Surgicopathological classification of hepatic space-occupying lesions:A single-center experience with literature review

Accompanying rapid developments in hepatic surgery,the number of surgeries and identifications of histological types of primary hepatic space-occupying lesions (PHSOLs) have increased dramatically.This has led to many changes in the surgicopathological spectrum of PHSOLs,and has contributed to a theoretical basis for modern hepatic surgery and oncological pathology.Between 1982 and 2009 at the Eastern Hepatobiliary Surgery Hospital (EHBH) in Shanghai,31 901 patients underwent surgery and were diagnosed as having a PHSOL.In this paper,we present an analysis of the PHSOL cases at the EHBH for this time period,along with results from a systematic literature review.We describe a surgicopathological spectrum comprising more than 100 types of PHSOLs that can be stratified into three types:tumor-like,benign,and malignant.We also stratified the PHSOLs into six subtypes derived from hepatocytes;cholangiocytes;vascular,lymphoid and hemopoietic tissues;muscular,fibrous and adipose tissues;neural and neuroendocrine tissues;and miscellaneous tissues.The present study provides a new classification system that can be used as a current reference for clinicians and pathologists to make correct diagnoses and differential diagnoses among various PHSOLs.

Reduced expression of E-cadherin/catenin complex in hepatocellular carcinomas

AIM： TO examine the immunoreactivity of E-cadherin and four subtypes of catenin family in human hepatocellular carcinomas （HCCs） and to investigate the correlation between expression of E-cadherin/ catenin complex and clinicopathologic parameters of HCC patients. METHODS： An immunohistochemical study for E-cadherin and catenins was performed on 97 formalin-fixed, paraffin-embedded specimens of HCC. RESULTS： Reduced expression of E-cadherin, ^-, 13-, y-catenin and p120 was observed in 69%, 76%, 63%, 71% and 73%, respectively. Both expressions of E-cadherin and catenin components were significantly correlated with tumor grade （P = 0.000）. It showed significant difference between expression of catenin members and tumor stage （P = 0.003, P = 0.017, P = 0.007 and P = 0.000, respectively）. The reduced expression of E-cadherin in HCCs was significantly correlated with intrahepatic metastasis （IM） and capsular invasion （P = 0.008, P = 0.03, respectively）. A close correlation was also observed between the expression of catenins and the tumor size （P = 0.002, P = 0.034, P = 0.016 and P = 0.000, respectively）. In addition, the expression of each catenin was found correlated with IM （P = 0.012, P = 0.049, P =0.026 and P = 0.014, respectively）. No statistically significant difference was observed between the expression level of E-cadherin/catenin complex and lymph node permission, vascular invasion and satellite nodules. Interestingly, only expression of p120 showed correlation with AFP value （P = 0.035）. The expression of E-cadherin was consistent with α-, β-, γ-catenin and p120 expression （P = 0.000）. Finally, the abnormal expression of E-cadherin/catenin complex was significantly associated with patients＇ survival （P = 0.0253, P = 0.0052, P = 0.003, P = 0.0105 and P = 0.0016, respectively）. Nevertheless, no component of E-cadherin/catenin complex was the independent prognostic factor of HCC patients. CONCLUSION： Down-regulated expressions of E-cadherin, catenins and p120 occur frequently in HCCs and contribute to the progression and development of tumor. It may be more exact and valuable to detect the co-expression of E-cadherin/catenin complex than to explore one of them in predicting tumor invasion, metastasis and patient＇s survival.

Risk factors and surgical outcomes for spontaneous rupture of BCLC stages A and B hepatocellular carcinoma: A case-control study

AIM: To investigate the risk factors and surgical outcomes for spontaneous rupture of Barcelona Clinic Liver Cancer (BCLC) stages A and B hepatocellular carcinoma (HCC).

Portal vein tumor thrombus is a bottleneck in the treatment of hepatocellular carcinoma

The effect of portal vein tumor thrombus(PVTT) on the prognosis of patients with hepatocellular carcinoma has become clear over the past several decades. However, identifying the mechanisms and performing the diagnosis and treatment of PVTT remain challenging. Therefore, this study aimed to summarize the progress in these areas. A computerized literature search in Medline and EMBASE was performed with the following combinations of search terms: "hepatocellular carcinoma" AND "portal vein tumor thrombus." Although several signal transduction or molecular pathways related to PVTT have been identified, the exact mechanisms of PVTT are still largely unknown. Many biomarkers have been reported to detect microvascular invasion, but none have proved to be clinically useful because of their low accuracy rates. Sorafenib is the only recommended therapeutic strategy in Western countries. However, more treatment options are recommended in Eastern countries, including surgery, radiotherapy(RT), transhepatic arterial chemoembolization(TACE), transarterial radioembolization(TARE), and sorafenib. Therefore, we established a staging system based on the extent of portal vein invasion. Our staging system effectively predicts the long-term survival of PVTT patients. Currently, several clinical trials had shown that surgery is effective and safe in some PVTT patients. RT,TARE, and TACE can also be performed safely in patients with good liver function. However, only a few comparative clinical trials had compared the effectiveness of these treatments. Therefore, more randomized controlled trials examining the extent of PVTT should be conducted in the future.

Inhibition of autophagy significantly enhances combination therapy with sorafenib and HDAC inhibitors for human hepatoma cells

AIM: To clarify whether histone deacetylase inhibitors histone deacetylase inhibitors (HDACIs) can sensitize hepatocellular carcinoma (HCC) cells to sorafenib treatment. METHODS: Bax, Bcl-2, ATG5-ATG12, p21, and p27 protein levels in Hep3B, HepG2, and PLC/PRF/5 cells were examined by Western blot. CCK8 and a fluoro-metric caspase-3 assay were used to examine cellular viability and apoptosis levels. The effect of Beclin-1 on sensitization of HCC cells to sorafenib was examined by transfecting Beclin-1 siRNA into Hep3B, HepG2, and PLC/PRF/5 cells. RESULTS: Autophagy inhibition enhances the inhibitory effects of vorinostat and sorafenib alone or in combination on HCC cell growth. Vorinostat and sorafenib synergistically induced apoptosis and cell cycle alterations. Western blot data indicated that HDACIs and Beclin- 1 knockdown increased the p53 acetylation level. The knockdown of Beclin-1 enhanced the synergistic effect of the combination of vorinostat with sorafenib. CONCLUSION: HDACIs can sensitize HCC cells to sorafenib treatment by regulating the acetylation level of Beclin-1. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Surgical treatment of hepatocellular carcinoma with inferior vena cava tumor thrombus: a new classification for surgical guidance

BACKGROUND: Hepatic resection is the main treatment modality for hepatic tumors. Advances in diagnostic technique, preoperative preparation, surgical technique, and postoperative management increased the success rate. The present study aimed to evaluate hepatectomy and resection of inferior vena cava tumor thrombus (IVCTT) in patients with hepatocellular carcinoma, and the relationship between IVCTT classification and selection of surgical technique. METHODS: We retrospectively reviewed 13 patients with hepatocellular carcinoma who had undergone hepatectomy with IVCTT resection between May 1997 and August 2009. Age, gender, diagnosis, findings of physical examination, results of preoperative laboratory investigations, radiological examination, criteria for resection, postoperative pathological results, incisions, operative technique, intraoperative transfusion, drains, and intraoperative and postoperative complications were evaluated for all patients. RESULTS: Type Ⅰ IVCTT (10 patients) was posterior to the liver and below the diaphragm; type Ⅱ IVCTT (2 patients) was above the diaphragm but still outside the atrium; and type Ⅲ IVCTT (1 patient) was above the diaphragm and in the right atrium. Type Ⅰ was treated by radical hepatectomy and removal of IVCTT with total hepatic vascular exclusion. Type Ⅱ was treated by radical hepatectomy and removal of IVCTT by incision of the diaphragm. Type Ⅲ was treated by hepatectomy and resection of the thrombus from the right atrium under cardiopulmonary bypass. There were no surgical complications and one patient has been survived for 4 years with cancer-free status. The median survival time was 18.2 months, and the 1-and 2-year survival rates were 53.8% and 15.4%, respectively. CONCLUSION: Surgical treatment is safe and feasible for treatment of IVCTT in patients with hepatocellular carcinoma, and surgical resectability can be judged according to the classification of tumor thrombus.

Combined hepatocellular and cholangiocarcinoma originating from the same clone:a pathomolecular evidence-based study

Background:Combined hepatocellular and cholangiocarcinoma(CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC);however,its cellular origin remains unclear.The purpose of this study was to investigate the clinicopathologic features and the clonal relationship between HCC and ICC in 34 patients with CHC.Methods:The clinicopathologic features and prognosis of the 34 CHC patients were compared with those of 29 patients with separated HCC and ICC(5HC).Loss of heterozygosity(LOH) at 10 highly polymorphic microsatellite markers was detected in 16 CHC and 10 SHC tissues for determination of the clonal origin of CHC.Expression of hepatocyte markers[hepatocyte paraffin 1(Hep Par 1) and glypican 3(GPC3)]and cholangiocyte markers[cytokeratin(CK)7 and 19]in tumor tissues was examined by immuno histochemical analysis.Results:In the 16 CHC specimens,the difference in LOH patterns between HCC and ICC was less than 30%,suggesting the same clonal origin of HCC and ICC.Consistent with this finding,immunohistochemical analysis revealed that hepatocyte markers(Hep Par 1 and GPC3) and cholangiocyte markers(CK7 and CK19) were simultaneously expressed in both the HCC and ICC components in 52.9%of CHC specimens,suggesting that the two components shared a similar phenotype with hepatic progenitor cells(HPCs).On the contrary,in all 10 SHC cases,the difference in LOH patterns between the HCC and ICC components was greater than 30%,suggesting different clonal origins of HCC and ICC.Overall survival and disease-free survival were shorter for patients with CHC than for patients with SHC(P < 0.05).Conclusions:Our results suggest that the HCC and ICC components of CHC may originate from the same clone,having the potential for dual-directional differentiation similar to HPCs.CHC tended to exhibit the biological behaviors of both HCC and ICC,which may enhance the infiltrative capacity of tumor cells,leading to poor clinical outcomes for patients with CHC.

Anti-tumor effect of 5-aza-2'-deoxycytidine by inhibiting telomerase activity in hepatocellular carcinoma cells

AIM:To investigate the effect of the demethylating reagent 5-aza-2'-deoxycitidine(DAC) on telomerase activity in hepatocellular carcinoma(HCC) cell lines,SMMC-7721 and HepG2.METHODS:The related gene expression in cell lines was examined by real-time reverse transcription-polymerase chain reaction and Western blotting analysis.The telomerase activity was examined by telomeric repeat amplification protocol-enzyme-linked immunosorbent assay and DNA methylation was determined by methylation-specific polymerase chain reaction.RESULTS:The telomerase activity was significantly reduced in both cell lines treated with DAC,accompanied by downregulation of telomerase reverse transcriptase(hTERT).We also observed the effect of DAC on the methylation status of hTERT promoter and the expression of regulatory genes,such as c-myc,p15,p16,p21,E2F1,and WT1.The methylation status of hTERT promoter could be reversed in SMMC-7721 by DAC,but not in HepG2 cells.However,p16 expression could be reactivated by demethylation of its promoter,and c-Myc expression was repressed in both cell lines.Moreover,DAC could enhance the sensitivity to the chemotherapeutic agents,such as cisplatin,by induction of apoptosis of HCC cells.CONCLUSION:The DAC exerts its anti-tumor effects in HCC cells by inhibiting the telomerase activity.

Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic adenovirus in human hepatocellular carcinoma

AIM: To construct a tumor-selective replication-competent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT). METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice. RESULTS: SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells. CONCLUSION: hTERT promoter-regulated replicativeadenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.

Reduced expression of P120 catenin in cholangiocarcinoma correlated with tumor clinicopathologic parameters

AIM： To investigate the relationship between the expression of P120 and the clinicopathologic parameters in intrahepatic cholangiocarcinoma （ICC）. METHODS： An immunohistochemical study of E-cadherin and P120 catenin was performed on 42 specimens of ICC with a Dako Envision kit. RESULTS： The expression of E-cadherin and P120 was reduced in 27 cases （64.3%） and 31 cases （73.8%）, respectively. Both E-cadherin and P120 expressions were significantly correlated with the tumor histological grade （χ^2 = 9.333, P = 009 and χ^= 11.71, P = 0.003）, TNM stage （χ^= 8.627, P = 0.035 and χ^= 13.123, P = 0.004）, intrahepatic metastasis （χ^= 7.292, P = 0.007 and χ^= 4.657, P = 0.041, respectively） and patients′ survival （χ^= 6.351, P = 0.002 and χ^= 4.023, P = 0.000, respectively）. In addition, the expression of P120 was in concordance with that of E-cadherin （χ^ = 13.797, P = 0.000）, indicating that the expression of P120 may be dependent on that of E-cadherin. Finally, only P120 expression was found to be an independent prognostic factor in Cox regression model （r = 0.088, P = 0.049）. CONCLUSION： Down-regulated expression of E-cadherin and P120 occurs frequently in ICC and contributes to the progression and development of tumor. Both of them may be valuable biologic markers for predicting tumor invasion, metastasis and patients′ survival, but only P120 is an independent prognostic factor for ICC.

Grey zone in the Barcelona Clinic Liver Cancer Classification for hepatocellular carcinoma: Surgeons' perspective

Hepatocellular carcinoma(HCC) is the sixth most common cancer and the third most common cause of cancer-related deaths worldwide. The Barcelona Clinic Liver Cancer(BCLC) classification has been endorsed as the optimal staging system and treatment algorithm for HCC by the European Association for the Study of Liver Disease and the American Association for the Study of Liver Disease. However, in real life, the majority of patients who are not considered ideal candidates based on the BCLC guideline still were performed hepatic resection nowadays, which means many hepatic surgeons all around the world do not follow the BCLC guidelines. The accuracy and application of the BCLC classification has constantly been challenged by many clinicians. From the surgeons' perspectives, we herein put forward some comments on the BCLC classification concerning subjectivity of the assessment criteria, comprehensiveness of the staging definition and accuracy of the therapeutic recommendations. We hope to further discuss with peers and colleagues with the aim to make the BCLC classification more applicable to clinical practice in the future.

Concomitant lung metastasis in patients with advanced hepatocellular carcinoma

AIM:To investigate the clinical features and prognostic factors of advanced hepatocellular carcinoma (HCC)patients presenting with lung metastasis at initial diagnosis. METHODS:Between 2001 and 2010,we recruited 76 consecutive HCC patients initially presenting with lung metastasis,without co-existing metastasis from other sites.These patients were divided into three groups:untreated group(n=22),single treatment group(n= 19),and combined treatment group(n=35). RESULTS:Metastasis of bilateral lung lobes was common and noted in 35 patients(46.1%),and most of patients(59/76,77.6%)presented with multiple lung metastatic nodules.Nineteen patients(25.0%) received single-method treatment,including hepatectomy in 4,transcatheter arterial chemoembolization in 6,radiotherapy in 5,and oral sorafenib in 4.Thirty-five patients(46.1%)received combined treatment modalities.The overall median survival of the all patients was 8.7±0.6 mo;4.1±0.3,6.3±2.5 and 18.6±3.9 mo, respectively in the untreated group,single treatment group and combined treatment group,respectively, with a significant difference(log-rank test,P<0.001). Multivariate analysis revealed that Child-Pugh score, the absence or presence of portal vein tumor thrombus,and treatment modality were three independent prognostic factors affecting survival of patients with advanced HCC and concomitant lung metastasis. CONCLUSION:Combined treatment modalities tend to result in a better survival as compared with the conservative treatment or single treatment modality for HCC patients initially presenting with lung metastasis.

Postoperative adjuvant transcatheter arterial chemoembolization improves the prognosis of patients with huge hepatocellular carcinoma

Background: Surgical resection of huge hepatocellular carcinoma(HCC, ≥ 10 cm) is potentially curative. More adjuvant treatments are needed to reduce relapses in these patients. We evaluated the influence of postoperative adjuvant transcatheter arterial chemoembolization(PA-TACE) on the prognosis of huge HCC. Methods: Data from consecutive patients who underwent curative resection for huge HCC in our center were retrospectively collected. Recurrence-free survival(RFS) and overall survival(OS) were compared between patients who did and did not undergo PA-TACE. Propensity score matching(PSM) was used. Results: Among the 255 enrolled patients, 93 underwent PA-TACE. The clinical outcomes were significantly better in the PA-TACE group than those in the non PA-TACE group(5-year RFS rate: 33.5% vs. 18.0%;5-year OS rate: 47.0% vs. 28.0%, all P<0.001). After PSM, similar results were obtained(5-year RFS rate: 28.8% vs. 17.6%, P<0.001;5-year OS rate: 42.5% vs. 25.0%, P=0.004). PA-TACE decreased the possibility of early recurrence(<2 years, crude cohort: P<0.001, PSM cohort: P<0.001) but not late recurrence( ≥ 2 years, crude cohort: P=0.692, PSM cohort: P=0.325). Multivariable Cox regression analysis suggested that PA-TACE was an independent protective factor prolonging early RFS, RFS and OS. Conclusions: PA-TACE is a safe intervention for huge HCC patients after liver resection and improves outcomes.

Detection of circulating hepatocellular carcinoma cells in peripheral venous blood by reverse transcription-polymerase chain reaction

Objective: To detect circulating hepatocellular carcino-ma by demonstrating hepatocellular carcinoma cells orhepatocyte-associated mRNA in the nuclear cell com-ponent of peripheral blood (PBL).Methods: Peripheral blood (5 ml) samples were ob-tained from 93 patients with hepatocellular carcinoma(HCC) and from 33 control subjects (9 with liver cir-rhosis after hepatitis B,14 with chronic hepatitis B,10with normal liver function). To identify HCC cells inperipheral blood, liver-specific human alpha-fetopro-tein (AFP) mRNA was amplified from total RNA ex-tracted from whole blood by reverse transcription-polymerase chain reaction.Results: AFPmRNA was detected in 50 blood samplesfrom the HCC patients (50/93, 53.8%). In contrast,there were no clinical control patients whose samplesshowed detectable AFPmRNA in PBL. The presence ofAFPmRNA in blood seemed to be correlated with thestage (by TNM classification) of HCC, the serum AFPvalue, and the presence of intrahepatic metastasis,portal vein thrombosis, tumor diameter and/or distantmetastasis. In addition, AFPmRNA was detected in theblood of 21 patients with metastasis at extrahepaticorgans (100%) in contrast to 29 (40.3%)of 72 pa-tients without metastasis.Conclusion: The presence of AFPmRNA in peripheralblood may be an indicator of malignant hepatocytes,which might predict hematogenous spreading metasta-sis of tumor cells in patients with HCC.

Predictors and clinical outcomes for spontaneous rupture of hepatocellular carcinoma

AIM:To determine the risk factors for hepatocellular carcinoma(HCC) rupture,and report the management and long-term survival results of patients with spontaneous rupture of HCC.METHODS:Among 4209 patients with HCC who were diagnosed at Eastern Hepatobiliary Surgery Hospital from April 2002 to November 2006,200(4.8%) patients with ruptured HCC(case group) were studied retrospectively in term of their clinical characteristics and prognostic factors.The one-stage therapeutic approach to manage ruptured HCC consisted of initial management by conservative treatment,transarterial embolization(TACE) or hepatic resection.Results of various treatments in the case group were evaluated and compared with the control group(202 patients) without ruptured HCC during the same study period.Continuous data were expressed as mean ± SD or me-dian(range) where appropriate and compared using the unpaired t test.Categorical variables were compared using the Chi-square test with Yates correction or the Fisher exact test where appropriate.The overall survival rate in each group was determined using the Kaplan-Meier method and a log-rank test.RESULTS:Compared with the control group,more patients in the case group had underlying diseases of hypertension(7.5% vs 3.0%,P =0.041) and liver cirrhosis(87.5% vs 56.4%,P < 0.001),tumor size >5 cm(83.0% vs 57.4%,P < 0.001),tumor protrusion from the liver surface(66.0% vs 44.6%,P < 0.001),vascular thrombus(30.5% vs 8.9%,P < 0.001) and extrahepatic invasion(36.5% vs 12.4%,P < 0.001).On multivariate logistic regression analysis,underlying diseases of hypertension(P = 0.002) and liver cirrhosis(P < 0.001),tumor size > 5 cm(P < 0.001),vascular thrombus(P = 0.002) and extrahepatic invasion(P < 0.001) were predictive for spontaneous rupture of HCC.Among the 200 patients with spontaneous rupture of HCC,105 patients underwent hepatic resection,33 received TACE,and 62 were managed with conservative treatment.The median survival time(MST) of all patients with spontaneous rupture of HCC was 6 mo(range,1-72 mo),and the overall survival at 1,3 and 5 years were 32.5%,10% and 4%,respectively.The MST was 12 mo(range,1-72 mo) in the surgical group,4 mo(range,1-30 mo) in the TACE group and 1 mo(range,1-19 mo) in the conservative group.Ninety-eight patients in the control group underwent hepatic resection,and the MST and median diseasefree survival time were 46 mo(range,6-93 mo) and 23 mo(range,3-39 mo) respectively,which were much longer than that of patients with spontaneous rupture of HCC undergoing hepatic resection(P < 0.001).The 1-,3-,and 5-year overall survival rates and the 1-,3-and 5-year disease-free survival rates in patients with ruptured HCC undergoing hepatectomy were 57.1%,19.0% and 7.6%,27.6%,14.3% and 3.8%,respectively,compared with those of 77.1%,59.8% and 41.2%,57.1%,40.6% and 32.9% in 98 patients with-CONCLUSION:Prolonged survival can be achieved in selected patients undergoing one-stage hepatectomy,although the survival results were inferior to those of the patients without ruptured HCC.

A special growth manner of intrahepatic biliary cystadenoma

We report a case of a 56-year-old woman with intrahepatic biliary cystadenoma(IBC)accompanying a tumor embolus in the extrahepatic bile duct,who was admitted to our department on October 13,2008.Imaging showed an asymmetry dilation of the biliary tree,different bile signals in the biliary tree,a multiloculated lesion and an extrahepatic bile duct lesion with internal septation.A regular left hemihepatectomy en bloc was performed with resection of the entire tumor,during which a tumor embolus protruding into the extrahepatic bile duct and originating from biliary duct of segment 4 was revealed.Microscopically,the multiloculated tumor was confirmed to be a biliary cystadenoma with an epithelial lining composed of biliary-type cuboidal cells and surrounded by an ovarian-like stroma.An aggressive en bloc resection was recommended for the multiloculated lesion.Imaging workup,clinicians and surgeons need to be aware of this different presentation.

Treatment of liver metastases from uveal melanoma: a retrospective single-center analysis

BACKGROUND:Metastatic liver melanoma is a rare event in the Chinese population with extremely poor prognosis.Any treatment that controls a metastatic hepatic lesion potentially prolongs survival.This study aimed to evaluate the survival of patients with isolated liver metastases from uveal melanoma treated with partial hepatectomy or non-surgical management and to find the best therapeutic modality for these patients.METHODS:From January 1996 to September 2008,eight patients with liver metastases secondary to uveal melanoma were admitted to our hospital.Five patients underwent partial hepatectomy and 3 received other treatments(TACE,RFA,PEI).Their medical records were reviewed and overall survival was analyzed.RESULTS:The patients comprised 3 men and 5 women,with a median age of 44 years.Six patients presented with liver metastases at the time the primary tumor was diagnosed.The interval from the diagnosis of uveal melanoma to liver metastasis in the remaining 2 patients was 9.5 and 32.5 months,respectively.The median survival after the treatment of liver metastasis was 11.5 and 7.5 months in the surgical and nonsurgical groups,respectively.There was no procedure-related mortality in the whole study cohort.CONCLUSIONS:Partial hepatectomy or other therapies were safe and feasible for isolated liver metastases from uveal mela-noma.Aggressive treatment with multidisciplinary modalities may result in prolonged survival.

Impact of delayed time from diagnosis to treatment on the stage of hepatocellular carcinoma

To the Editor:We read with interest of the article by Dr.Lim et al.[1].The authors concluded that a delay of≥3 months from diagnosis to treatment in patients with Barcelona clinic liver cancer(BCLC)0-A st age hepatocellular carcinoma(HCC)does not affect long-term outcomes after curative resection compared with those with a delay of<3 months.Undoubtedly,this is a challenging viewpoint,which is contrary to traditional concept– the sooner the tumor removal,the better the oncologic prognosis.Herein,we would like to raise the following comments.

Nested RT-PCR in detection of blood AFPmRNA in animal model of human hepatocellular carcinoma

OBJECTIVES: To detect blood AFPmRNA in the nude mice bearing with human hepatocellular carcinoma (HCC) by using nested reverse transcriptase polymerase chain reaction (nested RT-PCR), and assess its significance in HCC distant metastasis. METHOD: We detected 20 blood samples from the nude mice bearing with human HCC by nested RT-PCR to find out AFPmRNA. RESULT: AFPmRNA was detected in 6 blood samples from the nude mice hearing with human HCC (30. 0%), in which 4 mice developed distant metastasis. CONCLUSION: AFPmRNA may be used as an efficient and sensitive marker to detect blood spread of HCC cells. It can predict the occurrence of HCC distant metastasis.

Changes of AFPmRNA in blood after percutaneous ethanol injection treatment of hepatocellular carcinoma

Objective: To study the effects of percutaneous etha- nol injection (PEI) in treatment of hepatocellular carcinoma (HCC). Methods: Blood samples were taken from 9 HCC pa- tients and detected by nested RT-PCR to find out AFPmRNA after PEI treatment 3-5 times within 2 weeks. Results: Three (44.44%) of 4 patients with AFPmR- NA positive turned to be negative after PEI treatment and 1 with AFPmRNA positive (11.11%) lasted within 2 weeks. Conclusion: PEI may diminish the possibility of dis- tant metastasis of HCC.