Combined hepatocellular cholangiocarcinoma: A clinicopathological update

Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling prognosis.The diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists alike.The diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored recently.With a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare disease.In this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.

Pathologic complete response to conversion therapy in hepatocellular carcinoma using patient-derived organoids:A case report

BACKGROUND For primary liver cancer,the key to conversion therapy depends on the effectiveness of drug treatment.Patient-derived tumor organoids have been demonstrated to improve the efficacy of conversion therapy by identifying individualtargeted effective drugs,but their clinical effects in liver cancer remain unknown.CASE SUMMARY We described a patient with hepatocellular carcinoma(HCC)who achieved pathologic complete response(pCR)to conversion therapy guided by the patientderived organoid(PDO)drug sensitivity testing.Despite insufficiency of the remaining liver volume after hepatectomy,the patient obtained tumor reduction after treatment with the PDO-sensitive drugs and successfully underwent radical surgical resection.Postoperatively,pCR was observed.CONCLUSION PDOs contributes to screening sensitive drugs for HCC patients to realize the personalized treatment and improve the conversion therapy efficacy.

Clinicopathological features and surgical outcome of patients with fibrolamellar hepatocellular carcinoma(experience with 22 patients over a 15-year period)

AIM To evaluate the clinicopathological features and the surgical outcomes of patients with fibrolamellar hepato-cellular carcinoma(FL-HCC)over a 15-year period. METHODS This is a retrospective study including 22 patients with a pathologic diagnosis of FL-HCC who underwent hepatectomy over a 15-year period. Tumor characteristics,survival and recurrence were evaluated. RESULTS There were 11 male and 11 female with a median age of 29 years(range from 21 to 58 years). Two(9%)patients had hepatitis C viral infection and only 2(9%)patients had alpha-fetoprotein level > 200 ng/m L. The median size of the tumors was 12 cm(range from 5-20 cm). Vascular invasion was detected in 5(23%)patients. Four(18%)patients had lymph node metastases. The median follow up period was 42 mo and the 5-year survival was 65%. Five(23%)patients had a recurrent disease,4 of them had a second surgery with 36 mo median time interval. Vascular invasion is the only significant negative prognostic factor CONCLUSION FL-HCC has a favorable prognosis than common HCC and should be suspected in young patients with non cirrhotic liver. Aggressive surgical resection should be done for all patients. Repeated hepatectomy should be considered for these patients as it has a relatively indolent course.

Contrast-enhanced ultrasound for predicting differentiation degree of hepatocellular carcinoma

Objective To explore the value of contrast-enhanced ultrasound(CEUS)for predicting differentiation degree of hepatocellular carcinoma(HCC).Methods Totally 86 HCC patients confirmed by postoperative pathology were retrospectively enrolled and divided into poorly differentiated,moderately differentiated and highly differentiated groups according to postoperative Edmondson-Steiner grading.Preoperative CEUS parameters were compared among groups,and binary logistic regression was used to analyze CEUS-related independent predictors of HCC with different differentiation.The receiver operating characteristic curves of parameters being significant different among groups were drawn,the areas under the curve(AUC)were calculated,and the efficacy for predicting HCC with different differentiation degree was evaluated.Results There were 29 cases in poorly differentiated group,37 in moderately differentiated group and 20 cases in highly differentiated group.The arrival time of contrast agent in poorly differentiated group was earlier than that in moderately and high differentiated groups(both P<0.05),while in moderately differentiated group was not significantly different with that in highly differentiated group(P>0.05).The washout grade were significantly different between each 2 groups(all P<0.05).The arrival time of contrast agent and washout grade were independent predictors of highly or poorly differentiated,moderately or poorly differentiated,moderate-highly or poorly differentiated HCC,and washout grade also was independent predictor of highly or moderately differentiated HCC(all P<0.05).The AUC of the arrival time of contrast agent for predicting highly or moderately differentiated,highly or poorly differentiated,moderately or poorly differentiated,moderate-highly or poorly differentiated HCC was 0.615,0.787,0.690 and 0.724,respectively,while of washout grade was 0.801,0.927,0.795 and 0.841,respectively.Conclusion CEUS could be used to effectively predict differentiation degree of HCC.

Multidisciplinary approaches in the management of advanced hepatocellular carcinoma:Exploring future directions

Recently,we read the article“Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of the literature”published in the World Journal of Gastrointestinal Oncology.The prognosis of advanced hepatocellular carcinoma(HCC)is poor,and multidisciplinary comprehensive treatment is currently the main research direction.This case report demonstrated the efficacy of the combination therapy of transcatheter arterial chemoembolization,hepatic arterial infusion chemotherapy,epclusa,lenvatinib and sintilimab for a patient with advanced HCC,and the report can serve as a reference for clinical practice.We would also like to share some of our views.

Pathological Study of Excised Specimens from Resectable Large Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization

Objective: To investigate pathological changes in surgically excised specimens from resectable large hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE ) and their signi?cance. Methods: From January 2002 to January 2003, 83 patients with resectable large HCC were randomized into two groups: group A, 36 patients who underwent preoperative TACE, and group B, 47 patients who underwent one-stage operation without TACE. Hepatectomy was performed in 31 patients of group A (two-stage operation group) and 47 patients of group B (one-stage operation group). The remaining 5 patients in group A were not operable. The diagnosis of HCC was pathologically con?rmed in all 78 patients after hepatectomy. Pathological changes of the excised specimens between the two groups were compared, including main tumors, capsular containment, daughter nodules, tumor thrombi and liver cirrhosis. Results: There were no signi?cant di?erences in the incidence of daughter nodules , portal vein tumor thrombi (PVTT) and extrahepatic metastasis between the two groups, but the area of main tumor necrosis was more extensive and the rate of encapsulation was higher in two-stage operation group than those in one-stage operation group. No signi?cant shrinkage in the average tumor size was seen in two- stage operation group, where daughter nodules and PVTT necrosis were less, and liver cirrhosis was more serious. Conclusion: Preoperative TACE for resectable large HCC should be used on the basis of strict selection because it does not provide complete tumor necrosis and may result in delayed surgery in some cases.

Histopathology of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is currently the sixth most common type of cancer with a high mortality rate and an increasing incidence worldwide.Its etiology is usually linked to environmental,dietary or lifestyle factors.HCC most commonly arises in a cirrhotic liver but interestingly an increasing proportion of HCCs develop in the non-fibrotic or minimal fibrotic liver and a shift in the underlying etiology can be observed.Although this process is yet to be completely understood,this changing scenario also has impact on the material seen by pathologists,presenting them with new diagnostic dilemmas.Histopathologic criteria for diagnosing classical,progressed HCC are well established and known,but with an increase in detection of small and early HCCs due to routine screening programs,the diagnosis of these small lesions in core needle biopsies poses a difficult challenge.These lesions can be far more difficult to distinguish from one another than progressed HCC,which is usually a clear cut hematoxylin and eosin diagnosis.Furthermore lesions thought to derive from progenitor cells have recently been reclassified in the WHO.This review summarizes recent developments and tries to put new HCC biomarkers in context with the WHOs reclassification.Furthermore it also addresses the group of tumors known as combined hepatocellular-cholangiocellular carcinomas.

Histopathological study of hepatocellular carcinoma after transcatheter hepatic arterial embolization

AIMS To study the histopathological changes in hepatocellular carcinoma (HCC) after transcatheter arterial embolization (TAE). METHODS Histopathological analysis was made in 39 cases of liver neoplasms after TAE and 11 cases of liver neoplasms after digital selective angiography (DSA), including pathological type, histological grade, necrotic degree, capsule, times of treatment, injured vessel and lymphocyte infiltration. RESULTS Six cases with 100% necrosis, 14 cases with 30% 95% necrosis, 19 cases with 0% 5% necrosis after TAE and 11 cases without necrosis after DSA were found histologically. The necrosis was related to the pathological type, capsule, injured vessels, but not to the histological grade, time of treatment and lymphocyte infiltration of the liver neoplasms. CONCLUSIONS TAE is an effective therapy for the late stage HCC. The encapsulated HCC is a preferable indicator for TAE.

Value of α-fetoprotein in association with clinicopathological features of hepatocellular carcinoma

AIM:To explore the relationship between α-fetoprotein(AFP) and various clinicopathological variables and different staging system of hepatocellular carcinoma(HCC) thoroughly.METHODS:A retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and December 2009 in West China Hospital was enrolled in our study.The association of serum AFP values with the HCC clinicopathological features was analysed by univariate and multivariate analysis,such as status of hepatitis B virus(HBV) infection,tumor size,tumor number,vascular invasion and degree of tumor differentiation.Also,patients were divided into four groups at the time of enrollment according to different cutoff values for serum value of AFP(≤ 20 μg/L,21-400 μg/L,401-800 μg/L,and ≥ 801 μg/L),to compare the positive rate of patient among four groups stratified by various clinicopathological variables.And the correlation of different kinds of tumor staging systems,such as TNM,Barcelona Clinic Liver Cancer(BCLC) staging classification and China staging,were compared with the serum concentration of AFP.RESULTS:A total of 2304 HCC patients were enrolled in this study totally;the mean serum level of AFP was 555.3 ± 546.6 μg/L.AFP levels were within the normal range(< 20 μg/L) in 27.4%(n = 631) of all the cases.81.4%(n = 1875) patients were infected with HBV,and those patients had much higher serum AFP level compared with non-HBV infection ones(573.9 ± 547.7 μg/L vs 398.4 ± 522.3 μg/L,P < 0.001).The AFP level in tumors ≥ 10 cm(808.4 ± 529.2 μg/L) was significantly higher(P < 0.001) than those with tumor size 5-10 cm(499.5 ± 536.4 μg/L) and with tumor size ≤ 5 cm(444.9 ± 514.2 μg/L).AFP levels increased significantly in patients with vascular invasion(694.1 ± 546.9 μg/L vs 502.1 ± 543.1 μg/L,P < 0.001).Patients with low tumor cell differentiation(559.2 ± 545.7 μg/L) had the significantly(P = 0.007) highest AFP level compared with high differentiation(207.3 ± 420.8 μg/L) and intermediate differentiation(527.9 ± 538.4 μg/L).In the multiple variables analysis,low tumor cell differentiation [OR 6.362,95%CI:2.891-15.382,P = 0.006] and tumor size(≥ 10 cm)(OR 5.215,95%CI:1.426-13.151,P = 0.012) were independent predictors of elevated AFP concentrations(AFP > 400 μg/L).Serum AFP levels differed significantly(P < 0.001) in the D stage of BCLC(625.7 ± 529.8 μg/L) compared with stage A(506.2 ± 537.4 μg/L) and B(590.1 ± 551.1 μg/L).CONCLUSION:HCC differentiation,size and vascular invasion have strong relationships with AFP,poor differentiation and HCC size ≥ 10 cm are independent predictors of elevated AFP.BCLC shows better relationship with

Molecular pathological epidemiology in diabetes mellitus and risk of hepatocellular carcinoma

Molecular pathological epidemiology(MPE) is a multidisciplinary and transdisciplinary study field,which has emerged as an integrated approach of molecular patho-logy and epidemiology,and investigates the relationship between exogenous and endogenous exposure factors,tumor molecular signatures,and tumor initiation,progression,and response to treatment.Molecular epidemiology broadly encompasses MPE and conventional-type molecular epidemiology.Hepatocellular carcinoma(HCC) is the third most common cause of cancer-associated death worldwide and remains as a major public health challenge.Over the past few decades,a number of epidemiological studies have demonstrated that diabetes mellitus(DM) is an established independent risk factor for HCC.However,how DM affects the occurrence and development of HCC remains as yet unclearly understood.MPE may be a promising approach to investigate the molecular mechanisms of carcinogenesis of DM in HCC,and provide some useful insights for this pathological process,although a few challenges must be overcome.This review highlights the recent advances in this field,including:(1) introduction of MPE;(2) HCC,risk factors,and DM as an established independent risk factor for HCC;(3) molecular pathology,molecular epidemiology,and MPE in DM and HCC;and(4) MPE studies in DM and risk of HCC.More MPE studies are expected to be performed in future and I believe that this field can provide some very important insights on the molecular mechanisms,diagnosis,personalized prevention and treatment for DM and risk of HCC.

Pathological images for personal medicine in Hepatocellular carcinoma:Cross-talk of gene sequencing and pathological images

Background:Considering the great heterogeneity of Hepatocellular carcinoma(HCC),more accurate prognostic models are urgently needed.This paper combined the advantages of genomics and pathomics to construct a prognostic model.Methods:First,we collected data from hepatocellular carcinoma patients with complete mRNA expression profiles and clinical annotations from the TCGA database.Then,based on immune-related genes,we used random forest plots to screen prognosis-related genes and build prognostic models.Bioinformatics was used to identify biological pathways,evaluate the tumor microenvironment,and perform drug susceptibility testing.Finally,we divided the patients into different subgroups according to the gene model algorithm.Pathological models were constructed by obtaining HE-stained sections from TCGA in corresponding subgroups of patients.Results:In this study,we constructed a stable prognostic model that could predict overall survival in HCC patients.The signature consisted of six immune-related genes(BX537318.1,TMEM147,CSPG4P12,AC015908.3,CEBPZOS,and SRD5A3).We found increased levels of infiltration of immune cells in the tumor microenvironment in patients with low risk scores,indicating significant antitumor immunity and corresponding to better clinical outcomes.We then screened nine drugs that were more sensitive in the low-risk group than in the high-risk group.Finally,we addressed the complex cellular changes and phenotypic heterogeneity in the HCC microenvironment by combining genomics and pathomics analysis methods.Conclusion:Our study showed that the prognostic evaluation model of HCC based on the immune signaling pathway is feasible and provided a reference value for potential immunotherapy for HCC.

Pathologic and molecular features of hepatocellular carcinoma:An update

Morphological diversity and several new distinct pathologic subtypes of hepatocellular carcinoma(HCC)are now well-recognized.Recent advances in tumor genomics and transcriptomics have identified several recurrent somatic/genetic alterations that are closely related with histomorphological subtypes and have therefore,greatly improved our understanding of HCC pathogenesis.Pathologic subtyping allows for a diagnosis which is clinically helpful and can have important implication in patient prognostication as some of these subtypes are extremely aggressive with vascular invasion,early recurrence,and worst outcomes.Several targeted treatments are now being considered in HCC,and the reporting of subtypes may be quite useful for personalized therapeutic purpose.This manuscript reviews the recently identified histomorphological subtypes and molecular alterations in HCC.

A comparative study on CT imaging and pathologic presentation of the periphery of hepatocellular carcinoma using in vivo specimens of liver transplantation

Objective:To examine CT and pathologic presentations of the periphery of hepatocelllar carcinoma (HCC) by using in vivo liver specimens from orthotopic liver transplantation (OLT) and to see whether there is any correlation between them. Materials and Methods:Forty-two patients with HCC confirmed by pathology and liver transplantation were included. Plain CT scan covering the whole liver was done, followed by arterial and portal venous phase scanning. The delay time was 25 s and 60 s after injection of contrast medium. Fresh liver samples were evaluated, sliced and stained with HE and the standard immunoperoxidase method using facterⅧrelated antigen (F8RA) monoclonal antibody to study CT presentation of the periphery of tumor and compare them with pathologic findings. Results: (1) Tumors with clear boundaries on CT scan reflected the presence of tumor capsules in pathologic sections. Most tumors with unclear boundaries had no capsules and grew in an invasive pattern; (2) Tumors with unclear boundaries or high density on dynamic enhancement usually had abundant newborn vessels in the periphery and were poorly differentiated, while those with low density had few newborn vessels and were well differentiated; (3) When microvessel density (MVD) was>30, the occurrence of intrahepatic daughter foci was higher. Conclusion: (1) CT morphologic classification of the HCC periphery can well reflect the intactness of tumor capsules, which is helpful for preoperative assessment of tumor infiltration and cancer cell grading; (2) CT enhancement presentation of the HCC periphery in arterial and portal phases may reflect pathologic changes and help predict the prognosis at large.

Anticancer Effect of PS-T on the Experimental Hepatocellular Carcinoma

Objective: To apply PS-T in di?erent phases of carcinoma formation and development, and research the mechanism of anti-carcinoma of PS-T in the cytological level. Methods: N-nitrosodiethylamine (DENA) and CCl4 were applied jointly to duplicate the rat hepatocirrhosis and hepatic cancer model. The rats were divided into 7 groups and were administrated via nasal-stomach tube with PS-T in di?erent phases to interfere the cancer genesis and development. All the rats were killed in 20 weeks for pathological observation. Results: The loss of body weight of rats slowed down in the PS-T-treated group, and the carcinogenesis rate was signi?cantly decreased correspondingly. PS-T could also inhibit the carcinogenesis by supressing the hepatocirrhosis, which showed the positive correlation between the curative e?ect and the curative period. Conclusion: Application of PS-T during cancer induction showed a signi?cant e?ect on preventing and supressing cancer. PS-T might be an ideal drug for clinical anti-cancer therapy. And it will be a main drug in both combined and single treatments for tumor.

Clinicopathological characteristics in the differential diagnosis of hepatoid adenocarcinoma:A literature review

Hepatoid adenocarcinoma (HAC) is a rare but important special type of extrahepatic adenocarcinoma with clinicopathological presentation mimicking hepatocellular carcinoma (HCC), and prompt and correct diagnosis can be a challenge, especially in endemic areas with a high incidence of HCC. To date, HAC has only been reported in case series or single case reports, so we aimed to review the clinicopathological characteristics of HAC to obtain a more complete picture of this rare form of extrahepatic adenocarcinoma. All the articles about HAC published from 2001 to 2011 were reviewed, and clinicopathological findings were extracted for analysis. A late middle-aged male with high serum α-fetoprotein and atypical image finding of HCC should raise the suspicion of HAC, and characteristic pathological immunohistochemical stains can help with the differential diagnosis. Novel immunohistochemical markers may be useful to clearly differentiate HAC from HCC. Once metastatic HAC is diagnosed, the primary tumor origin should be identified for adequate treatment. The majority of HAC originates from the stomach, so panendoscopy should be arranged first.

Intravoxel incoherent motion diffusion-weighted magnetic resonance imaging for predicting histological grade of hepatocellular carcinoma:Comparison with conventional diffusion-weighted imaging

AIM To compare intravoxel incoherent motion(IVIM)-derived parameters with conventional diffusion-weighted imaging(DWI) parameters in predicting the histological grade of hepatocellular carcinoma(h CC) and to evaluate the correlation between the parameters and the histological grades.METHODS A retrospective study was performed. Sixty-two patients with surgically confirmed h CCs underwent diffusion-weighted magnetic resonance imaging with twelve b values(10-1200 s/mm^2). The apparent diffusion coefficient(ADC), pure diffusion coefficient(D), pseudo-diffusion coefficient(D*), and perfusion fraction(f) were calculated by two radiologists. The IVIM and conventional DWI parameters were compared among the different grades by using analysis of variance(ANOVA) and the Kruskal-Wallis test. Receiver operating characteristic(ROC) analysis was performed to evaluate the diagnostic efficiency of distinguishing between low-grade(grade 1, G1) and high-grade(grades 2 and 3, G2 and G3) hC C. The correlation between the parameters and the histological grades was assessed by using the Spearman correlation test. Bland-Altman analysis was used to evaluate the reproducibility of the two radiologists' measurements.RESULTS The differences in the ADC and D values among the groups with G1, G2, and G3 histological grades of HCCs were statistically significant(P < 0.001). The D* and f values had no significant differences among the different histological grades of h CC(P > 0.05). The ROC analyses demonstrated that the D and ADC values had better diagnostic performance in differentiating the low-grade h CC from the high-grade h CC, with areas under the curve(AUCs) of 0.909 and 0.843, respectively, measured by radiologist 1 and of 0.911 and 0.852, respectively, measured by radiologist 2. The following significant correlations were obtained between the ADC, D, and D~* values and the histological grades: r =-0.619(P < 0.001), r =-0.628(P < 0.001), and r =-0.299(P = 0.018), respectively, as measured by radiologist 1; r =-0.622(P < 0.001), r =-0.633(P < 0.001), and r =-0.303(P = 0.017), respectively, as measured by radiologist 2. The intra-class correlation coefficient(ICC) values between the two observers were 0.996 for ADC, 0.997 for D, 0.996 for D*, and 0.992 for f values, which indicated excellent interobserver agreement in the measurements between the two observers.CONCLUSION The IVIM-derived D and ADC values show better diagnostic performance in differentiating high-grade hC C from low-grade hC C, and there is a moderate to good correlation between the ADC and D values and the histological grades.

Combined hepatocellular cholangiocarcinoma: Controversies to be addressed

Combined hepatocellular cholangiocarcinoma(CHC) accounts for 0.4%-14.2% of primary liver cancer cases and possesses pathological features of both hepatocellular carcinoma and cholangiocarcinoma. Since this disease was first described and classified in 1949, the classification of CHC has continuously evolved. The latest definition and classification of CHC by the World Health Organization is based on the speculation that CHC arises from hepatic progenitor cells. However, there is no evidence demonstrating the common origin of different components of CHC. Furthermore, the definition of CHC subtypes is still ambiguous and the identification of CHC subtype when a single tumor contains many components has remained unresolved. In addition, there is no summary on the newly recognized histopathology features or the contribution of CHC components to prognosis and outcome of this disease. Here we provide a review of the current literature to address these questions.

Hepatic angiomyolipoma-misdiagnosis as hepatocellular carcinoma:A report of 14 cases

Angiomyolipoma (AML) is a rare benign mesenchymal tumor of the liver, composed of a varying heterogeneous mixture of three tissue components: blood vessels, smooth muscle, and adipose cells. It has recently been proposed that the perivascular epithelial cell (PEC) is the common progenitor[1，2] Since its first description by Ishak in 1976[3], there have been more than 100 cases reported in the English literature[4-6]. With the advance of radiological techniques, many more tumors are being diagnosed by the means. But radiological findings of AML may only be suggestive of the lesion; its definitive diagnosis requires histological confirmation[9-19]. Some authors regard renal and hepatic AMLs, pulmonary and soft tissue lymphangiomyomatosis[2], pulmonary and pancreatic clear cell “sugar” tumor, and cardiac rhabdomyoma as closely related groups of tumors, based on their morphologic overlap and common immunoreactivity for HMB-45[l]. They show different microscopic appearances, however, according to their organ of origin. The goals of this study were to highlight more subtle morphology and to gain possible insights into the differential diagnosis that could provide important information about this disease.

Expressions of chromogranin A and cathepsin D in human primary hepatocellular carcinoma

AIM To determine the expression and clinicalsignificance of chromogranin A and cathepsin Din hepatocellular carcinoma(HCC).METHODS Double immunofluorescence stain-ing techniques combined with laser confocalscanning microscopy(LSCM)was used toinvestigate chromogranin A and cathepsin Dexpressions in 85 HCC patients.RESULTS Cathepsin D was expressed in :3normal liver tissues,while in HCC the stainingshowed regional variation and the fraction ofstrongly stained cells increased as the tumorsbecame less differentiated and usually clinicallymore malignant.Cells which showed strongpositivity for cathepsin D were present in 71/85(83.5%)cases.Strong expression of cathepsinD in cancer cells was related tohistopathological features.They were morecommon in grade 3-4(26/28,92.9%)and grade2(46/53,86.8%)tumors than in grade 1 tumors(1/4,25.0%)(P【0.01).No significantcorrelation was found between age andcathepsin D expression.In patients with positivecathepsin D reaction,the mean age was 52.1±2.8 years(range 32-68 years)and in the groupwith negative reaction,the mean age was 51.3±4.5 years(range 28-71 years).No obvious relationship was observed between CgAexpression in cancer cells and thehistopathological features.The CgA positiverate was 75.0%(3/4)in grade 1,71.7%(38/53)in grade 2,and 71.4%(20/28)in grade 3-4(P】0.05)tumors.The coexpression of CgA andcathepsin D was found by double labeledimmunofluorescence staining techniques.Theprocessing of cathepsin D was disturbed in HCCcells and accumulated in the cells.Cathepsin Dhad proteolytic activity and autocrine mitogeniceffect,suggesting their functions in invasion.These findings demonstrated that the expressionof cathepsin D in HCC had prognostic value.CONCLUSION Chromogranin A and cathepsin Dare expressed in a high proportion of HCC andthe existence of cathepsin D in HCC might berelated to processing of CgA.This is clearly asubject for further studies because of itspotential clinical applications.

Feasibility of terahertz imaging for discrimination of human hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC) is one of the most common malignant tumors worldwide, and novel methods for early/rapid diagnosis of HCC are needed.Terahertz(THz) spectroscopy is considered to have the potential to distinguish between normal liver tissue and HCC tissue; however, there are few reports on it.We conduct this observational study to explore the feasibility of THz imaging for the diagnosis of HCC.AIM To evaluate the feasibility of THz for discriminating between HCC and normal liver tissues using fresh tissue specimens obtained from HCC patients who had undergone surgery.METHODS Normal liver tissue and HCC tissue were cryosectioned into 50 μm-thick slicesand placed on cover glass. Two adjacent tissue sections were separated subjected to histopathological examination by hematoxylin and eosin staining or THz transmission examination, and THz images were compared with pathologically mapped images. We determined the typical tumor and normal liver tissue regions by pathological examination; the corresponding areas of adjacent sections were examined by THz transmission.RESULTS The transmission rate of HCC tissue was 0.15-0.25, and the transmission rate of typical HCC tissue was about 0.2. THz transmittance in normal liver tissue is slightly higher than 0.4, but there were many influencing factors, including the degree of liver cirrhosis, fat components, ice crystals in frozen sections, and apoptosis.CONCLUSION In conclusion, this study shows that THz imaging can detect HCC tissue. Further research will yield more detailed data of the THz transmission rates of HCC tissue with different degrees of differentiation.