Well-differentiated Hepatocellular Carcinoma Research Articles

Contrast-enhanced ultrasound features of hepatocellular carcinoma in dogs

BackgroundThis study aimed to describe the contrast-enhanced ultrasound (CEUS) features of canine hepatocellular carcinoma (HCC) in relation to cellular differentiation and lesion size.MethodsSixty dogs with a cytological diagnosis of HCC...

Diagnostic accuracy of quantitative diffusion parameters in the pathological grading of hepatocellular carcinoma: A meta-analysis.

Accurate preoperative assessment of the pathological grade of hepatocellular carcinoma (HCC) could greatly benefit prognostic predictions. To assess and compare the diagnostic accuracy of the apparent diffusion coefficient (ADC) and tissue diffusivity (D) for the noninvasive pathological grading of HCC. Meta-analysis. PubMed/Medline, EMBASE, the Web of Science, and the Cochrane Library were searched to find related original articles published up to May 30, 2019. Diffusion-weighted imaging (DWI) and/or intravoxel incoherent motion (IVIM) were performed with a 1.5T or 3.0T scanner. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the methodologic quality. The bivariate random-effects model was used to obtain the pooled sensitivity and specificity, and the area under summary receiver operating characteristic curve (AUROC) was obtained. Subgroup analyses were performed. A total of 16 original articles (1428 HCCs) were included. Most studies had a low to unclear risk of bias and minimal concerns regarding applicability. For the discrimination of well-differentiated HCCs, the pooled sensitivity and specificity of the ADC value were 85% and 92%, respectively. For the discrimination of poorly differentiated HCCs, the pooled sensitivity and specificity of the ADC value and D were 84% and 80%, and 92% and 77%, respectively. The summary AUROC of D (0.94) was significantly higher than that of ADC (0.89) (z = -2.718, P = 0.007). The subgroup analyses identified three covariates including size, number of included lesions in the studies, and blindness to the reference standard as possible sources of heterogeneity. This meta-analysis showed that the ADC and D values had a high to excellent accuracy for the noninvasive pathological grading of HCCs and that the D value was superior to the ADC value for discriminating poorly differentiated HCCs. 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1581-1593.

Analysis of competing endogenous RNA network identifies a poorly differentiated cancer-specific RNA signature for hepatocellular carcinoma.

Plenty of evidence has suggested that long noncoding RNAs (lncRNAs) play a vital role in competing endogenous RNA (ceRNA) networks. Poorly differentiated hepatocellular carcinoma (PDHCC) is a malignant phenotype. This paper aimed to explore the effect and the underlying regulatory mechanism of lncRNAs on PDHCC as a kind of ceRNA. Additionally, prognosis prediction was assessed. A total of 943 messenger RNAs (mRNAs), 86 miRNAs, and 468 lncRNAs that were differentially expressed between 137 PDHCCs and 235 well-differentiated HCCs were identified. Thereafter, a ceRNA network related to the dysregulated lncRNAs was established according to bioinformatic analysis and included 29 lncRNAs, 9 miRNAs, and 96 mRNAs. RNA-related overall survival (OS) curves were determined using the Kaplan-Meier method. The lncRNA ARHGEF7-AS2 was markedly correlated with OS in HCC (P = .041). Moreover, Cox regression analysis revealed that patients with low ARHGEF7-AS2 expression were associated with notably shorter survival time (P = .038). In addition, the area under the curve values of the lncRNA signature for 1-, 3-, and 5-year survival were 0.806, 0.741, and 0.701, respectively. Furthermore, a lncRNA nomogram was established, and the C-index of the internal validation was 0.717. In vitro experiments were performed to demonstrate that silencing ARHGEF7-AS2 expression significantly promoted HCC cell proliferation and migration. Taken together, our findings shed more light on the ceRNA network related to lncRNAs in PDHCC, and ARHGEF7-AS2 may be used as an independent biomarker to predict the prognosis of HCC.

2218 Recurrent Hepatocellular Carcinoma From Needle Tract Seeding 13 Years Post-Transplant

INTRODUCTION: Liver biopsy (LB) is a known risk factor for tumor seeding and hepatocellular carcinoma (HCC) recurrence. The time from LB to confirmed needle tract seeding (NTS) varies from 3 months to 4 years. We present case of recurrent HCC due to NTS 13 years after LB who presented with a right intercostal wall mass. CASE DESCRIPTION/METHODS: A 32-year-old Caucasian male presented to his primary care provider (PCP) in 2004 with recurrent right upper abdominal pain. A CT abdomen & pelvis showed 15 × 12 × 12 cm lesion in the right lobe of the liver with central hypodensity and 1-2 cm solid peripheral rim. His PCP requested CT guided percutaneous needle biopsy. Cytologic analysis was negative for malignant cells. After referral to our institution he underwent posterior right hepatectomy. A 14 × 12 × 7 cm well circumscribed tumor was removed with histopathology confirming well-differentiated HCC with negative margins (Figure 1A). In 2007, new hepatic lesions were noted during HCC surveillance for which he underwent orthotopic liver transplantation (OLT). He continued HCC surveillance which included CT abdomen, pelvis and thorax every 1- and 3-years, whole body bone scintigraphy every 3 years and abdominal US every 6-month intervals; which were negative for HCC recurrence. In 2017 (13 years post OLT), he returned with six months of right intercostal pain and swelling. CT chest & abdomen showed a large mass involving the right 10th rib, soft tissue, and lung nodules (Figure 2). Biopsy of the mass showed well-differentiated HCC, suspicious for vascular invasion (Figures 1B and 3). He was initially started sorafenib however could not tolerate it. He could not receive nivolumab due to risk of rejection and is currently on cabozatinib. He received palliative radiation for pain related to metastasis. DISCUSSION: This case highlights NTS from the LB resulting in HCC recurrence and potentially compromising curative therapies such as hepatectomy and OLT. NTC in HCC is rare with a reported incidence from 1 to 5% and could potential implant 1,000 to 100,000 malignant cells along the needle tract. Due to the risk of NTS, percutaneous biopsy is avoided in indeterminate nodules and should be used only in selected cases. Prompt referral to an experienced hepatologist is imperative. LB should be reserved for lesions in which no definitive surgical intervention is planned, and pathological confirmation is necessary for non-surgical therapy.

2220 Incidental Finding of Hepatocellular Neoplasms in Non-Cirrhotic Patients: A Case Series

INTRODUCTION: About 20% of hepatocellular cancers (HCC) arise in the absence of cirrhosis, such as in the setting of glycogen storage disease (GSD) and anabolic steroid use. Non-cirrhotic HCC tends to have a lower male predominance, bimodal age distribution, and lower prevalence of hepatitis B, C, and alcohol abuse. There is a larger tumor burden at time of HCC diagnosis but a higher amenability to hepatic resection given preserved liver function and better overall survival than cirrhotic patients. CASE DESCRIPTION/METHODS: Case 1 A 16-year-old male presented after a motor vehicle accident for evaluation of traumatic injuries. He was a body-builder who used anabolic steroids. Physical exam showed a palpable liver edge. Labs were unremarkable. Computed tomography scan of the abdomen showed an incidentally discovered mass in the right hepatic lobe. Magnetic resonance imaging (MRI) of the abdomen showed a 15.1 × 15.0 × 10.8 cm right hepatic lobe mass concerning for a hepatic neoplasm. He underwent partial hepatectomy. Resected surgical specimen showed a β-catenin activated well-differentiated hepatocellular carcinoma. Case 2 A 26-year-old man with GSD type 1a was evaluated for iron-deficiency anemia. Physical exam showed tachycardia, conjunctival pallor, and palpable liver edge. Labs were notable for hemoglobin of 12.6 gm/dL, platelet count of 529 × 103/µL, alanine aminotransferase 92 U/L, and aspartate aminotransferase 82 U/L. MRI of the abdomen showed multiple large arterially enhancing liver masses within the right and left hepatic lobes. The largest lesion within the right lobe of the liver measured 20.2 × 17.7 × 13.5 cm. Endoscopic ultrasound showed a large right heterogenous hepatic lobe lesion, appearing malignant which underwent fine needle aspiration. Pathology was consistent with β-catenin activated hepatocellular neoplasm. The patient is scheduled for a right hepatectomy with possible living donor liver transplantation given the large and multifocal nature of his liver masses. DISCUSSION: There are four different phenotypes of hepatocellular adenomas; the β-catenin subtype has the highest malignant potential. Anemia in GSD appears to be related to large hepatic adenoma formation and warrants imaging of the abdomen to evaluate for a bleed or growth of the lesions. No effective imaging tool or biomarker separates hepatocellular adenoma from HCC, so it is important to keep a low threshold to biopsy a hepatic adenoma with suspicious imaging features.

Living donor liver transplantation in Alagille syndrome—Single center experience from south Asia

To analyze the clinical characteristics and the outcomes of living donor liver transplantation in children with Alagille syndrome (AGS). Clinical data of children with AGS who underwent liver transplantation between July 2009 and May 2019 in our unit were retrospectively analyzed. Primary end-points were patient and graft survival. Ten children with AGS underwent living donor liver transplantation at a median age of 28months (range, 12-84months). Jaundice was the most common initial symptom and was noted after a median duration of 20days after birth (range, 7-60days). Two patients had undergone Kasai porto-enterostomy for misdiagnosis of biliary atresia. The most common indication for transplantation was severe pruritus with poor quality of life. Explant livers in three children showed cirrhosis with early well-differentiated hepatocellular carcinoma. We have 100% patient and graft survival at a mean follow-up of 32months (range 3-72months). The median z-score for weight and height at liver transplantation was -2.66 (range: -6.44 to -0.9) and -3.6 (range: -7.96 to -0.93) while at follow-up was -1.7 (range: -3.4 to -0.35) and -2.1 (range: -3.9 to -1.4), respectively. The estimated glomerular filtration rate was normal pretransplant and follow-up. This is the first series of LDLT for Alagille syndrome in the Indian sub-continent. We report excellent post-transplant outcomes in contrast to outcomes reported from Western literature.

Intraoperative fluorescence angiography and cholangiography with indocyanine green in hepatobiliary surgery

Intraoperative fluorescence angiography and cholangiography with indocyanine green (ICG) are increasingly used in routine hepatobiliary surgery. Its usage is manifold. It improves and facilitates navigation especially in minimal invasive and robotic surgery and therefore increases the safety of the surgical intervention. In laparoscopic cholecystectomy for example, the bileduct anatomy can be easily visualized, even in complicated cholecystitis or anatomical variants without being too time consuming. ICG fluorescence also enables the visualization of vascular structures and perfusion. Anatomical liver resections, for example in hepatocellular carcinoma (HCC), can be performed easily as liver segments and territories can be identified. Anatomical resection is becoming more important, e.g. in the treatment of HCC. Another useful application is the intraoperative detection of bile leakages after liver resection. In particular, the intraoperative control of a biliodigestive anastomosis is possible with ICG fluorescence cholangiography and therefore reduces morbidity. Even primary and secondary liver tumors can be detected with ICG fluorescence. Whereas well-differentiated HCCs homogeneously take up ICG, poorly differentiated HCCs and metastases do not: however, in these cases the adjacent liver parenchyma stores ICG more intensively than healthy liver tissue, which creates aring-like fluorescence pattern. To conclude, the use of ICG fluorescence in hepatobiliary surgery is diverse but in Germany it is still at the beginning compared to other countries.

Congenital Portosystemic Shunts in Children: Associations, Complications, and Outcomes.

Congenital portosystemic shunt (CPSS) is a rare malformation in which splanchnic venous flow bypasses the liver. CPSS is associated with other congenital anomalies and syndromes and can be associated with life-threatening complications. CPSS and their management remain underreported in the literature. Here, we review the clinical characteristics, management, and outcomes of a cohort of children and young adults with CPSS from two pediatric centers. Cases of CPSS from Cincinnati Children's Hospital Medical Center and C.S. Mott Children's Hospital were reviewed to define CPSS anatomy, associated anomalies, complications, interventions, and outcomes. The imaging features and histopathology of liver lesions were characterized in detail. A total of 11 cases were identified. Median age was 10years (range 0-26); 8 (73%) cases were female. Associated anomalies included six patients with heterotaxy (55%), five patients with congenital heart disease (45%), three patients with Turner syndrome (27%), and two patients with omphalocele, exstrophy, imperforate anus, spinal defects (OEIS) complex (18%). Eight (73%) cases had hyperammonemia ± encephalopathy. A 4-month-old presented with hepatopulmonary syndrome, and 12-year-old presented with pulmonary hypertension. Eight patients (73%) had liver lesions including five with premalignant adenomas and three with well-differentiated hepatocellular carcinoma (HCC). Four children underwent successful CPSS occlusion/ligation. Three children underwent liver transplant (2) or resection (1) for HCC without recurrence at extended follow-up. CPSS is associated with multiple anomalies (heterotaxy, congenital heart disease) and syndromes (Turner syndrome). CPSS liver lesions should be very carefully evaluated due to risk of premalignant adenomas and HCC. Serious complications of CPSS can occur at a young age but can be managed endovascularly or with open surgery.

Characteristics of atypical large well-differentiated hepatocellular carcinoma: a specific subtype of hepatocellular carcinoma?

BackgroundHepatocellular carcinoma (HCC) de-differentiation is thought to correlate with size, therefore well-differentiated HCC ≥3 cm are considered rare and not fully understood. MethodsPatients who underwent hepatectomy for HCC between 1998–2016 were retrospectively analyzed. Patient's characteristics and recurrence-free (RFS) and overall (OS) survival were compared between those with atypical- (well-differentiated-HCC ≥3 cm) and typical-HCC (moderate-to-poorly-differentiated HCC ≥3 cm). ResultsOf 176 patients included in this study, 37 (21%) had atypical-HCC. Patients with atypical-HCC were less likely to be Asian ethnicity (3% vs. 17%, p = 0.062), have lower rate of viral infection (14% vs. 43%, p = 0.003), cirrhosis (8% vs. 27%, p = 0.015). The tumors were less likely to demonstrate vascular invasion (30% vs. 59%, p = 0.002), and were associated with a lower alpha-fetoprotein level (3.5 ng/ml vs. 33.2 ng/ml, p < 0.001). Patients with atypical-HCC had a longer RFS (5-y RFS: 58.3% vs. 35.7%, p = 0.016) and OS (5-y OS: 79.1% vs 53.3%, p = 0.029) as compared to those with typical-HCC following univariate analysis, however this did not appear following multivariate analysis. ConclusionPatients with atypical-HCC have different characteristic in terms of epidemiology, etiology, cirrhosis and vascular invasion as compared to typical-HCC. The etiology of atypical-HCC may be non-alcoholic fatty liver disease-related and/or malignant transformation of hepatocellular adenoma.

Immunohistochemical Study of Cell Proliferation in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), the most common primary liver cancer, with a poor prognosis, is the fifth most common cancer in men and the seventh in women. The study was made on 32 surgically removed liver carcinomas. In order to compare results, we included a group of non-tumor lesions obtained by liver biopsy. Assessment of the proliferative activity of the studied liver lesions was made using immunohistochemical stains with the monoclonal Ki-67 antibody, clone MIB-1 ready-to-use (DAKO Cytomation CA, USA), in the LSAB-HRP work system. To appreciate the proliferation index of Ki-67 (PI Ki-67), we used the semi-automated method of counting the nuclei on digital images. The statistical analysis was performed using SPSS software, Version 20.0 (IBM SPSS Statistics) and Microsoft Office Excel 2007. Mean value of Ki-67 index was 0.4 � 0.2 in normal liver, 3.52 � 0.2 in non-tumor liver lesions and 13.4�7.7 in HCC (p [ 0.001). In chronic hepatitis, PI Ki-67 varied between 2.5 and 5.8 %, with a mean value of 5.2% in portal chronic hepatitis and 5.5% in active chronic hepatitis with cirrhotic evolution. In HCC, the values of Ki-67 index were between 0.7% and 52%, with a mean of PI Ki-67 of 13.43�7.7. 66.6% of HCC associated with hepatitis B virus infection and those developped from a cirrhotic lesion had a high Ki-67 score (p = 0.1). The results we obtained showed: a low Ki-67 score in patients with well-differentiated HCC (G1) (p[0.001), with or without capsule infiltration (p = 0.003); high PI Ki-67 in 33.33% of HCC detected in the right hepatic lobe and those extended bilaterally at the moment of diagnosis (p = 0.142) and a significant relationship between high Ki-67 score and vascular invasion (p [ 0.001), the presence of intrahepatic metastasis being correlated with a high proliferative rate (p [ 0.001). Differences between the proliferation rate of HCC and non-tumor liver lesions (p [ 0.001) show that the uncontrolled division of tumor cells can play an important role in the developpment of HCC.

Hepatocellular carcinoma grading and recurrence prediction using T1 mapping on gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging.

The aim of the present study was to explore the value of T1 mapping on gadolinium-ethoxybenzyl diethylenetriamine pentaacetic (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for grading hepatocellular carcinoma (HCC) and predicting its recurrence rate. A retrospective study was performed that included 75 patients (66 men and 9 women; mean age, 52.89 years; age range, 23–79 years) with HCC who had undergone Gd-EOB-DTPA-enhanced MRI with T1 mapping before surgery. The T1 relaxation time of the 81 lesions and non-tumorous liver parenchyma in 75 patients with HCC were measured before Gd-EOB-DTPA was injected and then at 5, 10 and 20 min after administration, respectively. T1[lesion (L)-hepatic parenchyma (H)]/H (%) was calculated as the increment rate of the T1 value in the lesions relative to the non-tumorous liver parenchyma. One-way analysis of variance and Spearman's correlation analysis was used to compare the differences and relationship of T1 mapping values among the three grades of HCC. A total of 81 lesions were divided into well-differentiated HCC (grades I; n=21), moderately differentiated HCC (grades II; n=40) and poorly differentiated HCC (grades III; n=20) according to the histopathology. The T1(L-H)/H (%) value among grades I, II and III HCC on pre-contrast results and on post-contrast results at the 5-, 10- and 20-min hepatobiliary phase (HBP) were significantly different (P<0.05), and T1(L-H)/H (%) was correlated with the histological grade of HCC at each time point (r=0.637, r=0.554, r=0.499 and r=0.560, respectively, P<0.001). A total of 41 recurrence cases [grade I (n=5), grade II (n=23) and grade III (n=13)] were verified by imaging (CT, MRI or ultrasound) or reoperation. Patients with grade III and grade II HCC had higher recurrence rates compared with that in patients with grade I HCC (P<0.05; median recurrence times were 258 days, 605 days and undefined, respectively). According to the optimal cut-off point for the T1(L-H)/H (%) of the three grades of HCC, patients with HCC in the low T1(L-H)/H (%) value group (≤155.15%) had lower cumulative recurrence rates compared with that in the medium (T1(L-H)/H (%) >155.15% and T1(L-H)/H (%) ≤241.20%) and high (T1(L-H)/H (%) >241.20%) value groups at the 20-min HBP (P<0.05; median recurrence times were undefined, 530 days and 447 days, respectively). These results indicate that the parameters of T1 mapping would be beneficial for predicting the grading and recurrence of HCC.

Abstract 5172: Deposition of platelets in sinusoids and its contribution to hepatocarcinogenesis

Abstract Platelets can activate hepatocyte proliferation not only via releasing the platelet factors, but also promoting for liver sinusoidal endothelial cells (LSEC) and Kupffer cells to produce the factors such as IL-6 and TGF-α that are indispensable for hepatocyte proliferation. We previously reported that in the transgenic (TG) mice with liver specific human BRAFV600E mutation, which corresponds to the mouse BrafV637E that is highly prevalent in mouse DEN-induced hepatic tumors, exhibit increased liver weight five times larger than that of normal mice. Furthermore, hepatocytes in these mice overexpress thrombopoietin (TPO) in association with megakaryocytosis/thrombocytosis, and large numbers of platelets were deposited in the liver sinusoids. In the present study, we investigated whether platelets are deposited in liver sinusoids in hepatic tumors in human and mice. CD61 immunohistochemical staining revealed the increased numbers of platelets were deposited in the sinusoids in foci, adenomas and hepatocellular carcinomas (HCC) induced by neonatal treatment with DEN compared to surrounding normal hepatic tissues. Moreover, increased numbers of platelets were deposited in sinusoids of dysplastic nodules and well-differentiated HCC compared to normal liver tissue and cirrhotic nodules in human. In addition, we evaluated the correlation between the tumor diameters and peripheral platelets numbers in the patients who were primarily diagnosed as HCC in our institute. The result indicated that the numbers of peripheral platelets are positively correlated with the tumor diameters. These results indicate that platelets contribute to development of HCC via interacting sinusoidal cells. Citation Format: Hiroki Tanaka, Kie Horioka, Masahiro Yamamoto, Koji Sawada, Takumu Hasebe, Kosuke Yamazaki, Katsuhiro Ogawa. Deposition of platelets in sinusoids and its contribution to hepatocarcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5172.

Antitumor efficacy of biosynthesized manganese nanoparticles

This study aimed to evaluate the in vitro and in vivo antitumor potential of manganese nanoparticles, in management of hepatocellular carcinoma (HCC) induced in rats. Manganese nanoparticles were biosynthesized using Lactobacillus helveticus cells. In vitro study of manganese nanoparticles on HepG-2 (human cell line of a well-differentiated HCC) revealed an IC50 of 21.5 mM. The in vivo efficacy of manganese nanoparticles was evaluated by measuring the antioxidant activities against oxidative stress caused by diethylnitrosamine (DEN) in rates liver tissues. This treatment significantly improved the alanine aminotransferase (ALT) activity and total protein compared to DEN group. Results showed that manganese nanoparticles were effective in treatment of HCC induced by diethylnitrosamine (DEN) in rats. So manganese nanoparticles can serve as a good therapeutic agent for the treatment of hepatocellular carcinoma, and deserve further studies in the future.

Serum Biomarkers AFP, CEA And CA19-9 Combined Detection for Early Diagnosis of Hepatocellular Carcinoma

We aimed to evaluate the whether AFP levels alone is an adequate screening indicator, or a combination of Generally, alpha-fetoprotein (AFP), CA19-9 and CEA could provide a better diagnostic tool in detecting and screening asymptomatic patients with primary hepatic cancer (PHC), and also evaluate the correlation of degree of differentiation with serum biomarker levels. We retrospectively reviewed the medical records of 1362 patients form 2014-2018 who visited the first Affiliated Hospital of Zhejiang University, Hangzhou, China for health check-ups or were diagnosed with cancer or cirrhosis. We then analyzed preoperative tumor markers level of AFP, CA19-9, and CEA. The standard reference values (AFP ≤20 ng/L CEA ≤ 5 ng/L, and CA19-9 ≤ 37 U/mL) were as positive or negative cut off values. Further, the histological sections of patients were categorized and correlated them with the three serum biomarkers. Serum AFP, CEA, and CA19-9 levels in the PHC group were significantly higher compared to those with liver cirrhosis and healthy control groups (P < 0.03). With AFP as a single tumor marker for PHC diagnosis, it had a sensitivity of 63.3% with a specificity of 80.8%. AFP combined with CA19-9 and CEA showed specificity of 100%, a sensitivity 2.5% with the positive and negative predictive values of 100% and 22% respectively. Furthermore, histological evaluation revealed the highest AFP level of 9366.14±23902.61 ng/L associated with poorly differentiated HCC, while well-differentiated HCC, had the lowest mean AFP level of 45.19±181.27 ng/L. Combined serum levels of AFP, CA19-9 and CEA does not provide a superior advantage over AFP alone as a screening and diagnostic tool for HCC detection.

Noninvasive Evaluation of the Pathologic Grade of Hepatocellular Carcinoma Using MCF-3DCNN: A Pilot Study.

Purpose To evaluate the diagnostic performance of deep learning with a multichannel fusion three-dimensional convolutional neural network (MCF-3DCNN) in the differentiation of the pathologic grades of hepatocellular carcinoma (HCC) based on dynamic contrast-enhanced magnetic resonance images (DCE-MR images). Methods and Materials Fifty-one histologically proven HCCs from 42 consecutive patients from January 2015 to September 2017 were included in this retrospective study. Pathologic examinations revealed nine well-differentiated (WD), 35 moderately differentiated (MD), and seven poorly differentiated (PD) HCCs. DCE-MR images with five phases were collected using a 3.0 Tesla MR scanner. The 4D-tensor representation was employed to organize the collected data in one temporal and three spatial dimensions by referring to the phases and 3D scanning slices of the DCE-MR images. A deep learning diagnosis model with MCF-3DCNN was proposed, and the structure of MCF-3DCNN was determined to approximate clinical diagnosis experience by taking into account the significance of the spatial and temporal information from DCE-MR images. Then, MCF-3DCNN was trained based on well-labeled samples of HCC lesions from real patient cases by experienced radiologists. The accuracy when differentiating the pathologic grades of HCC was calculated, and the performance of MCF-3DCNN in lesion diagnosis was assessed. Additionally, the areas under the receiver operating characteristic curves (AUC) for distinguishing WD, MD, and PD HCCs were calculated. Results MCF-3DCNN achieved an average accuracy of 0.7396±0.0104 with regard to totally differentiating the pathologic grade of HCC. MCF-3DCNN also achieved the highest diagnostic performance for discriminating WD HCCs from others, with an average AUC, accuracy, sensitivity, and specificity of 0.96, 91.00%, 96.88%, and 89.62%, respectively. Conclusions This study indicates that MCF-3DCNN can be a promising technology for evaluating the pathologic grade of HCC based on DCE-MR images.

18F-FDG PET/CT AS AN ASSESSMENT TOOL OF HEPATOCELLULAR CARCINOMA SECONDARY TO NON-ALCOHOLIC FATTY LIVER DISEASE DEVELOPMENT IN EXPERIMENTAL MODEL.

Hepatocellular carcinoma (HCC) can be the last step of non-alcoholic fatty liver disease (NAFLD) evolution. Experimental models are crucial to elucidate the pathogenesis of HCC secondary to NAFLD. The 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in evaluating HCC development and progression. To standardize the imaging method of PET/CT with 18F-FDG as an evaluation tool of the experimental model of HCC secondary to NAFLD. Ten male Sprague-Dawley rats were fed with choline-deficient high-fat diet and diethylnitrosamine (DEN) in the drinking water for 16 weeks and then received 1 mL of saline solution (0.9%) daily by gavage for three weeks. At the 16th and 19th weeks, abdominal ultrasonography (USG) was performed. 18F-FDG PET/CT images were obtained before the beginning of experiment (week 0) and at the end (week 19). Histological and immunohistochemically analysis were also performed. The USG results showed a homogeneous group at the 16th week with an average of 4.6±2.74 nodules per animal. At the 19th week, PET/CT findings demonstrated an average of 8.5±3.7 nodules per animal. The mean values of SUVmed and SUVmax were 2.186±0.1698 and 3.8±1.74, respectively. The average number of nodules per animal in the histological analysis was 5.5±1.5. From all nodules, 4.6% were classified as well-differentiated HCC and 81.8% were classified as poorly-differentiated HCC. 18F-FDG PET/CT was able to evaluate the development of HCC in an experimental model of NAFLD non-invasively. From the standardization of PET/CT in this model, it is possible to use this tool in future studies to monitor, in vivo and non-invasively, the progression of HCC.

The Diagnostic Value of Arginase-1, FTCD, and MOC-31 Expression in Early Detection of Hepatocellular Carcinoma (HCC) and in Differentiation Between HCC and Metastatic Adenocarcinoma to the Liver

Early detection of small HCC and differentiation between HCC from AC metastatic to the liver is very essential for surgical pathologists, due to different treatment modalities. Immunohistochemistry plays a very important role in such conditions. In our study, we aimed to identify the diagnostic benefits of Arginase-1, FTCD& MOC-31 in the early detection of HCC in normal or cirrhotic liver, differentiation between HCC and metastatic ACs to the liver, and for early detection of small micro-metastases from ACs to liver. We included 20 samples from liver cirrhosis, 10 samples from normal liver tissue, 30 samples from primary HCCs in the liver, and 30 samples from metastatic ACs to the liver. We have evaluated Arginase-1, FTCD, and MOC-31 expression using immunohistochemistry. The sensitivity of Arginase-1 expression in differentiation between HCC and metastatic carcinoma was 93.3% and the specificity was 93.3%. The sensitivity of FTCD expression in differentiation between HCC and normal or cirrhotic liver and early detection of well-differentiated HCC was 90% and the specificity was 86.7%. The sensitivity of MOC-31 expression in differentiation between HCC and metastatic carcinoma was 90% and the specificity was 90%. The sensitivity of combination of panel of Arginase 1 + FTCD + MOC 31 expression in differentiation between HCC, metastatic carcinoma, and normal and cirrhotic liver was 93.3% and the specificity was 93.3%. The combination of Arginase 1 + FTCD + MOC 31 expression was helpful in diagnosing most cases of HCC and metastatic carcinoma with high sensitivity and specificity.

Diagnosis of Liver Neoplasms by Computational and Statistical Image Analysis.

BackgroundDistinguishing well-differentiated hepatocellular carcinoma (WD-HCC), hepatocellular adenoma (HA) and non-neoplastic liver tissue (NNLT) solely on morphology is often challenging. The purpose of this study was to evaluate the use of computational image analysis to distinguish WD-HCC, HA and NNLT.MethodsSeventy-seven cases comprising of WD-HCC (n = 26), HA (n = 23) and NNLT (n = 28) were retrieved and reviewed. A total of 485 hematoxylin and eosin (H&E) photomicrographs (× 400, 0.09 µm2) of WD-HCC (n = 183), HA (n = 173), NNLT (n = 129) and nine whole-slide scans (three of each diagnosis) were obtained, color deconvoluted and digitally transformed. Quantitative data including nuclear density, nuclear sphericity, nuclear perimeter, and nuclear eccentricity from each image were acquired. The data were analyzed by one-way analysis of variance (ANOVA) with Tukey post hoc test, followed by unsupervised and supervised (Chi-square automatic interaction detection (CHAID)) cluster analysis.ResultsUnsupervised cluster analysis identified three well defined clusters of WD-HCC, HA and NNLT. Employing the four most discriminating nuclear features, supervised analysis was performed on a training set of 383 images, and validated on the remaining 102 test images. The analysis identified WD-HCC (sensitivity 100%, specificity 98%), HA (sensitivity 71%, specificity 85%) and NNLT (sensitivity 70%, specificity 86%). An analysis of whole-slide images identified WD-HCC with sensitivity and specificity of 100%.ConclusionsWe have successfully demonstrated that computational image analysis of nuclear features can differentiate WD-HCC from non-malignant liver with high accuracy, and can be used to assist in the histopathological diagnosis of hepatocellular carcinoma.

Malignant degeneration of hepatic adenomas to hepatocellular carcinoma

Background Hepatic adenomas (HA) are rare, benign proliferations of hepatocytes with high glycogen and fat content that lack normal hepatic architecture. In general, the long-term incidence of malignant degeneration to HCC has not been well characterized. This case report discusses a 37 male with a 10-year history of weekly anabolic steroid abuse who presented with bilobar hepatic adenomas with subsequent malignant degeneration to hepatocellular carcinoma (HCC). Case Presentation Our patient is a 37 old male with a 10-year history of weekly anabolic steroid abuse who presented to his primary care physician (PCP) in July 2013 with intermittent right upper quadrant (RUQ) pain. He was subsequently referred to our cancer center after abdomen/pelvis computed tomography (CT A/P) with oral and intravenous (IV) contrast at an outside hospital revealed two large hepatic masses. The larger mass in segment 2 measured 6.5 x 9.1 cm, while the segment 6/7 mass measured 7.5 x 7.6 cm. Abdomen magnetic resonance imaging (MRI) with and without IV contrast performed at our institution on July 23, 2013 confirmed the presence of the two above noted masses, which were felt to be consistent with probable HA, although HCC could not be definitely ruled out. Of note, his carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) were within normal limits. Percutaneous, ultrasound-guided (US) biopsy of the left lobe mass was consistent with probable HA, although HCC could not be definitely ruled out. Conclusion We present the case of a 37-year-old male 10-year history of weekly anabolic steroid abuse who presented to us in 2013 with HA which had malignant degeneration to HCC while on surveillance over a 2-year period. This case report stresses the importance of having a high clinical suspicion for HA in patients with a history of anabolic steroid abuse and liver masses. Additionally, it reiterates that it can be difficult to differentiate HA from well-differentiated HCC on imaging and/or with a limited biopsy. Furthermore, it is important to keep in mind that the growth of a mass, especially off steroids is highly concerning for malignancy (and masses that fail to regress completely can harbor occult HCC).

Application of real-time contrast-enhanced ultrasound in differential diagnosis of liver malignancies.

The objective of this study was to evaluate the value of real-time contrast-enhanced ultrasound in differential diagnosis of malignant liver tumors. Sixty patients pathologically diagnosed with liver cancer from May 2016 to May 2017 were selected as the subjects. All patients received ultrasonic diagnosis followed by the observation on dynamic contrast enhancement of the image and the analysis on perfusion characteristics and difference in contrast-enhanced ultrasound results in patients with different types of liver cancer. The signal during the arterial phase of 21 patients with well-differentiated hepatocellular carcinoma increased, including 12 cases of slow withdrawal of portal venous phase. The relative height of artery of 30 patients with middle-low differentiation of hepatocellular carcinoma increased along with the speed at which the contrast media was washed out at the end of the portal phase. In 9 patients with intrahepatic bile duct cancer, the enhancement of the arteries was slightly increased in the periphery of the tumor and low enhancement was found in the portal venous phase. There were some differences in the timing and the intensity of the enhancement of the ultrasound signals with 3 different types of diseases (P < 0.05). There are obvious differences in real-time contrast-enhanced ultrasound features of patients with different types of malignant liver tumor, which may provide references for clinical diagnosis.