Efficacy and safety of transhepatic arterial chemoembolization with drug-loaded microspheres in unresectable primary liver cancer

BACKGROUND Transhepatic arterial chemoembolization(TACE),as a local treatment,has been widely used in the treatment of unresectable liver cancer.The introduction of drug carrier microspheres has brought new hope for the therapeutic effect of TACE.Microspheres can realize the slow release and directional delivery of drugs,reduce systemic toxicity and improve local curative effect.AIM To compare the effectiveness of traditional transcatheter arterial chemoembolization against microsphere-assisted transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma that is incurable.METHODS We searched the PubMed,Embase,Cochrane Library,and CNKI databases for clinical trials of drug-luting beads TACE(DEB-TACE)vs conventional TACE(cTACE)for the treatment of unresectable liver cancer.We screened references based on inclusion and exclusion criteria and then selected valid data for meta-analysis using RevMan 53 software.The complete response(CR)rate,partial response(PR)rate,postoperative stable disease(SD)rate,and 6-month and 12-month survival rates were compared.RESULTS A total of 12 articles were included,including 1177 patients,519 of whom received DEB-TACE and 658 of whom received cTACE.The CR rate in the DEB-TACE group was much greater than that in the cTACE group[relative risk(RR)=1.42,95%CI:1.18-1.72,P=0.0002].The 12-month survival rate significantly increased(RR=1.09;95%CI:1.01-1.17,P=0.03);the PR rate(RR=1.13;95%CI:0.97-1.30,P=0.12);the SD rate(RR=0.82;95%CI:0.64-1.05,P=0.12);and the 6-month survival rate(RR=1.05;95%CI:1.00-1.10,P=0.07).There was no significant difference(P<0.05).CONCLUSION Compared with those of iodized oil TACE,the drug-loaded microspheres tended to have therapeutic advantages.

Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer

As a highly aggressive tumor,the pathophysiological mechanism of primary liver cancer has attracted much attention.In recent years,factors such as ferroptosis regulation,lipid peroxidation and metabolic abnormalities have emerged in the study of liver cancer,providing a new perspective for understanding the development of liver cancer.Ferroptosis regulation,lipid peroxidation and metabolic abnormalities play important roles in the occurrence and development of liver cancer.The regulation of ferroptosis is involved in apoptosis and necrosis,affecting cell survival and death.Lipid peroxidation promotes oxidative damage and promotes the invasion of liver cancer cells.Metabolic abnormalities,especially the disorders of glucose and lipid metabolism,directly affect the proliferation and growth of liver cancer cells.Studies of ferroptosis regulation and lipid peroxidation may help to discover new therapeutic targets and improve therapeutic outcomes.The understanding of metabolic abnormalities can provide new ideas for the prevention of liver cancer,and reduce the risk of disease by adjusting the metabolic process.This review focuses on the key roles of ferroptosis regulation,lipid peroxidation and metabolic abnormalities in this process.

Nomogram predicting the prognosis of primary liver cancer after radiofrequency ablation combined with transcatheter arterial chemoembolization

BACKGROUND The incidence and mortality rates of primary hepatocellular carcinoma(HCC)are high,and the conventional treatment is radiofrequency ablation(RFA)with transcatheter arterial chemoembolization(TACE);however,the 3-year survival rate is still low.Further,there are no visual methods to effectively predict their prognosis.AIM To explore the factors influencing the prognosis of HCC after RFA and TACE and develop a nomogram prediction model.METHODS Clinical and follow-up information of 150 patients with HCC treated using RFA and TACE in the Hangzhou Linping Hospital of Traditional Chinese Medicine from May 2020 to December 2022 was retrospectively collected and recorded.We examined their prognostic factors using multivariate logistic regression and created a nomogram prognosis prediction model using the R software(version 4.1.2).Internal verification was performed using the bootstrapping technique.The prognostic efficacy of the nomogram prediction model was evaluated using the concordance index(CI),calibration curve,and receiver operating characteristic RESULTS Of the 150 patients treated with RFA and TACE,92(61.33%)developed recurrence and metastasis.Logistic regression analysis identified six variables,and a predictive model was created.The internal validation results of the model showed a CI of 0.882.The correction curve trend of the prognosis prediction model was always near the diagonal,and the mean absolute error before and after internal validation was 0.021.The area under the curve of the prediction model after internal verification was 0.882[95%confidence interval(95%CI):0.820-0.945],with a specificity of 0.828 and sensitivity of 0.656.According to the Hosmer-Lemeshow test,χ^(2)=3.552 and P=0.895.The predictive model demonstrated a satisfactory calibration,and the decision curve analysis demonstrated its clinical applicability.CONCLUSION The prognosis of patients with HCC after RFA and TACE is affected by several factors.The developed prediction model based on the influencing parameters shows a good prognosis predictive efficacy.

Correction to“Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence of primary liver cancer”

Correction to“Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer”in World J Gastrointest Oncol 2024;16:2335-2349,published by Shu YJ,Lao B,and Qiu YY.In this article,we added the correct citations of images.

Clinical efficacy of Gamma Knife® combined with transarterial chemoembolization and immunotherapy in the treatment of primary liver cancer

BACKGROUND This study was designed to investigate the clinical efficacy and safety of Gamma Knife®combined with transarterial chemoembolization(TACE)and immunotherapy in the treatment of primary liver cancer.AIM To investigate the clinical efficacy and safety of Gamma Knife®combined with TACE and immune-targeted therapy in the treatment of primary liver cancer.METHODS Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively collected.All patients underwent Gamma Knife®treatment combined with TACE and immunotherapy.The clinical efficacy,changes in liver function,overall survival(OS),and progression-free survival(PFS)of patients with different treatment responses were evaluated,and adverse reactions were recorded.RESULTS The last follow-up for this study was conducted on October 31,2023.Clinical evaluation of the 51 patients with primary liver cancer revealed a partial response(PR)in 27 patients,accounting for 52.94%(27/51);stable disease(SD)in 16 patients,accounting for 31.37%(16/51);and progressive disease(PD)in 8 patients,accounting for 15.69%(8/51).The objective response rate was 52.94%,and the disease control rate was 84.31%.Alanine aminotransferase,aspartate aminotransferase,lactate dehydrogenase,and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment(all P=0.000).The median OS was 26 months[95%confidence interval(95%CI):19.946-32.054]in the PR group and 19 months(95%CI:14.156-23.125)in the SD+PD group,with a statistically significant difference(P=0.015).The median PFS was 20 months(95%CI:18.441-34.559)in the PR group and 12 months(95%CI:8.745-13.425)in the SD+PD group,with a statistically significant difference(P=0.002).Common adverse reactions during treatment included nausea and vomiting(39.22%),thrombocytopenia(27.45%),and leukopenia(25.49%),with no treatment-related deaths reported.CONCLUSION Gamma Knife®combined with TACE and immune-targeted therapy is safe and effective in the treatment of primary liver cancer and has a good effect on improving the clinical benefit rate and liver function of patients.

Analysis of alkaline phosphatase and γ-glutamyltransferase after radiofrequency ablation of primary liver cancer: A retrospective study

BACKGROUND Changes in alkaline phosphatase(ALP)andγ-glutamyltransferase(GGT)levels in patients with primary liver cancer(PLC)after radiofrequency ablation(RFA).Hepatocellular carcinoma is a malignant tumor with high incidence worldwide.As a common local treatment,RFA has attracted much attention for its efficacy and influence on liver function.AIM To investigate the effect of serum ALP and GGT levels on the prognosis of patients with PLC treated by RFA.METHODS The preoperative clinical data of 165 patients who were pathologically or clinically diagnosed with PLC and who received RFA in our hospital between October 2018 and June 2023 were collected.The chi-square test was used to compare the data between groups.The Kaplan-Meier method and Cox regression were used to analyze the associ-ations between serum ALP and GGT levels and overall survival,progression-free survival(PFS)and clinical characteristics of patients before treatment.RESULTS The 1-year survival rates of patients with normal(≤135 U/L)and abnormal(>135 U/L)serum ALP before treatment were 91%and 79%,respectively;the 2-year survival rates were 90%and 68%,respectively;and the 5-year survival rates were 35%and 18%,respectively.The difference between the two groups was statistically significant(P=0.01).Before treatment,the 1-year survival rates of patients with normal serum GGT levels(≤45 U/L)and abnormal serum GGT levels(>45 U/L)were 95%and 87%,the 2-year survival rates were 85%and 71%,and the 5-year survival rates were 37%and 21%,respectively.The difference between the two groups was statist-ically significant(P<0.001).Serum ALP[hazard ratio(HR)=1.766,95%confidence interval(95%CI):1.068-2.921,P=0.027]and GGT(HR=2.312,95%CI:1.367-3.912,P=0.002)is closely related to the overall survival of PLC patients after RF ablation and is an independent prognostic factor.The 1-year PFS rates were 72%and 50%,the 2-year PFS rates were 52%and 21%,and the 5-year PFS rates were 14%and 3%,respectively.The difference between the two groups was statistically significant(P<0001).The 1-year PFS rates were 81%and 56%in patients with normal and abnormal serum GGT levels before treatment,respectively;the 2-year PFS rates were 62%and 35%,respectively;and the 5-year PFS rates were 18%and 7%,respectively,with statistical significance between the two groups(P<0.001).The serum ALP concentration(HR=1.653,95%CI:1.001-2.729,P=0.049)and GGT(HR=1.949,95%CI:1.296-2.930,P=0.001)was closely associated with PFS after RFA in patients with PLC.The proportion of male patients with abnormal ALP levels is high,the Child-Pugh grade of liver function is poor,and the incidence of ascites is high.Among GGT-abnormal patients,the Child-Pugh grade of liver function was poor,the tumor stage was late,the proportion of patients with tumors≥5 cm was high,and the incidence of hepatic encephalopathy was high.CONCLUSION Serum ALP and GGT levels before treatment can be used to predict the prognosis of patients with PLC after RFA,and they have certain guiding significance for the long-term survival of patients with PLC after radiofrequency therapy.

Efficacy and safety of B-ultrasound-guided radiofrequency ablation in the treatment of primary liver cancer: Systematic review and metaanalysis

BACKGROUND Primary liver cancer is one of the most lethal malignancies in the world.Tradi-tional treatment methods have limitations in terms of efficacy and safety.Ra-diofrequency ablation(RFA)guided by B-ultrasound,as a minimally invasive treatment,has attracted increasing attention in the treatment of primary liver cancer in recent years.AIM To study the efficacy and safety of RFA were compared with those of traditional surgery(TS)for treating small liver cancer.METHODS At least 2 people were required to search domestic and foreign public databases,including foreign databases such as EMBASE,PubMed and the Cochrane Library,and Chinese databases such as the China National Knowledge Infrastructure database,China Biomedical Literature database,Wanfang database and VIP database.Controlled trials of RFA vs conventional surgery for small liver cancer were retrieved from January 2008 to January 2023.They were screened and eva-luated according to the quality evaluation criteria in the Cochrane Handbook of Systematic Reviews.The meta-analysis was performed using RevMan 5.3 soft-ware.RESULTS A total of 10 studies were included in this study,including 1503 patients in the RFA group and 1657 patients in the surgery group.The results of the meta-ana-lysis showed that there was no significant difference in 1-year overall survival between the two groups(P>0.05),while the 3-year and 5-year overall survival rates and 1-year,3-year and 5-year tumor-free survival rates in the surgery group were greater than those in the RFA group(P<0.05).In terms of complications,the incidence of complications in the RFA group was lower than that in the surgery group(P<0.05).CONCLUSION In terms of long-term survival,TS is better than RFA for small liver cancer patients.However,RFA has fewer complications and is safer.

Effect of CT-Guided Microwave Ablation Combined with TACE on Liver Function and Survival of Patients with Primary Liver Cancer

Objective:To explore the effect of transarterial chemoembolization(TACE)+CT-guided microwave ablation(MWA)on treating patients with primary liver cancer.Methods:78 primary liver cancer cases were enrolled and divided into groups according to their assigned surgical plans.The control group was treated with TACE alone,and the observation group was treated with TACE+CT-guided MWA.The efficacy of the treatment and the liver function indicators and follow-up results of the patients of the two groups were compared.Results:The efficacy of the treatment received by the observation group was higher than that of the control group.Besides,the patients in the observation group exhibited better improvement in liver function indicators after 3 months of treatment.Furthermore,the survival rates of 1 and 2 years after surgery of the observation group were all higher than those of the control group(P<0.05).Conclusion:TACE combined with CT-guided MWA is more effective in treating primary liver cancer compared to TACE alone.Besides,it resulted in better improvement of liver function and long-term survival rate.Therefore,this treatment regime should be popularized.

Primarily screening and analyzing ESTs differentially expressed in rats' primary liver cancer

Objective： To screen and analyze key express sequence tags （ESTs） which were differentially displayed in every period of SD rats＇ primary hepatic carcinoma and reveal the molecular mechanism of carcinogenesis. Methods： Using diethylnitrosamine （DENA） as a cancerigenic agent, animal models with different phases of primary hepatic cancer were constructed in SD rats. Rats were respectively sacrificed at d 14, d 28, d 56, d 77, d 105 and d 112 after the rats received DENA by gavage, then the livers were harvested. One part of the livers was classified according to their pathological changes, while the other was reserved for molecular mechanism studies on hepatocarcinogenesis. The differentially expressed genes were isolated from both normal and morbid tissues by mRNA differential display technique （DDRT-PCR）. After the fragments were sequenced, bioinformatics were .used to analyze the results. Results： Twelve differentially expressed cDNA fragments were obtained. Nine fragments had the homology with known cDNA clones, especially EST-7 was similar to BN/SsNHsdMCW mitochondrion gene and the identity was 100% which suggested EST-7 may be the part of BN/SsNHsdMCW mitochondrion gene. In contrast, other three fragments （EST-1, EST-3 and EST-5） had extremely low identity to any genes registered in GENBANK databases. Conclusions： BN/SsNHsdMCW mitochondrion gene was expressed in different periods of hepatocarcinogenesis. Moreover, EST-I, EST-3 and EST-5 were suggested to contribute to the development of rat hepatocarcinogenesis, and thus may be candidates of new targets of oncogenes or cancer suppressor genes.

Comprehensive treatment for primary liver cancer

IntroductionPrimary liver cancer (PLC) is one of the mostcommon malignancies in China. Since the1990s, it has been the first leading cause of cancerdeath in the rural areas versus the 2nd in the urbanareas in this country. 45% of all the newly en-countered cases in the world each year are from themainland of China, and the situation is extremelyworsened in its high risk southeast coastal area.Liver resection is chosen as an optimal treatmentfor liver cancer, yet the low resectability and highpostoperative recurrence prevent the long-term sur-vival of patients. Therefore, proper comprehensivetreatment of PLC for the improvement of the overalltherapeutic efficacy has been the focus of clinicalpractice and research. In comparison with single treatment, compre-

A race to uncover a panoramic view of primary liver cancer

Introduction Primary liver cancer, the second most common cause of cancer related death worldwide, presents ethnic, etiological, sex, and geographical diversity2 （Figure 1A）. At the histological level, liver cancer includes two major types： hepatocellular carcinoma （HCC, about 80%） and cholangiocarcinoma （CCA, about 15%）. Many etiological factors contribute to HCC development, such as hepatitis B virus （HBV）, hepatitis C virus （HCV）, aflatoxin B1 （AFB1）, alcohol, and metabolic diseases3. By contrast, the major risk factors for CCA are liver flukes （Opisthorchis viverrini and Clonorchis sinensis） and primary sclerosing cholangitis4,

Current status of yttrium-90 microspheres radioembolization in primary and metastatic liver cancer

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.

HIGH DOSE INTRA-ARTERIAL HEPATIC INFUSIONAL CHEMOTHERAPY WITH DRUG FILTRATION (HAI-F) FOR PRIMARY LIVER CANCER(A PRELIMINARY REPORT)

Fifteen patients with unresectable hepatocellular carcinoma were treated with unresectable hepatocellular carcinoma were treated with high dose MMC or ADR via hepatic artery with drug filtration in our hospital from April to December 1988. Among them, 11 cases (73%) had symptoms relief, 3 cases (20%) tumor minimal remission and AFP decreased in 4 cases (33%). One case dide of hep'atoma 8 months after HAI-F and another case was followed up only 2 months after treatment, the remaining 13 cases are alive for 5 to 10 months after HAI-F. The reasons of unsatisfactory results were analyzed and possible ways of improvement were suggested.

EXPERIMENTAL PRIMARY LIVER CANCER IN TREE SHREWS EXPOSED TO HUMAN HEPATITIS B VIRUS AND AFLATOXIN B_(1)

On the basis of the successful establishment of an animal model in tree shrews experimentally in fected with human hepatitis B virus (HHBV), a study on the hepatocarcinogenic effects of HHBV and aflatoxin B1 (AFB1) by using this animal model was conducted through a lifelong experiment. Among 41 tree shrews exposed to AFB1, 17 were experimentally infected by HHBV and 24 were uninfected. After 158 weeks, significant difference of primary liver cancer (PLC) incidence was present between the HHBV infected (52.94%) and uninfected (12.5%) groups (p<0.05). No difference was found between these two groups in the amount of AFB4 ingestion. Moreover, 1/9 of the tree shrews infected only by HHBV but not exposed to AFB4 developed PLC. No PLC was found in 6 tree shrews that had neither been infected with HHBV nor been exposed to AFB4. These results suggest the possible etiologic relationship between HHBV infection and PLC, as well as the synergetic effects of HHBV and AFB4 during PLC development.

Changed clinical aspects of primary liver cancer in China during the past 30 years

BACKGROUND: Primary liver cancer (PLC) is one of the most frequently seen tumors in China. Thirty years ago, patients with PLC were often detected at relatively late stage, with a palpable mass or marked clinical symptoms and poor prognosis. In the past 30 years, the diagnosis and treatment of PLC have been greatly improved with better prognosis. METHODS: In order to study the changes of PLC during the 30 years, the clinical data of 3250 patients with PLC from 10 medical institutions of China were collected, ana- lyzed , and compared with those of 3254 PLC patients be- fore the 30 years. RESULTS: In the 3250 patients aged 1-80 years, with an average age of 49.1 years, the male to female ratio (2.3:1) was lower than that before the 30 years. 73.5% of the 3250 patients sought medical advice within 3 months after the onset of the disease in contrast to 63.8% before the 30 years. Compared with those patients before the 30 years the symptoms and signs were alleviated generally. The HBsAg positive rate was 81.0%, but the HCV-Ab positive rate was 13.2%. The AFP level in 75% of patients was elevated, but in the remaining 25% was normal. 1912 patients (58.8%) were confirmed pathologically. Among them 1755 patients (91.8%) had hepatocellular carcinoma. The overall resec- tion rate was 46.3%. Those who had early, middle, late stage carcinoma accounted for 29.9%, 51.5%, and 18.6%respectively in contrast to 0.4%, 47.0%, and 52.6% repor- ted before the 30 years. The 1-, 3-, 5-year survival rates of the patients were 66.1%, 39.7%, and 32.5% respectively, whereas 93.5%, 70.1%, and 59.1% for the early stage pa- tients, and 65.3%, 30.5%, and 23.5% for the middle stage patients. The half and 1-year survival rates of the late stage patients were 52.5%, and 14.7%, respectively. CONCLUSION: Comparison with the clinical data before and after the 30 years show that PLC can be diagnosed ear- ly. More PLC patients tend to undergo resection while re- ceiving a better conservative treatment, which ensures a prognosis.

Incidence and mortality of primary liver cancer in England and Wales: Changing patterns and ethnic variations

AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales.

Impact of Operative and Peri-operative Factors on the Long-term Prognosis of Primary Liver Cancer Patients Undergoing Hepatectomy

This study examined the impact of the operative and peri-operative factors on the long-term prognosis of patients with primary liver cancer undergoing hepatectomy. A total of 222 patients with primary liver cancer who underwent hepatectomy were followed up from January 1986 to December 2010 at Chinese PLA General Hospital. The post-operative complication rate was 14.0% for all cases, 13.7% for hepatocellular carcinoma（HCC）, 10.0% for cholangiocarcinoma. The 1-, 3-, 5- and 10-year overall survival rates in patients with primary liver cancer after resection were 76.6%, 57.6%, 41.4%, and 21.0%. The survival rates were significantly higher in the HCC group than in the cholangiocarcinoma group（P=0.000）, in the non-anatomical resection group than in the anatomical resection group（P=0.005）, in the female group than in the male group（P=0.002）, in patients receiving no blood transfusion than in those who were given intra-operative blood transfusion（P=0.000）, in patients whose intra-operative blood loss was less than 400 m L than in those who intra-operatively lost more than 400 m L（P=0.000）. No significant difference was found in the survival rate between the HBs Ag-positive group and the HBs Ag-negative group（P=0.532）. Our study showed that anatomical resection, blood loss and blood transfusion were predictors of poor survival after hepatectomy for primary liver cancer patients, and concomitant hepatitis B virus infection bore no relation with the post-resection survival.

Factors related to pleural effusion following hepatectomy for primary liver cancer

BACKGROUND: Pleural effusion frequently complicates hepatectomy and multiple factors contribute to its development following hepatectomy for primary liver cancer. The purpose of this study was to evaluate these factors. METHODS: From March 2003 to May 2005, 228 consecutive patients with primary liver cancer underwent hepatectomy in our department were evaluated retrospectively to identify factors related to postoperative pleural effusion. RESULTS: Among the 228 patients, postoperative pleural effusions arose in 58 (25.4%). Univariate analysis showed significant differences in postoperative ascites, subphrenic collection, Pringle manoeuvre length, drainage amount on postoperative day 1, albumin level on postoperative day 7, alanine aminotransferase (ALT) level on postoperative days I and 3, prealbumin level on postoperative days 3 and 7, and tumor size (P<0.05). Ordinal regression analysis revealed that subphrenic collection, drainage on postoperative day I and ALT plus prealbumin on postoperative days I and 3 were statistically significantly related to postoperative pleural effusion (P<0.05). CONCLUSION: Subphrenic collection and operative injury to the liver appeared to be significantly related to pleural effusion after hepatectomy for primary liver cancer.

Micrometastasis in surrounding liver and the minimal length of resection margin of primary liver cancer

AIM： To describe the distribution of micrometastases in the surrounding liver of patients with primary liver cancer （PLC）, and to describe the minimal length of resection margin （RM） for hepatectomy. METHODS： From November 2001 to March 2003, 120 histologically verfied PLC patients without macroscopic tumor thrombi or macrosatellites or extrahepatic metastases underwent curative hepatectomy. Six hundreds and twenty-nine routine pathological sections from these patients were re-examined retrospectively by light microscopy. In the prospective study, curative hepatectomy was performed from November 2001 to March 2003 for 76 histologically verfied PLC patients without definite macroscopic tumor thrombi or macrosatellites or extrahepatic metastases in preoperative imaging. Six hundreds and forty-five pathological sections from these patients were examined by light microscopy. The resected liver specimens were minutely examined to measure the resection margin and to detect the number of daughter tumor nodules, dominant lesions, and macroscopic tumor thrombi inside the lumens of the major venous system. The paraffin sections were microscopically examined to detect the microsatellites, microscopic tumor thrombi, fibrosis tumor capsules, as well as capsule invasion and the distance of histological spread of the micrometastases. RESULTS： In the retrospective study, 70 micrometastases were found in surrounding liver in 26 of the 120 cases （21.7%）. The farthest distance of histological micrometastasis was 3.5 mm, 5.3 mm and 6.0 mm in 95%, 99% and 100% cases, respectively. Macroscopic tumor thrornbi or rnacrosatellites were observed in 18 of 76 cases, and 149 rnicrometastases were found in the surrounding live in 25 （43.1%） of 58 cases with no macroscopic tumor thrombi. The farthest distance of histological micrometastasis was 4.5 mm, 5.5 mm and 6.0 mm in 95%, 99% and 100% cases, respectively. Two hundred and sixty-seven rnicrometastases were found in surrounding liver in 14 （77.8%） out of 18 cases with macroscopic tumor thrombi or macrosatellites. The farthest distance of histological micrometastasis was 18.5 mm, 18.5 mm and 19.0 mm in 95%, 99% and 100% cases, respectively. CONCLUSION： The required minimal length of RM is 5.5 mm and 6 mm respectively to achieve 99% and 100% rnicrometastasis clearance in surrounding liver of PLC patients without macroscopic tumor thrornbi or rnacrosatellites, and should be greater than 18.5 mm to obtain 99% rnicrometastasis clearance in surrounding liver of patients with macroscopic tumor thrornbi or rnacrosatellites.

Practice guidelines for the pathological diagnosis of primary liver cancer: 2015 update

In 2010, a panel of Chinese pathologists reported the first expert consensus for the pathological diagnosis of primary liver cancers to address the many contradictions and inconsistencies in the pathological characteristics and diagnostic criteria for PLC. Since then considerable clinicopathological studies have been conducted globally, prompting us to update the practice guidelines for the pathological diagnosis of PLC. In April 18, 2014, a Guideline Committee consisting of 40 specialists from seven Chinese Societies(including Chinese Society of Liver Cancer, Chinese Anti-Cancer Association; Liver Cancer Study Group, Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Pathology, Chinese Anti-Cancer Association; Digestive Disease Group, Chinese Society of Pathology, Chinese Medical Association; Chinese Society of Surgery, Chinese Medical Association; Chinese Society of Clinical Oncology, Chinese Anti-Cancer Association; Pathological Group of Hepatobiliary Tumor and Liver Transplantation, Chinese Society of Pathology, Chinese Medical Association) was created for the formulation of the first guidelines for the standardization of the pathological diagnosis of PLC, mainly focusing on the following topics: gross specimen sampling, concepts and diagnostic criteria of small hepatocellular carcinoma(SHCC), microvascular invasion(MVI), satellite nodules,and immunohistochemical and molecular diagnosis. The present updated guidelines are reflective of current clinicopathological studies, and include a novel 7-point baseline sampling protocol, which stipulate that at least four tissue specimens should be sampled at the junction of the tumor and adjacent liver tissues in a 1:1 ratio at the 12, 3, 6 and 9 o'clock reference positions. For the purposes of molecular pathological examination, at least one specimen should be sampled at the intratumoral zone, but more specimens should be sampled for tumors harboring different textures or colors. Specimens should be sampled at both adjacent and distant peritumoral liver tissues or the tumor margin in order to observe MVI, satellite nodules and dysplastic foci/nodules distributed throughout the background liver tissues. Complete sampling of whole SHCC ≤ 3 cm should be performed to assess its biological behavior, and in clinical practice, therapeutic borders should be also preserved, even in SHCC. The diagnostic criteria of MVI and satellite nodules, immunohistochemical panels, as well as molecular diagnostic principles, such as clonal typing, for recurrent HCC and multinodule HCC were also proposed and recommended. The standardized process of pathological examination is aimed at ensuring the accuracy of pathological PLC diagnoses as well as providing a valuable frame of reference for the clinical assessment of tumor invasive potential, the risk of postoperative recurrence, long-term survival, and the development of individualized treatment regimens. The updated guidelines could ensure the accuracy of pathological diagnoses of PLC, and provide a valuable frame of reference for its clinical assessment.