Contrast-enhanced power doppler sonography in detection and differentiation of focal liver lesions

The aim of the study is to evaluate the contrast enhanced power doppler technique as a method to detect and differentiate vascular patterns of focal liver lesions. Fourty-nine patients with focal liver lesions were included in the study, twenty-nine of them with malignant liver lesions (9 HCC, 20 metastatic), twenty patients with benign lesions (12 haemangiomas, 5 focal nodular hyperplasia, 3 focal steatosis). In all patients classic B-mode and power doppler sonography was performed prior to administration of the contrast medium Levovist (300 mg/ml) and a power doppler examination subsequent to medium administration. Contrast administration led to lowering the number of "no-flow" lesions from 19 to 11. Postcontrast scan analysis revealed markedly enhanced flow in 15 cases in comparison to only 4 in pre-contrast examinations. The pre-contrast power doppler showed central flow in 7, and peripheral in 26 focal liver lesions. On the other hand, the postcontrast study revealed a central flow in 14, and peripheral in 34 focal liver lesions. Statistical significance between pre- and post-contrast power doppler detection of vascularization existed in malignant focal liver lesions and haemangiomas. The same pre- and post-contrast evaluation proved to be statistically non-significant in the focal nodular hyperplasia and focal steatosis groups. Administration of contrast medium enables a better visualization of intratumor blood vessels in focal liver lesions. This, in combination with the power doppler technique, brings such scans close to angiographic findings.     

Characterization of Incidental Liver Lesions: Comparison of Multidetector CT versus Gd-EOB-DTPA-Enhanced MR Imaging

As a result of recent developments in imaging modalities and wide spread routine medical checkups and screening, more incidental liver lesions are found frequently on US these days. When incidental liver lesions are found on US, physicians have to make a decision whether to just follow up or to undergo additional imaging studies for lesion characterization. In order to choose the next appropriate imaging modality, the diagnostic accuracy of each imaging study needs to be considered. Therefore, we tried to compare the accuracy of contrast-enhanced multidetector CT (MDCT) and Gd-EOB-DTPA-enhanced MRI for characterization of incidental liver masses. We included 127 incidentally found focal liver lesions (94 benign and 33 malignant) from 80 patients (M∶F = 45∶35) without primary extrahepatic malignancy or chronic liver disease. Two radiologists independently reviewed Gd-EOB-DTPA-enhanced MRI and MDCT. The proportion of confident interpretations for differentiation of benign and malignant lesions and for the specific diagnosis of diseases were compared. The proportion of confident interpretations for the differentiation of benign and malignant lesions was significantly higher with EOB-MRI(94.5%–97.6%) than with MDCT (74.0%–92.9%). In terms of specific diagnosis, sensitivity and accuracy were significantly higher with EOB-MRI than with MDCT for the diagnosis of focal nodular hyperplasia (FNH) and focal eosinophilic infiltration. The diagnoses of the remaining diseases were comparable between EOB-MRI and MDCT. Hence, our results suggested that Gd-EOB-MRI may provide a higher proportion of confident interpretations than MDCT, especially for the diagnosis of incidentally found FNH and focal eosinophilic infiltration.     

Value of cytologic examination in diagnosis of focal lesions to the liver and pancreas]

Four hundred fifty three percutaneous fine-needle biopsies (FNB) guided ultrasonically of the focal lesions to the liver and 418 to the pancreas were subjected to retrospective analysis. Biopsies were performed with the aid of real time ultrasound equipment ALOKA SSD-280. The needles of 0.7 and 0.8 mm in outer diameter were used for the aspiration. Smears were fixed with alcohol and stained with hematoxylin and eosin, and examined under light microscope. Specimens suitable for the examination were obtained in 97% of liver biopsies and 90% of pancreatic biopsies. Sensitivity of FNB in the diagnosis of hepatic and pancreatic carcinoma was 97% and 91%, respectively. Its specificity was 100%. ENB efficiency in the diagnosis of the focal lesions to the liver was 98% and in case of the focal lesions to pancreas -95%.     

Hepatic lesions in experimental Campylobacter jejuni infection of mice

Mice orally infected with Campylobacter jejuni developed focal infiltrative necrotic lesions in the liver, as determined by both histology and liver function tests. The initial histopathological feature was a focal infiltrative lesion in the parenchyma and portal triads. Foci of infiltrative lesions became necrotic between days 30 and 60 post-inoculation (p.i.). During this period, portal infiltrates increased in severity. From month 4 p.i., focal areas of infiltrative necrosis in the liver parenchyma became extensive. Study of liver function demonstrated mild elevations of transaminases, alkaline phosphatase and lactic dehydrogenase, and also the presence of hypoalbuminaemia. Although histopathological changes of the liver became gradually more marked after day 30 p.i., liver functions of infected mice were most affected at 2 months p.i. The capacity of C. jejuni to induce hepatic lesions seemed to be related to that of organisms to persist in the gall bladder; there was no correlation between biliary carriage in infected mice and positive faecal culture.     

Fine needle aspiration biopsy for improving the diagnostic accuracy of cut needle biopsy of focal liver lesions

OBJECTIVE: To determine the value of fine needle aspiration biopsy (FNAB) in comparison to cut needle biopsy (CNB) for the diagnosis of malignancy of focal liver lesions. STUDY DESIGN: A retrospective analysis was conducted on 68 FNAB and 49 CNB procedures performed on 62 patients with focal liver lesions. RESULTS: Cytology permitted a diagnosis of the lesion in 78% of cases. When punctures with insufficient material were excluded (11), the diagnostic accuracy of FNAB was 93%. For the 49 patients who underwent both procedures, FNAB and CNB had the same diagnostic accuracy, 78%, when considered separately and of 88% when considered in combination. Sensitivity, specificity and positive predictive value were similar for the 2 techniques. The negative predictive value was 64% for FNAB and CNB used separately and reached 78% when the 2 techniques were combined. There were no complications during the execution of FNAB and CNB. CONCLUSION: FNAB is an effective and safe method for the diagnosis of focal hepatic lesions, with diagnostic accuracy similar to that of CNB. When the 2 techniques are combined, the accuracy of the diagnosis of malignancy of focal liver lesions increases.     

Immunohistochemical and biochemical detection of uridine-diphosphate-glucuronyltransferase (UDP-GT) activity in putative preneoplastic liver foci

Preneoplastic liver foci were produced in female Wistar rats by the administration of 2-acetylaminofluorene (0.03% w/w) in the diet for 174 days. Increased UDP-glucuronyltransferase (UDP-GT) could be visualized immunohistochemically in the same focal areas which were ATPase-negative and gamma-glutamyltranspeptidase-positive. Immunohistochemical detection was possible using rabbit anti-UDP-GT and peroxidase-labeled swine anti-rabbit immunoglobulins. The results of immunohistochemistry were substantiated by enzyme determination in microdissected material. UDP-GT activity was 5-fold higher in focal areas in comparison with the surrounding liver tissue. Increased UDP-GT activity in conjunction with the altered pattern of other drug-metabolizing enzymes is consistent with increased resistance of preneoplastic cells to the cytotoxicity of carcinogens. Immunohistochemical detection of UDP-GT may provide a new marker for preneoplastic lesions which, in conjunction with other markers, may prove useful in analyzing the various stages of liver carcinogenesis and the remodeling of preneoplastic lesions after cessation of carcinogenic stimuli.     

Fine needle aspiration cytology of focal nodular hyperplasia of the liver

In five cases, the fine needle aspiration (FNA) cytologic study of ultrasonically detected solitary liver tumors yielded a diagnosis of focal nodular hyperplasia. Cytomorphologically, the lesions were characterized by the presence of both abundant normal hepatocytes and numerous epithelial cells in ductal formations, clusters or tightly packed groups in the FNA samples. In two of the five cases, the cytologic diagnosis was confirmed by subsequent histologic studies; in the remaining three cases, the clinical data were consistent with focal nodular hyperplasia of the liver. All five patients were women, four of whom had used oral contraceptives for long periods of time (5 to 15 years), which has previously been linked to the development of focal nodular hyperplasia of the liver. Based on the findings in this study, FNA cytology should be adequate for making the differential diagnosis of focal nodular hyperplasia versus liver-cell adenoma when solitary liver tumors are detected in such cases; it can yield a morphologic diagnosis and facilitate the decision as to whether surgical intervention is required.     

Pathology of naturally occurring toxoplasma abortion and neonatal mortality in Black Bengal goat

Characteristic pathological lesions in Black Bengal goat abortions due to naturally occurring toxoplasmosis consist of focal inflammation of the placenta. No specific macroscopic changes were marked in other organs of the fetuses. The main microscopic changes were focal or diffuse infiltrations with round cells in the liver, brain and heart. These lesions were more common in the brain than in other organs. Toxoplasma organisms were demonstrated in these organs as single trophozoites or within the cyst. No characteristic gross or histological changes were demonstrated in lymph nodes, spleen, lung and kidney. These results could be useful for histopathological diagnosis of toxoplamosis in Black Bengal goats.     

Altered glycosaminoglycan composition in reactive and neoplastic human liver

We have investigated the glycosaminoglycan composition of normal human liver, focal nodular hyperplasia, hepatic adenoma, and hepatocellular carcinoma. Uronic acid increased about 4 fold in the benign and reactive lesions, and greater than 7 fold in the carcinoma. Whereas in focal nodular hyperplasia and adenoma dermatan sulfate was the predominant glycosaminoglycan, in hepatocellular carcinoma chondroitin sulfate was the predominant species; it increased 24 fold over normal liver and 3-5 fold over all the other tissues. HPLC analysis of chondroitinase ABC or AC digests showed a 58 fold increase in Delta-Di-OS disaccharides in hepatocellular carcinoma, indicating significant undersulfation of chondroitin sulfate. Surprisingly, the normal-appearing liver surrounding the carcinoma showed glycosaminoglycan changes similar to adenoma and nodular hyperplasia. These results thus indicate that specific glycosaminoglycan changes occur in hepatocellular carcinoma, and suggest for the first time that proteoglycan metabolism is also altered in the non-cirrhotic, hepatic parenchyma adjacent to liver carcinoma.     

Histochemical and immunohistochemical detection of putative preneoplastic liver foci in women after long-term use of oral contraceptives

Localized areas with altered enzyme patterns were observed in liver tissue surrounding focal nodular hyperplasia in women after long-term use of oral contraceptives. These localized lesions were of three different types. Type I lesions were characterized by glycogen storage, a reduction in ATPase and an increase in gamma-glutamyltranspeptidase (gamma-GT) and UDP-glucuronyltransferase (UDP-GT) detected immunohistochemically. Type II lesions, which were morphologically very similar to small hyperplastic nodules, showed only a decreased ATPase reaction. Type III lesions showed an increase in gamma-GT (detected histochemically) and a slight reduction in ATPase. The results indicated that in human liver from patients given oral contraceptives long-term, localized lesions with altered enzyme patterns may occur which are very similar to those observed in animal models during experimental hepatic carcinogenesis.     

Fine needle aspiration of focal liver lesions

Fourteen percutaneous fine needle aspirates (FNAs) of focal liver lesions performed under ultrasound guidance at the Sultan Qaboos University Hospital (SQUH), Oman, between January 1991 and October 1992, are presented. Ten of these were cytologically diagnosed as hepatocellular carcinomas (HCC). the patients' ages ranged from 50 to 70 years and eight of these were males. the important diagnostic cytological criteria of HCC were found to be increased nucleocytoplasmic (N/C) ratio, trabecular pattern, atypical naked nuclei, bile production by malignant hepatocytes and absence of bile duct epithelium. Carcinoembryonic antigen (CEA) positivity of bile canaliculi by cross-reaction with biliary glycoprotein I (BGP I) made possible the differentiation of HCC from metastases. We stress the importance of cell blocks as these often constitute microbiopsies. Ultrasound-guided FNA of focal liver lesions is recommended as a simple, easy and quick procedure.     

Mouse hepatitis virus S in weanling Swiss mice following intranasal inoculation

Three-week-old outbred mice were inoculated intranasally with a mildly pathogenic strain of mouse hepatitis virus (MHV-S). Tissues were analyzed for distribution of infectious virus, lesions, and viral antigen at intervals up to 49 days after inoculation. Sera were tested for neutralizing antibody to MHV-S. Within the first week of infection, virus was isolated from lung and brain of most mice and liver of one mouse, but not from blood, spleen, or intestine. Microscopic lesions consisted of mild olfactory mucosal necrosis, neuronal necrosis of olfactory bulbs and tracts, lymphoplasmacytic infiltrates and vacuolation in the brain, mild nonsuppurative pulmonary perivascular lymphocyte infiltration, focal interstitial pneumonia, and focal necrotizing hepatitis. The presence and distribution of MHV antigen, as determined by indirect immunofluorescence, correlated with virus recovery and acute lesions. No virus or antigen was demonstrable beyond day 7. Serum antibody was first detected on day 10, and titers peaked on day 28 after infection.     

Solitary liver nodules.

There has been confusion in the literature over the nomenclature of solitary liver nodules. Several such lesions have recently been reported in patients taking oral contraceptives. Similarities exist between these cases that suggest they may be examples of focal nodular hyperplasia. Here three further cases are presented. The criteria for making the diagnosis and its importance are discussed.     

Radiologic diagnosis of focal liver lesions

The paper is concerned with analysis of the results of combined investigation of 54 patients with focal liver lesions. USI, CT, angiography and radionuclide scintigraphy were performed. The diagnostic efficacy of USI and CT was 94.4 and 90.7%, respectively, that of scintigraphy was 68.5%, that of angiography was 55.5%. A scheme of the effective use of radiation methods in the diagnosis of sizable formations of the liver was worked out.     

Liver lesions in hepatitis B viral infection

A review is made of the various histological lesions observed in hepatitis B virus-related liver diseases, including different forms of acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The elementary lesions discussed include acidophil necrosis (apoptosis), confluent lytic necrosis in its different patterns, piecemeal necrosis, focal necrosis, and dysplastic hepatocytes. Their pathogenesis is explained in the framework of recent developments in the immunopathology of hepatitis B viral infections.     

Fine needle aspiration biopsy of the liver. A study of 102 consecutive cases

One hundred five CT-guided or ultrasound-guided fine needle aspirations of liver in 102 consecutive patients were reviewed. Adequate histologic confirmation or clinical follow-up of the final diagnosis was available for 86 of the 105 aspirations. A definite diagnosis of malignancy was made in 53 of the 61 aspirations performed on patients with malignant hepatic disease (86.9%). There were no false positives. The most common tumors detected were metastatic adenocarcinomas from an unknown primary or from the colon and rectum. The tumors were typed correctly in nearly all cases. Benign lesions encountered included cysts, abscesses, hemangiomas, cirrhosis and fatty metamorphosis. No serious complications were encountered as a result of aspiration. Guided fine needle aspiration biopsy of focal liver lesions appears to be an accurate, safe and relatively inexpensive method of diagnosis.     

The growth pattern of transplanted normal and nodular hepatocytes

Overt neoplasia is often the end result of a long biological process beginning with the appearance of focal lesions of altered tissue morphology. While the putative clonal nature of focal lesions has often been emphasized, increasing attention is being devoted to the possible role of an altered growth pattern in the evolution of carcinogenesis. Here we compare the growth patterns of normal and nodular hepatocytes in a transplantation system that allows their selective clonal proliferation in vivo. Rats were pre-treated with retrorsine, which blocks the growth of resident hepatocytes, and were then transplanted with hepatocytes isolated from either normal liver or hepatocyte nodules. Both cell types were able to proliferate extensively in the recipient liver, as expected. However, their growth pattern was remarkably different. Clusters of normal hepatocytes integrated in the host liver, displaying a normal histology; however, transplanted nodular hepatocytes formed new hepatocyte nodules, with altered morphology and sharp demarcation from surrounding host liver. Both the expression and distribution of proteins involved in cell polarity, cell communication, and cell adhesion, including connexin 32, E-cadherin, and matrix metalloproteinase-2, were altered in clusters of nodular hepatocytes. Furthermore, we were able to show that down-regulation of connexin 32 and E-cadherin in nodular hepatocyte clusters was independent of growth rate. These results support the concept that a dominant pathway towards neoplastic disease in several organs involves defect(s) in tissue pattern formation.     

Imaging Liver Lesions Using Grating-Based Phase-Contrast Computed Tomography with Bi-Lateral Filter Post-Processing

X-ray phase-contrast imaging shows improved soft-tissue contrast compared to standard absorption-based X-ray imaging. Especially the grating-based method seems to be one promising candidate for clinical implementation due to its extendibility to standard laboratory X-ray sources. Therefore the purpose of our study was to evaluate the potential of grating-based phase-contrast computed tomography in combination with a novel bi-lateral denoising method for imaging of focal liver lesions in an ex vivo feasibility study. Our study shows that grating-based phase-contrast CT (PCCT) significantly increases the soft-tissue contrast in the ex vivo liver specimens. Combining the information of both signals – absorption and phase-contrast – the bi-lateral filtering leads to an improvement of lesion detectability and higher contrast-to-noise ratios. The normal and the pathological tissue can be clearly delineated and even internal structures of the pathological tissue can be visualized, being invisible in the absorption-based CT alone. Histopathology confirmed the presence of the corresponding findings in the analyzed tissue. The results give strong evidence for a sufficiently high contrast for different liver lesions using non-contrast-enhanced PCCT. Thus, ex vivo imaging of liver lesions is possible with a polychromatic X-ray source and at a spatial resolution of ∼100 µm. The post-processing with the novel bi-lateral denoising method improves the image quality by combining the information from the absorption and the phase-contrast images.     

Pathological studies on corynebacterial ulcerative entero-colitis in rats treated with ACTH (author's transl)]

Ulcerative entero-colitis was developed in 6-week-old male Sprague-Dawley rats treated daily with ACTH (4 mg/kg. s. c.) as well as necrotic purulent lesions in liver, kidney, lung or heart. Incidence of ulcerative lesions was 6.3% in Farm-A rats and 56% in Farm-B rats. Although ulcerative lesions were mostly observed in cecum, the similar lesions were also detected in distal ileum or proximal colon in some cases. Histologically, the lesions were characterized by focal necrosis demarcated from surrounding normal tissue containing a number of clumps of bacteria and cellular debris. Bacteriological examination revealed that provocation of Coryne-bacterium kutscheri by ACTH-treatment resulted in appearance of the lesions. By means of intravenous or intraperitoneal inoculation with the strain isolated from lesion similar lesions were produced in the cecum of inoculated rats under the ACTH-treatment.     

Pathological evaluation of Polystichum squarrosum (D. Don) fern in laboratory rats

Polystichum squarrosum fern fed (30% w/w) rats showed moderate mortality, decrease in body weight, less body fat and splenomegaly. On post-mortem examination, significant gross lesions were not seen in sacrificed animals. Histopathologically, Polystichum fed rats showed dilated Virchow Robin's space in brain, mild to moderate vascular changes likeoedema, engorgement of blood vessels and haemorrhages in most of the visceral organs, interstitial pneumonia in lungs, focal necrosis and generalised vacuolative degenerative changes in liver, more haemosiderin deposition and presence of higher number of megakaryocytes in spleen, shrunken glomeruli, more peri-glomerular space and more number of glomeruli per microscopic field in kidneys, focal hyperplasia of urinary bladder and moderate to marked depletion of germinal epithelium and spermatids in seminiferous tubules of testes. Pathologically, progressive changes were observed only in liver, urinary bladder and testes on 180 days post feeding (DPF). One fern fed rat sacrificed on 135 DPF showed hepatic tumour which was diagnosed as hepatocellular carcinoma. The results showed that P. squarrosum produced almost comparable pathological changes/preneoplastic lesions as reported in bracken fern fed animals. Long term exposure studies (i.e. 2 yrs) are desired.