Plasma amino acids of the transsulfuration pathway and plasma lactate in septic patients.

OBJECTIVES: In sepsis increasing plasma lactate, even if unrelated to hypoperfusion and hypoxia, is a cause of concern. Among the patterns associated with increasing lactate, several plasma amino acid (AA) abnormalities, more in particular those of sulfur AAs, have remained unexplored, and their assessment has been the purpose of our study. MATERIALS AND METHODS: A systematic and detailed analysis of 183 simultaneous determinations of plasma AA-grams and lactate, from 12 trauma surgery patients who had developed sepsis, was performed. Sepsis severity ranged from moderate to extreme illness. Correlations between changes in lactate and in AA levels were assessed by regression analysis. RESULTS: Increasing lactate was related to increasing alanine, proline, asparagine, tyrosine, cystathionine, histidine, glutamine, citrulline, methionine, phenylalanine and hydroxyproline (r from 0.62 to 0.36, p < 0.001 for all) and to decreasing taurine (r = -0.62, p < 0.001). Furthermore, increasing lactate was strongly related to increasing cystathionine/taurine ratio (r = 0.77, p < 0.001). These correlations were independent of the simultaneous relationship found between increasing lactate and decreasing mixed venous O2 tension. CONCLUSIONS: The overall findings and the correlation with the cystathionine/taurine ratio support the hypothesis that increasing lactate in sepsis may be paralleled by impaired hepatic AA transsulfuration. Because this may disable antioxidant protection by limiting glutathione and taurine availability, the metabolic perturbations associated with septic hyperlactatemia may include enhanced exposure to oxidative stress.

Plasma cholinesterase correlations in acute surgical and critical illness.

AIM: The properties of plasma cholinesterase (CHE) are partly undiscovered. Equally unknown are the correlations between changes in CHE and other blood variables during the acute phase response related to acute surgical and critical illness. METHODS: Data from 432 measurements of CHE and other variables performed in 92 patients were systematically evaluated and processed by regression analysis. RESULTS: There was a strong direct correlation between CHE and albumin (r=0.77, P<0.0001). CHE was also directly correlated to cholesterol, iron binding capacity, hematocrit, prothrombin activity, and inversely correlated to bilirubin and to presence of sepsis or liver dysfunction (P<0.0001 for all). Postoperatively CHE decreased to about 60% of the preoperative value, remaining directly related to it (r=0.69, P<0.0001), and decreasing further in the presence of sepsis or liver dysfunction, with slow reversal of the decrease during recovery from illness. In parenterally fed septic patients the decrease in CHE was moderated by increasing the amino acid dose (P<0.0001). CONCLUSION: In acute surgical and critical illness CHE mostly behaves as a negative acute phase reactant, independently of the modifications related to other already known factors. This should be taken into account when interpreting the implications of decreased CHE in the clinical setting.

Gas in portal circulation and pneumatosis cystoides intestinalis during chemotherapy for advanced rectal cancer.

OBJECTIVES: Acute abdominal symptoms with CT scan evidence of intramural gas in bowel walls (pneumatosis cystoides intestinalis, PCI) and of gas in the portal venous blood (PBG) in patients undergoing chemotherapy may represent a worrisome picture, suggestive of bowel necrosis. This picture remains a major clinical clue and the reporting of new cases may help to share awareness and experience on management. We describe a patient with acute abdominal symptoms and evidence of PCI with PBG under cetuximab, oxaliplatin, tegafur-uracil and folinic acid chemotherapy for metastatic adenocarcinoma of the rectosigmoid junction. METHODS: After admission for mucositis with diarrhea and profound dehydration, and subsequent emergency laparotomy for derotation of an intestinal volvulus, on the tenth postoperative day the patient developed fever and abdominal pain, with CT scan evidence of PCI with PBG. The exam of the abdomen did not suggest major problems requiring emergency surgery, and antibiotic treatment with close monitoring were performed, followed by rapid improvement. RESULTS: Twelve days later, after resumption of oral diet, the patient unexpectedly suffered a spontaneous jejunal microperforation, requiring emergency laparotomy and bowel resection. Pathology showed that the perforation was within an area of ulceration involving the inner superficial layer of the bowel. Subsequently recovery was normal and at present, after 15 months, the patient is well and continuing chemotherapy. CONCLUSIONS: This is probably the first report of PCI with PBG related to intestinal toxicity during cetuximab, oxaliplatin, tegafur-uracil and folinic acid chemotherapy in a patient with advanced rectal carcinoma, followed by delayed small bowel perforation. It provides an example of the challenges involved in the management of this type of patient.

The relationship between albumin, other plasma proteins and variables, and age in the acute phase response after liver resection in man.

A large series of plasma albumin (ALB, g/dl) and simultaneous blood and clinical measurements were prospectively performed on 92 liver resection patients, and processed to assess the correlations between ALB, other plasma proteins, additional variables and clinical events. The measurements were performed preoperatively and at postoperative day 1, 3 and 7 in all patients, and subsequently only in those who developed complications or died. In patients who recovered normally ALB was 4.3 +/- 0.4 g/dl (mean +/- SD) preoperatively, 3.7 +/- 0.7 at day 1 and 3, and 3.9 +/- 0.4 at day 7. In patients with complications its decrease was more prolonged. In non-survivors it was 3.4 +/- 0.4 preoperatively, 3.0 +/- 0.4 at day 1, and then decreased further. Regression analysis showed direct correlations between ALB and pseudo-cholinesterase (CHE, U/l, nv 5300-13000), cholesterol (CHOL, mg/dl), iron binding capacity (IBC, mg/dl), prothrombin activity (PA, % of standard reference) and fibrinogen, an inverse correlation with blood urea nitrogen (BUN, mg/dl) for any given creatinine level (CREAT, mg/dl), and weaker direct correlations with hematocrit, other variables and dose of exogenous albumin. An inverse relationship found between ALB and age (AGE, years) became postoperatively (POSTOP) also a function of outcome, showing larger age-related decreases in ALB associated with complications (COMPL: sepsis, liver insufficiency) or death (DEATH). Main overall correlations: CHE = 287.4(2.014)(ALB), r = 0.73; CHOL = 16.5(1.610)(ALB) (1.001)(ALKPH), r = 0.71; IBC = 68.6(1.391)(ALB), r = 0.64; PA = 13.8 + 16.0(ALB), r = 0.51; BUN = 21.3 + 20.2(CREAT) - 6.2(ALB), r = 0.91; ALB = 5.0-0.013(AGE) - {0.5 + 0.003(AGE)( COMPL ) + 0.012(AGE)( DEATH )}( POSTOP ), r = 0.74 [p < 0.001 for each regression and each coefficient; ALKPH = alkaline phosphatase, U/l, nv 98-279, independent determinant of CHOL; discontinuous variables in italics label the change in regression slope or intercept associated with the corresponding condition]. These results suggest that altered albumin synthesis (or altered synthesis unable to compensate for albumin loss, catabolism or redistribution) is an important determinant of hypoalbuminemia after hepatectomy. The correlations with age and postoperative outcome support the concept that hypoalbuminemia is a marker of pathophysiologic frailty associated with increasing age, and amplified by the challenges of postoperative illness.

Plasma arginine correlations in trauma and sepsis.

Arginine (ARG) is an amino acid (AA) with unique properties and with a key-role in the metabolic, immune and reparative response to trauma and sepsis. This study has been performed to characterize the correlations between plasma levels of ARG, of other AA and of multiple metabolic variables in trauma and sepsis. Two-hundred and sixty-three plasma amino-acidograms with a large series of additional biochemical and blood variables were obtained consecutively in 9 trauma patients who developed sepsis, undergoing total parenteral nutrition with dextrose, fat and a mixed AA solution containing 10.4% arginine. ARG was low soon after trauma, then it increased with increasing distance from trauma and with the development of sepsis. ARG was also directly related to the AA infusion rate (AAIR) and for any given AAIR, was lower after trauma than after the development of sepsis. ARG was also related directly to the plasma levels of most of the other AA, the best correlation being that with lysine (r(2) = 0.81, p < 0.001). These correlations were often shifted downwards (showing lower ARG for any given level of the other AA) in measurements performed after trauma, compared to those performed after development of sepsis; this effect was more pronounced for the correlations with branched chain AA. Correlations between ARG and non-AA variables were not particularly relevant. The best simultaneous correlates of ARG, among variables involved in plasma ARG availability, were citrulline level, AAIR and urinary 3-methylhistidine excretion (accounting for the effect of endogenous proteolysis) (multiple r(2) = 0.70, p < 0.001). Plasma ornithine (ORN), the AA more specifically linked to ARG metabolism, correlated with AAIR better than ARG and, for any given AAIR, was lower after trauma than after the development of sepsis. Correlations of ORN with other AA levels were poorer than those found for ARG, however ORN was directly related to white blood cell and platelet count, fibrinogen, transferrin, cholesterol and many AA clearances. These data show that changes in ARG in trauma and sepsis are correlated with changes in other AA and, within these correlations, reconfirm a tendency to lower ARG in trauma compared to sepsis. The strong correlation with lysine warrants a deeper assessment of the practical implications of interdependency between these two AA. The data also suggest that changes in plasma ORN in trauma and sepsis may reflect adequacy of AA substrate to support acute-phase and other synthetic processes.

The relationship between plasma cholesterol, amino acids and acute phase proteins in sepsis.

The purpose of the study was to correlate degree of hypocholesterolemia to changes in plasma levels of amino acids and other metabolic variables in severely injured septic patients. Measurements included plasma cholesterol, full amino-acidograms, acute phase proteins, complementary variables and blood cell counts. The Fischer plasma molar amino acid ratio (leucine+isoleucine+valine)/(phenylalanine+tyrosine) was calculated. Plasma cholesterol for all measurements (n=145) was 3.1+/-1.1 mmol/L and, upon entry in the study, it was correlated inversely with sepsis severity score (p<0.05). Along the clinical course, changes in cholesterol were clearly paralleled by opposite changes in C-reactive protein, which was the best correlate of cholesterol (r2=0.70, p<0.0001). Furthermore cholesterol was inversely related to phenylalanine, fibrinogen, lactate and white blood cell count, and directly to the Fischer molar amino acid ratio, cystathionine, methionine, glycine and transferrin (r2 between 0.36 and 0.15, p<0.0001 for all). Within this pattern of correlations, cholesterol was also directly related to alkaline phosphatase, which accounted for the effect of cholestasis, when present. For any given value of the other variables, cholesterol increased significantly with increase in alkaline phosphatase (p<0.0001). C-reactive protein (CRP, mg/dl) and alkaline phosphatase (ALKPH, U/L) together in the same regression explained 79% of the variability of cholesterol (CHOL, mmol/L): CHOL=5.90-0.74[Log(e)CRP]+0.004[ALKPH]; multiple r2=0.79, p<0.0001. Inclusion in this regression of other variables did not increase the r2. By using only amino acid variables, the best fit was provided by a regression including the Fischer ratio and cystathionine, which explained 55% of the variability of cholesterol (multiple r2=0.55 p<0.0001), and this result was not improved by the inclusion of other amino acids. These data show that severity of hypocholesterolemia in sepsis is quantifiably related to changes in plasma amino acids, and to severity of acute phase response and metabolic decompensation. More study is needed to understand whether hypocholesterolemia in sepsis has only diagnostic or prognostic implications, or that it may also contribute actively to worsening of the disease.

[Use of unconventional lipid substrates in parental nutrition]. / Uso dei substrati lipidici "non convenzionali" in nutrizione parenterale.

In addition to the classic soybean oil fat emulsion, developed more than 40 years ago and still widely used, emulsions with other lipid substrates are available today for parenteral nutrition; these substrates implement the benefits offered by soybean oil when mixed with it in given proportions. Soybean oil triglycerides are rich in linoleic acid, a long chain omega-6 polyunsaturated fatty acid, which is essential and is an indispensable component of parenteral nutrition. However, very high doses of omega-6 polyunsaturated fatty acids should be avoided, particularly in some critical illnesses. Medium chain triglycerides, long well known to nutritionists and dietitians for their easy intestinal absorption, have become available in parenteral nutrition emulsions in a mixture with soybean oil. Medium chain triglycerides are completely and readily used for energy production and do not interfere significantly in the production of inflammatory mediators, in the composition of cell membranes and in body organ and system functions. Omega-3 polyunsaturated fatty acids, essential fatty acids derived from fish oil, permeate cell structure and affect cell activity with different mechanisms, playing also an important role in the modulation of inflammatory processes. Omega-3 emulsions in parenteral nutrition are currently added as a supplement to other fat emulsions. Knowledge of these "non-conventional" fat emulsions is being continuously improved by investigative work and clinical experience.

Co-variation of plasma sodium, taurine and other amino acid levels in critical illness.

This study investigates the relationship between changes in plasma sodium and changes in amino acid levels in a patient with post-traumatic sepsis and prolonged critical illness. Ninety-two consecutive measurements were performed at regular intervals over a period of many weeks; these consisted in the determination of full amino-acidograms, plasma sodium and complementary variables. A unique, highly significant inverse correlation between taurine and plasma sodium was found (r(2) = 0.48, p < 0.001). All other amino acids were unrelated, or much more weakly related, to sodium. Taurine was also strongly and directly related to phosphoethanolamine, glutamate and aspartate. Changes in sodium and in levels of these amino acids explained up to 86% of the variability of taurine. Besides, levels of these amino acids maintained a high degree of co-variation, remaining reciprocally related one to each other, directly, with r(2) ranging between 0.33 and 0.59 (p < 0.001 for all). There were similar findings for beta-alanine, which however was measured inconsistently. These data provide gross clinical evidence of a specific link binding plasma sodium and taurine levels, and may be consistent with occurrence of opposite and interdependent shifts of sodium and taurine between intravascular and extravascular space, to maintain osmoregulation. Co-variation of taurine with the other amino acids may be related to the same phenomenon, and/or to similarities in transport systems and chemical structure, or true metabolic interactions.

The relationship between plasma taurine and other amino acid levels in human sepsis.

Although reports of decreased plasma taurine in trauma, sepsis and critical illness are available, very little is known about the relationships among changes in plasma taurine, other amino acid levels and metabolic variables. We analyzed a large series of plasma amino acid profiles obtained in trauma patients with sepsis who were undergoing total parenteral nutrition. The correlations between plasma taurine, other amino acid levels, parenteral substrate doses and metabolic and cardiorespiratory variables were assessed by regression analysis. Post-traumatic hypotaurinemia was followed by partial recovery toward less abnormal values when sepsis developed. Levels of taurine were directly and significantly related to levels of glutamate, aspartate, beta-alanine and phosphoethanolamine (and unrelated to other amino acids). Levels of these amino acids increased simultaneously with increasing doses of leucine, isoleucine and valine in total parenteral nutrition. Decreasing taurine was associated with increasing lactate, arteriovenous O(2) concentration difference and respiratory index, and with decreasing cholesterol and cardiac index. These results characterize the relationships between plasma taurine and other amino acid levels in sepsis, provide evidence of amino acid interactions that may support taurine availability and show more severe decreases in plasma taurine with the worsening of metabolic and cardiorespiratory patterns.

Taurine and pulmonary hemodynamics in sepsis.

This study has been performed to characterize the relationship between changes in plasma taurine (TAU) and hemodynamic patterns in sepsis. Analysis of 249 plasma aminoacidograms (AA-grams) and associated measurements in a group of critically ill, mechanically ventilated septic patients, showed that decreases in TAU were significantly correlated with increases in pulmonary artery pressure and pulmonary vascular resistance, and with worsening of pulmonary dysfunction. All cases requiring positive end-expiratory pressure greater than 10cmH2O had TAU lower than 50 microM/L. Low TAU was paralleled by decreases in other sulfur-containing AA, phosphoethanolamine, beta-alanine, glutamate and aspartate, within a pattern of greater metabolic dysregulation. These data provide evidence of a link between severity of pulmonary dysfunction and reduced TAU availability in clinical sepsis. The implications relate also to the need for specific investigations of the clinical effect of exogenous TAU on proinflammatory mediator-induced pulmonary dysfunction.

Pathophysiologic correlates of hypocholesterolemia in critically ill surgical patients.

OBJECTIVE: To assess correlates of hypocholesterolemia in moderate to critical surgical illness. DESIGN: Prospective analysis of laboratory and clinical data. SETTING: Department of surgery in a university hospital. PATIENTS: 135 patients undergoing uncomplicated abdominal surgery or with sepsis, liver failure, hemorrhage, severe cholestasis, or multiple organ dysfunction syndrome (MODS). INTERVENTIONS: Surgical and/or medical therapy according to clinical status. MEASUREMENTS AND MAIN RESULTS: Determinations of total cholesterol, additional variables, and clinical data. Cholesterol decreased after surgery, in sepsis, liver failure, acute hemorrhage, and MODS and increased in cholestasis. Hypocholesterolemia correlated with decreases in plasma proteins and indices of hepatic protein synthetic adequacy, with hemodilution from blood loss, and was moderated or prevented by cholestasis. CONCLUSIONS: These results help to explain the dynamics of the development, clinical relevance, and negative prognostic value of hypocholesterolemia in critical illness.

Quantitative assessment of changes in blood CO(2) tension mediated by the haldane effect.

Adequate assessment of circulatory and gas-exchange interactions may involve the quantification of the Haldane effect (HE) and of the changes in blood PCO(2) mediated by changes in Hb-O(2) saturation and O(2)-linked CO(2) binding. This is commonly prevented by the complexity of the involved calculations. To simplify the task, a large series of patient measurements has been processed by regression analysis, thus developing an accurate fit for this quantification (v-a) PCO(2)HE + 0.460 [(a-v) HbO(2)]0.999e0.015(PvCO(2))-0.852(Hct) (n = 247, r(2) = 0. 99, P << 0.001), where (v-a)PCO(2 HE) is the reduction in venous PCO(2) (Pv(CO(2)), Torr) allowed by the chemical binding of CO(2) in blood due to the HE (Torr), (a-v)HbO(2) is the arteriovenous difference in Hb-bound O(2) (ml/dl), and Hct is hematocrit fraction. Values of (v-a)PCO(2 HE) estimated by this expression compared well with the results of previously published experiments. This formula is useful in assessing the impact of HE on Pv(CO(2)) and venoarterial PCO(2) gradient and the survival advantage offered by HE in extreme conditions. Use may be extended to all investigative and clinical settings in which changes in blood O(2) saturation and O(2)-linked CO(2) binding must be converted into the corresponding changes in dissolved CO(2) and PCO(2).

Computer-assisted analysis of the impact of respiratory quotient on blood CO2 tension and pH changes.

A computer model for the accurate quantification of blood gas exchange components was used to assess the impact of respiratory quotient (RQ) on venoarterial CO2 tension and pH differences over a large group of patient measurements. The combined use of measured and computer-generated data has shown that, for any given increase in blood CO2 concentration (i.e., when the arterial blood becomes venous), the associated increase in CO2 tension and decrease in pH are inversely related to the RQ, and that this relationship is mediated by the Haldane effect. These results are useful for a through understanding of blood gas and metabolic interactions in normal and abnormal states, and for improving the interpretation of changes in venoarterial CO2 tension gradient in clinical monitoring.

The relationship between oxygen extraction and venous pH in sepsis.

This study was performed to quantify the impact of Haldane effect (HE) on the relationship between O2 extraction (O2Ex; mL O2/dL blood) and venous pH in 247 measurements performed in 91 septic patients (73 patients with intra-abdominal sepsis, 11 with retroperitoneal abscesses, 6 with severe cholangitis, and 1 with gangrenous fasclitis). The severity of sepsis varied from relatively compensated to extremely diseased conditions. This allowed a detailed assessment of the impact of HE over a wide range of cardiorespiratory and metabolic abnormalities. A recently developed model was used to quantify blood CO2 exchange and Haldane relationships and, in particular, the buffering of venous pH allowed by O2Ex (O2-linked H+ binding) on the basis of arterial and mixed venous blood gas measurements. Arterio-venous pH difference (a-vDpH) was .033 +/- .024 (mean +/- SD). It increased with venoarterial CO2 concentration difference (v-aDCO2; mL CO2/dL blood), but the increase was moderated by a simultaneous increase in O2Ex, as the likely consequence of HE: a-vDpH = .006 + .017 (v-aDCO2) - .009 (O2Ex) [r2 = .96, p < < .001]. To confirm this, the moderation of a-vDpH allowed by the HE (DpH) was calculated. A first component, due to O2-linked H+ binding, had a value of .016 +/- .012, and a second component, due to the Haldane-mediated reduction in venous CO2 tension and plasma carbonic acid concentration, had a value of .019 +/- .006. Their sum (total DpH) was .033 +/- .017 and was related directly and strongly to O2Ex: DpH = -.002 + .009 (O2Ex) [r2 = .85, p < < .001], thus confirming the quantitative impact of HE in moderating the decrease in venous pH relative to arterial pH. The loss of this effect was responsible for the larger decreases in venous pH observed in hypodynamic patients developing impaired O2Ex. These results allow an easy quantification of the Haldane component, separated from the other components affecting pH, and are also useful for assessing the protective role exerted by HE against excessive decreases in venous pH in circulatory failure.

[The branched-chain amino acids]. / Gli aminoacidi ramificati.

Branched-chain amino acids (BCAA: leucine, isoleucine and valine) are not just structural constituents of proteins, but have ''pharmacologic'' properties, known for several years: BCAA are catabolized mainly in muscle; can be oxidized with energy production, being nitrogen donors for other amino acids; regulate protein synthesis and degradation; modulate metabolism of neuroactive mediators. These properties make the clinical use of BCAA particularly suitable in critical conditions such as liver cirrhosis, sepsis, surgical or nonsurgical trauma, acute renal failure, acute pancreatitis, cancer, in which energy production from conventional substrates is altered and, at the same time, reduction of protein catabolism and enhancement of synthetic processes is advisable. Recently, the changes of plasma aminoacidograms induced by the administration of high-dose BCAA in sepsis have been better detailed: 1) a tendency to normalization of high levels of proline and of other amino acids transported intracellularly by transport system ''A''; 2) less relevant reduction of the levels of other amino acids; 3) increase of the levels of taurine, glutamate and aspartate; more complex interactions with specific amino acids. These changes, and changes of other variables, reconfirm in part some well-known properties of BCAA, and are also objective indicators of an improvement of the metabolic abnormalities of sepsis induced by BCAA administration. In sepsis and in other stress conditions it is recommended to administer, within balanced parenteral nutritional regimens, AA solutions with a 35-50% BCAA concentration.

[Medium-chain triglycerides in artificial nutrition]. / I trigliceridi a catena media (MCT) in nutrizione artificiale.

Medium Chain Triglycerides (MCT) are lipids which are commonly present in nature, for instance in milk and in some vegetable oils. The MCT molecule is composed of glycerol esterified with saturated linear-chain fatty acids containing 6 to 12 carbon atoms (MCFA: Medium Chain Fatty Acids: C(6:0), esanoic acid; C(8:0), octanoic acid; C(10:0), decanoic acid; C(12:0), dodecanoic acid). MCT for clinical use are currently obtained from vegetable fat through industrial processing. The large interest for MCT in clinical nutrition is due to unique physico-chemical, biochemical and metabolic features, which characterize MCT compared to conventional lipids (LCT: Long Chain Triglycerides). In particular, MCT represent a source of rapidly, fully available and ''high density'' energy, which makes their use very advantageous and suitable in a wide range of clinical situations, from the premature newborn to the adult patient. In addition to the MCT oil, known to physicians and nutritionists since the 1950s, and to the many commercially available MCT-containing compounds for oral-enteral use, in the last years it has become possible also to administer MCT-containing emulsions in parenteral nutrition. This has allowed to improve further knowledge of the effects of MCT, expanding the indications for use, often as a ''first-choice'' substrate in different types of critically ill patients.

[Dynamic computed tomography in the characterization of focal hepatic lesions]. / La Tomografia Computerizzata dinamica nella caratterizzazione delle lesioni focali epatiche.

The main goal of our study was to test dynamic CT capability to characterize focal liver lesions. We examined 57 patients: 6 were affected with focal nodular hyperplasia (FNH), 19 with hepatocellular carcinoma (HCC), 1 with a regenerating nodule on cirrhosis; 14 patients had metastases, 3 focal fatty infiltration, 1 a necrotic nodule, 1 a non-Hodgkin's lymphoma, 1 a cysto-adeno-cholangiocarcinoma and 11 hemangiomas. All lesions were identified with US and the diagnosis was confirmed with the gold standard technique--that is, biopsy or surgery, and red blood cell SPECT for hemangiomas. All lesions were studied with a CT multiphase protocol consisting of a single-level dynamic phase followed by an incremental dynamic phase and finally by a delayed phase to study prolonged and delayed enhancement. Single-level dynamic bolus CT requires an injection of 60 ml nonionic contrast agent administered with a power injector into a cubital vein, at a rate of 5 ml/s. Scanning begins 10 seconds after the injection and consists of 6 series of 2 scans each; each scan lasts 2 seconds and is obtained during the same respiratory apnea, with a 5-second interscan pause. In this phase, 12 scans 5 mm thick are obtained, lasting 24 seconds in all, with pauses lasting 25 seconds--in all, 49 seconds. The next phase is the dynamic incremental scanning, to study the whole liver: this phase requires a 50-ml contrast agent injection at a rate of 4 ml/s, followed by 70 ml at a rate of 1 ml/sec, using 5 mm slice thickness and 8 mm scan interval. This results in 16 scans, beginning 20 seconds after the injection, with a scan time of 2 seconds and 4 seconds of interscan delay, 92 seconds in all. In the last phase, scanning begins 5 minutes after the injection, with a maximum delay of 10-15 minutes. Enhancement variations in both the lesions and the surroundings parenchyma, as related to time, were collected together with morphological data. Time density curves were grouped according to histologic classification and red blood cells SPECT findings; the curves were analyzed with the regression analysis. The results were obtained by analyzing a series of equations describing the different densities of the lesion and the surrounding parenchyma at fixed time intervals, integrated with morphological data, and then comparing the groups of lesions with each other. The regression analysis of the density curves and of the morphological data allowed us to correctly differentiate the 4 most frequent types of lesions--that is, hemangioma, HCC, FNH and metastasis--in 89% of the patients.

[The tissue characterization of focal liver lesions by color Doppler echography]. / Caratterizzazione tissutale delle lesioni focali epatiche mediante eco color Doppler.

To investigate color-Doppler capabilities in tissue characterization, 47 hepatic lesions were studied. The real-time morphologic appearance of the lesions was studied first and then color flow images were acquired, assessing color areas and the distribution of blood flow for each lesion. For quantitative Doppler study, the color Doppler signal was used as a guide to obtain the Doppler spectrum and to measure flow velocities and pulsatility index (PI) values. Data were plotted and analyzed statistically; criteria for differentiating malignant from benign hepatic tumors and the patterns suggestive of either condition were proposed. Absolutely no Doppler signal was observed in avascular or necrotic lesions and in low-flow tumors, e.g., metastases (10%) and hemangiomas (63%). Many color signals at the periphery and within tumor masses were observed in highly vascular lesions, e.g., hepatocellular carcinomas (60%) and focal nodular hyperplasia (80%). Multiple afferent vessels and a "basket-like" pattern were detected in a high percentage of hepatocellular carcinomas. High-flow velocities (> 0.85 m/s perilesional systolic velocity and > 0.80 m/s intralesional systolic velocity) and high PI values (> 1.5 perilesional PI and > 0.90 intralesional PI) are suggestive of malignancy. Particularly, 0.90 intralesional PI cutoff value exhibits 89% specificity and 82% sensitivity in benign versus malignant differential diagnosis. Our results suggest that color-Doppler US is a useful means of studying the hemodynamics of hepatic tumors which increases US diagnostic accuracy.