Objective: To investigate the clinical value of serum glypican-3 (GPC3) detection in predicting recurrence of primary hepatocellular carcinoma (HCC). Methods: Through univariate and multivariate logistic regression analysis, the patients pathologically diagnosed with HCC in our hospital from March 2019 to January 2021 were enrolled as the experimental group (n=113), and patients with follow-up time longer than 6 months were included in the prognosis group(n=64). At the same time,20 healthy individuals and 20 individuals with benign liver disease from the physical examination center were enrolled by simple random sampling as control group (n=40). The serum GPC3 and alpha-fetoprotein (AFP) levels were respectively detected by ELISA and chemiluminescence. Then, the study explored the influential factors of the recurrence in HCC patients and constructed the HCC-GPC3 recurrence predicting model by logistic regression. Results: In the research, the sensitivity of GPC3 for the diagnosis of HCC was 61.95% (70/113) and AFP was 52.21% (59/113), meanwhile, the specificity of GPC3 could reach 87.50% (35/40) and AFP was 90.00% (36/40),respectively; The serum GPC3 levels of HCC patients with progressive stage, tumor size≥3 cm, vascular cancer thrombosis and portal venous thromboembolism were significantly higher than that of HCC patients with early stage, tumor size<3 cm, vascular cancer thrombosis and portal venous thromboembolism (Z=2.677, 2.848, 2.995, 2.252, P<0.05), independent of different ages, presence or absence of ascites, peritoneal metastasis, cirrhosis, intrahepatic metastasis (Z=-1.535, 1.011, 0.963, 0.394, 1.510, P>0.05), respectively. Univariate analysis showed that there were no statistically significant differences between the recurrence group and the non-recurrence group in terms of different age, tumor size, presence or absence of vascular cancer thrombosis, ascites, peritoneal metastasis, cirrhosis and AFP levels (χ²=2.012, 0.119, 2.363, 1.041, 0.318, 0.360, Z=0.748, P>0.05); The ratio of those with the progressive stage, portal venous thromboembolism and intrahepatic metastasis and GPC3 levels were all higher in the recurrence group than in the non-recurrence group (χ²=4.338, 11.90, 4.338, Z=2.805, P<0.05).Including the above risk factors in the logistic regression model, the logistic regression analysis showed that the stage, the presence of portal venous thromboembolism,intrahepatic metastasis and GPC3 levels were correlated with the prognosis recurrence of HCC patients (Wald χ² =4.421, 5.681, 4.995, 4.319, P<0.05), and the HCC-GPC3 recurrence model was obtained as: OcScore=-2.858+1.563×[stage]+1.664×[intrahepatic metastasis]+2.942×[ portal venous thromboembolism]+0.776×[GPC3]. According to the receiver operating characteristic curve(ROC), the area under the curve(AUC)of the HCC-GPC3 prognostic model was 0.862, which was better than that of GPC3 alone (AUC=0.704). The cut-off value of model SCORE was 0.699 (the cut-off value of GPC3 was 0.257 mg/L), furthermore, the total sensitivity and specificity of model were 83.3% and 82.4%, which were better than those of GPC3(60.0% and 79.4%).Kaplan-Meier showed that the median PFS was significantly shorter in HCC patients with high GPC3 levels (≥0.257 mg/L) and high values of the model SCORE (≥0.700) (χ²=12.73, 28.16, P<0.05). Conclusion: Besides diagnosing of HCC, GPC3 can may be an independent risk indicator for the recurrence of HCC and can more efficiently predicting the recurrence of HCC patients when combined with the stage, the presence or absence of intrahepatic metastasis and portal venous thromboembolism.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/diagnosis* ; alpha-Fetoproteins/analysis* ; Biomarkers, Tumor ; Glypicans ; Ascites ; Venous Thromboembolism ; Peritoneal Neoplasms ; Liver Cirrhosis

Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.
Humans ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/pathology* ; Prognosis ; Carnosine ; alpha-Fetoproteins/metabolism* ; Biomarkers, Tumor/genetics* ; Liver Cirrhosis/diagnosis* ; ROC Curve

What are the new contents of the guideline since 2010?A.Patients with primary and non-primary sclerosing cholangitis (PSC) are included in these guidelines for the diagnosis and management of cholangiocarcinoma.B.Define "related stricture" as any biliary or hepatic duct stricture accompanied by the signs or symptoms of obstructive cholestasis and/or bacterial cholangitis.C.Patients who have had an inconclusive report from MRI and cholangiopancreatography should be reexamined by high-quality MRI/cholangiopancreatography for diagnostic purposes. Endoscopic retrograde cholangiopancreatography should be avoided for the diagnosis of PSC.D. Patients with PSC and unknown inflammatory bowel disease (IBD) should undergo diagnostic colonoscopic histological sampling, with follow-up examination every five years until IBD is detected.E. PSC patients with IBD should begin colon cancer monitoring at 15 years of age.F. Individual incidence rates should be interpreted with caution when using the new clinical risk tool for PSC for risk stratification.G. All patients with PSC should be considered for clinical trials; however, if ursodeoxycholic acid (13-23 mg/kg/day) is well tolerated and after 12 months of treatment, alkaline phosphatase (γ- Glutamyltransferase in children) and/or symptoms are significantly improved, it can be considered to continue to be used.H. Endoscopic retrograde cholangiopancreatography with cholangiocytology brushing and fluorescence in situ hybridization analysis should be performed on all patients suspected of having hilar or distal cholangiocarcinoma.I.Patients with PSC and recurrent cholangitis are now included in the new unified network organ sharing policy for the end-stage liver disease model standard.J. Liver transplantation is recommended after neoadjuvant therapy for patients with unresectable hilar cholangiocarcinoma with diameter < 3 cm or combined with PSC and no intrahepatic (extrahepatic) metastases.
Child ; Humans ; Cholangitis, Sclerosing/diagnosis* ; Constriction, Pathologic/complications* ; In Situ Hybridization, Fluorescence ; Cholangiocarcinoma/therapy* ; Liver Diseases/complications* ; Cholestasis ; Inflammatory Bowel Diseases/therapy* ; Bile Ducts, Intrahepatic/pathology* ; Bile Duct Neoplasms/therapy*

Hepatocellular carcinoma (HCC) is the most common type of primary hepatocellular carcinoma (PHC). Early diagnosis of HCC remains the key to improve the prognosis. In recent years, with the promotion of the concept of precision medicine and more in-depth analysis of the biological mechanism underlying HCC, new diagnostic methods, including emerging serum markers, liquid biopsies, molecular diagnosis, and advances in imaging (novel contrast agents and radiomics), have emerged one after another. Herein, we reviewed and analyzed scientific advances in the early diagnosis of HCC and discussed their application and shortcomings. This review aimed to provide a reference for scientific research and clinical practice of HCC.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Prognosis ; Early Diagnosis ; Precision Medicine

Objective: To investigate the clinical manifestations, histomorphology, and differential diagnosis of primary hepatic angiosarcoma. Methods: Nine cases of primary hepatic angiosarcoma diagnosed in the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from January 2014 to December 2021 were collected, including biopsy and surgical specimens. The histomorphology, clinical, and radiologic findings were analyzed. The relevant literature was also reviewed. Results: There were six males and three females, aged 30 to 73 years (mean 57 years). Grossly, the growth pattern of the tumor was classified as either mass formation or non-mass formation (sinusoidal). Microscopically, the mass-forming primary hepatic angiosarcoma were further subdivided into vasoformative or non-vasoformative growth patterns; and those non-vasoformative tumors had either epithelioid, spindled, or undifferentiated sarcomatoid features. Sinusoidal primary hepatic angiosarcoma on the other hand presented with markedly dilated and congested blood vessels of varying sizes, with mild to moderately atypical endothelial cells. Follow-up in all nine cases revealed 8 mortality ranging from 1 to 18 months (mean 5 months) from initial diagnosis. One patient was alive with disease within a period of 48 months. Conclusions: Primary hepatic angiosarcoma is a rare entity with a wide spectrum of histomorphology, and often misdiagnosed. It should be considered when there are dilated and congested sinusoids, with overt nuclear atypia. The overall biological behavior is aggressive, and the prognosis is worse.
Male ; Female ; Humans ; Hemangiosarcoma/diagnosis* ; Endothelial Cells/pathology* ; Liver Neoplasms/surgery* ; Prognosis ; Biopsy

Objective: To investigate the utility of albumin RNAscope in situ hybridization in the diagnosis and differential diagnosis of hepatocellular carcinoma and its mimics. Methods: One hundred and fifty-two cases of hepatocellular carcinoma and its mimics and 33 cases of normal tissue were selected from the pathology database of the Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2019. Tissue microarrays were constructed and RNAscope in situ hybridization was performed to detect the expression of albumin mRNA. Results: No albumin mRNA expression was detected in normal tissues except for the liver. All hepatocellular carcinoma regardless of its degree of differentiation and primary or metastatic nature had detectable albumin mRNA, with strong and diffuse staining in 90.7% (49/54) of cases. While the positive rate of HepPar-1, Arg-1 or one of them by immunohistochemistry was 87.0% (47/54), 85.2% (46/54) and 92.6% (50/54) respectively. The positive rates of albumin mRNA in intrahepatic cholangiocarcinoma and biphenotypic hepatocellular carcinoma were 7/15 and 9/10, respectively. The former showed focal or heterogeneous staining, while the latter showed strong and diffuse staining. The positive rate of hepatoid adenocarcinoma was 8/19, and the albumin expression could be diffuse or focal. Sporadic cases of poorly differentiated gastric adenocarcinoma and metastatic colon adenocarcinoma showed focal staining of albumin mRNA. Conclusions: Detection of albumin mRNA by RNAscope in situ hybridization is of great value for the diagnosis and differential diagnosis of HCC, and the sensitivity may be improved by combining with HepPar-1 and Arg-1. It also offers different diagnostic clues according to different expression patterns.
Adenocarcinoma/diagnosis* ; Albumins/genetics* ; Bile Duct Neoplasms/pathology* ; Bile Ducts, Intrahepatic/pathology* ; Biomarkers, Tumor/genetics* ; Carcinoma, Hepatocellular/genetics* ; China ; Colonic Neoplasms ; Diagnosis, Differential ; Humans ; In Situ Hybridization ; Liver Neoplasms/pathology* ; RNA, Messenger

The diagnosis of cystic liver disease has made great progress with the advent of enhanced imaging techniques. At the same time, its management has gradually improved over the past few decades, providing the basis for the development of appropriate diagnostic and treatment guidelines. To this end, the European Association for the Study of the Liver has developed clinical guidelines for the diagnosis and treatment of non-infectious cystic liver disease. This guideline put forward recommendations based on an in-depth review of the relevant literature for addressing clinical issues, including the diagnosis and treament of hepatic cysts, hepatic mucocystic tumors, biliary hamartomas, polycystic liver disease, Caroli disease or Caroli syndrome, biliary hamartomas, and peribiliary cyst.
Humans ; Liver Diseases/pathology* ; Cysts/pathology* ; Caroli Disease/diagnosis* ; Liver Neoplasms/therapy* ; Hamartoma

The liver is one of the most common sites to which malignancies preferentially metastasize. Although a substantial number of liver malignancies are primary tumors, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, the metastasis of carcinomas to the liver is relatively common and frequently encountered in clinical settings. Representative carcinomas that frequently metastasize to the liver include colorectal carcinoma, breast carcinoma, neuroendocrine tumors, lung carcinoma, and gastric carcinoma. The diagnostic confirmation of suspected metastatic lesions in the liver is generally achieved through a histopathologic examination of biopsy tissues. Although morphology is the most important feature for a pathologic differential diagnosis of metastatic carcinomas, immunohistochemical studies facilitate the differentiation of metastatic carcinoma origins and subtypes. Useful immunohistochemical markers for the differential diagnosis of metastatic carcinomas in the liver include cytokeratins (CK7, CK19, and CK20), neuroendocrine markers (CD56, synaptophysin, and chromogranin A), and tissue-specific markers (CDX2, SATB2, TTF-1, GCDFP-15, mammaglobin, etc.). Here, we provide a brief review about the pathologic differential diagnosis of major metastatic carcinomas in the liver.
Biopsy ; Breast Neoplasms ; Carcinoma, Hepatocellular ; Cholangiocarcinoma ; Colorectal Neoplasms ; Diagnosis, Differential ; Immunohistochemistry ; Keratins ; Liver Neoplasms ; Liver ; Lung ; Neoplasm Metastasis ; Neuroendocrine Tumors ; Pathology ; Synaptophysin

The liver is the most common anatomical site for hematogenous metastases of colorectal cancer, and colorectal liver metastases is one of the most difficult and challenging points in the treatment of colorectal cancer. In order to improve the diagnosis and comprehensive treatment in China, the Guidelines have been edited and revised for several times since 2008, including the overall evaluation, personalized treatment goals and comprehensive treatments, to prevent the occurrence of liver metastases, improve the resection rate of liver metastases and survival. The revised Guideline includes the diagnosis and follow-up, prevention, MDT effect, surgery and local ablative treatment, neoadjuvant and adjuvant therapy, and comprehensive treatment, and with advanced experience, latest results, detailed content, and strong operability.
Chemotherapy, Adjuvant ; China ; Colorectal Neoplasms ; pathology ; Hepatectomy ; Humans ; Liver Neoplasms ; diagnosis ; secondary ; therapy ; Neoadjuvant Therapy ; Practice Guidelines as Topic

OBJECTIVE: To explore the prognostic factors of patients with unresectable liver metastasis colorectal cancer after failed conversion chemotherapy. METHODS: A retrospective, case-controlled study was performed. Study subjects were 105 patients who were diagnosed with synchronous liver metastasis colorectal cancer after failed chemotherapy (metastasis evaluated as unresectable after the conversion chemotherapy) at Xinhua Hospital, Shanghai Jiaotong University from January 2012 to December 2015. Overall survival(OS) was retrospectively analyzed using Kaplan-Meier method. Log-rank test was used to compare survival among groups. Univariate and multivariate analysis was conducted for prognosis using Cox regression model. RESULTS: Of 105 cases,70 were male and 35 were female with median age of 60 years old. Twenty-one patients had right colon cancer, 41 had left colon cancer, 42 had rectal cancer and 1 had synchronous cancers(sigmoid colon and rectum). One hundred and two (97.1%) patients were cT3-4 and 90 patients were cN+ (imaging diagnosis). Eighty-nine (84.8%) patients were loaded with 2 or more liver metastases with the median maximum diameter of 48.3 mm. The patients were followed up for 3 to 43 months from the day of diagnosis. The median OS was 11 months (interquartile range, 8-18). The median OS of patients with cN0, cN1 and cN2 stage was 17, 13 and 10 months, respectively(P=0.026). The median OS of patients with single lesion, 2-3 lesions, 4-10 lesions and more than 10 lesions was 15, 15, 17 and 9 months, respectively (P=0.002). OS of patients with maximum diameter of liver metastatic lesion ≤ 50 mm, 51-100 mm and >100 mm was 15, 10 and 8 months, respectively(P=0.003). The median OS of patients with chemotherapy response of partial response (PR), stable disease (SD) and progressive disease (PD) was 17, 14 and 8 months, respectively(P<0.001). OS was 17 months in patients receiving second line chemotherapy and was 10 months in those without second line chemotherapy (P<0.001). OS in patients undergoing primary tumor resection was 13 month and in those without primary tumor resection was 9 months; the difference was not significant (P=0.060). Multivariate analysis showed that cN2(HR=2.115, 95%CI:1.089-4.109, P=0.027), the maximum diameter of liver metastatic lesion more than 100 mm (HR=3.112, 95%CI:1.455-6.657, P=0.003), chemotherapy response of PD (HR=4.435, 95%CI:2.506-7.533,P<0.001) and without second line chemotherapy(HR=4.432,95%CI:2.186-8.986, P=0.010) were independent prognostic factors. CONCLUSIONS For patients with unresectable liver metastasis from colorectal cancer after failed conversion chemotherapy, prognostic factors include cN2, the maximum diameter of liver metastatic lesion, chemotherapy response and second line chemotherapy. Whether the resection of primary tumor can prolong OS further study.
Antineoplastic Agents ; therapeutic use ; China ; Colorectal Neoplasms ; drug therapy ; pathology ; Female ; Humans ; Liver Neoplasms ; diagnosis ; secondary ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Failure