Hepatic Fine Needle Aspiration Research Articles

Feasibility of hepatic fine needle aspiration as a minimally invasive sampling method for gene expression quantification of pharmacogenetic targets in dogs.

BackgroundQuantifying hepatic gene expression is important for many pharmacogenetic studies. However, this usually requires biopsy (BX), which is invasive.ObjectivesThe objectives of this study were to determine the feasibility of using minimally invasive fine needle aspirate (FNA) to quantify hepatic gene expression and to assess expression variability between different sampling sites.MethodsBiopsy and FNA samples were acquired from central and peripheral locations of the right and left lateral liver lobes of a dog. Relative expression of ABCB1, GSTT1 and CYP3A12 were measured via reverse transcriptase, quantitative PCR. The effect of sampling method, lobe and location within the lobe on gene expression was assessed using a three‐way ANOVA.ResultsRelative expression of ABCB1 and GSTT1 were not statistically different between sampling methods but CYP3A12 expression was higher in samples collected by BX (p = .013). Lobe sampled affected ABCB1 expression (p = .001) and site within lobe affected ABCB1 (p = .018) and GSTT1 (p = .025) expression.ConclusionsFNA appears to be a feasible technique for minimally invasive evaluation of hepatic gene expression but results should not be directly compared to biopsy samples. Sampling location impacts expression of some targets; combination of FNAs from multiple sites may reduce variation.

Hepatic fine-needle aspiration cytology: The role of rapid on-site evaluation in the assessment of hepatic lesions.

Radiologically guided fine-needle aspiration cytology (FNAC) of internal organs is not cost-effective. Rapid on-site evaluation (ROSE) of smears by a cytopathologist can improve the diagnostic yield of FNACs and save time and money by reducing the need for repeat procedure/biopsy. To determine the role of ROSE in the diagnostic outcome of hepatic lesions by comparative analysis of FNAC with and without ROSE by a cytopathologist. Hepatic FNACs were retrospectively analyzed over two separate time periods from January 2011 to June 2013 and from January 2015 to July 2016. Smears from 2015-2016 were subjected to ROSE by a cytopathologist after staining with toluidine blue for 1 min to assess adequacy of the material. Final report was given after hematoxylin and eosin, May Grünwald Giemsa, and Papanicolaou staining were performed. Chi-square test (non-parametric) was used to determine if there was a statistically significant increase in the diagnostic yield with ROSE. During 2011-2013, of the 160 radiologically guided FNACs for hepatic lesions, 22 were non-diagnostic, whereas during 2015-2016, of 142 radiologically guided hepatic FNACs, only six were non-diagnostic. With the application of ROSE, there was a statistically significant increase in the diagnostic yield of hepatic FNACs from 86.25% to 95.8% (p=0.015). ROSE performed by a cytopathologist using toluidine blue can increase the diagnostic yield of hepatic FNACs and reduce the cost of healthcare by eliminating the need for a repeat procedure.

Telaprevir-based treatment effects on hepatitis C virus in liver and blood.

Understanding hepatitis C virus (HCV) replication has been limited by access to serial samples of liver, the primary site of viral replication. Our understanding of how HCV replicates and develops drug-resistant variants in the liver is limited. We studied 15 patients chronically infected with genotype 1 HCV treated with telaprevir (TVR)/pegylated-interferon alpha/ribavirin. Hepatic fine needle aspiration was performed before treatment and at hour 10, days 4 and 15, and week 8 after initiation of antiviral therapy. We measured viral kinetics, resistance patterns, TVR concentrations, and host transcription profiles. All patients completed all protocol-defined procedures that were generally well tolerated. First-phase HCV decline (baseline/treatment day 4) was significantly slower in liver than in plasma (slope plasma: -0.29; liver, -0.009; P < 0.001), whereas second-phase decline (posttreatment days 4-15) did not differ between the two body compartments (-0.11 and -0.15, respectively; P = 0.1). TVR-resistant variants were detected in plasma, but not in liver (where only wild-type virus was detected). Based upon nonstructural protein 3 sequence analysis, no compartmentalization of viral populations was observed between plasma and liver compartments. Gene expression profiling revealed strong tissue-specific expression signatures. Human intrahepatic TVR concentration, measured for the first time, was lower, compared to plasma, on a gram per milliliter basis. We found moderate heterogeneity between HCV RNA levels from different intrahepatic sites, indicating differences in hepatic microenvironments. These data support an integrated model for HCV replication wherein the host hepatic milieu and innate immunity control the level of viral replication, and the early antiviral response observed in the plasma is predominantly driven by inhibition of hepatic high-level HCV replication sites.

Gene expression analysis in serial liver fine needle aspirates

No method with low morbidity presently exists for obtaining serial hepatic gene expression measurements in humans. While hepatic fine needle aspiration (FNA) has lower morbidity than core needle biopsy, applicability is limited due to blood contamination, which confounds quantification of gene expression changes. The aim of this study was to validate FNA for assessment of hepatic gene expression. Liver needle biopsies and FNA procedures were simultaneously performed on 17 patients with chronic hepatitis C virus infection with an additional FNA procedure 1week later. Nine patients had mild/moderate fibrosis and eight advanced fibrosis. Gene expression profiling was performed using Affymetrix microarrays and TaqMan qPCR; pathway analysis was performed using Ingenuity. We developed a novel strategy that applies liver-enriched normalization genes to determine the percentage of liver in the FNA sample, which enables accurate gene expression measurements overcoming biases derived from blood contamination. We obtained almost identical gene expression results (ρ=0.99, P<0.0001) comparing needle biopsy and FNA samples for 21 preselected genes. Gene expression results were also validated in dogs. These data suggest that liver FNA is a reliable method for serial hepatic tissue sampling with potential utility for a variety of preclinical and clinical applications.

Fine needle aspiration biopsy of hepatocellular carcinoma and hepatocellular nodular lesions: role, controversies and approach to diagnosis

The role of fine needle aspiration (FNA) biopsy of the liver has evolved. Advances in imaging modalities have obviated the need for tissue confirmation in clinically classic hepatocellular carcinoma (HCC). The risks of needle tract seeding and haematogenous dissemination have been actively debated. Nowadays, cytopathologists are confronted by smaller and smaller nodules, detected due to increased surveillance of high-risk cirrhotic patients. Tissue characterization of small well-differentiated hepatocellular nodular lesions (size less than and equal to 2 cm) is extremely challenging and has therapeutic implications. Major issues in the cytodiagnosis of HCC include: (i) distinguishing benign hepatocellular nodular lesions, namely, large regenerative nodules, dysplastic nodules, focal nodular hyperplasia and hepatocellular adenoma from reactive hepatocytes; (ii) distinguishing well-differentiated HCC from benign hepatocellular nodular lesions; (iii) distinguishing poorly differentiated HCC from intrahepatic cholangiocarcinoma and metastatic carcinomas; (iv) determining the histogenesis of a malignant tumour; and (v) determining the site of origin of a malignant tumour. An overview of the biological evolution and histopathological aspects of dysplastic nodules, small HCCs and 'nodule-in-nodule' lesions is presented in tandem with clinically relevant nomenclature. An algorithmic approach to FNA diagnosis of HCC and hepatocellular nodular lesions is outlined. Optimal results depend on (i) a dedicated radiologist-cytopathologist team; (ii) an on-site cytology service, (iii) a combined cytohistological approach, (iv) immunohistochemistry, and (v) clinicopathological correlation. As we move towards personalized medicine, it is envisaged that hepatic FNA is likely to become a point of care in the management protocol as it takes on the additional role of procurement of tumour and peritumoural tissues for genomic and proteomic profiling to enable targeted molecular therapy.

Fine-Needle Aspiration Biopsy of Hepatocellular Carcinoma and Related Hepatocellular Nodular Lesions in Cirrhosis: Controversies, Challenges, and Expectations

The role of hepatic fine-needle aspiration (FNA) biopsy has evolved. Advances in imaging modalities have obviated the need for tissue confirmation in most hepatocellular carcinomas (HCCs). There is risk of needle-tract seeding. Increasingly, small nodules are being detected on ultrasound surveillance of high-risk patients. Diagnostic challenges associated with cirrhosis include distinction of benign hepatocellular nodules, namely, large regenerative nodules and dysplastic nodules, from reactive hepatocytes; and distinction of well-differentiated HCCs from benign hepatocellular nodules. This paper will discuss (i) controversies regarding preoperative/pretransplantation FNA diagnosis of HCC, (ii) update of biological evolution, nomenclature, and histopathologic criteria for diagnosis of precancerous nodules and small HCCs, and (iii) algorithmic approach to FNA diagnosis of hepatocellular nodules. Optimal results depend on dedicated radiologist-cytopathologist team, on-site cytology service; combined cytohistologic approach, immunohistochemistry, and clinicopathologic correlation. Hepatic FNA is likely to be incorporated as a point of care as we move towards personalized medicine.

Non-traumatic pseudocyst of Glisson capsule complicating a ventriculoperitoneal shunt

Cerebrospinal fluid pseudocysts in the peritoneal cavity following ventriculoperitoneal shunt are relatively uncommon. In these complications, perforation of solid organs is unusual. A case of subcapsular hepatic pseudocyst is described. A 48-year-old man treated by ventriculoperitoneal shunt presented with abdominal pain. Laboratory examinations revealed hepatic cytolysis. The CT-scan of the abdomen demonstrated a small ovoid non-enhanced cystic collection in the subcapsular area of hepatic segment V. Percutaneous hepatic fine-needle aspiration of the cyst guided by abdominal ultrasonography showed no abnormal findings. Peritoneal reimplantation at a different site was performed. The clinicopathological features of this entity are described and treatments are discussed. Reinsertion of the catheter at a different abdominal site is effective in non-infections cases. In contrast, a temporary external drainage with adequate antibiotic treatment followed by shunt reinsertion is necessary to treat a documented infection of CSF collections.

Cytophotometric study on 89 hepatic fine needle aspiration

Cytophotometric study on 89 hepatic fine needle aspiration

An approach to fine‐needle aspiration biopsy diagnosis of hepatic masses

After reviewing collection techniques and the cytology of normal and reactive hepatocytes, a systematic approach to the evaluation of fine-needle aspiration biopsy smears of hepatic mass lesions is presented. One of the main problems facing the cytopathologist is the differentiation of cirrhosis from well-differentiated hepatocellular carcinoma. Smears from patients with cirrhosis often contain clusters of bile duct epithelial cells and chronic inflammatory cells, while properly sampled hepatocellular carcinoma smears should contain no bile duct epithelial cells and few inflammatory cells. Key criteria which favor the diagnosis of hepatocellular carcinoma over cirrhosis are: increased nuclear to cytoplasmic ratio, trabecular pattern, and atypical naked hepatocytic nuclei. Key criteria which favor the diagnosis of primary hepatocellular carcinoma over metastatic disease include polygonal cells with centrally placed nuclei, cells separated by sinusoidal capillaries, and bile. This systematic approach to the evaluation of hepatic fine-needle aspiration biopsies must be used with the realization that other uncommon mass lesions of the liver do exist (focal nodular hyperplasia, adenoma, hepatoblastoma, bile duct carcinoma, vascular tumors, mesenchymal tumors, and lymphomas).