Malignant progression of a small HCC nodule: hypovascular 'early HCC' converted to hypervascular 'small HCC' within six months.

We report a case of hepatocellular carcinoma superimposed on chronic hepatitis C virus (HCV) hepatitis in which final diagnosis of hepatocellular carcinoma was delayed because there was no consensus on hypervascularity with two diagnostic methods at the time of presentation. A 3 cm lesion was initially observed as hypovascular at multidetector-row computed tomography. Conversely, two months later the lesion appeared hypervascular at contrast-ultrasonography and gadolinium-enhanced dynamic magnetic resonance, and hyperintense after superparamagnetic iron oxide-enhanced T2W studies. Only in the late follow-up it was definitively confirmed as hypervascular in the arterial phase of multidetector-row computed tomography. This case clearly highlights some pitfalls in the European Association for the study of the liver guidelines for hepatocellular carcinoma management, which were readdressed in the last American Association for the Study of Liver Diseases (AASLD) and in the forthcoming international proposals, leading to more pragmatic suggestions for clinical practice.

Alterations of exocrine pancreas in end-stage renal disease. Do they reflect a clinically relevant uremic pancreopathy?

Serum pancreatic enzyme behavior, exocrine function, and morphology of the pancreas were studied in 28 patients with end-stage renal disease undergoing regular hemodialysis, in order to better delineate and assess the clinical relevance of the pancreatic alterations that occur in these patients. Twenty-eight healthy subjects served as controls. Initial studies included serum amylase, isoamylase, and lipase assays; fecal chymotrypsin measurement; and abdominal ultrasonography. The amylase, lipase, and chymotrypsin determinations, as well as ultrasound examination, were repeated four years later. None of the patients had clinical evidence of pancreatic disease at entry into the study, but one had had previous attacks of pancreatitis and another developed mild acute pancreatitis one month after entry. Initial mean serum enzyme levels were significantly higher in patients than in controls (amylase, pancreatic isoamylase, and lipase, P < 0.001; salivary isoamylase P < 0.05). Serum amylase was raised in 16/28 patients; pancreatic isoamylase in 15/28, and lipase in 7/28; these elevations were generally mild. Mean fecal chymotrypsin was significantly lower (P < 0.001) in patients than in controls: abnormally low values were found in 9/28 patients. Amylase, lipase and chymotrypsin measurements repeated after four years showed no significant difference with respect to the first study. Ultrasonographic changes were rare and mild: one patient had a small cyst in the pancreas head, another, an increase in echogenicity of the gland not related to age; these findings were unchanged at repeat examination. The results demonstrate that the frequent elevations of serum pancreatic enzymes and the rare sonographic changes found in patients undergoing hemodialysis do not generally reflect a relevant pancreopathy. However, the finding of significantly decreased fecal chymotrypsin may indicate the presence of pancreatic dysfunction in end-stage renal disease.

Changes in mesenteric venous flow due to celiac sprue.

Villus atrophy in celiac sprue determines not only a great reduction of the intestinal absorptive surface, but also destroys the underlying microcirculation which depends on the small artery of the villus and the rich network of capillaries. This may result in a significant shortening of the mesenteric vascular bed. We describe three cases of celiac sprue in which duplex Doppler ultrasound flowmetry revealed a high blood flow velocity in the superior mesenteric vein during the acute stage of the disease. A gluten withdrawal diet produced in all cases a restoration of the normal thickness of the mucosa, together with a significant decrease of blood flow velocity in the superior mesenteric vein.

Caliber of splenic and hepatic arteries and spleen size in cirrhosis of different etiology.

The caliber of the splenic and hepatic arteries, the hepatic to splenic artery ratio and the spleen size (area of widest spleen section) were evaluated by real time ultrasonography (US) in 88 patients affected by liver cirrhosis of different etiology (26 alcoholic cirrhosis, 43 hepatitis B virus (HBV) related cirrhosis, 8 cryptogenic cirrhosis and 11 primary biliary cirrhosis) and in a control group of 21 normal subjects, in order to assess the possible influence of the etiology of the disease on these morphological parameters. The mean caliber of the hepatic artery was larger, and the mean caliber of the splenic artery smaller in alcoholic than in HBV-related, cryptogenic and in primary biliary cirrhosis. This difference is emphasized when considering the hepatic to splenic artery ratio: this parameter was never greater than 0.9 in all cases of primary biliary cirrhosis, in 38 out of 43 patients with HBV-related cirrhosis and in 6 out of 8 cryptogenic cirrhosis, while in the alcoholic group only in one out of 26 was it less than 0.9. The sensitivity, specificity and accuracy of this ratio in differentiating alcoholic from non-alcoholic cirrhosis was 96%, 88% and 91%, respectively. Splenomegaly resulted more in primary biliary cirrhosis, in HBV-related cirrhosis and in cryptogenic cirrhosis than in the alcoholic form. Finally, a significant correlation was found in all groups of cirrhotic patients between the diameter of the splenic artery and the spleen size. These results show that some ultrasonographic morphological features of liver cirrhosis differ according to its varied etiology, probably reflecting different pathophysiological mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis of Budd-Chiari syndrome by pulsed Doppler ultrasound.

Computed tomography and real-time ultrasonography may not be conclusive for the diagnosis of the Budd-Chiari syndrome; in many cases more information may be needed, especially on vascular alterations. Doppler ultrasonography provides qualitative data on flow direction and pattern, thereby contributing significantly to diagnosis. Eight cases in which hepatic vein patency was unclear and presence of intrahepatic vessels resembling hepatic veins raised problems of interpretation in real-time ultrasonography are described. In some cases, patency or occlusion of the upper portion of the inferior vena cava were difficult to identify with real-time ultrasonography. Doppler ultrasonographic investigation showed flow in the hepatic veins to be completely absent in two cases and reversed in another two. In the remaining four cases, a flat waveform was evident. Flow in the inferior vena cava was reversed in four cases and showed a flat waveform in three other cases. Portal vein thrombosis was detected in only one case, whereas the remaining seven patients showed slow hepatopetal flow. These findings demonstrate that absent or reversed flow in the hepatic veins and/or flat flow in the hepatic veins associated with reversed flow in the inferior vena cava may be considered diagnostic for the Budd-Chiari syndrome. For this series the sensitivity of Doppler ultrasonography was 87.5%.

Liver cirrhosis: changes of Doppler waveform of hepatic veins.

The authors compared the Doppler ultrasonographic pattern of hepatic veins (HVs) in a group of 60 patients affected by liver cirrhosis and in 65 healthy subjects comparable for sex and age to (a) detect possible differences in HV waveform in the two groups and (b) investigate the relationship of these differences with the severity of the disease (according to Child-Pugh classification) and the modifications of systemic hemodynamics. The waveform of HVs was arbitrarily classified into three patterns: HV0, a normal waveform; HV1, lower oscillations without the reversed phase; and HV2, completely flat waveform. The resistivity index of the superior mesenteric artery, reflecting the peripheral splanchnic impedance and the hyperdynamic circulation, was also measured in a subgroup of 45 cirrhotic patients. The waveform of HVs in all healthy subjects corresponded to the HV0 pattern. Among cirrhotic patients, HV0 was found in 30 (50%), HV1 in 19 (31.7%), and HV2 in 11 (81.3%). The severity of functional impairment was greatest in the HV2 group and least in the HV0 group. This was significantly correlated with the decrease of the resistivity index in the superior mesenteric artery in the subgroup of 45 patients. Changes in the normal HV waveform could be considered a useful adjunctive tool for the noninvasive evaluation of liver disease. The pathophysiology of these changes in HV blood flow is still unclear. The significant correlation with the severity of the disease and with the decrease of splanchnic resistances indicates that these changes in the HV waveform occur in the presence of marked rearrangements of liver tissue and of hyperdynamic systemic circulation.

Prevalence of spontaneous hepatofugal portal flow in liver cirrhosis. Clinical and endoscopic correlation in 228 patients.

The prevalence of spontaneous reversal of flow in the portal venous system was non invasively evaluated by Doppler ultrasound in 228 patients with liver cirrhosis and portal hypertension. Reversed flow was detected in the portal vein in 7 patients (3.1%), in the splenic vein in 7 patients (3.1%), and in the superior mesenteric vein in 5 patients (2.1%), with an overall prevalence of 8.3% (19/228). This prevalence did not differ in relation to the etiology of liver cirrhosis, whereas hepatofugal flow was found in more patients classified as Child's C (15.4%) and B (12.5%) than those classified as Child's A (2.7%) (P less than 0.02) and was associated with a higher frequency of hepatic encephalopathy (21% vs. 7.2%; P less than 0.05). Endoscopic evaluation of esophageal varices did not reveal any correlation between the presence and size of varices and hepatofugal flow, whereas red signs were detected more frequently in patients with this hemodynamic pattern (42.1% vs. 24.4%; NS). The rate of previous variceal bleeding was not significantly different in patients with and without hepatofugal flow (30.8% vs. 24.4%; NS). Conversely, the prospective evaluation of 15 patients with hepatofugal flow and 29 matched patients with hepatopetal flow, derived from the group of 228 patients, followed up for a period of 12-18 months, showed that variceal bleeding occurred in 9 of 29 patients with hepatopetal flow and in none of the 15 patients with hepatofugal flow (P less than 0.02). However, no statistical difference was found in the survival rates. This study indicates that the actual prevalence of reversed flow in the portal, splenic, and superior mesenteric veins in a nonselected cirrhotic population is 8.3%. From a clinical point of view, the data suggest that this finding might be considered an important prognostic factor because, while occurring in cirrhotic patients with more severe functional impairment, it might play a protective role against the risk of bleeding.

Effect of secretin on portal venous flow.

In this study we evaluated the effect of two different doses of secretin on portal haemodynamics (by pulsed Doppler associated with real time ultrasound) in 24 healthy humans. In 12 subjects (group A) we administered an intravenous dose of 75 clinical units of secretin and in the remaining 12 (group B) a dose of 20 CU. In all subjects the following parameters were studied before, during, and for 10 minutes after secretin administration: (a) calibre of the portal vein, (b) mean velocity of portal venous flow, and (c) volume of portal venous flow. In three subjects in each group we also evaluated the changes in flow in the superior mesenteric artery. Secretin injection induced a slight increase in both groups in comparison to basal values of portal vein calibre (mean of maximal per cent increase +25% in group A, not significant, and +16.7% in group B, not significant) and a noticeable increase of mean velocity (mean of maximal per cent increases +61.4% in group A, p less than 0.005, and +65.4% in group B, p less than 0.01) and flow volume (mean of maximal per cent increase +127% group A, p less than 0.005, and +114% group B, p less than 0.005). The magnitude of the haemodynamic changes did not differ significantly between the two groups. Doppler investigation of the superior mesenteric artery showed a marked increase of flow velocity (mean of maximal per cent increase +218% in group A and +246% in group B) and flow volume (mean of maximal per cent increase +276% in group A and +311% in group B). These data suggest that secretin has an appreciable vasoactive effect and induces a significant increase in portal venous flow even at doses much lower than those necessary for a maximal stimulation of exocrine pancreatic secretion.

Relationship between alpha-fetoprotein serum levels, tumour volume and growth rate of hepatocellular carcinoma in a western population.

In order to detect a possible relationship between alpha-fetoprotein (AFP) levels, total tumour volume at the moment of the discovery and the tumour volume doubling time, we studied a population of 138 patients, affected by Hepatocellular Carcinoma (HCC) discovered at abdominal ultrasound (US) examination and confirmed by liver biopsy in all cases. In each patient the serum AFP level was determined within a week before or after the US examination. A small therapy-free subgroup of 23 patients, was also serially observed for a mean period of 4 months, so making possible the evaluation of the tumour volume doubling time and its relationship with the initial value of AFP. In 81 patients (58.7%) the serum AFP resulted less than 20 ngr/ml in 21 (15.2%), between 20 and 200 and in 36 (26.1%) greater than 200ngr/ml. No statistical correlation was found between the tumour volume calculated on the basis of the US image at the moment of the discovery and the AFP level, even though very high levels (greater than 3000) were found only in large tumours. Furthermore the tumour doubling time was not correlated with the initial value of AFP.

Diagnosis of islet cell tumor by means of endoscopic ultrasonography.

A 31-year-old man with recurrent attacks of hypoglycemia was hospitalized with the clinical suspicion of an insulinoma. Computed tomography and conventional (transabdominal) ultrasound were doubtful, showing a small solid low-density mass probably originating from the tail of the pancreas. Selective angiography and transhepatic venous sampling for pancreatic hormone assay were not discriminant. Finally, an endoscopic ultrasonographic examination, allowing a better visualization of the pancreas, established with certainty the origin of the lesion from the tail of the gland. This was subsequently confirmed at operation.

Sonography of chronic pancreatitis.

Morphologic alterations detectable by US in CP may be schematically classified as: (1) size increase or decrease; (2) variations in shape with particular regard to contour irregularities; (3) changes in the parenchymal echo-texture; (4) presence of calcifications; (5) dilatation of the MPD; (6) presence of fluid collections; (7) dilatation of the biliary tree; and (8) obstruction of the portal venous system. These findings are associated in various combinations and occur with differing frequencies. Changes in pancreatic size may be found in many physiologic and pathologic conditions other than CP. The pancreas is usually larger during and shortly after acute relapses, whereas gland atrophy occurs in more advanced cases. A diagnosis of CP cannot generally be made only on the basis of a diffuse enlargement of the gland without changes in the echo-texture or in the MPD. Abnormalities of the parenchymal echo-texture are relatively sensitive but nonspecific for the diagnosis of CP. Calcifications can often be missed by US, and CT is clearly superior. Dilatation of the MPD is the most reliable sign of pancreatic disease. In CP, it generally has irregular walls, which is a distinctive finding that aids in differentiation of MPD dilatation occurring in pancreatic cancer. Changes in the MPD that are not visible under basal conditions may become evident under maximal hormonal (secretin) stimulation. Cysts and pseudocysts complicating the course of CP may present various shapes, contain necrotic debris, and even show a completely solid pattern. Dilatation of the CBD may also be seen as a consequence of a stricture of the intrapancreatic portion of the duct. Other complications, such as obstruction of the portal venous system, ascites, and pleural effusion, occur more rarely and are easily visualized by US. Despite the great technologic improvement of US in recent years, there is still general agreement that the US diagnosis of CP remains difficult owing to the polymorphism of anatomic changes and the relatively high incidence of false-negative results in early stages of the disease. It is, however, accepted that in clinical practice US currently is the first diagnostic step when CP is suspected.

Impaired response of main pancreatic duct to secretin stimulation in early chronic pancreatitis.

In the present study we compared sonographic measurements of the main pancreatic duct (MPD) following maximal secretin stimulation (75 CU intravenous in 1 min) in 15 chronic pancreatitis patients (CP) with those of 18 normal control subjects. The mean caliber of the main pancreatic duct was 1.2 +/- 0.4 mm in controls and 1.8 +/- 0.9 in patients with chronic pancreatitis (P less than 0.025). In the control group a dilatation of the duct with a peak at the third minute was found. In patients with chronic pancreatitis a flatter profile of the response curve with a slower increase and inconstant return to basal values was found. A statistically significant difference was found between absolute variations of MPD caliber over basal values (1.7 +/- 1.06 in controls vs 0.8 +/- 0.69 in CP, P less than 0.005) and the dilatation index [(Dmax - D)/D] (1.31 +/- 0.6 in controls vs 0.66 +/- 0.69 in CP, P less than 0.005). The mean percent increase at the third minute was 131% in control subjects vs 53% of patients with CP (P less than 0.0005). In the five cases of CP showing a caliber increase greater than 100%, a persistent dilatation (100-200%) was found 15 min after secretin administration. At this time, the mean percent increase over basal value in controls was 25%.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of meal on portal hemodynamics in healthy humans and in patients with chronic liver disease.

The effect of a standard Italian meal on portal hemodynamics was evaluated in 12 normal subjects, in 11 patients with chronic active hepatitis and in 11 patients with liver cirrhosis using duplex Doppler ultrasound, which allows a noninvasive assessment of portal blood flow. In the fasting state, the portal vein caliber was significantly higher in patients with liver cirrhosis than in normal subjects and patients with chronic active hepatitis, whereas the mean flow velocity in the portal vein was significantly lower in this group. Basal flow volume of the portal vein was greater in patients with liver cirrhosis than in normal subjects and patients with chronic active hepatitis. Sixty minutes after the standard meal, we observed both in normal subjects and in patients with chronic active hepatitis a significant increase of mean caliber, mean velocity and flow volume in the portal vein, whereas in patients with liver cirrhosis, these parameters remained almost unchanged. In addition, the examination of individual patterns showed that flow velocity and flow volume in the portal vein decreased in some cirrhotic patients after the meal. This behavior is probably related to the hypertensive state in the splanchnic venous bed and diversion of splanchnic blood flow into spontaneous portosystemic collaterals.

Relationship between morphological changes detected by ultrasonography and pancreatic exocrine function in chronic pancreatitis.

We have studied the degree of pancreatic secretory alterations assessed by secretin-cerulein test (S-C) in relation to various morphological changes detected by real-time ultrasonography (US) in 42 patients affected by chronic pancreatitis. Exocrine insufficiency was found in 41 patients (97.6%), while morphological alterations were detected in 32 (76.1%). In the 10 patients with normal US, a mild or moderate exocrine insufficiency was present. Significant negative linear correlations of decreasing volumes of duodenal aspirate (r = 0.528, p less than 0.001) and output of bicarbonate (r = 0.635, p less than 0.001), lipase (r = 0.583, p less than 0.001), and chymotrypsin (r = 0.592, p less than 0.001) were found with increasing ultrasonographic alterations. However, a wide overlap was found in the secretory behavior in the various categories of change as determined by ultrasound. Hence, the attempt to predict exocrine function on the basis of morphological alterations proved unsuccessful.