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 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

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 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

Heterogeneous features of liver cancer can mimic liver abscess. Therefore it is essential to double-check tumor markers in the diagnosis of liver abscess. Herein, we report a case of combined hepatocellular-cholangiocarcinoma (cHC) occurred in an unrecognized chronic hepatitis B patient initially misdiagnosed as liver abscess. A 49-year old male initially presented with chill, right upper quadrant pain, and a liver mass. Mass showed peripheral enhancement in arterial phase of computed tomography, which was not typical for hepatocellular carcinoma (HCC). Strikingly elevated alpha-fetoprotein and fine needle aspirated pathology revealed HCC. Despite discordant image findings he was treated with transarterial chemoembolization. He was treated with sorafenib due to metastatic retrocaval lymphadenopathy afterwards. The mass presumed to be HCC progressed with sorafenib. It was surgically resected and he was finally confirmed as cHC. Discordant tumor markers with presumptive image findings should prompt the suspicion of rare type of primary liver cancer, the cHC.
alpha-Fetoproteins ; Biomarkers, Tumor ; Carcinoma, Hepatocellular ; Diagnosis ; Hepatitis B, Chronic ; Humans ; Liver ; Liver Abscess ; Liver Abscess, Pyogenic* ; Liver Neoplasms ; Lymphatic Diseases ; Male ; Needles ; Pathology

BACKGROUNDLiver abscess is a serious complication following transcatheter arterial chemoembolization (TACE). Much attention has been paid to this condition as it may interfere with the treatment process and result in a poor prognosis of the patient. This study aimed to analyze the causes of liver abscess, a complication, after TACE for hepatic tumors and to summarize management approaches.

METHODSFrom June 2012 to June 2014, of 1480 consecutive patients who underwent TACE at our hospital, five patients developed liver abscess after TACE procedures for hepatic tumors. Of the five patients, each receiving conventional TACE, one underwent three sessions, two underwent two sessions, and the remaining two underwent one session of TACE. Demographic and clinical characteristics, together with management approaches and prognosis, were collected through a review of medical records.

RESULTSThese five patients were confirmed to have post-TACE liver abscess through clinical manifestations, laboratory, and imaging tests. After percutaneous drainage and anti-inflammatory treatments, the symptoms present in four patients with liver abscess significantly improved as evidenced by shrinkage or disappearance of the abscess cavity, and the patients recovered completely after sufficient drainage. The remaining patient experienced recurrent symptoms and abdominal abscess, achieved no significant improvement after treatment, and eventually died of severe infection and multiple organ failures.

CONCLUSIONSTACE must be implemented with extreme caution to avoid liver abscess. An effective management relies on an early diagnosis, prompt use of sufficient doses of appropriate antibiotics, and active implementation of abscess incision, drainage, and aspiration.

Adult ; Aged ; Carcinoma, Hepatocellular ; therapy ; Chemoembolization, Therapeutic ; adverse effects ; Humans ; Liver ; pathology ; Liver Abscess ; diagnosis ; etiology ; Liver Neoplasms ; therapy ; Male ; Middle Aged ; Retrospective Studies

Radiation dermatitis can develop after fluoroscopy-guided interventional procedures. Cases of fluoroscopy-induced radiation dermatitis have been reported since 1996, mostly documented in the fields of radiology, cardiology and dermatology. Since diagnosis and treatment of fluoroscopy-induced radiation dermatitis can be difficult, high grade of suspicion is required. The extent of this reaction is determined by radiation dose, duration of exposure, type of procedure, and host factors and can be aggravated by concomitant use of photosensitizers. Follow-up is important after long and complicated procedures and efforts to minimize radiation exposure time will be necessary to prevent radiation dermatitis. Herein, we report a case of a 58-year-old man with hepatocellular carcinoma presenting with subacute radiation dermatitis after prolonged fluoroscopic exposure during transarterial chemoembolization and chemoport insertion. Physicians should be aware that fluoroscopy is a potential cause of radiation dermatitis.
Carcinoma, Hepatocellular/*radiotherapy ; Embolization, Therapeutic ; Fluoroscopy ; Fluorouracil/therapeutic use ; Gamma Rays ; Humans ; Liver Neoplasms/*radiotherapy ; Male ; Middle Aged ; Radiodermatitis/*diagnosis/pathology

Hepatocellular carcinoma (HCC) can be diagnosed based on characteristic findings of arterial-phase enhancement and portal/delayed "washout" in cirrhotic patients. Several countries and major academic societies have proposed varying specific diagnostic criteria for HCC, largely reflecting the variable HCC prevalence in different regions and ethnic groups, as well as different practice patterns. In 2014, a new version of Korean practice guidelines for management of HCC was released by the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC). According to the KLCSG-NCC Korea practice guidelines, if the typical hallmark of HCC (i.e., hypervascularity in the arterial phase with washout in the portal or 3 min-delayed phases) is identified in a nodule > or = 1 cm in diameter on either dynamic CT, dynamic MRI, or MRI using hepatocyte-specific contrast agent in high-risk groups, a diagnosis of HCC is established. In addition, the KLCSG-NCC Korea practice guidelines provide criteria to diagnose HCC for subcentimeter hepatic nodules according to imaging findings and tumor marker, which has not been addressed in other guidelines such as Association for the Study of Liver Diseases and European Association for the Study of the Liver. In this review, we briefly review the new HCC diagnostic criteria endorsed by the 2014 KLCSG-NCC Korea practice guidelines, in comparison with other recent guidelines; we furthermore address several remaining issues in noninvasive diagnosis of HCC, including prerequisite of sonographic demonstration of nodules, discrepancy between transitional phase and delayed phase, and implementation of ancillary features for HCC diagnosis.
Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular/*diagnosis/pathology ; Contrast Media ; Female ; Hepatitis B, Chronic/complications ; Hepatitis C, Chronic/complications ; Humans ; Liver/*pathology ; Liver Neoplasms/*diagnosis/pathology ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Practice Guidelines as Topic ; Republic of Korea ; Young Adult

OBJECTIVETo assess the value of detecting peripheral blood circulating tumor cells (CTCs) in the diagnosis and treatment of hepatocellular carcinoma (HCC).

METHODSA total of 296 patients diagnosed with HCC admitted in our department from July 2013 to January 2015 were analyzed, with 39 patients with benign liver disease serving as the control group. The distribution of CTCs in the peripheral blood of HCC patients were detected by CanPatrol(TM) CTCs, and its relationship with the clinical features and prognosis of the patients were analyzed.

RESULTSs CTCs were detected in 64.5% (191/296) of the HCC patients but in none of the control group (P<0.05). Positive CTCs in peripheral blood of HCC patients were significantly correlated with serum AFP level, tumor number, TNM stage, BCLC stage, portal vein tumor thrombus and metastasis (P<0.05). In 127 HCC patients receiving radical surgery, the patients positive for CTCs showed significantly shorter relapse-free survival time (P<0.05).

CONCLUSIONPositive CTCs in the peripheral blood may indicate a poor prognosis in HCC patients. CTCs may serve as a indicator for monitoring the prognosis of HCC.

Carcinoma, Hepatocellular ; blood ; diagnosis ; Case-Control Studies ; Humans ; Liver Neoplasms ; blood ; diagnosis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neoplastic Cells, Circulating ; Portal Vein ; pathology ; Prognosis