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Nutritional assessment in the seriously ill patient.

A consensus definition of malnutrition does not exist. We define "clinically relevant malnutrition" as the state of altered nutritional status that adversely affects clinical outcome. Over four years we have attempted to delineate a clinically applicable and validated nutritional assessment approach. This was accomplished through multiple clinical studies on a large number of surgical patients many of whom were seriously ill. Although an initial prospective study in 64 patients confirmed the relationship between certain nutritional markers and outcome, we found that 97% of patients had at least one abnormality, while 35% had three or more abnormalities, clearly documenting the imprecision in unselected battery testing. In a subsequent retrospective analysis of 161 patients, serum albumin (Alb), serum transferrin (TFN), triceps skinfold (TSF), and skin test reactivity (DH) proved to be the best markers of clinically relevant malnutrition and their relative quantitative importance is embodied in our Prognostic Nutritional Index (PNI), where PNI (% risk) = 158 - 16.6 (Alb) - 0.78 (TSF) - 0.20 (TFN) - 5.8 (DH). In numerous prospective studies of different patient groups, a large percentage of which were critically ill, the PNI has been shown to be a reliable nutritional assessment tool for diagnosing clinically relevant malnutrition. Furthermore, we have shown that seriously malnourished patients classified by the PNI will clinically benefit from preoperative nutritional support. The relevance of baseline and serial nutritional assessment to the nutritional care of the critically ill patient is discussed.

Critical Care↗

The prognostic inflammatory and nutritional index in traumatized patients receiving enteral nutrition support.

The prognostic inflammatory and nutritional index (PINI) is a clinical assessment tool which aggregates serum C-reactive protein (CRP), alpha 1-acid glycoprotein (AAG), prealbumin (PA), and albumin (ALB) concentrations into a single score. This study was conducted to characterize the index and its determinants over time in 15 critically ill trauma patients receiving enteral nutritional support (ENS). Patients received 1.4 g of protein/kg/day and 32 kcal/kg/day for at least 7 days using a nutritionally complete formula supplemented with whey protein. The PINI was calculated at baseline and on days 4, 7, 10, 14, 21, and 28. The PINI decreased significantly from baseline (186 +/- 202) to day 4 (116 +/- 86) and reached a nadir at day 14 (27 +/- 40). Serum CRP concentrations decreased significantly during the study period, while PA and ALB concentrations increased significantly. There was no change in the AAG concentration. Nitrogen balance increased significantly during the study period. The PINI was positively correlated with CRP concentration (r = 0.72, p = 0.0001) and negatively correlated with PA concentration (r = 0.56, p = 0.0004 and nitrogen balance (r = -0.51, p = 0.0018). The PINI decreased significantly during ENS of critically ill trauma patients, influenced primarily by a decrease in CRP concentration. Further studies are needed to characterize the PINI's performance as a prognostic tool.

Adolescent↗

Cellular mechanisms and signalling pathways activated by high glucose and AGE-albumin in the aortic endothelium.

This review summarizes evidence on the effect of excess circulating glucose concentration and AGE-albumin on the aortic endothelial cells (ECs) phenotype, transport function, and expression of signalling molecules. The recent reports on the ECs dysfunction in diabetes are briefly reviewed, to provide a broader view on the link between ECs structural changes, functional alterations, and the underlying biochemical mechanisms. The original results emerging from streptozotocin-injected mice and human aortic endothelial cells grown in high (25 mM) glucose concentration are presented. Compared to physiological condition, in diabetes aortic ECs switch to a biosynthetic phenotype, present an increased number of caveolae, and enhance (by approximately 20%) transcytosis of AGE-albumin (AGE-Alb). In cultured ECs, 25 mM glucose induces approximately 2.6 fold increase in pSTAT-3 and pERK1 and approximately 1.8 fold increase in pERK2; further exposure to 5 microM AGE-Alb causes approximately 4.3 fold increase in pERK1/2 (vs. 5 mM glucose). Together, these data may explain the phenotypic change, enhanced permeability, and proliferation of aortic ECs in diabetic conditions.

Animals↗

Sialometrical and sialochemical analysis of patients with chronic graft-versus-host disease--a prolonged study.

Patients with graft-versus-host disease (cGVHD) suffer from oral dryness and increased levels of oral infections and mucosal pathologies. The purpose of the current study was dual: 1) to investigate the salivary functional (sialometry) and compositional (sialochemistry) alterations induced by the disease during a 12-month period following the onset of the disease; and 2) to evaluate the effect of Salagen 30 mg/d on the salivary biochemical and immunological composition in cGVHD patients. Significant higher concentrations of salivary sodium (Na), magnesium (Mg), total protein (TP), albumin (Alb), epidermal growth factor (EGF), and total IgG accompanied by a concomitant increase in total IgA that did not reach significant value was observed in cGVHD patients in comparison with controls at both resting and stimulated conditions (p < 0.05) while salivary levels of potassium (K), calcium (Ca), and phosphate (P) were not altered. Two weeks of oral Salagen 30 mg/d resulted in normalization of the salivary biochemical and immunological compositional alterations in the cGVHD patients. Oral pilocarpine was able to reduce and normalize the elevated levels of Na, Mg, TP, Alb, EGF, IgG, and IgA salivary concentrations at both resting and stimulated conditions. The ability of oral pilocarpine to normalize and reverse salivary biochemical and immunological alterations induced by cGVHD is parallel to its stimulatory effect on salivary flow rates, as we previously showed. As the biochemical and immunological composition of the saliva results in its antimicrobial protective characteristics, the ability of oral pilocarpine (Salagen) to abrogate cGVHD salivary gland abnormalities may be of clinical importance.

Adolescent↗

Identification of albumin-binding proteins in capillary endothelial cells.

Isolated fat tissue microvessels and lung, whose capillary endothelia express in situ specific binding sites for albumin, were homogenized and subjected to SDS-gel electrophoresis and electroblotting. The nitrocellulose strips were incubated with either albumin-gold (Alb-Au) and directly visualized, or with [125I]albumin (monomeric or polymeric) and autoradiographed. The extracts of both microvascular endothelium and the lung express albumin-binding proteins (ABPs) represented by two pairs of polypeptides with major components of molecular mass 31 and 18 kD. The ABP peptides have pIs 8.05 to 8.75. Rabbit aortic endothelium, used as control, does not express detectable amounts of ABPs. The ABPs subjected to electrophoresis bind specifically and with high affinity (Kd = approximately 60 X 10(-9)M) both monomeric and polymeric albumin: the binding is saturable at approximately 80 nM concentration and 50% inhibition is reached at 5.5 micrograms/ml albumin concentration. Sulfhydryl-reducing agents beta-mercaptoethanol and dithiothreitol do not markedly affect the ABPs electrophoretic mobility and binding properties. As indicated by cell surface iodination of isolated capillary endothelium followed by electroblotting, autoradiography, and incubation with Alb-Au, the bands specifically stained by this ligand are also labeled with radioiodine.

Adipose Tissue↗

The lymphatic route. V. Distribution of human natural interferon-beta in rabbit plasma and lymph.

Human natural interferon-beta (HuIFN-beta) was administered through different routes (intravenous [i.v.], intramuscular [i.m.], and subcutaneous [s.c.]) and its distribution in lymph and plasma was evaluated. After i.v. (bolus) administration the lymph/plasma ratio was about 0.35 but it significantly increased (11-fold) after i.m. administration. Addition of human albumin (ALB) to the IFN solution did not favor IFN absorption through the lymphatics. On the other hand, addition of ALB improved IFN absorption through the lymphatics after s.c. administration. These results are interesting because they clarify why IFN-beta can exert immunomodulatory activities in spite of very low plasma levels.

Animals↗

Embryoid body-mediated differentiation of mouse embryonic stem cells along a hepatocyte lineage: insights from gene expression profiles.

Pluripotent embryonic stem (ES) cells represent a promising renewable cell source for the generation of functional differentiated cells. Previous studies incorporating embryoid body (EB)-mediated stem cell differentiation have, either spontaneously or after growth factor and extracellular matrix protein supplementation, yielded populations of hepatocyte lineage cells expressing mature hepatocyte markers such as albumin (ALB). In an effort to promote ES cell commitment to the hepatocyte lineage, we have evaluated the effects of four culture conditions on albumin and gene expression in differentiating ES cells. Quantitative in situ immunofluorescence and cDNA microarray analyses were used to describe not only lineage specificity but also to provide insights into the effects of disparate culture environments on the mechanisms of differentiation. The results of these studies suggest that spontaneous and collagen-mediated differentiation induce cells with the highest levels of ALB expression but mature liver specific genes were only expressed in the spontaneous condition. Further analysis of gene expression profiles indicated that two distinct mechanisms may govern spontaneous and collagen-mediated differentiation.

Acute-Phase Proteins↗

A new gene mapping resource: interspecies hybrids between Père David's deer (Elaphurus davidianus) and red deer (Cervus elaphus).

Three male F1 hybrids between Père David's deer and red deer were mated to red deer to produce 143 backcross calves. The pedigrees are a rare example of a fertile hybrid between evolutionarily divergent species. We examined the use of these families for genetic mapping of evolutionarily conserved (Type I) loci by testing for genetic linkage between five species-specific protein variants and 12 conserved DNA probes. Two probes were homologous, and the remainder syntenic, to the protein coding loci in cattle or humans. Using six restriction enzymes, each DNA probe detected one or more restriction fragments specific to Père David's deer. Linkage analyses among the species-specific variants placed the loci into four linkage groups within which linkage between adjacent loci and gene order was supported by a LOD > 3. The linkage groups were (HPX, HBB)-FSHB-ACP2, LDHA-CD5-IGF2, BMP3-(GC, ALB)-(KIT, PDGFRA) and LDLR-C3-FGF1. Southern and protein analysis of LDHA and ALB provided identical segregation data. These linkage groups were consistent with the cattle gene map and provide new information for comparing the gene maps of ruminants, humans and mice. The deer hybrids are an important new resource that can contribute to the comparative analysis of the mammalian genome.

Animals↗

Impact of low-dose acetylsalicylic acid on kidney function in type 2 diabetic patients with elevated urinary albumin excretion rate.

BACKGROUND: Low-dose treatment with acetylsalicylic acid (ASA) is widely recommended to type 2 diabetic patients as primary prevention against cardiovascular disease. High-dose treatment with cyclooxygenase inhibitors reduces urinary albumin excretion rate (AER) in type 1 diabetic patients with micro- or macroalbuminuria. Whether a similar effect on AER exists during low-dose ASA treatment, which may confound the diagnosis and monitoring of micro- and macroalbuminuria in type 2 diabetic patients, remains to be elucidated. METHODS: In a randomized, double-blind, crossover trial, 31 type 2 diabetic patients with elevated levels of AER (>30 mg/24 h) were, in random order, given ASA (150 mg/day) for 4 weeks followed by placebo for 4 weeks with a 2 week washout period or vice versa. At the end of each treatment period AER, glomerular filtration rate (GFR), blood pressure (BP), transcapillary escape rate (TER(alb)) of albumin and haemoglobin A(1c) (HbA(1c)) were measured. RESULTS: The following variables remained unchanged (mean (95% CI) unless otherwise noted) (ASA vs placebo, paired Student's t-test): AER (201 (119-341) vs 205 (124-340) mg/24 h (geometric mean, 95% CI); P=0.78), GFR (103 (94-111) vs 102 (93-110) ml/min; P=0.58), systolic BP (151 (146-158) vs 152 (146-158) mmHg; P=0.68), diastolic BP (87 (83-91) vs 87 (82-91) mmHg; P=0.88), TER(alb) (6.3 (5.7-6.9) vs 5.9 (5.1-6.7); P=0.45) and HbA(1c) (8.6 (8.1-9.0) vs 8.5 (8.1-9.0) %; P=0.60). CONCLUSIONS: Low-dose treatment with 150 mg ASA daily does not have any impact on AER or GFR in type 2 diabetic patients with micro- or macroalbuminuria. Consequently, the widely recommended prescription of low-dose ASA as a primary and secondary prevention strategy against cardiovascular disease in these patients does not confound the diagnosis or monitoring of micro- or macroalbuminuria.

Adult↗

The prognostic impact of fluctuating levels of C-reactive protein in Brazilian haemodialysis patients: a prospective study.

BACKGROUND: A single elevated C-reactive protein (CRP) value predicts mortality in haemodialysis (HD) patients, but the relative importance of repeated vs occasional positive systemic inflammatory response findings is not known. METHODS: To assess the influence on survival of occasional inflammation, CRP, serum albumin (S-Alb) and fibrinogen were analysed bimonthly in 180 HD patients (54% male, 49+/-14 years). Clinically significant inflammation was defined as CRP >5.1 mg/l, based on the receiver operating characteristics curve for CRP as predictor of death. Based on four consecutive measurements of CRP, patients were assigned into three groups: group 1 (n = 74; 41%), no inflammation (CRP < or = 5.1 mg/l in all measurements); group 2 (n = 65; 36%), occasional inflammation (1-3 measurements of CRP > 5.1 mg/l); and group 3 (n = 41; 23%), persistent inflammation (all measurements of CRP >5.1 mg/l). The nutritional status was evaluated by subjective global assessment (SGA) and body mass index (BMI), and the survival (21 months of follow-up) by Kaplan-Meier curve and Cox model. RESULTS: The median and range of CRP values (mg/l) for group 1, 2 and 3 were: 3.2 (3.2-5.1), 3.6 (3.2-54.9) and 13.8 (5.2-82), respectively (P<0.001), whereas the prevalence of malnutrition, assessed by SGA and BMI, did not differ significantly between the groups. The survival rate by Kaplan-Meier analysis was significantly different among the groups (chi2 = 12.34; P = 0.0004). Patients in group 3 showed the highest mortality (34%; P = 0.001), compared with group 1 (8%) and group 2 (14%; P = 0.01), respectively, whereas there was no significant difference in mortality between groups 1 and 2. Age, CRP, S-Alb level and SGA were independent predictors of mortality. CONCLUSION: The patients with a persistent elevation of CRP had a higher mortality rate than the patients with occasional CRP elevation. Thus, persistent, rather than occasional, inflammation is an important predictor of death in HD patients.

Brazil↗

Albumin and hydroxyethyl starch 130 kDa/0.4 improve filter clearance and haemocompatibility in haemo- and plasmafiltration--an in vitro study.

BACKGROUND: Apart from their standard applications, haemofiltration (HF) and plasmafiltration (PF) may provide helpful therapy for sepsis, multiple organ- and acute liver-failure. Some colloids cause either decreases or increases in blood cell agglomeration. We hypothesized that solutions which reduce cell aggregability may lead to both improved filter clearance and better haemocompatibility due to decreasing rates of clogged hollow fibres. METHODS: Heparinized porcine blood (5 IU/ml) was used in an in vitro circuit. The filter types tested were from GAMBRO: HF66D (effective membrane surface: 0.6 m2) and PF1000N (effective membrane surface: 0.15 m2). Albumin (ALB), hydroxyethyl starch (HES) 200/0.5, HES 130/0.4, gelatin (GEL) or normal saline (0.9%) were added to the blood (n = 6/group). Recirculation systems were run for 2 h. Spontaneous haemolysis and filter resistance >420 mmHg were selected as indications of maximal flow rates. Sieving coefficients were determined for 17 parameters at the lowest and highest blood flows and filtration rate. RESULTS: Based on the filter types used, supplementation of ALB and HES130/0.4 led to an improved filter clearance without increasing the number of clogged capillary membranes or causing impaired haemocompatibility. Sieving coefficients for most solutes were independent of volume substitute and flow rate. Haemocompatibility and filter clearance deteriorated after addition of HES200 or GEL to the blood. CONCLUSIONS: Under standardized in vitro conditions, we found that colloids which reduce cell aggregability cause improved HF- and PF-performance. This phenomenon may provide new options for higher clearances and may lead to new concepts in low dose anticoagulation.

Animals↗

Linkage of tobiano coat spotting and albumin markers in a pony family.

Genetic segregation patterns among blood type markers and various phenotypically observed traits were studied in a small herd of ponies. The herd consisted of 10 mares without white spotting and a single stallion with the dominant pattern of tobiano spotting. Comparison of segregation patterns at loci for which the stallion was heterozygous showed tight linkage for the Alb-B and tobiano markers. In 17 cases in which the Alb contribution of the sire could be determined, all 10 foals that inherited AlbB from him were tobiano spotted, and all 7 non-spotted foals inherited his AlbA. The use of the symbol To is proposed for dominantly inherited tobiano spotting linked to the albumin.

Animals↗

Evaluation of the efficacy of bentonite from the south of Argentina to ameliorate the toxic effects of aflatoxin in broilers.

In vitro studies indicated that a sodium bentonite (SB) from southern Argentina had a high ability to sorb aflatoxin B1 (AFB1) from aqueous solution. We evaluated this compound for its ability to reduce the effects of total aflatoxins (AF; 5 mg AFB1/kg) in the diet of growing broiler chickens from 30 to 52 d of age. The diets were amended with 0.3% Argentinean SB to determine the effect of this compound during aflatoxicosis. When compared with the controls, BW gains were significantly (P < 0.05) lower for broilers fed diets containing AF alone (1,865 vs. 1,552 g). No differences were found between the BW gains of broiler chickens fed diets without AF (1,785 g) and those of chickens fed AF + SB (1,809 g). These results suggest that effects of AF treatment were ameliorated when SB was used in the broiler chick diets. The AF significantly (P < 0.05) decreased feed efficiency. Liver, kidney, and pancreas relative weights increased in chickens fed the diet containing AF alone. Alterations in the levels of serum total protein, albumin (ALB), and globulins (GLOB) were observed for AF diets, and moderate protection was provided by the sorbent. The ALB:GLOB ratio decreased in both groups of birds fed with the AF-contaminated diet, and we observed a moderate increase in this ratio by 0.3% addition of SB. The histopathological findings in liver sections of broiler fed diets with AF + SB indicated a nonprotective effect of this adsorbent, because a moderate hepatic steatosis was observed.

Adsorption↗

Oral treatment of mule ducks with arsenicals for inducing fatty liver.

The aim of this study was to determine the dosage and the compounds of arsenic that induce fatty liver in mule ducks and also to investigate their effects on tissue residues. One hundred four ducks, 8 wk old, were randomly selected for one of six dietary treatments in Trial 1 or one of seven dietary treatments in Trial 2. Different levels of roxarsone were administrated: 0, 10, 20, 30, 40, or 50 mg/d, respectively, in Trial 1. In Trial 2, the experimental treatments were of the same level (11.36 mg/d) with different sources of arsenic that included the control without As, roxarsone (3-nitro-4-hydroxyphenylarsonic acid), arsanilic acid, phenylarsonic acid, O-nitro-phenylarsonic acid, As2O3, or As2O5. Both trials lasted 3 wk, with 1 wk on the treatment followed by 2 wk of withdrawal. Results in Trial 1 showed that a dose of 40 mg roxarsone/d increased liver weight and caused fatty liver, whereas administration of 50 mg/d was lethal. In Trial 2, administration of arsenic (11.36 mg/d) for 1 wk significantly depressed feed intake in the roxarsone, As2O3, and As2O5 groups (P < 0.05), whereas the treatment significantly decreased only live weight gain in the roxarsone group (P < 0.05). Administration of roxarsone alone increased (P < 0.05) serum cholesterol (CHOL), albumin (ALB), and total protein (TP), whereas only As2O3 among treatments significantly decreased serum triacylglycerol (TG) concentration (P < 0.05). In the roxarsone, arsanilic acid, and phenylarsonic acid groups, serum high density lipoprotein (HDL) decreased to a greater extent (P < 0.05), and arsanilic acid treatment significantly increased the very low density lipoprotein (VLDL) (P < 0.05). After 2 wk of withdrawal, liver weights and relative liver weights were heavier in the treatment groups of roxarsone, As2O3, and As2O5 as compared to the control (P < 0.05). Levels of CHOL, TG, TP, and ALB were significantly higher in the groups treated with As2O3 or As2O5 as compared to the control (P < 0.05). The roxarsone and arsanilic acid treatments significantly decreased HDL and increased VLDL in plasma (P < 0.05). The creatine kinase (CK) level in the roxarsone, As2O3, and As2O5 groups was significantly higher compared to the control group (P < 0.05). Among the As sources, roxarsone, As2O3, and As2O5 caused fatty liver in mule ducks.

Administration, Oral↗

Sequential exposure to cytokines reflecting embryogenesis: the key for in vitro differentiation of adult bone marrow stem cells into functional hepatocyte-like cells.

Differentiation of adult bone marrow stem cells (BMSC) into hepatocyte-like cells is commonly performed by continuous exposure to a cytokines-cocktail. Here, it is shown that the differentiation efficacy in vitro can be considerably enhanced by sequential addition of liver-specific factors (fibroblast growth factor-4, hepatocyte growth factor, insulin-transferrin-sodium selenite, and dexamethasone) in a time-dependent order that closely resembles the secretion pattern during in vivo liver embryogenesis. Quantitative RT-PCR analysis and immunocytochemistry showed that, upon sequential exposure to liver-specific factors, different stages of hepatocyte differentiation, as seen during liver embryogenesis, can be mimicked. Indeed, expression of the early hepatocyte markers alpha-fetoprotein and hepatocyte nuclear factor (HNF)3beta decreased as differentiation progressed, whereas levels of the late liver-specific markers albumin (ALB), cytokeratin (CK)18, and HNF1alpha were gradually upregulated. In contrast, cocktail treatment did not significantly alter the expression pattern of the hepatic markers. Moreover, sequentially exposed cells featured highly differentiated hepatic functions, including ALB secretion, glycogen storage, urea production, and inducible cytochrome P450-dependent activity, far more efficiently compared to the cocktail condition. In conclusion, sequential induction of the differentiation process, analogous to in vivo liver development, is crucial for in vitro differentiation of adult rat BMSC into functional hepatocyte-like cells. This model may not only be applicable for in vitro studies of endoderm differentiation but it also provides a "virtually unlimited" source of functional hepatocytes, suitable for preclinical pharmacological research and testing, and cell and organ development.

Animals↗

Status of antioxidants and other biochemical abnormalities in children with dengue fever.

During an outbreak of dengue fever in 1996, 66 children between 45 days and 12 years of age with dengue fever and 25 healthy controls were studied for antioxidants and other biochemical abnormalities. As per World Health Organization (WHO) criteria, 14 children were classified as having classical dengue (DEN), 42 with dengue haemorrhagic fever (DHF), and 10 (including three who died) as having dengue shock syndrome (DSS). Superoxide dismutase (SOD), glutathione peroxidase (GPX), and albumin (ALB), the three main antioxidants studied, were found to be abnormal in 96, 94, and 40 per cent of the cases respectively. The levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine phosphokinase (CPK), total protein (TP), total cholesterol (CHO), and triglycerides (TGL) were abnormal in 79, 50, 30, 93, and 67 per cent of the cases respectively. Among the different groups of dengue the abnormalities were more marked in children with DSS than in those with DEN and DHF, especially with respect to ALB, TP, TGL, AST, ALT, and CPK (p < 0.005). This preliminary report of dengue confirms the assumption of free radical generation and alteration in antioxidant status during acute illness. However, to understand their complex interaction in disease progression and therapeutic utility, further studies are required.

Antioxidants↗

Does treatment change the outcome of seizures and computerized tomographic lesions in intracranial granulomas?

In children, intracranial granuloma diagnosed on computerized tomography (CT) scan and presenting with seizures as the sole manifestation has traditionally been treated with antitubercular (ATB) therapy or albendazole (Alb) in addition to antiepileptic drugs (AED). This study was conducted to determine whether AED therapy alone or specific treatment (ATB + Alb) influences the outcome of seizures and the CT lesion. Sixty-eight children presenting with seizures along with intracranial granuloma on CT scan were selected for the study. They were randomly divided into two groups. Group A (n = 34) was treated with AED alone and group B (n = 34) received antitubercular therapy and albendazole in addition to AED. Seizure type was noted and electroencephalogram (EEG) and CT scan were done in all. They were followed up for a period of 2 to 9 years, during which a record of seizure count and type was maintained. CT scans were repeated at 3 monthly intervals and EEGs were repeated whenever indicated. Four patients in each group were lost to follow-up. Seizures persisted in four out of 30 in group A and six out of 30 in group B. There was no statistically significant difference (p > 0.05) in the outcome of seizures in the two groups. Taking the whole group together (n = 60), of the 13 who had presented with multiple seizures at onset, epilepsy was a sequela in five (p < 0.05); and of the 17 in whom the lesion had calcified, seizures persisted in seven (p < 0.05), irrespective of treatment modality. In conclusion, though specific treatment did not alter the outcome of seizures, children with multiple seizures at presentation and calcification of CT lesion had epilepsy as a sequela.

Adolescent↗

The frequency and histology of hepatic tissue in germ cell tumors.

The frequency of hepatic tissue and its histological characteristics were examined in 516 germ cell tumors. Hepatic tissue was observed in 48 cases (9.3%). The incidence of hepatic tissue was low in tumors of the ovary (5%), high in both retroperitoneal (27%) and sacro-coccygeal (24%) tumors, and low in both mature (0.3%) and immature teratomas (11%). It was usually encountered in infancy, and the frequency was high in both yolk sac tumors (48%) and mixed germ cell tumors (52%). The hepatic tissue found mainly in mature or immature grade 1 teratomas was similar to adult normal human liver tissue (Ha-type). Tissue in areas consisting of some immature somatic elements of a mixed germ cell tumor was similar to embryonic or fetal liver tissue (Hf-type). Many hepatic nests found in a polyembryoma were of both Ha- and Hf-types. The hepatic tissue found in close relation to yolk sac elements showed predominantly hepatocellular carcinoma-like features (HCLS). Immunohistochemically, the cytoplasm of adult liver-type cells was positive for alpha-1-antitrypsin (AAT), human albumin (ALB), and the third (C3) and fourth (C4) components of the complement system. The cytoplasm of fetal liver-type cells showed the same positivity; in addition, these cells were positive for alpha-fetoprotein (AFP) in 25% of the cases. The cytoplasm of hepatic cells of HCLS was positive for AFP, AAT, ALB, C3, and C4. A weakly positive reaction for CEA and CA19-9 was observed in bile duct-like structure in some Hf-type cases.

Adult↗