virus-related HCC.The hospital stay was longer in the LLS group than in the RFA group(8 d vs 2 d,P<0.001).The 1-,2-,and 3-year disease-free survival and overall survival rates were 80.0%,68.2%,and 60.0%,and 95.4%,92.3%,and 92.3%,respectively,for the LLS group;and 80.8%,59.9%,and 39.6%,and 98.2%,92.0%,and 74.4%,respectively,for the RFA group.The disease-free survival curve and overall survival curve were higher in the LLS group than in the RFA group(P=0.012 and P=0.013,respectively).Increased PIVKA-Ⅱlevels and small tumor size were associated with HCC recurrence in multivariate analysis.CONCLUSION:Liver resection is suitable for single HCC≤3 cm in the left lateral segments.展开更多
AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 norm...AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.展开更多
In recent years, the incidence of hepatocellular carcinoma (HCC) has been increasing worldwide, and its high mortality seriously threatens public health. Early detection and treatment are crucial to improving the surv...In recent years, the incidence of hepatocellular carcinoma (HCC) has been increasing worldwide, and its high mortality seriously threatens public health. Early detection and treatment are crucial to improving the survival rate. Imaging examination widely used for the diagnosis of HCC and provides a non-invasive means of tumor visualization. The rapid development of medical imaging technology is expected to improve early-stage diagnosis rates for HCC. This article summarizes the methods for the differential diagnosis of premalignant dysplastic nodule (DN) and small hepatocellular carcinoma during the carcinogenesis of cirrhosis and reviews their application. In addition, a discussion on some recently patented medical imaging development was also presented.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality worldwide.Molecular magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new...BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality worldwide.Molecular magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new strategies to enhance specificity and help early diagnosis of HCC.However,the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3,which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors<1 cm(MHCC).We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC diagnosis.AIM To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular level.METHODS A double antigen-targeted MRI probe for MHCC anti-AFP-USPIO-anti-GPC3(UAG)was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle(USPIO).At the same time,the singly labeled probes of anti-AFP-USPIO(UA)and anti-GPC3-USPIO(UG)and non-targeted USPIO(U)were also prepared for comparison.The physical characterization including morphology(transmission electron microscopy),hydrodynamic size,and zeta potential(dynamic light scattering)was conducted for each of the probes.The antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/GPC3.First,AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and immunocytochemistry.Then,the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI(T2-weighted and T2-map)with a 3.0 Tesla clinical MR scanner.RESULTS Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-6/GPC3 cells expressing AFP and GPC3 antigens compared with single antibody-conjugated and unconjugated USPIO probes.The iron Prussian blue staining and quantitative T2-map MRI analysis showed that,compared with UA,UG,and U,the uptake of double antigen-targeted UAG probe demonstrated a 23.3%(vs UA),15.4%(vs UG),and 57.3%(vs U)increased Prussian stained cell percentage and a 14.93%(vs UA),9.38%(vs UG),and 15.3%(vs U)reduction of T2 relaxation time,respectively.Such bi-specific probe might have the potential to overcome tumor heterogeneity.Meanwhile,the coupling of two antibodies did not influence the magnetic performance of USPIO,and the relatively small hydrodynamic size(59.60±1.87 nm)of double antibodyconjugated USPIO probe makes it a viable candidate for use in MHCC MRI in vivo,as they are slowly phagocytosed by macrophages.CONCLUSION The bi-specific probe presents enhanced targeting efficiency and MRI sensitivity to HCC cells than singly-or non-targeted USPIO,paving the way for in vivo translation to further evaluate its clinical potential.展开更多
基金The study was reviewed and approved by the Ethics Committee of Yokohama Municipal Citizen's Hospital Institutional Review Board(Approval No.21-02-01).
文摘BACKGROUND In hepatocellular carcinoma(HCC),detection and treatment prior to growth beyond 2 cm are important as a larger tumor size is more frequently associated with microvascular invasion and/or satellites.In the surveillance of very small HCC nodules(≤2 cm in maximum diameter,Barcelona clinical stage 0),we demonstrated that the tumor markers alpha-fetoprotein and PIVKA-Ⅱare not so useful.Therefore,we must survey with imaging modalities.The superiority of magnetic resonance imaging(MRI)over ultrasound(US)to detect HCC was confirmed in many studies.Although enhanced MRI is now performed to accurately diagnose HCC,in conventional clinical practice for HCC surveillance in liver diseases,unenhanced MRI is widely performed throughout the world.While,MRI has made marked improvements in recent years.AIM To make a comparison of unenhanced MRI and US in detecting very small HCC that was examined in the last ten years in patients in whom MRI and US examinations were performed nearly simultaneously.METHODS In 394 patients with very small HCC nodules,those who underwent MRI and US at nearly the same time(on the same day whenever possible or at least within 14 days of one another)at the first diagnosis of HCC were selected.The detection rate of HCC with unenhanced MRI was investigated and compared with that of unenhanced US.RESULTS The sensitivity of unenhanced MRI for detecting very small HCC was 95.1%(97/102,95%confidence interval:90.9-99.3)and that of unenhanced US was 69.6%(71/102,95%confidence interval:60.7-78.5).The sensitivity of unenhanced MRI for detecting very small HCC was significantly higher than that of unenhanced US(P<0.001).Regarding the location of HCC in the liver in patients in whom detection by US was unsuccessful,S7-8 was identified in 51.7%.CONCLUSION Currently,unenhanced MRI is a very useful tool for the surveillance of very small HCC in conventional clinical follow-up practice.
文摘AIM:To investigate the clinicopathologic features of bile duct tumor thrombus(BDTT) occurrence after treatment of primary small hepatocellular carcinoma(sHCC) .METHODS:A total of 423 patients with primary sHCC admitted to our hospital underwent surgical resection or local ablation.During follow-up,only six patients were hospitalized due to obstructive jaundice,which occurred 5-76 mo after initial treatment.The clinicopathologic features of these six patients were reviewed.RESULTS:Six patients underwent hepatic resection(n=5) or radio-frequency ablation(n=1) due to primary sHCC.Five cases had an R1 resection margin,and one case had an ablative margin less than 5.0 mm.No vascular infiltration,microsatellites or bile duct/canaliculus affection was noted in the initial resected specimens.During the follow-up,imaging studies revealed a macroscopic BDTT extending to the common bile duct in all six patients.Four patients had a concomitant intrahepatic recurrent tumor.Surgical re-resection of intrahepatic recurrent tumors and removal of BDTTs(n=4) ,BDTT removal through choledochotomy(n= 1) ,and conservative treatment(n=1) was performed.Microscopic portal vein invasion was noted in three of the four resected specimens.All six patients died,with a mean survival of 11 mo after BDTT removal or conservative treatment.CONCLUSION:BDTT occurrence is a rare,special recurrent pattern of primary sHCC.Patients with BDTTs extending to the common bile duct usually have an unfavorable prognosis even following aggressive surgery.Insufficient resection or ablative margins against primary sHCC may be a risk factor for BDTT development.
文摘Background: More than two decades have gone bysince the early report of resection for small hepatocel-lular carcinoma (HCC), which resulted in improvedprognosis of HCC.Objective: To review the past and recent data, andprospect the future in this field.Data sources: Literature and recent data from theLiver Cancer Institute of Fudan University, Shang-hai, China.Data synthesis: 1232 patients with small HCC fromthe institute were analyzed between 1960-1984 (n=107) and 1985-1999 (n=1125). The increase of li-mited resection rate from 69.5 % to 82.5 % contribu-ted in part to the increase of resectability from76.6 % to 95.5 %, decrease of operative mortalityfrom 2.4 % to 1.2 %, and improvement of 5-year sur-vival after resection (from 53.1% to 64.0%). The5-year survival was higher after limited resectionthan after lobectomy, being 64.4 % versus 55.9%.The 5-year survival after resection was superior tothat after cryosurgery and other regional cancertherapies (32.8 %). However, molecular studiesfound that biological characteristics were only slightlybetter in small HCC than in large HCC.Conclusions: Resection remains the treatment choicefor small HCC with compensated liver function,while regional cancer therapies and liver transplanta-tion are alternatives for patients with incompensatedliver function. Biological characteristics remain theleading factor influencing prognosis of small HCC.
基金supported by the grants from the National Natural Science Foundation of China (No.81302139,81172340,81202111,and 81225018)
文摘Background: Small hepatocellular carcinoma(sHCC) is a unique variant of HCC that is characterized by small tumor size(maximum tumor diameter predic≤3 cm) and favorable long?term outcomes. The present study aimed to define clin?icopathologic factors that t survival in patients with s HCC.Methods: The study population consisted of 335 patients who underwent hepatectomy for solitary s HCC between December 1998 and 2010. Prognostic factors were evaluated using Kaplan–Meier curves and Cox proportional hazard models.Results: The 5?year overall survival(OS) and recurrence?free survival(RFS) rates were 77.7% and 59.9%, respectively. Kaplan–Meier curves showed that tumor size and vascular invasion had prognostic significance within this relatively selected cohort(P < 0.05). Multivariate analysis confirmed that increased tumor size and vascular invasion were independent prognostic factors for short OS(hazard ratio [HR] = 2.367, 95% confidence interval [CI] 1.406–3.985; HR = 2.954, 95% CI 1.781–4.900) and RFS(HR = 1.779, 95% CI 1.259–2.514; HR < 0.05). Importantly, a proposed prognostic scoring model was deri= 1.699, 95% CI 1.165–2.477) in s HCC patients(Pved according to the two variables; tumor size and extent of vascular invasion were significantly associated with OS and RFS in patients with s HCC(P < 0.001).Conclusions: Tumor size and vascular invasion are feasible and useful prognostic factors for s HCC. The proposed prognostic model, based on tumor size and vascular invasion, is informative in predicting survival in s HCC patients undergoing hepatectomy.
文摘Early resection of hepatocellular carcinoma is a key measure to prolong the survival of patients. This study was designed to summarize our experience in surgical resection of small hepatocellular carcinoma (HCC), and to analyze the factors influencing the postoperative survival of patients. METHODS:The clinicopathologic data of 105 patients with small HCC after resection from 1986 through 2003 were analyzed ; the patients had been followed up for more than half a year (median 33 months). Nine clinicopathologic factors, preoperative α-fetoprotein (AFP) level, liver cirrhosis, Child-Pugh score, tumor size (】2cm vs.≤2 cm) and number (single vs. multiple), capsule formation, portal vein tumor thrombi (PVTT), Edmondson tumor grade and surgical method, were analyzed by the log-rank test and the Cox proportional harzards model analysis. RESULTS:The cumulative 1-,3- and 5-year survival rates after the operation were 86.5%, 70.3% and 55.2%, respectively, and the 1-, 3- and 5-year disease-free survival rates were 78%, 58. 9% and 45. 6%, respectively. One patient died from esophagogastric varices hemorrhage in 2 weeks after reoperation. Thirty-six patients had intrahepatic recurrence or metastasis postoperatively and 34 patients died. The Kaplan-Meier method and the Cox proportional harzards model analysis indicated that poor Child-Pugh score, tumor more than 2 cm in diameter, PVTT and multiple lesions (including satellitic lesions) were adverse factors affecting postoperative survival. The Cox proportional harzards model analysis indicated that tumor size, PVTT and multiple lesions were the factors influencing postoperative disease-free survival. CONCLUSIONS:Limited hepatectomy with a margin more than 1 cm is an appropriate surgical approach. Adverse preoperative Child-Pugh score and postoperative intrahepatic recurrences are the main factors leading to the death of patients with small HCC.
文摘AIM:To clarify the effect of a high des-gamma-carboxy prothrombin (DCP) level on the invasiveness and prognosis of small hepatocellular carcinoma. METHODS: Among 142 consecutive patients with known DCP levels, who underwent hepatectomy because of hepatocellular carcinoma, 85 patients met the criteria for small hepatocellular carcinoma, i.e. one ≤ 5 cm sized single tumor or no more than three ≤ 3 cm sized tumors. RESULTS: The overall survival rate of the 142 patients was 92.1% for 1 year, 69.6% for 3 years, and 56.9% for 5 years. Multivariate analysis showed that microscopic vascular invasion (P = 0.03) and serum DCP ≥ 400 mAU/mL (P = 0.02) were independent prognostic factors. In the group of patients who met the criteria for small hepatocellular carcinoma, DCP ≥ 400 mAU/mL was found to be an independent prognostic factor for recurrence-free (P = 0.02) and overall survival (P = 0.0005). In patients who did not meet the criteria, the presence of vascular invasion was an independent factor for recurrence-free (P = 0.02) and overall survivals (P = 0.01). In 75% of patients with small hepatocellular carcinoma and high DCP levels, recurrence occurred extrahepatically. CONCLUSION: For small hepatocellular carcinoma, a high preoperative DCP level appears indicative fortumor recurrence. Because many patients with a high preoperative DCP level develop extrahepatic recurrence, it is necessary to screen the whole body.
基金Supported by the Project of Shanghai Municipal Commission of Health,No.2022LJ024.
文摘BACKGROUND Vessels encapsulating tumor clusters(VETC)represent a recently discovered vascular pattern associated with novel metastasis mechanisms in hepatocellular carcinoma(HCC).However,it seems that no one have focused on predicting VETC status in small HCC(sHCC).This study aimed to develop a new nomogram for predicting VETC positivity using preoperative clinical data and image features in sHCC(≤3 cm)patients.AIM To construct a nomogram that combines preoperative clinical parameters and image features to predict patterns of VETC and evaluate the prognosis of sHCC patients.METHODS A total of 309 patients with sHCC,who underwent segmental resection and had their VETC status confirmed,were included in the study.These patients were recruited from three different hospitals:Hospital 1 contributed 177 patients for the training set,Hospital 2 provided 78 patients for the test set,and Hospital 3 provided 54 patients for the validation set.Independent predictors of VETC were identified through univariate and multivariate logistic analyses.These independent predictors were then used to construct a VETC prediction model for sHCC.The model’s performance was evaluated using the area under the curve(AUC),calibration curve,and clinical decision curve.Additionally,Kaplan-Meier survival analysis was performed to confirm whether the predicted VETC status by the model is associated with early recurrence,just as it is with the actual VETC status and early recurrence.RESULTS Alpha-fetoprotein_lg10,carbohydrate antigen 199,irregular shape,non-smooth margin,and arterial peritumoral enhancement were identified as independent predictors of VETC.The model incorporating these predictors demonstrated strong predictive performance.The AUC was 0.811 for the training set,0.800 for the test set,and 0.791 for the validation set.The calibration curve indicated that the predicted probability was consistent with the actual VETC status in all three sets.Furthermore,the decision curve analysis demonstrated the clinical benefits of our model for patients with sHCC.Finally,early recurrence was more likely to occur in the VETC-positive group compared to the VETC-negative group,regardless of whether considering the actual or predicted VETC status.CONCLUSION Our novel prediction model demonstrates strong performance in predicting VETC positivity in sHCC(≤3 cm)patients,and it holds potential for predicting early recurrence.This model equips clinicians with valuable information to make informed clinical treatment decisions.
基金supported by a grant from the National Key R&D Program of China(2017YFC0112100).
文摘Surgical resection or radiofrequency ablation(RFA)is considered first-choice treatment for small hepatocellular carcinomas(HCCs).When a patient has a small HCC that is inoperable or unsuitable for RFA,what are alternative treatments?Some oncologists recommend transarterial chemoembolization(TACE),chemotherapy,molecular-targeted therapy,or immunotherapy.However,these treatments have minimally beneficial effects in small HCCs.Stereotactic body radiation therapy(SBRT)is a liver-directed radical therapy for small HCCs,with treatment outcomes similar to those for surgical resection or RFA,but many oncologists do not comprehend its efficacy or accept this therapy.We herein discuss 11 typical patients who received SBRT for various indications:refusal to undergo resection or RFA;surgical resection or RFA considered difficult or unfeasible;residual cancer after surgical resection or RFA or incomplete iodized oil retention after TACE;or tumor recurrence after resection or RFA.We describe each case,including the radiation field,tumor radiation dose,and response to SBRT in both the tumor and liver parenchyma.These clinical data should help readers understand this new therapeutic technique.We also conducted a literature review and found evidence to support survival benefit with SBRT,including good three-and five-year overall survival rates.The purpose of this article is to encourage readers to accept the concept that SBRT is a low-toxicity and effective therapeutic option for patients with small HCCs,which offers substantial local control and improved overall survival,especially for patients with a tumor that is unresectable or unsuitable for RFA,residual tumor after local therapy,or intrahepatic recurrent tumor.
基金Supported by"Fondazione Cassa di Risparmio of Trieste"the"Fondazione Benefica Kathleen Foreman Casali of Trieste"+2 种基金the"Beneficentia Stiftung"of Vaduz Liechtensteinthe Italian Minister of Instruction,UniversityResearch(MIUR),PRIN 2010-11,No.20109PLMH2(in part)
文摘Hepatocellular carcinoma(HCC) is the predominant form of primary liver cancer and represents the third leading cause of cancer-related death worldwide. Current available therapeutic approaches are poorly effective,especially for the advanced forms of the disease. In the last year,short double stranded RNA molecules termed small interfering RNAs(si RNAs) and micro interfering RNAs(mi RNA),emerged as interesting molecules with potential therapeutic value for HCC. The practical use of these molecules is however limited by the identification of optimal molecular targets and especially by the lack of effective and targeted HCC delivery systems. Here we focus our discussion on the most recent advances in the identification of si RNAs/mi RNAs molecular targets and on the development of suitable si RNA/mi RNAs delivery systems.
文摘BACKGROUND:Primary sclerosing cholangitis(PSC)is a chronic progressive cholestatic liver disease,which usually affects young adults and is diagnosed by cholangiography.On a few occasions,the disease either starts in or exclusively involves the small intrahepatic bile ducts,referred to as small-duct PSC. METHODS:A 31-year-old man presented with severe hematemesis secondary to liver cirrhosis.Over a course of 8 years,his liver decompensated and required an orthotopic liver transplantation. In this report we discuss his disease presentation,course of management,and the post-transplantation course of manage- ment,and review the morphologic diagnosis,and differential diagnosis of the disease with large-duct type and other diseases that involve small intrahepatic bile ducts. RESULTS:The patient's explanted liver showed changes of PSC affecting only the small-and medium-sized bile ducts in addition to three incidental nodules of hepatocellular carcinoma. CONCLUSIONS:Small-duct PSC has a substantially better prognosis than the large-duct type,with less chance of developing cirrhosis and an equal risk for developing hepato- cellular carcinoma,but no increased risk for developing cholangiocarcinoma.Treatment seems to help relieve the symptoms but not necessarily improve survival.Liver transplantation remains the ultimate cure.
文摘BACKGROUND: Early recurrence(ER) after hepatic resection(HR) is a poor prognostic factor for patients with hepatocellular carcinoma(HCC). This study aimed to identify the clinicopathological features, outcomes, and risk factors for ER after HR for small HCC in order to clarify the reasons why ER is a worse recurrence pattern.METHODS: We retrospectively examined 130 patients who underwent HR for small HCC(≤30 mm). Recurrence was classified into ER(<2 years) and late recurrence(LR)(≥2 years). The clinicopathological features, outcomes, and risk factors for ER were analyzed by multivariate analysis.RESULTS: ER was observed in 39 patients(30.0%). The survival rate of the ER group was significantly lower than that of the LR group(P<0.005), and ER was an independent prognostic factor for poor survival(P=0.0001). The ER group had a significantly higher frequency(P=0.0039) and shorter interval(P=0.027) of development to carcinoma beyond the Milan criteria(DBMC) compared with the LR group, and ER was an independent risk factor for DBMC(P<0.0001). Multi-nodularity, non-simple nodular type, and microvascular invasion were independent predictors for ER(P=0.012, 0.010, and 0.019, respectively).CONCLUSIONS: ER was a highly malignant recurrence pattern associated with DBMC and subsequent poor survival after HR for small HCC. Multi-nodularity, non-simple nodular type, and microvascular invasion predict ER, and taking these factors into consideration may be useful for the decision of the treatment strategy for small HCC after HR.
文摘AIM:To evaluate the long-term results of radiofrequency ablation(RFA)compared to left lateral sectionectomy(LLS)in patients with Child-Pugh class A disease for the treatment of single and small hepatocellular carcinoma(HCC)in the left lateral segments.METHODS:We retrospectively reviewed the data of133 patients with single HCC(≤3 cm)in their left lateral segments who underwent curative LLS(n=66)or RFA(n=67)between 2006 and 2010.RESULTS:The median follow-up period was 33.5mo in the LLS group and 29 mo in the RFA group(P=0.060).Most patients had hepatitis B virus-related HCC.The hospital stay was longer in the LLS group than in the RFA group(8 d vs 2 d,P<0.001).The 1-,2-,and 3-year disease-free survival and overall survival rates were 80.0%,68.2%,and 60.0%,and 95.4%,92.3%,and 92.3%,respectively,for the LLS group;and 80.8%,59.9%,and 39.6%,and 98.2%,92.0%,and 74.4%,respectively,for the RFA group.The disease-free survival curve and overall survival curve were higher in the LLS group than in the RFA group(P=0.012 and P=0.013,respectively).Increased PIVKA-Ⅱlevels and small tumor size were associated with HCC recurrence in multivariate analysis.CONCLUSION:Liver resection is suitable for single HCC≤3 cm in the left lateral segments.
基金Supported by A grant of the Korea Healthcare technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A092258)FG08-11-06 of the 21C Frontier Functional Human Genome Project from the Ministry of Education, Science and Technology
文摘AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.
文摘In recent years, the incidence of hepatocellular carcinoma (HCC) has been increasing worldwide, and its high mortality seriously threatens public health. Early detection and treatment are crucial to improving the survival rate. Imaging examination widely used for the diagnosis of HCC and provides a non-invasive means of tumor visualization. The rapid development of medical imaging technology is expected to improve early-stage diagnosis rates for HCC. This article summarizes the methods for the differential diagnosis of premalignant dysplastic nodule (DN) and small hepatocellular carcinoma during the carcinogenesis of cirrhosis and reviews their application. In addition, a discussion on some recently patented medical imaging development was also presented.
基金Supported by CAMS Innovation Fund for Medical Sciences,No.2016-I2M-1-001PUMC Youth Fund,No.2017320010+1 种基金Chinese Academy of Medical Sciences Research Fund,No.ZZ2016B01Beijing HopeRun Special Fund of Cancer Foundation of China,No.LC2016B15
文摘BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality worldwide.Molecular magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new strategies to enhance specificity and help early diagnosis of HCC.However,the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3,which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors<1 cm(MHCC).We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC diagnosis.AIM To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular level.METHODS A double antigen-targeted MRI probe for MHCC anti-AFP-USPIO-anti-GPC3(UAG)was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle(USPIO).At the same time,the singly labeled probes of anti-AFP-USPIO(UA)and anti-GPC3-USPIO(UG)and non-targeted USPIO(U)were also prepared for comparison.The physical characterization including morphology(transmission electron microscopy),hydrodynamic size,and zeta potential(dynamic light scattering)was conducted for each of the probes.The antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/GPC3.First,AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and immunocytochemistry.Then,the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI(T2-weighted and T2-map)with a 3.0 Tesla clinical MR scanner.RESULTS Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-6/GPC3 cells expressing AFP and GPC3 antigens compared with single antibody-conjugated and unconjugated USPIO probes.The iron Prussian blue staining and quantitative T2-map MRI analysis showed that,compared with UA,UG,and U,the uptake of double antigen-targeted UAG probe demonstrated a 23.3%(vs UA),15.4%(vs UG),and 57.3%(vs U)increased Prussian stained cell percentage and a 14.93%(vs UA),9.38%(vs UG),and 15.3%(vs U)reduction of T2 relaxation time,respectively.Such bi-specific probe might have the potential to overcome tumor heterogeneity.Meanwhile,the coupling of two antibodies did not influence the magnetic performance of USPIO,and the relatively small hydrodynamic size(59.60±1.87 nm)of double antibodyconjugated USPIO probe makes it a viable candidate for use in MHCC MRI in vivo,as they are slowly phagocytosed by macrophages.CONCLUSION The bi-specific probe presents enhanced targeting efficiency and MRI sensitivity to HCC cells than singly-or non-targeted USPIO,paving the way for in vivo translation to further evaluate its clinical potential.