Multicentric Hepatocellular Carcinoma Research Articles

Des-gamma-carboxy prothrombin and alpha-fetoprotein levels as biomarkers for hepatocellular carcinoma and their correlation with radiological characteristics.

Alpha-fetoprotein (AFP), a commonly used biomarker for hepatocellular carcinoma (HCC), is normal in up to one-third of patients. To evaluate the diagnostic performance of des-gamma-carboxy-prothrombin (DCP) alone and in combination with AFP. In this study, 202 patients with radiologically proven HCC were enrolled, and their DCP and AFP levels were evaluated for their diagnostic performance. The mean age of the enrolled patients was 58.5 years; 72.0% were male. DCP was elevated in 86.6% (n = 175) of all patients, 100.0% (n = 74) of patients with portal vein thrombus, and 87.4% (n = 111) of patients with multicentric HCC. AFP was elevated in 64.3% (n = 130) of all the patients, 74% (n = 55) of the patients with portal vein thrombus, and 71.6% (n = 91) of the patients with multicentric HCC (P = 0.030, 0.001, and 0.015, respectively). In tumors less than 2 cm in size (n = 46), DCP was increased in 32 (69.5%) patients, and AFP was increased in 25 (54.3%) patients (P = 0.801). There was good pairing between DCP and AFP for HCCs of 2 cm size or larger (P < 0.001); however, the pairing among tumors < 2 cm size was not significant (P = 0.210). In 69 of the patients (34.1%), only one of the tumor markers was positive; DCP was elevated alone in 57/202 (28.2%) of all patients, and AFP alone was elevated in 12/202 (5.9%) of the patients. The areas under receiver operating characteristic curves (AUROC) for tumors > 2 cm was 0.74 for DCP and 0.59 for AFP; combining both markers resulted in an AUROC of 0.73. For tumors < 2 cm, the AUROC was 0.25 for DCP and 0.40 for AFP. DCP, as an individual marker, had a better diagnostic performance in many cases of HCC. Hence, DCP may replace AFP as the primary HCC biomarker.

Multicentric Fibrolamellar Hepatocellular Carcinoma: A Rare Case Report

AbstractMulticentric fibrolamellar hepatocellular carcinoma has not been reported yet in the world as of our knowledge. A Medline search for the term “multicentric fibrolamellar HCC” did not return any results. To our knowledge, this is the first case report of multi-centric fibrolamellar hepatocellular carcinoma (HCC). We present the case of a 22-year-old male patient who had complaints of epigastric pain for 1 month. His general physical examinations were normal. Computed tomography of the abdomen revealed multiple hyper-enhancing space-occupying lesions, one of which showed a central scar. The final diagnosis of the case was multicentric fibrolamellar HCC, which was biopsy proven.

Acute pulmonary embolism in a patient with hepatitis C virus infection and hepatocellular carcinoma: a case report

BackgroundCardiac metastases in hepatocellular carcinoma patients are infrequently encountered and usually associated with a very poor prognosis.Case presentationHereby, we report a case of an acute pulmonary embolism (PE) on top of HCC with direct cardiac invasion to the right atrium (RA) through the inferior vena cava with another metastasis to the right ventricular apex in the form of highly mobile cauliflower mass protruding through the tricuspid valve into RA and nearly obliterating right ventricular outflow tract in a multi-centric hepatocellular carcinoma patient.ConclusionAcute dyspnea in a patient with a long history of hepatitis C virus infection raises the suspicion of acute PE due to either hypercoagulable state induced by malignancy or by cardiac extension of the tumor which usually carries high mortality rates. To the best of our knowledge, this case is the first case in the literature to show cardiac metastases in HCC with two different pathological mechanisms.

Synchronous dual malignancies: Carcinoma larynx and hepatocellular carcinoma

Synchronous cancers are defined as two or more primary cancers diagnosed in the same patient at the same time or within 6 months of diagnosis of each other. The diagnosis of multiple primary malignancies is not uncommon. A 70-year-old male reported to our hospital with chief complaints of change in voice and difficulty in swallowing solid food for 2 months accompanied anorexia since 20 days. The patient revealed occasional consumption of alcohol for 3 years and bidi smoking for 50 years (10 bidis per day). The patient was conscious, cooperative, and well oriented to time, place and person with an Eastern Cooperative Oncology Group of 0. On physical examination, the oral cavity and oropharynx were unremarkable. Direct laryngoscopy revealed ulceroproliferative growth in right-sided vallecula, right-sided aryepiglottic fold, right side arytenoid and pyriform sinus, and right vocal cord. Biopsy from this growth turned out to be poorly differentiated squamous cell carcinoma. Computed tomography (CT) scan of the neck and thorax revealed 1.5 cm × 2.6 cm heterogeneously contrast enhancing lesion involving right aryepiglottic fold, pyriform fossa, posterior hypopharyngeal wall, and posterior aspect of both false vocal cords. Few subcentimeter lymph nodes were noted in right side Level II. The CT scan also showed some mass lesion abnormality in the upper section of liver images which could not be properly made out. Hence, triple-phase CT scan of the liver was done which to a great surprise showed 7.7 cm × 6.5 cm × 5.5 cm lesion in segment V and VIII, it showed enhancement on arterial phase, became prominent on portovenous phase and a delayed phase washout. Similar lesion measuring 4.4 cm × 4.1 cm was seen in segment VIII of liver; which was diagnosed radiologically as a multicentric hepatocellular carcinoma. Serum alpha fetoprotein was markedly elevated to a value of 28,600 ng/mL. A multidisciplinary tumor board discussion was done, and an intense literature review was done, and a decision was taken keeping in mind the overall performance score of the patient to commence with a high palliative radiotherapy for laryngeal cancer to a dose of 45 Gray in 15 fractions at a dose of 3 Gray per fraction and tablet tamoxifen at a dose of 60 mg/day till the end of radiation followed by switching over to tablet sorafenib. The patient ultimately developed uremia due to liver failure and died. The patient survived for a period of 3 months from the time of diagnosis of malignancy. Such cases need a meticulous approach for the diagnosis as well as treatment approaches. Keeping in mind the general condition of the patient and available therapeutic options, a patient-based specific approach could be developed.

Lenvatinib in severe hypoglycemia associated with hepatocelular carcinoma

We present the case of a 24-year-old man with multicentric hepatocellular carcinoma over HBV cirrhosis treated with Sorafenib and Tenofovir. He comes to our center for repeated episodes of symptomatic hypoglycemia that cannot be managed with standard measures. After ruling out different possibilities, the suspicion of hypoglycemia due to a non-islet cell tumor was finally confirmed. Given the impossibility of a curative treatment due to a reduced functional reserve, Sorafenib was changed to Lenvatinib, thereby improving glycemic control.

Assessment the Association of Fatty Acid Binding Protein 1 with Hepatocellular Carcinoma.

Background & Objectives: Hepatocellular carcinoma and its complications with the multiplicity is crucial worldwide health problem especially in the presence of heterogeneous liver. We aimed to assess the value of fatty acid binding protein-1in the diagnosis of hepatocellular carcinoma in comparison to alpha-fetoprotein. Methodology: One hundred subjects were enrolled in this observational case-control study who attended the Hepatology, Gastroenterology and Infectious Diseases Department in Benha University Hospitals between January 2018 and January 2019 and divided into 80 patients (40 HCC &40 LC and 20 healthy subjects). Serum level of fatty acid binding protein-1 was determined by enzyme-linked immunosorbent assay. Results: Hepatocellular carcinoma patients were slightly older than healthy subjects as mean age in group І was (56.1±9 yrs) while in group III was (52.9±17.1 yrs). There was a marked increase in hepatocellular carcinoma in males with male to female ratio 4:1. There was a high prevalence of hepatocellular carcinoma in the rural population. Fatty acid binding protein-1 was higher in hepatocellular carcinoma compared to liver cirrhosis and the control group, ranged from (107-1224 ng/L, 48-981 ng/L and 34-460 ng/L) respectively. Analysis of ROC curve revealed that at a level 214 ng/L sensitivity, specificity, PPV, NPV and accuracy were 60%, 77.5%, 72.7%, 66% respectively with AUC 0.715 Conclusion: The use of fatty acid binding protein-1especially in multicentric hepatocellular carcinoma will be valuable because the difficulty in most cases to prove the multiplicity of hepatocellular carcinoma.

Prognostic factors of gadoxetic acid-enhanced MRI for postsurgical outcomes in multicentric hepatocellular carcinoma.

The primary aim of this study was to determine the clinical and histopathological prognostic factors for patients who underwent surgical resection of multiple hepatocellular carcinomas (HCCs) of multicentric occurrence. The secondary aim of this study was to evaluate whether specific imaging-related factors, including arterial phase hyperenhancement (APHE) and the LI-RADS category of each lesion on gadoxetic acid-enhanced MRI, would provide additional prognostic information about multicentric HCCs. In this retrospective study, 54 patients with 120 multicentric HCCs were diagnosed by surgical resection at a single tertiary hospital between 2009 and 2014. Two independent readers evaluated patients' preoperative gadoxetic acid-enhanced MR images and recorded APHE and LI-RADS category for each HCC, with discrepancies resolved through consensus sessions if necessary. Potential clinicopathologic and imaging parameters for predicting disease-free survival (DFS) and overall survival (OS) were analyzed using Cox regression analysis. Presence of microvascular invasion (MVI) (p = 0.003) and of three or more HCCs (p = 0.013) were both independent predictors of a shorter DFS. Patients with concurrent MVI and three or more HCCs had the shortest DFS. MVI was the only statistically significant parameter (p = 0.023) predicting OS. The number of HCCs with APHE or LR-5/M category was not associated with survival. Presence of MVI and of three or more HCCs were associated with poorer outcomes after surgical resection of multicentric HCCs. Imaging parameters on gadoxetic acid-enhanced MRI such as APHE or LI-RADS category were not associated with postsurgical outcomes. • Patients with three or more hepatocellular carcinomas showed worse disease-free survival than those with two hepatocellular carcinomas after surgical resection. • Microvascular invasion was the only significant factor to affect both the disease-free and overall survivals of patients after surgical resection of multicentric hepatocellular carcinomas. • Preoperative MRI findings related to multicentric hepatocellular carcinomas such as arterial phase hyperenhancement and LI-RADS category of lesions did not provide significant prognostic information.

S3275 Y90 Radioembolization: A Case Series in a Community-Based Setting

INTRODUCTION: Hepatocellular carcinoma (HCC) represents the second-most common cause of cancer mortality worldwide and the most common primary liver cancer in the United States. Loco-regional therapies (LRT) with curative intent include resection, energy ablation, chemo or radioembolization, and liver transplantation. Frequently sequencing of different therapeutic modalities is required for cure or prolongation of survival. Trans arterial LRT include chemoembolization (TACE) and Yttrium-90 radioembolization (Y-90 TARE) have been successfully utilized in the management of primary multicentric HCC, recurrent HCC after other LRT, as well as metastatic colorectal cancer and neuroendocrine carcinoma. Current scientific literature describes the methodology, safety and clinical outcomes from major academic centers. Our series describes the experience in the management of primary and secondary liver malignancies with Y-90 TARE a community hospital. METHODS: After IRB approval, we conducted a retrospective review. De-identified data was collected for patients treated with Y-90 TARE with primary, multicentric HCC, and patients with metastatic cancer who did not meet criteria for any other LRT. Baseline patient and tumor characteristics pre Y-90 TARE were assessed (Table 1). This series report the initial experience with forty-two patients. Of those, 20 patients that had complete data suitable for analysis Modified Resist criteria (mRESIST) was utilized to assess radiographic response within the first year of treatment. Complications that required post treatment emergency department (ED) visit or hospitalization within 30 and 90 days after Y-90 TARE were recorded. RESULTS: Of the twenty patients with pre and post therapy imaging, 40% had partial and stable responses, 15% had a complete response, and 5% had progressive disease. Of the 42 patients initially treated with Y-90 TARE, 52% did not undergo subsequent radioembolization treatment, 38% underwent one additional treatment and 10% required two or more. 5% of the patients required ED of hospitalization in the first 90 days after y 90 TARE. There were no deaths (Table 2). CONCLUSION: The management of hepatocellular carcinoma varies tremendously without one single modality being ideal. Surgical resection and transplantation remain as the gold standard for cure. Our series documents, Y-90 TARE to be a safe, reproducible technique in a community hospital with minimal morbidity and no mortality.Table 1.: Pre treatment baseline characteristicsTable 2.: Post treatment outcomes

Hepatocellular carcinoma: An Update

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not significantly improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and the limited therapeutic options. The therapeutic options fall into several categories: (i) surgical interventions including tumor resection and liver transplantation, (ii) percutaneous interventions including ethanol injection and radiofrequency thermal ablation, (iii) transarterial interventions including embolization, chemoembolization and selective internal radiotherapy, (iv) external radiation therapy and (v) systemic strategies with cytotoxic agents and molecularly targeted therapies as well as immunotherapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for actual therapeutic recommendations. While surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, &lt;5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% of patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care (BSC). In order to reduce the morbidity and mortality from HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including cytotoxic agents, molecular targeted and immunotherapies is most important. New analytical technologies, including gene expression profiling and proteomic analyses and others, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.

Convergent Evolution of Copy Number Alterations in Multi-Centric Hepatocellular Carcinoma

In the recent years, new molecular methods have been proposed to discriminate multicentric hepatocellular carcinomas (HCC) from intrahepatic metastases. Some of these methods utilize sequencing data to assess similarities between cancer genomes, whilst other achieved the same results with transcriptome and methylome data. Here, we attempt to classify two HCC patients with multi-centric disease using the recall-rates of somatic mutations but find that difficult because their tumors share some chromosome-scale copy-number alterations (CNAs) but little-to-no single-nucleotide variants. To resolve the apparent conundrum, we apply a phasing strategy to test if those shared CNAs are identical by descent. Our findings suggest that the conflicting alterations occur on different homologous chromosomes, which argues for multi-centric origin of respective HCCs.

Comprehensive molecular and immunological characterization of hepatocellular carcinoma.

BackgroundHepatocellular carcinoma (HCC) is a heterogeneous disease with various etiological factors, and ranks as the second leading cause of cancer-related mortality worldwide due to multi-focal recurrence. We herein identified three major subtypes of HCC by performing integrative analysis of two omics data sets, and clarified that this classification was closely correlated with clinicopathological factors, immune profiles and recurrence patterns.MethodsIn the test study, 183 tumor specimens surgically resected from HCC patients were collected for unsupervised clustering analysis of gene expression signatures and comparative analysis of gene mutations. These results were validated by using genome, methylome and transcriptome data of 373 HCC patients provided from the Cancer Genome Atlas Network. In addition, omics data were obtained from pairs of primary and recurrent HCC.FindingsComprehensive molecular evaluation of HCC by multi-platform analysis defined three major subtypes: (1) mitogenic and stem cell-like tumors with chromosomal instability; (2) CTNNB1-mutated tumors displaying immune suppression; and (3) metabolic disease-associated tumors, which included an immunogenic subgroup characterized by macrophage infiltration and favorable prognosis. Although genomic and epigenomic analysis explicitly distinguished between HCC with intrahepatic metastasis (IM) and multi-centric HCC (MC), the phenotypic similarity between the primary and recurrent tumors was not correlated to the IM/MC origin, but to the classification. Interpretation: Identification of these HCC subtypes provides further insights into patient stratification as well as presents opportunities for therapeutic development.FundMinistry of Education, Culture, Sports, Science and Technology of Japan (16H02670 and 18K19575), Japan Agency for Medical Research and Development (JP15cm0106064, JP17cm0106518, JP18cm0106540 and JP18fk0210040).

Synchronous multicentric small hepatocellular carcinomas: defining the capsule on high-frequency intraoperative ultrasonography with pathologic correlation.

PurposeThe aim of this study was to define the capsules of synchronous multicentric small hepatocellular carcinomas (HCCs) with use of high-frequency intraoperative ultrasonography (IOUS).MethodsAmong the 131 consecutive patients undergoing hepatic resection and high-frequency IOUS for HCC, 16 synchronous multicentric small HCCs in 13 patients were histologically diagnosed in the resected specimens. High-frequency IOUS and pathologic findings of these lesions were compared, with particular focus on the presence and appearance of the capsule in or around each lesion.ResultsSynchronous multicentric small HCCs were pathologically classified into distinctly nodular (n=12) or vaguely nodular (n=4) types. All 12 distinctly nodular HCCs including six subcentimeter lesions showed detectable capsules on high-frequency IOUS and pathology. The capsules appeared as a hypoechoic rim containing hyperechoic foci (n=6), hypoechoic rim (n=5), or hyperechoic rim (n=1) with varying degrees of coverage around each lesion. Histologically, the capsules were composed of a combination of one to four layers consisting of a fibrous capsule, peritumoral fibrosis, prominent small vessels, and entrapped hepatic parenchyma.ConclusionSynchronous multicentric small HCCs with distinctly nodular type, even at subcentimeter size, can show capsules with varying coverage and diverse echogenicity on high-frequency IOUS.

Current management of patients with hepatocellular carcinoma.

The current management therapies for hepatocellular carcinoma (HCC) patients are discussed in this review. Despite the development of new therapies, HCC remains a "difficult to treat" cancer because HCC typically occurs in advanced liver disease or hepatic cirrhosis. The progression of multistep and multicentric HCC hampers the prevention of the recurrence of HCC. Many HCC patients are treated with surgical resection and radiofrequency ablation (RFA), although these modalities should be considered in only selected cases with a certain HCC number and size. Although there is a shortage of grafts, liver transplantation has the highest survival rates for HCC. Several modalities are salvage treatments; however, intensive care in combination with other modalities or in combination with surgical resection or RFA might offer a better prognosis. Sorafenib is useful for patients with advanced HCC. In the near future, HCC treatment will include stronger molecular targeted drugs, which will have greater potency and fewer adverse events. Further studies will be ongoing.

Specific miRNA expression profiles of non‐tumor liver tissue predict a risk for recurrence of hepatocellular carcinoma

It is reasonable to investigate non-tumor liver tissues to predict a risk for development of hepatocellular carcinoma (HCC). A molecular analysis of chronically damaged liver tissues may identify specific miRNA expression profiles associated with a risk for multicentric (MC) HCC. Twenty HCC patients, who underwent a curative hepatectomy were classified into two groups: a non-MC group (no MC recurrence in more than 3 years, n = 10) and an MC group (MC recurrence within 3 years after hepatectomy, n = 10). An miRNA microarray (955 probes) was used to compare the miRNA expression patterns of the non-cancerous liver tissues between the two groups. This study identified the differentially expressed miRNA related to MC recurrence in the liver remnant. No differences were observed between the two groups in the liver function tests and pathological variables including both tumor factors and non-tumor liver tissues. The investigation selected 20 differentially expressed miRNA related to MC recurrence. Eighteen miRNA were downregulated, while two miRNA were upregulated in the MC group. A hierarchical clustering analysis identified a cluster that may be associated with risk of the MC recurrence of HCC. The MC recurrence-related miRNA included let-7d*, miR-328 and miR18a*, which potentially regulate K-ras gene expression. A significant inverse correlation between the miR-18a* expression and the K-ras mRNA expression was confirmed by quantitative reverse transcription polymerase chain reaction. Specific miRNA expression signatures in non-cancerous liver tissue may help to predict the risk for de novo development of HCC.

Transarterial Chemoembolization Plus Sorafenib: A Sequential Therapeutic Scheme for HCV-Related Intermediate-Stage Hepatocellular Carcinoma: A Randomized Clinical Trial

Recurrence of hepatocellular carcinoma (HCC) is a major problem after surgical or ablative treatments. The aim of this prospective, single-center, placebo-controlled, randomized, double-blind clinical study was to evaluate the effectiveness of transarterial chemoembolization (TACE) combined with sorafenib as a sequential treatment regimen in delaying time to progression (TTP) of intermediate-stage HCC in patients with chronic hepatitis C virus (HCV) infection. Between October, 2007 and January, 2011, 80 HCV-infected patients with Barcelona Clinic Liver Cancer stage B HCC underwent the TACE procedure. All had Child-Pugh class A disease. They were randomized 1:1 to receive sorafenib at a dose of 400 mg twice daily or placebo. Endpoints were the TTP and the rates of adverse events and toxicity. Sixty-two of 80 patients (77%), 31 in the sorafenib group and 31 in the control group, completed the study. The median TTP was 9.2 months in the sorafenib group and 4.9 months in the placebo group (hazard ratio, 2.5; 95% confidence interval, 1.66-7.56; p < .001). Metachronous, multicentric HCC progression occurred less frequently in sorafenib-treated patients (p < .05). Adverse reactions to sorafenib caused withdrawal from the study of 9 (22%) patients. A conventional TACE procedure followed by sorafenib treatment resulted in a significantly longer TTP in patients with intermediate-stage HCV-related HCC, with no unexpected side effects.

Percutaneous Radiofrequency Ablation versus Partial Hepatectomy for Multicentric Small Hepatocellular Carcinomas: A Nonrandomized Comparative Study

The aim of this study was to compare the results of percutaneous radiofrequency ablation (RFA) with those of partial hepatectomy (PH) in the treatment of multicentric small hepatocellular carcinomas (HCCs). With advances in RFA, it is not known whether the minimally invasive approach with percutaneous RFA could attain comparable survival outcomes but with a lower morbidity in patients with multicentric HCCs. From January 2002 and December 2007, 159 patients who had two or three HCCs, with the largest tumor no more than 5cm in diameter, had no major vascular invasion or extrahepatic metastases, and were treated with either PH (n=73) or RFA (n=86) were included in the study. There was no procedure-related mortality in both groups of patients. Major complications happened significantly more often after PH than after RFA (19.2 vs. 8.1%). The hospital stay was significantly longer after PH than after RFA (median=9 vs. 3days). The 1-, 3-, and 5-year overall survival rates for the PH and RFA groups were 91.8, 68.7, 44.5% and 94.2, 64.4, 21.2%, respectively. The corresponding disease-free survival rates for the two groups were 62.1, 33.6, 3.6% and 29.4, 2.7, 0%, respectively. The PH group had significantly longer overall survival and disease-free survival than the RFA group. PH resulted in better survival outcomes than RFA for patients with multicentric small HCCs. However, RFA had the benefits of lower procedure-related morbidity and shorter hospital stay.

Weight Loss in an Asian Man

Question: A 28-year-old Filipino man, a known chronic hepatitis B carrier, presented with a 1-year history of significant weight loss. He did not have fever or cough, or any other systemic complaints. Physical examination was unremarkable. His blood results were: Protein, 98 g/L; albumin, 24 g/L; bilirubin, 21 μmol/L; alkaline phosphatase, 165 U/L; alanine aminotransferase, 433 U/L; aspartate aminotransferase, 394 U/L; alpha-fetoprotein, 117 μg/L; hemoglobin, 12.9 g/dL; white cell count, 5.61 × 109/L; platelets, 204 × 109/L; and erythrocyte sedimentation rate 103 mm/hr. Multiphasic contrast-enhanced computed tomography (CT) scan of the liver was performed (Figure A). Chest radiograph (not shown) was normal. What is the likely diagnosis from the CT scan? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Liver CT shows several centrally calcified nodular lesions in the right lobe with relatively low-density soft tissue surrounding them, best seen in the portal venous phase (Figure B,arrows). Similar lesions were present in the left lobe (not shown). There is no arterial enhancement or venous washout pattern to suggest multicentric hepatocellular carcinoma. The most likely cause of hypovascular infiltrative liver lesions with coarse nodular calcified foci are granulomatous infections, especially macronodular tuberculosis. Ultrasound-guided fine needle and core biopsy of the liver nodules was performed. Histopathologic analysis showed stromal fibrosis and chronic inflammation, residual bile ductular structures and epithelioid histiocytes (Figure C) Liver tissue culture grew Mycobacterium tuberculosis complex. Fungal culture was negative, as were serum cryptococcal, Histoplasma, and Treponema serologies. He was treated with a combination of 4 antituberculosis drugs for 2 months followed by 2 drugs for another 4 months. There was marked clinical improvement with return of his weight to baseline and normalization of liver function tests. There are 2 main radiologic manifestations of hepatic parenchymal tuberculosis.1Mortelé K.J. Segatto E. Ros P.R. The infected liver: radiologic-pathologic correlation.Radiographics. 2004; 24: 937-955Crossref PubMed Scopus (245) Google Scholar, 2Yu R.S. Zhang S.Z. Wu J.J. et al.Imaging diagnosis of 12 patients with hepatic tuberculosis.World J Gastroenterol. 2004; 10: 1639-1642Crossref PubMed Scopus (77) Google Scholar, 3Vanhoenacker F.M. De Backer A.I. Op de B.B. et al.Imaging of gastrointestinal and abdominal tuberculosis.Eur Radiol. 2004; 14: E103-E115PubMed Google Scholar Miliary hepatic involvement is seen in patients with miliary pulmonary tuberculosis and is characterized by innumerable tiny 0.5–2 mm nodules, which may sometimes be missed at CT, manifesting often as hepatomegaly only. Macronodular hepatic tuberculosis although less uncommon, is easily detected at CT and are typically low-density, hypovascular lesions measuring about 1–3 cm each and may show irregular, ill-defined margins. Tuberculomas eventually tend to calcify over time, and the presence of calcified granulomas at CT in the absence of a known primary malignancy should always raise suspicion for tuberculosis. Other granulomatous infections such as histoplasmosis typically occur in the setting of disseminated disease and presents with miliary sized lesions. Calcified metastases, typically from primary colorectal carcinoma, especially the mucinous histologic subtype, may also have this appearance, but this is highly unlikely in the given clinical context. This case also demonstrates the value of tissue culture over tissue staining in diagnosis of hepatic tuberculosis.

Occurrence of hepatocellular carcinoma after hepatoblastoma resection in an adult with hepatitis C virus

Hepatoblastoma is a rare malignancy in adults. It is often diagnosed after the appearance of symptoms, therefore, the tumor size tends to be larger. In patients with no indication for a hepatic resection, the prognosis of adult hepatoblastoma is quite poor. A 54-year-old man with hepatitis C virus-associated liver cirrhosis was initially treated with a hepatic resection for a hepatic tumor, 3 cm in diameter. The tumor consisted of osteoid-like and cartilaginous foci, myxomatous stroma, and poorly differentiated hepatocellular carcinomatous cells and was diagnosed as a mixed epithelial and mesenchymal hepatoblastoma. Two years after the first operation, multicentric hepatocellular carcinomas developed in the remnant liver and were successfully treated with a secondary hepatic resection combined with radio-frequency ablation. The patient is now alive with no recurrence at 5 years after the initial hepatectomy. To the best of our knowledge, the primary hepatoblastoma was the smallest such tumor reported and this is the first report of a metachronous hepatoblastoma and hepatocellular carcinoma in an adult hepatitis patient.

Strategy and mechanism for the prevention of hepatocellular carcinoma: Phosphorylated retinoid X receptor α is a critical target for hepatocellular carcinoma chemoprevention

Hepatocellular carcinoma (HCC) is a major health care problem worldwide. The prognosis of patients with HCC is poor because even in the early stages when surgical treatment might be expected to be curative, the incidence of recurrence in patients with underlying cirrhosis is very high due to multicentric carcinogenesis. Therefore, strategies to prevent recurrence and second primary HCC are required to improve the prognosis. One of the most practical approaches to prevent the multicentric development of HCC is 'clonal deletion' therapy, which is defined as the removal of latent (i.e. invisible) (pre)malignant clones from the liver in a hypercarcinogenic state. Retinoids, a group of structural and functional analogs of vitamin A, exert their biological function primarily through two distinct nuclear receptors, retinoic acid receptors and retinoid X receptors (RXR), and abnormalities in the expression and function of these receptors are highly associated with the development of various cancers, including HCC. In particular, a malfunction of RXRalpha due to phosphorylation by the Ras-mitogen-activated protein kinase signaling pathway is profoundly associated with the development of HCC and thus may be a critical target for HCC chemoprevention. Acyclic retinoid, which has been clinically shown to reduce the incidence of a post-therapeutic recurrence of HCC, can inhibit Ras activity and phosphorylation of the extracellular signal-regulated kinase and RXRalpha proteins. In conclusion, the inhibition of RXRalpha phosphorylation and the restoration of its physiological function as a master regulator for nuclear receptors may be a potentially effective strategy for HCC chemoprevention and clonal deletion. Acyclic retinoid, which targets phosphorylated RXRalpha, may thus play a critical role in preventing the development of multicentric HCC.

Embolotherapy in the Management of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) ranks fifth in frequency of cancers worldwide. The incidence of HCC in the United States is rising, primarily due to the number of patients who were infected by hepatitis in the 1960s and 1970s coupled with the rising migrant population from Asia, where hepatitis is widely prevalent. Up to 80% of the patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the option of resection or liver transplantation. The dual blood supply (arterial and portal) to the liver with predominantly arterial supply to the tumor has made embolotherapy a cornerstone in the management of inoperable HCC. The techniques have become refined not only due to the development of microcatheter angiographic capabilities, but also in the ability to deliver a wide variety of therapeutic agents to these tumors. This article reviews the fundamental principles of bland embolization, chemoembolization, and radioembolization in the management of HCC.