Needle biopsy of the liver. A critique of four currently available methods.

There are currently four needle biopsy methods for obtaining tissue from patients with possible diffuse liver disease or cancer. These include percutaneous blind needle biopsy, a visually guided needle biopsy at laparoscopy, guided fine-needle biopsies with ultrasonography or computed tomography, and the transvenous liver biopsy. We and others have found the guided fine-needle biopsy technique to be safe, relatively cheap, and highly accurate in the diagnosis of liver cancer. Blind percutaneous biopsy should be reserved for patients with possible diffuse, noncancerous, liver disease. Guided biopsies at laparoscopy can be done if the other two methods fail to give a tissue diagnosis. The transvenous approach is useful in patients with a coagulation disorder.     

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.     

Tyramine oxidase activity in needle biopsy of normal livers and diseased livers.

Tyramine oxidase and UDP-glucuronyl transferase activities were determined in 52 diseased livers obtained by needle biopsy. 14 liver specimens were also subjected to acetyl CoA carboxylase determination. Tyramine oxidase level was elevated in livers with nonalcoholic fatty change or toxic hepatitis, and reduced in livers with fibrosis or chronic alcoholic injury. UDP-glucuronyl transferase activity was reduced in livers with severe parenchymal damage or hyperbilirubinemia. Acetyl CoA carboxylase activity decreased markedly in an active alcoholic cirrhotic liver, and was elevated in alcoholic fatty livers as well as in a liver with acute venous stasis.     

Fine needle aspiration cytology of infantile haemangioendothelioma of the liver: a report of two cases

E. Sigamani, V. K. Iyer and S. Agarwala Fine needle aspiration cytology of infantile haemangioendothelioma of the liver: a report of two cases Background: Fine needle aspiration cytology (FNAC) of infantile haemangioendothelioma of the liver (IHL) has not previously been described because routine use of FNAC is contraindicated due to the risk of bleeding. Methods and materials: Two patients presented with progressively increasing right upper quadrant abdominal mass. The index case was a girl aged two and a half years with a large single mass in the right lobe of the liver. The second was a 3‐month‐old girl in whom ultrasonography revealed multiple hypoechoic lesions in the liver. Ultrasound‐guided fine needle aspiration had been performed on both patients. May‐Grünwald‐Giemsa stained smears from these two patients were reviewed and correlated with histopathology. Results: Both aspirates showed predominantly normal hepatocytes and bile ductules amongst which tumour cells were admixed. The latter were oval to spindle‐shaped with scant cytoplasm and wavy, kinked and indented nuclear outlines. The non‐epithelial character of the tumour cells was apparent and helped to rule out hepatoblastoma. One case showed extramedullary haemopoiesis. The diagnosis of IHL was established on subsequent excision in the first case and a wedge biopsy in the second case. CD34 and factor VIII R antigen were positive in the tumour cells. Conclusion: Radiological diagnosis of IHL is possible in a majority of cases, but sometimes features may overlap with hepatoblastoma and fine needle aspiration may be performed inadvertently. Characteristic kinked nuclei and intermixed normal liver tissue might suggest IHL in the differential diagnosis of a spindle cell vasoformative tumour.     

Papillary carcinoma of the thyroid gland. Analysis of 94 cases with preoperative fine needle aspiration cytologic examination

From 1979 to 1983, 94 papillary carcinomas of the thyroid gland were examined histologically in our institute after a preoperative cytologic examination. Material for cytologic examination was obtained using fine needle aspiration (FNA) biopsy. Eighty-five (90.4%) of the 94 examined cytologic smears were representative. Among these 85 cases suspicion for malignancy or malignancy itself was found in 64 cases (75.3%). The remaining 21 smears, classified as cytologically not as suspect for malignancy, were reclassified and the previous diagnosis had to be revised in one case. In the other 20 cases no clue for malignancy could be demonstrated even after reexamination. In the 85 cases with representative cytologic findings, tumor size was determined on surgical material, in order to establish how many carcinomas with a diameter less than 3 cm could not be reached by FNA biopsy. Except for one case, all carcinomas with negative preoperative cytologic findings had a diameter less than or equal to 3 cm. The question arising is the possibility of improving the accuracy of FNA biopsy in tumor detection within cold nodules of the thyroid by combined use of scintigraphy and ultrasound-guided FNA biopsy.     

Hepatocellular carcinoma versus carcinoma metastatic to the liver. Value of stains for carcinoembryonic antigen and naphthylamidase in fine needle aspiration biopsy material

Staining for amino acid naphthylamidase and carcinoembryonic antigen (CEA) was examined as an ancillary technique to improve the accuracy of differentiating hepatocellular carcinoma from metastatic carcinoma to the liver in fine needle aspiration (FNA) biopsy specimens. Twenty-four cases of FNA specimens from the liver, in which air-dried smears and/or cell blocks were available, were examined. Naphthylamidase-positive bile canalicular structures were present in 2 cases of hepatocellular carcinoma and absent in 8 cases of metastatic carcinoma studied. Ninety percent of the hepatocellular carcinomas were immunoreactive with the antibody to CEA, showing a predominantly bile canalicular pattern. Ninety percent of the cases of metastatic carcinoma were positive with the antibody to CEA, showing a diffuse cytoplasmic pattern. These findings indicate that both staining techniques may be useful in differentiating hepatocellular carcinoma from metastatic carcinoma. Since the naphthylamidase stain requires air-dried smears, which may not be available, whereas immunocytochemistry can be done on fixed material, the latter technique is more practical.     

Needle biopsy of the liver; general considerations

Needle biopsy of the liver provides concrete diagnostic information that cannot be as readily obtained in any other way. This report reviews 401 liver biopsies in 312 patients. THE MAJOR INDICATIONS FOR USE OF THIS PROCEDURE ARE: To determine the cause of an obscure liver enlargement; to establish the cause of jaundice; to distinguish between malignant disease and cirrhosis of the liver; to determine when hepatitis has subsided; and to evaluate the results of treatment. At times, systemic disease that has not been recognized by other means may be diagnosed by this technique. There is risk in performing this test, and the 0.25 per cent mortality in this series compares favorably with that reported from other clinics. Where the diagnosis by biopsy could be compared with observations at operation or autopsy, the correct diagnosis was made by biopsy in 85 per cent of cases. Greater accuracy was obtained by two or more biopsic examinations in one case then by single biopsy. In several cases in which surgical operation was considered, biopsic information made it unnecessary, and vice versa.     

Computed tomography in the diagnosis of diffuse diseases of the liver

Methods of CT, echotomography and scintigraphy of the liver were used to investigate 95 patients with diffuse liver diseases (fatty dystrophy, hepatitis, cirrhosis, hemosiderosis and amyloidosis). CT changes in these diseases were described. A high efficacy of CT was established in the detection of diffuse liver lesions and portal hypertension permitting one to give up in some cases invasive puncture biopsy of the organ.     

Differential diagnosis of malignant intrahepatic tumors by ultrasonically guided fine needle aspiration biopsy and by laparoscopic/intraoperative biopsy. A comparative study

Thirty-six cases of ultrasonographically detected liver tumors (28 malignant and 8 benign lesions) were investigated by both fine needle aspiration (FNA) biopsy and laparoscopic or intraoperative tissue biopsy. The sensitivity of FNA biopsy in detecting a neoplasm was 85.7% while that of tissue biopsy was 82.1%. Specificity was 100% in both methods. A correct histologic diagnosis of the neoplasm could be made on the cytologic smear in only 14 cases (50.0%) due to technical and methodologic difficulties. Endoscopic and intraoperative tissue biopsy yielded sufficient material to make a definite histologic tumor diagnosis in 23 of 28 cases. Additional information on tumor spread and sequelae of liver infiltration was obtained by macroscopic tissue observations in nine cases. These results indicate that FNA biopsy is less sensitive in the classification of primary or secondary liver tumors and that tissue biopsies obtained during laparoscopy or laparotomy are required if a suspected hepatic neoplasm needs to be classified exactly to plan therapy and to establish a prognosis.     

Enzymatic studies of liver cells obtained by fine needle biopsy from mice with the obese-hyperglycemic syndrome (genesymbol ob).

In an enzymatic study of livers from obese hyperglycemic mice (obob) and their lean litter mates, microdissected freeze-dried fine needle biopsies were used. Carbohydrate, fatty acid and ketone body metabolism was examined through assays of phosphofructokinase (PFK), 3-hydroxyacyl-CoA dehydrogenase (HOADH) and D-3-hydroxybutyrate dehydrogenase (HBDH). At 2 months of age the obob-mice showed a significant increase in PFK activity as compared to their lean litter mates. No such difference was found for the activity of HOADH and HBDH. An early increase in the initial glycolysis in the livers of obob-mice might thus be one of the factors responsible for the accelerated synthesis of lipids resulting in the fatty livers of the adult obob-mice. The present results corroborate previous studies indicating no major derangement in the fatty acid and ketone body metabolism in the livers of obob-mice. In a methodological evaluation of the technique for tissue sampling and preparation, freeze-dried fine-needle punctates showed significantly higher enzyme activities of PFK and HOADH than freeze-dried liver sections or crude homogenates. Freeze-drying of fine needle biopsies appears to be a technique with good preservation of the enzyme activity. This is of significance for future metabolic studies also in humans.     

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.     

Solitary angiomyolipoma of the liver. Report of a case initially examined by fine needle aspiration biopsy

Transabdominal fine needle aspiration biopsy of a solitary space-occupying lesion in the liver produced smears containing irregular bundles of smooth muscle cells with granular or fibrillary cytoplasm and slightly pleomorphic nuclei. In a few bundles, aggregates of mature fat cells were present, which is characteristic for an angiomyolipoma. Histologic examination of the resected mass showed it to be a solitary angiomyolipoma of the liver. The diagnosis was further confirmed by immunohistochemical and electron microscopic studies.     

Abnormal blood chemistry data in Cushing's syndrome: comparison with those for fatty liver

It has been reported that fatty liver is not uncommon in Cushing's syndrome. Biochemical data obtained from routine blood chemistry in 10 patients with Cushing's syndrome were compared with those for 15 patients with histologically verified fatty liver. We found an absence of a decreased GOT/GPT ratio, low normal choline esterase and increased lactic dehydrogenase activities together with lowered serum protein and albumin, and increased blood sugar and total cholesterol in Cushing's syndrome when compared with those of fatty liver cases. These data and additional findings in liver histology obtained from one patient with Cushing's syndrome due to adrenocortical carcinoma indicated that fatty changes in the liver were not frequently encountered in Cushing's syndrome. These abnormal biochemical data might be a way of distinguishing Cushing's syndrome from fatty liver.     

Laser-heated needle for biopsy tract ablation: In vivo study of rabbit liver biopsy

PurposeTo investigate the efficacy of a newly-developed laser-heated core biopsy needle in the thermal ablation of biopsy tract to reduce hemorrhage after biopsy using in vivo rabbit’s liver model.Materials and methodsFive male New Zealand White rabbits weighed between 1.5 and 4.0 kg were anesthetized and their livers were exposed. 18 liver biopsies were performed under control group (without tract ablation, n = 9) and study group (with tract ablation, n = 9) settings. The needle insertion depth (~3 cm) and rate of retraction (~3 mm/s) were fixed in all the experiments. For tract ablation, three different needle temperatures (100, 120 and 150 °C) were compared. The blood loss at each biopsy site was measured by weighing the gauze pads before and after blood absorption. The rabbits were euthanized immediately and the liver specimens were stained with hematoxylin-eosin (H&E) for further histopathological examination (HPE).ResultsThe average blood loss in the study group was reduced significantly (p < 0.05) compared to the control group. The highest percentage of bleeding reduction was observed at the needle temperature of 150 °C (93.8%), followed by 120 °C (85.8%) and 100 °C (84.2%). The HPE results show that the laser-heated core biopsy needle was able to cause lateral coagulative necrosis up to 14 mm diameter along the ablation tract.ConclusionThe laser-heated core biopsy needle reduced hemorrhage up to 93.8% and induced homogenous coagulative necrosis along the ablation tract in the rabbits’ livers. This could potentially reduce the risk of tumor seeding in clinical settings.     

Steatorrhea in patients with liver disease

Intestinal function was studied in 26 patients with seven types of acute and chronic liver disease, documented by liver biopsy. Steatorrhea, defined by a stool fat higher than 6 g. per day, was present in 18 of 23 consecutive patients studied, an incidence of 78.3%. Two patients with infectious hepatitis associated with steatorrhea studied previously were added and the 20 cases were analyzed. The malabsorption found was confined to fat and fat-soluble vitamins; stool excretion varied from 6.1 to 22 g. per day in the seven groups studied. No histological abnormality was seen on jejunal biopsy, serum vitamin B₁₂, D-xylose and Schilling tests were normal, and no radiological findings associated with malabsorption were detected in the small bowel. It is concluded that steatorrhea is a common finding in a wide variety of acute and chronic liver diseases and cannot be attributed to a primary defect of the small bowel.     

77例不明原因肝功能异常患者的临床与病理特点

目的探讨不明原因肝功能异常患者的临床与病理特点。方法75例不明原因肝功能异常患者行1秒钟肝穿刺,2例外科手术肝活检,标本均送免疫组化双标记及HE染色、Masson染色、网状纤维染色、罗丹宁铜染色、普鲁士蓝染色,进一步分析其临床及病理特点。结果77例病因不明肝功能异常患者除6例无诊断学异常及3例非特异性炎症外,其余68例（88．31％）经肝组织病理检查分别诊断为急慢性肝炎12例、自身免疫性肝病27例、代谢性肝病4例、脂肪性肝病11例、药物性肝损伤10例、先天性肝纤维化及肝小静脉闭塞病各1例。结论肝组织病理检查在不明原因肝功能异常患者诊断价值较高,但由于病理检查存在一定的局限性,如果重视临床资料收集,通过临床及病理特点相结合的方法可进一步提高临床确诊率。     

Alpha-1-antitrypsin deficiency and juvenile liver disease Ultrastructural observations compared with light microscopy and routine liver tests

Sixteen children (aged between 1 month and 20 years) with alpha-1-antitrypsin deficiency (PiZ) were investigated by liver biopsy on one or more occasions. Eight patients had suffered from neonatal cholestasis, and two of them were investigated during the cholestatic period as well. The clinical status and liver function tests were compared with the light and electron microscopical findings. According to the light microscopical analyses at the latest investigation, the cholestatic and noncholestatic patients were classified as healthy, fibrotic or cirrhotic cases. All livers displayed periodic acid-Schiff positive, diastase-resistant globules in some but not all periportally located hepatocytes. By electron microscopy accumulation of retained secretory material was found in all PiZ patients. This accumulation was most conspicuous in the smooth endoplasmic reticulum of hepatocytes. alpha-1-antitrypsin deficiency seems to affect some, but not all hepatocytes. In the affected cells disappearance or hypotrophy of the Golgi complex could be observed. The intracellular transport of very low density lipoproteins (VLDL) was apparently not affected. The migration block in alpha-1-antitrypsin deficiency seems to occur before transportation to the Golgi complex. The extent of the involvement was not strictly age-dependent. There was no ultrastructural evidence of subclinical cholestasis as a possible triggering factor in the development of cirrhosis.     

High sucrose diet-induced dysbiosis of gut microbiota promotes fatty liver and hyperlipidemia in rats

Excess sucrose intake has been found to be a major factor in the development of metabolic syndrome, especially in promoting nonalcoholic fatty liver disease. The excess fructose is believed to targets the liver to promote de novo lipogenesis, as described in major biochemistry textbooks. On the contrary, in this study, we explored the possible involvement of gut microbiota in excess sucrose-induced lipid metabolic disorders, to validate a novel mechanism by which excess sucrose causes hepatic lipid metabolic disorders via alterations to the gut microbial community structure. Wistar male rats were fed either a control starch diet or a high-sucrose diet for 4 weeks. Half of the rats in each group were treated with an antibiotic cocktail delivered via drinking water for the entire experimental period. After 4 weeks, rats fed with the high-sucrose diet showed symptoms of fatty liver and hyperlipidemia. The architecture of cecal microbiota was altered in rats fed with high-sucrose diet as compared to the control group, with traits including increased ratios of the phyla Bacteroidetes/Firmicutes, reduced α-diversity, and diurnal oscillations changes. Antibiotic administration rescued high-sucrose diet-induced lipid accumulation in the both blood and liver. Levels of two microbial metabolites, formate and butyrate, were reduced in rats fed with the high-sucrose diet. These volatile short-chain fatty acids might be responsible for the sucrose-induced fatty liver and hyperlipidemia. Our results indicate that changes in the gut microbiota induced by a high-sucrose diet would promote the development of nonalcoholic fatty liver disease via its metabolites, such as short-chain fatty acids.     

Fatty acid synthesis in the regenerating liver of the rat.

1. Synthesis de novo of fatty acids in the rat liver, measured per g wet wt. of tissue, was increased by a factor of about two, between 1 and 4 days after partial hepatectomy, compared with rates in sham-operated control rat livers. 2. There were no associated changes in the rates of liver cholesterol synthesis or of adipose-tissue fatty acid synthesis in rats after partial hepatectomy, compared with rates in sham-operated rats. 3. In regenerating livers, perfused under three different conditions, there was no alteration in the capacity for fatty acid synthesis compared with that of control rats. 4. The increased synthesis of fatty acids in regenerating liver was associated with insignificant increases in plasma concentrations of tricylglycerols and free fatty acids, with a decrease in content of liver glycogen, and with no change in hepatic activity of acetyl-CoA carboxylase. 5. The accelerated rate of synthesis of fatty adids in regenerating liver appears not to be due to any intrinsic alteration in hepatic capacity for fatty acid synthesis, but it may be caused by the continuous action on liver of unidentified circulating factors.     

Cancer of the liver; needle biopsy as a means of detection

Needle biopsy of the liver was done in 25 patients suspected of having hepatic cancer. The results of biopsy were "positive" in 19 cases, and cancer later was proven to be absent in the livers of four of the other six. Multiple biopsy increased the incidence of positive findings. The procedure obviously provides no false-positive tests. It is recommended for the detection of hepatic neoplasm in patients who would otherwise require surgical exploration for diagnosis.