Moderately-differentiated Hepatocellular Carcinoma Research Articles

Dendritic cell-cytokine killer combined with microwave ablation reduced recurrence for hepatocellular carcinoma compared to ablation alone.

Several international practice guidelines have recommended local ablation as the first-line treatment for early-stage hepatocellular carcinoma (HCC). This study aims to investigate the synergetic anti-tumor impact of dendritic cell-cytokine killer (DC-CIK) combined with microwave ablation (MWA) for HCC. This retrospective study included 1,141 patients from the American Joint Committee on Cancer stage I-II HCC, who were treated with therapeutic MWA. The immunotherapy group encompassing 40 patients received additional immunotherapy with DC-CIK, whereas the control group consisting of 1,101 patients was treated with MWA alone. Propensity score matching (PSM) with ratio of 1:3 was employed to balance selection bias. The oncological outcome and immune status were measured after combination therapy. The immunotherapy group patients exhibited significant longer disease-free survival (DFS, primary HCC: p= 0.036; recurrent HCC: p= 0.026). For patients with primary HCC, the recurrence frequency was reduced (p= 0.002), and recurrence interval (19 months vs. 9 months, p< 0.001) was prolonged in the immunotherapy group. Subgroup analysis revealed that patients ⩽ 60 years old, moderately-differentiated HCC, or co-infected with Hepatitis B Virus (HBV) had a significant benefit over DFS in the immunotherapy group. After combination therapy, the serum CD3+ (p= 0.049), CD8/CD28+ (p= 0.045) were elevated. Combination therapy with DC-CIK and MWA can significantly reduce the recurrence and prolong DFS, especially for patients ⩽ 60 years old or with moderately-differentiated HCC or co-infected with HBV.

Hepatocellular Carcinoma's Characteristics in an Endemic Country: A Closer Examination of Tumor Grade and Microvascular Invasion

Objective: Although histological grade and microvascular invasion are known predictors for patient survival and recurrence in hepatocellular carcinoma (HCC), their relationship with various clinical and histomorphological features of HCC remains unclear. Materials and Methods: Medical records were retrieved from 61 patients who were diagnosed with HCC from 2008-2018. Clinical and histomorphological variables that were hypothesized to be associated with histological grade and microvascular invasion were analyzed statistically using the Chi-square test or the Fisher’s exact test as alternatives. Multivariate analysis was performed with logistic regression model. Results: The majority of the patients had well to moderately-differentiated HCC (67.2%) with some of them presenting microvascular invasion (57.4%). Alpha-fetoprotein level (AFP) ≥100 ng/ml (p=0.036), tumor size &gt;7cm (p=0.031) and mitotic index ≥5 per 10 high power field (p=0.009) were significantly correlated with poorly-differentiated HCC. Mitotic Index ≥5 per 10 high power field was an independent factor for poorly differentiated HCC. Meanwhile BCLC stage B and mitotic index were also an independent factor for the presence of microvascular invasion. Conclusion: Larger tumor size and higher mitotic index was significantly correlated and independent factors for poorly differentiated HCC and microvascular invasion. In biopsy specimens for which the microvascular invasion is difficult to assess, histological grade, tumor size and mitotic index may be beneficial to depict the prognosis of patients with HCC.

Metastatic lung tumor from hepatocellular carcinoma with tumor thrombus invasion in the pulmonary vein: a case report

BackgroundMetastatic lung tumor with a tumor thrombus in the peripheral pulmonary vein is very rare. We present a case of a metastatic lung tumor from hepatocellular carcinoma (HCC) with tumor thrombus invasion in the pulmonary vein that was diagnosed preoperatively and underwent complete resection by segmentectomy.Case presentationA 77-year-old man underwent laparoscopic lateral segment hepatectomy for HCC eight years ago. Protein induced by vitamin K absence or antagonist-II remained elevated from two years ago. Contrast-enhanced chest computed-tomography (CT) showed a 27 mm nodule in the right apical segment (S1). He was pathologically diagnosed with a metastatic lung tumor from HCC via transbronchoscopic biopsy. We planned to perform right S1 segmentectomy. Before surgery, contrast-enhanced CT in the pulmonary vessels phase for three-dimensional reconstruction showed that the tumor extended into the adjusting peripheral pulmonary vein, and we diagnosed tumor thrombus invasion in V1a. The surgery was conducted under 3-port video-assisted thoracic surgery. First, V1 was ligated and cut. A1 and B1 were cut. The intersegmental plane was cut with mechanical staplers. Pathological examination revealed moderately-differentiated metastatic HCC with tumor thrombus invasions in many pulmonary veins, including V1a. No additional postoperative treatments were performed.ConclusionsAs malignant tumors tend to develop a tumor thrombus in the primary tumor, it might be necessary to perform contrast-enhanced CT in the pulmonary vessel phase to check for a tumor thrombus before the operation for metastatic lung tumors.

Pre-operative MRI features predict early post-operative recurrence of hepatocellular carcinoma with different degrees of pathological differentiation

PurposeTo investigate the value of pre-operative gadoxetate disodium (Gd-EOB-DTPA) enhanced MRI predicting early post-operative recurrence (< 2 years) of hepatocellular carcinoma (HCC) with different degrees of pathological differentiation.MethodsRetrospective analysis of pre-operative MR imaging features of 177 patients diagnosed as suffering from HCC and that underwent radical resection. Multivariate logistic regression assessment was adopted to assess predictors for HCC recurrence with different degrees of pathological differentiation. The area under the curve (AUC) of receiver operating characteristics (ROC) was utilized to assess the diagnostic efficacy of the predictors.ResultsAmong the 177 patients, 155 (87.5%) were males, 22 (12.5%) were females; the mean age was 49.97 ± 10.71 years. Among the predictors of early post-operative recurrence of highly-differentiated HCC were an unsmooth tumor margin and an incomplete/without tumor capsule (p = 0.037 and 0.033, respectively) whereas those of early post-operative recurrence of moderately-differentiated HCC were incomplete/without tumor capsule, peritumoral enhancement along with peritumoral hypointensity (p = 0.006, 0.046 and 0.004, respectively). The predictors of early post-operative recurrence of poorly-differentiated HCC were peritumoral enhancement, peritumoral hypointensity, and tumor thrombosis (p = 0.033, 0.006 and 0.021, respectively). The AUCs of the multi-predictor diagnosis of early post-operative recurrence of highly-, moderately-, and poorly-differentiated HCC were 0.841, 0.873, and 0.875, respectively. The AUCs of the multi-predictor diagnosis were each higher than for those predicted separately.ConclusionsThe imaging parameters for predicting early post-operative recurrence of HCC with different degrees of pathological differentiation were different and combining these predictors can improve the diagnostic efficacy of early post-operative HCC recurrence.

Electrical conductivity spectra of hepatic tumors reflect hepatocellular carcinoma progression in mice

Background: Electrical impedance spectroscopy is a technique which evaluates differences in dielectric properties of tissues for cancer identification. Methods: Murine hepatic cancer model was developed by intraperitoneal administration of N-nitrosodiethylamine to male BALB/c mice. Tumors obtained were evaluated for their conductivity in frequency range of (4 Hz–5 MHz). All tumors were subjected to histopathological grading and parameters such as free spacing, necrosis, and cell density were estimated on histological slides. The status of gap junctions and gap junction intercellular communication (GJIC) were studied using enzyme-linked immunosorbent assay, immunohistochemistry, dye transfer assay, and electron microscopy. Results: Histopathological investigation revealed the presence of moderately to poorly-differentiated hepatocellular carcinoma (HCC) in mice. All types of tumors showed higher electrical conductivity than normal liver tissue in frequency range (4 Hz–1 kHz). However, in frequency range (10 kHz–5 MHz) only poorly-differentiated tumors showed higher conductivity compared to normal tissue. The most prominent findings in moderately-differentiated and poorly-differentiated HCC were increased visible free spaces and necrosis respectively. The status of cell gap junctions were significantly deteriorated in tumors and a corresponding significant reduction in GJIC was also observed. These biological indicators were correlated with electrical conductivity of hepatic tumors. Conclusion: Variations in electrical conductivity spectra of hepatic tumors reflect progression of HCC. General significance: Future studies can be planned to perform hierarchical clustering of dielectric parameters with more number of tumor samples to establish dielectric spectroscopy-based classification or staging of hepatic tumors.

S2469 A Rare Case of Hepatocellular Carcinoma With Isolated Recurrence to the Stomach

INTRODUCTION: Hepatocellular carcinoma (HCC) is the sixth-most common cancer worldwide and fourth leading cause of cancer-related mortality according to the WHO. It primarily metastasizes to the lungs, lymph nodes, and bones. Metastases of HCC to the gastrointestinal (GI) tract and specifically to the stomach are very infrequent. In this report, we present a unique case of HCC metastatic to the stomach. CASE DESCRIPTION/METHODS: A 61-year-old African-American (AA) female with hepatitis C-related cirrhosis complicated by HCC, originally diagnosed in 2015 and managed by partial hepatic resection. In April 2020, she underwent routine HCC surveillance imaging. MRI abdomen and pelvis (Figure 1) demonstrated no new liver lesions but was significant for an isolated 3.4 × 2.7 cm mass that was identified at the greater curvature of the stomach. She underwent upper endoscopy with endoscopic ultrasound revealing a 3.1 × 2.9 cm hypoechoic mass (Figure 2). Fine needle aspiration biopsy was performed, and pathology demonstrated an epithelioid mass compatible with HCC. Immunohistochemistry staining was positive for Cam5.2, glypican-3, and hepatocyte (partial) positive, confirming metastatic HCC. CT chest was negative for intrathoracic metastasis. The patient underwent partial gastrectomy in May 2020 given the isolated metastatic gastric lesion. Surgical pathology confirmed the diagnosis of moderately-differentiated metastatic HCC. DISCUSSION: We report a very rare case of metastatic HCC in an asymptomatic AA female, diagnosed on routine surveillance imaging for HCC. To our knowledge, this is the first reported case of HCC metastatic to the stomach in an African-American. Cases of HCC metastatic to the GI tract are exceedingly rare. The majority of cases of HCC with metastatic lesions in the stomach occur by direct extension rather than by hematologic dissemination. In documented cases, patients have presented most frequently with either iron deficiency anemia or abdominal pain. Almost all the reported cases have occurred in non-white individuals, and most have occurred in patients of East Asian ethnicities.Figure 1.: Greater curvature gastric mass.Figure 2.: EUS image of gastric mass.

Texture analysis of MR images to identify the differentiated degree in hepatocellular carcinoma: a retrospective study

BackgroundTo explore the clinical value of texture analysis of MR images (multiphase Gd-EOB-DTPA-enhanced MRI and T2 weighted imaging (T2WI) to identify the differentiated degree of hepatocellular carcinoma (HCC).MethodOne hundred four participants were enrolled in this retrospective study. Each participant performed preoperative Gd-EOB-DTPA-enhanced MR scanning. Texture features were analyzed by MaZda, and B11 program was used for data analysis and classification. The diagnosis efficiencies of texture features and conventional imaging features in identifying the differentiated degree of HCC were assessed by receiver operating characteristic analysis. The relationship between texture features and differentiated degree of HCC was evaluated by Spearman’s correlation coefficient.ResultsThe grey-level co-occurrence matrix -based texture features were most frequently extracted and the nonlinear discriminant analysis was excellent with the misclassification rate ranging from 3.33 to 14.93%. The area under the curve (AUC) of the combined texture features between poorly- and well-differentiated HCC, poorly- and moderately-differentiated HCC, moderately- and well-differentiated HCC was 0.812, 0.879 and 0.808 respectively, while the AUC of tumor size was 0.649, 0.660 and 0.517 respectively. The tumor size was significantly different between poorly- and moderately-HCC (p = 0.014). The COMBINE AUC values were not increased with tumor size combined.ConclusionsTexture analysis of Gd-EOB-DTPA-enhanced MRI and T2WI was valuable and might be a promising method in identifying the differentiated degree of HCC. The poorly-differentiated HCC was more heterogeneous than well- and moderately-differentiated HCC.

Expression of c-MET Protein in Various Subtypes of Hepatocellular Adenoma Compared to Hepatocellular Carcinoma and Non-Neoplastic Liver in Human Tissue

Hepatocellular adenoma (HA) is a benign neoplasm of the liver, whose aetiopathogenesis is little known. Newest research allowed dividing all cases into three types based on molecular characteristics: inflammatory HA, HA with HNF1A mutation, β-catenin- mutated HA. The clinical significance of HA is chiefly due to the possibility of malignant transformation into hepatocellular carcinoma (HCC). The aim of the present study was to immunohistochemically assess the expression pattern and level of c-MET protein in hepatocellular adenoma (taking into account its status of Wnt/β-catenin pathway functioning) and intertwining the results into a wider pattern of expression in non-neoplastic liver and hepatocellular carcinoma of various histological grades. It was found that expression of c-MET in poorly-differentiated HCC was significantly higher than in non-neoplastic liver and well- to moderately-differentiated HCC. The expression in HA was variable and differed between molecular subtypes of this neoplasm: inflammatory and HNF1A mutation-associated type are characterized by overexpression of c-MET to an extent comparable with poorly-differentiated HCC, whereas Wnt/β-catenin dysfunction-associated type lacks overexpression, and the amount of c-MET protein accumulated in its cells is similar to the levels in non-neoplastic tissue and well- to moderately-differentiated HCC. These findings suggest that c-MET overexpression in HA is not an early event in hepatocarcinogenesis, but constitutes a divergent molecular pathway leading to neoplastic change compared to overexpression observed in the late stages of tumour progression.

Intensity-Based Assessment of Microbubble-Enhanced Ultrasonography: Phase-Related Diagnostic Ability for Cellular Differentiation of Hepatocellular Carcinoma

This prospective study aimed to elucidate the effect of phase-related quantitative parameters of contrast-enhanced ultrasound (CEUS) with perflubutane microbubble agent to assess the cellular differentiation of hepatocellular carcinoma (HCC). Intensity was analyzed in 94 lesions (19.4 ± 4.9 mm, 86 patients), 47 well-differentiated HCCs (wHCCs) and 47 moderately-differentiated HCCs (mHCCs): Ie (early phase) = Ite (tumor) − Ile (liver), Ip (post-vascular phase) = Itp (tumor) − Ilp (liver), Iep = Ie − Ip. The area under the receiver operating characteristic curve with the best cutoff value (Ie, 13.2, Ip, −4.5, Iep, 21.3) for discriminating between wHCC and mHCC was 0.6922 for Ie, 0.7680 for Ip and 0.7925 for Iep, which indicated a significantly greater ability to differentiate between wHCC and mHCC compared with visual/qualitative assessment (early phase, 0.6170, p = 0.04; post-vascular phase, 0.6702, p = 0.01; both phases, 0.7021, p = 0.04). In conclusion, Iep was found to have the highest diagnostic ability, suggesting it is a promising parameter for the cellular differentiation of HCCs with CEUS.

Hepatocellular carcinoma presenting as thoracic spinal canal metastasis with no clinical primary foci: A report of a rare case and review of the literature.

Hepatocellular carcinoma (HCC) is the third most common malignant tumor worldwide and has a poor survival rate. The poor prognosis can be attributed to several of the characteristics of HCC, such as fast infiltrating growth, early-stage metastasis, high-grade malignancy and poor therapeutic efficacy. The current study presents a case of HCC that was metastatic to the spinal canal with an unknown primary site and discusses the diagnostic probabilities. The patient was a 48-year-old female who presented with chest paraesthesis of the back and numbness of the right lower limb. Computed tomography (CT) and magnetic resonance imaging indicated a possible lipomyoma in the thoracic spinal canal. Surgery was performed to remove the mass and the post-operative pathological diagnosis indicated a moderately-differentiated HCC. Subsequent abdominal CT scans and B-mode ultrasound failed to localize the primary foci in the liver and the tumor markers were normal. The patient had no history of chronic liver disease in the past. The patient refused any further examinations after surgery and was discharged from hospital. A post-operative follow-up 1.5 years later found that the patient was healthy and that the level of discomfort had been significantly reduced following the surgery. HCC presenting as thoracic spinal canal metastasis with an unknown primary site is extremely rare. The present study additionally reports the results of a literature review and provides a rational deduction for the unknown primary foci of HCC.

Case of hepatocellular carcinoma with multicentric Castleman's disease

A 27-year-old man and known hepatitis B carrier was incidentally found to have an 8-cm right lobe liver mass on computed tomography during evaluation of his recurrent pneumothorax. The α-fetoprotein was markedly elevated at 34834 ug/L. Dual-tracer positron emission tomography showed F-fluorodeoxyglucose (FDG)-avid and C-acetate non-avid liver mass (Fig. 1a). There were multiple hypermetabolic foci in portal, perigastric and left para-aortic lymph nodes and the mesentery (Fig. 1b). A clinical diagnosis of hepatocellular carcinoma with abdominal lymph node and peritoneal metastasis was made, and the patient was treated with a combination of sorafenib, capecitabine and oxaliplatin. After 6-month systemic treatment, follow-up computed tomography showed a size reduction of abdominal lymph nodes without the development of any new lesions. α-Fetoprotein decreased to 11243 ug/L. In view of his favourable response to systemic treatment and young age, he received right hepatectomy and excision of the mesenteric tumour and para-aortic lymph node. He had an uneventful recovery after operation. Pathology of the resected liver specimen showed a solitary moderately-differentiated hepatocellular carcinoma without any vascular invasion. Pathology of both the mesenteric mass and para-aortic lymph node revealed a plasma cell-rich lymphoproliferative lesion with multiple hyperplastic or involuted lymphoid follicles, which was most compatible with the plasma cell variant of Castleman’s disease. Subsequent work-up of this patient showed that he was HIV and HHV8 negative. He was regularly followed up by an oncologist with interval computed tomography for surveillance of recurrent liver cancer and monitoring of residual abdominal lymphadenopathy.

Reduced NKG2D ligand expression in hepatocellular carcinoma correlates with early recurrence

The activating receptor natural killer group 2, member D (NKG2D) and its ligands play a crucial role in immune response to tumors. NKG2D ligand expression in tumors has been shown to be associated with tumor eradication and superior patient survival, but the involvement of NKG2D ligands in the immune response against hepatocellular carcinoma (HCC) still remains to be elucidated. We investigated the expression of NKG2D ligands in HCC tissues collected from 54 patients and HCC cell lines. We also examined the proteasome expression and the effect of inhibition of proteasome activity on NKG2D ligand expression in HCC tissues and cell lines. In dysplastic nodules (DN), well-differentiated (well-HCC), and moderately-differentiated HCCs (mod-HCC), UL16-binding protein (ULBP) 1 was expressed predominantly in tumor cells, but not in poorly-differentiated HCCs (poor-HCC). Remarkably, recurrence-free survival of patients with ULBP1-negative HCC was significantly shorter than that of patients with ULBP1-positive HCC (p=0.006). Cox regression analysis revealed that loss of ULBP1 expression was an independent predictor of early recurrence (p=0.008). We confirmed that ULBP1 was expressed in the well- and mod-HCC cell lines, but not in the poor-HCC cell line KYN-2. However, inhibition of proteasome activity resulted in significant up-regulation of ULBP1 expression in KYN-2. Moreover, we found that 20S proteasome expression was more abundant in KYN-2 than that in the well- and mod-HCC cell lines. ULBP1 is prevalently expressed in DN to mod-HCC, but loss of its expression correlates with tumor progression and early recurrence.

Epithelial-to-mesenchymal transition and acquired resistance to sunitinib in a patient with hepatocellular carcinoma

Based on the success of sorafenib, several anti-angiogenic therapies are currently evaluated in advanced hepatocellular carcinomas. Few biological data are currently available from patients that may help understanding mechanisms of acquired resistance to these drugs. Herein, we report translational data from a post-treatment surgical specimen in a patient who experienced acquired resistance to sunitinib. Clinical, radiological, and pathological data were collected before treatment, under treatment, and at the time of tumor progression. In addition, a biomolecular analysis was performed at the time of progression. In this patient with non-alcoholic steatohepatitis, initial response to sunitinib was followed by tumor progression within 6 months of treatment, requesting salvage surgical resection. Surprisingly, pathological examination on post-treatment specimens revealed the presence of two juxtaposed tissue components containing either sarcomatoid-like mesenchymal cells or well- to moderately-differentiated hepatocellular carcinoma cells. Cancer cells retain a high α-fetoprotein expression in both components. However, while cells from carcinoma expressed E-cadherin but no vimentin, cancer cells from the mesenchymal component highly expressed vimentin and lost E-cadherin protein expression as measured by immunostaining. HMGA2 and Ki67 mRNA were also expressed at higher levels in mesenchymal than in carcinoma cells. This case report suggests the occurrence of an epithelial-to-mesenchymal transition in discrete areas of hepatocellular carcinomas developing resistance to sunitinib.

Hepatocellular Carcinoma in the Non-cirrhotic Liver is Associated with a High Body Mass Index Independent of Steatosis: 2010 Presidential Poster

Purpose: Hepatocellular carcinoma (HCC) in the absence of advanced fibrosis, cirrhosis or hepatitis B continues to be a relatively rare occurrence. However, it has been estimated that up to 10% of HCC occurs in non-cirrhotic livers. It has been suggested that obesity and insulin resistance may be risk factors for non-cirrhotic HCC. We aimed to review the clinical and histologic features of our patients with non-cirrhotic HCC to assess for an association with BMI and diabetes (DM). Methods: We analyzed data from a cohort of 12 patients with non-cirrhotic HCC who underwent partial hepatectomy between January 2008 and September 2009 at a single center. We evaluated preoperative data including age, gender, presence of liver disease, AFP, BMI, lesion size, number of lesions, prior locoregional therapy and other comorbidities. We also reviewed data related to the resection including background histology, tumor size, differentiation and vascular invasion (VI). Finally, we assessed post-operative complications and mortality. Results: The average age in our series was 60 with an equal mix of males and females. The average BMI was 27.6 (2 morbidly obese, 1 obese, 5 overweight, 4 normal), and 4/12 patients had DM. Overall, these patients had a higher prevalence of DM compared to the general population (33.3% vs. 5.8%), with a higher proportion being overweight or obese (67% vs. 60.3%), and an overall higher BMI (27.6 vs. 26.8). Preoperatively 7/12 had prior locoregional therapy, 12/12 had a single HCC (average size of 23.6 cm) and an average AFP of 1098.5 (available for 9/12). All patients had preoperative testing for underlying liver disease that was negative in all but 2 patients, both with hemochromatosis. Histology was obtained from resected specimens and was normal for all patients except one with hemochromatosis (stage 2 fibrosis), and 2/12 had mild steatosis. VI was present in 5/12 lesions, with 6 well and 6 moderately-differentiated HCCs, none were fibrolamellar. At the time of our review we had no known recurrences, and the average follow up was 17.5 (10-28) months. Conclusion: HCC in the absence of cirrhosis continues to be a rare occurrence. In our series, patients with non-cirrhotic HCC had a high prevalence of DM and elevated BMIs despite a lack of steatosis. This supports previous data that there may be an association with non-cirrhotic HCC and an elevated BMI as well as DM independent of steatosis. Patients were also noted to have advanced tumors that were large in size with VI. Despite advanced disease, patients tolerated resection very well with minimal complications, no operative mortality, and an average tumor-free follow-up of 17.5 months.

Expression and clinicalsignificance of candidate tumor suppressor gene RASSFIA,BIU and SEMA3B at 3p21,3 in livercancer

：Objective To investigatethe expression of candidate tumor suppressor gene RASSF1A,BIU and SEMA3B being located atthe commonly deleted region 3p21.3 in hepatocellular carcinoma(HCC).Methods RT-PCR wasused to detect RASSF1A,BIU and SEMA3B expression in HCC and its adjacent liver tissues in79 patients.Results(1)The lossing rates of RASSF1A,B1U and SEMA3B mRNAs were significantlyhigher in HCC than in the paracancerous tissue(P＜0.05).(2)The lossing rates ofthree genes' mRNAs were significantly higher in the patients with hepatic cirrhosis orHBsAg(+)than in those without hepatic cirrhosis or HBsAg(+)(P＜0.05).(3)The expression ofthree genes was reduced in poorly differentiated HCC compared with moderatelydifferentiated and well-differentiated HCC,but the difference was not significant forSEMA3B gene(P＞0.05).(4)There was no significant association of expression of the3 genes with age,sex,Child-Puch classification before operation or serum AFP level of thepatients(P＞0.05).ConclusionLoss or abnormal down-regulation of three genes' mRNAs is a frequent event in HCC,whichmay play an important role in the malignant progression of HCC. Key words: Carcinoma hepatocellular; 3p21.3; Tumor suppressorgene; Reverse transcriptase polymerase chain reaction

Apparent Diffusion Coefficient Value of Diffusion-Weighted Imaging for Hepatocellular Carcinoma: Correlation with the Histologic Differentiation and the Expression of Vascular Endothelial Growth Factor

ObjectiveTo evaluate whether the histopathological differentiation and the expression of vascular endothelial growth factor (VEGF) of hepatocellular carcinoma (HCC) do show correlation with the apparent diffusion coefficient (ADC) value on diffusion-weighted imaging (DWI).Materials and MethodsTwenty-seven HCCs from 27 patients who had undergone preoperative liver MRI (1.5T) and surgical resection were retrospectively reviewed. DWI was obtained with a single-shot, echo-planar imaging sequence in the axial plane (b values: 0 and 1,000 sec/mm2). On DWIs, the ADC value of the HCCs was measured by one radiologist, who was kept 'blinded' to the histological findings. Histopathologically, the differentiation was classified into well (n = 9), moderate (n = 9) and poor (n = 9). The expression of VEGF was semiquantitatively graded as grade 0 (n = 8), grade 1 (n = 9) and grade 2 (n = 10). We analyzed whether the histopathological differentiation and the expression of VEGF of the HCC showed correlation with the ADC value on DWI.ResultsThe mean ADC value of the poorly-differentiated HCCs (0.9 ± 0.13×10-3 mm2/s) was lower than those of the well-differentiated HCCs (1.2 ± 0.22×10-3 mm2/s) (p = 0.031) and moderately-differentiated HCCs (1.1 ± 0.01×10-3 mm2/s) (p = 0.013). There was a significant correlation between the differentiation and the ADC value of the HCCs (r = -0.51, p = 0.012). The mean ADC of the HCCs with a VEGF expression grade of 0, 1 and 2 was 1.1 ± 0.17, 1.1 ± 0.21 and 1.1 ± 0.18×10-3 mm2/s, respectively. The VEGF expression did not show correlation with the ADC value of the HCCs (r = 0.07, p = 0.74).ConclusionThe histopathological differentiation of HCC shows inverse correlation with the ADC value. Therefore, DWI with ADC measurement may be a valuable tool for noninvasively predicting the differentiation of HCC.

Hepatocellular carcinoma with massive lymphoid infiltration: A regressing phenomenon?

Spontaneous regression of hepatocellular carcinoma (HCC) is extremely rare. Among the numerous proposed mechanisms of spontaneous regression for HCC, immunological factors, which have yet to be fully understood, may have the most important roles in this rare phenomenon. A regressing HCC with lymphoid stroma is reported. A hepatic mass was detected in a 57-year-old man by abdominal computed tomography during a follow-up health check. The resected tumor was 2.7×2.4 cm 2 in size, and was composed of two distinct nodules with a complete rim of fibrous tissue separating the tumor from the adjacent liver parenchyma. Microscopically, one nodule was replaced by a remarkable infiltration of inflammatory cells with insignificant amounts of vital tumor cells. The other nodule demonstrated a small portion of well- to moderately-differentiated hepatocellular carcinoma cells forming 2–3 thick trabeculae with massive inflammatory infiltrates. Infiltrating inflammatory cells were composed of T cells (CD4+>CD8+), macrophages, B cells, and other cells in order of prevalence. Epstein-Barr virus was not detected. After 60 months of follow-up, the patient is in good health without evidence of tumor recurrence.

Scirrhous hepatocellular carcinoma displaying atypical findings on imaging studies

We describe a 15-mm scirrhous hepatocellular carcinoma (HCC) in a 60-year-old man with B-type cirrhosis. Ultrasound disclosed a 15-mm hypoechoic nodule in segment 7. Contrast-enhanced US revealed heterogeneous, not diffuse, hypervascularity in the early phase and a defect in the Kupffer phase. Contrast-enhanced computed tomography (CT) revealed a heterogeneous hypervascular nodule in the early phase and a low-density area in the late phase. Magnetic resonance imaging (MRI) revealed iso- to hypointensity at T1 and high intensity at T2-weighted sequences. Contrast-enhanced MRI also revealed a heterogeneous hypervascular nodule in the early phase and washout in the late phase. Super-paramagnetic iron oxide-MRI revealed a hyperintense nodule. CT during hepatic arteriography and CT during arterial portography revealed heterogeneous hyperattenuation and a perfusion defect, respectively. Based on these imaging findings the nodule was diagnosed as a mixed well-differentiated and moderately-differentiated HCC. Histologically, the nodule was moderately-differentiated HCC characterized by typical cytological and structural atypia with dense fibrosis. Immunohistochemically, the nodule was positive for heterochromatin protein 1 and alpha-smooth muscle actin, and negative for cytokeratin 19. From the above findings, the nodule was diagnosed as scirrhous HCC. Clinicians engaged in hepatology should exercise caution with suspected scirrhous HCC when imaging studies reveal atypical findings, as shown in our case on the basis of chronic liver disease.

Analysis of morphological vascular changes of hepatocellular carcinoma by microflow imaging using contrast‐enhanced sonography

To determine whether the findings of microflow imaging (MFI), composed of a flash replenishment and a maximum intensity holding sequence, using contrast-enhanced sonography, correlate with the degree of histological differentiation of hepatocellular carcinoma (HCC). This study was approved by the institutional review board; patients gave informed consent. The samples comprised of 61 nodules histologically diagnosed as HCC: 20 well-differentiated, 26 moderately-differentiated, and 15 poorly-differentiated HCC. SonoVue was used as the ultrasound (US) contrast agent. The US equipment used was a SSA-770 A with the imaging mode set at MFI. MFI is an imaging method combining flash replenishment imaging and maximum intensity holding. Two independent readers (readers 1 and 2) classified the microflow images into four patterns: (i) normal pattern; (ii) cotton pattern; (iii) vascular pattern; and (iv) dead wood pattern. The results were compared with the degree of histopathological differentiation of the HCC. In each of the 61 HCC, blood vessels in the tumor were clearly resolved down to their fine branches. With regard to the relationship between imaging patterns and thehistological findings, it was found (with high percentages) that the normal and cotton patterns were associated with well-differentiated HCC, that the vascular pattern was associated with moderately-differentiated HCC, and that the dead wood pattern was associated with poorly-differentiated HCC. If HCC with the normal and cotton patterns were assessed as well differentiated and those with the vascular or dead wood pattern were assessed as moderately or poorly differentiated, the sensitivity, specificity, and accuracy of these assessments were found to be 85%, 92.7%, and 90%, respectively, for reader 1, and 85%, 82.9%, and 83.6%, respectively, for reader 2. The angioarchitecture and hemodynamics of HCC could be evaluated in detail using MFI. The results of this study demonstrate the feasibility of a non-invasive preoperative diagnosis of the histological differentiation of HCC using MFI.

Intraperitoneal metastasis of hepatocellular carcinoma after spontaneous rupture: A case report

Rupture of hepatocellular carcinoma (HCC) is a life-threatening complication. Peritoneal metastasis of HCC after spontaneous rupture was seldom noted. We report a case of intraperitoneal metastasis of HCC after spontaneous rupture. A previously asymptomatic 72-year-old man was admitted due to dull abdominal pain with abdominal fullness. He had a history of HCC rupture 10 mo ago and transarterial embolization was performed at that time. Abdominal computer tomography (CT) scan showed a huge peritoneal mass over the right upper quadrant area. Surgical resection was arranged and subsequent microscopic examination confirmed a diagnosis of moderately-differentiated HCC.