Natural history of cirrhotic patients with small esophageal varices: a prospective study.

OBJECTIVE: Contrasting data are available on the natural history and bleeding risk of small esophageal varices. The aim of this prospective study was to evaluate a large series of consecutive cirrhotics with a first endoscopic diagnosis of small varices. METHODS: Between 1987 and 1992, 258 patients with small varices and no previous bleeding were enrolled. Patients were clinically examined every 6 months and were followed until a first episode of bleeding and/or death, or until June 1998. None received any treatment to prevent bleeding. Endoscopies were planned at 18-month intervals. RESULTS: The cumulative risk of bleeding was low (3% at 2 yr and 8% at 4 yr) and remained low in patients in whom varices remained small at 2nd endoscopy, whereas it increased significantly when varices enlarged. The increase of varices appeared to be rather linear in time: at the 2nd endoscopy varices remained small in 79% of patients and increased in 21%; at the 3rd endoscopy varices remained small in 55%, whereas at the 4th 33% of patients still had small varices. Clinical and biochemical data at the 1st and 2nd endoscopy were included in a multiple logistic regression analysis. Only the increase in Child-Pugh score appeared to be a significant predictor of enlarged varices; the risk of aggravation increased by 37.5% for every unit of impairment of the score. CONCLUSIONS: The present study shows that patients with small varices have a low bleeding risk. An increase in Child-Pugh score during follow-up suggests enlargement of varices, thus an increase in bleeding risk. In these patients closer endoscopic surveillance is recommended.

Total and functional hepatic blood flow decrease in parallel with ageing.

OBJECTIVES: To study changes in hepatic blood flow with age. DESIGN: Functional hepatic flow (FHF) and total hepatic flow (THF) were determined by non-invasive methods in 40 normal subjects in four age groups (<45, 45-60, 61-75 and >75 years). All subjects had normal routine liver function tests and no history of liver disease. RESULTS: THF was measured by pulsed echo-Doppler, as the sum of portal and hepatic artery blood flow; FHF was measured by the hepatic clearance of D-sorbitol. THF significantly decreased with age, particularly in subjects over 75 (from 1445+/-220 ml/min to 1020+/-148; P<0.001), and a similar reduction was observed in FHF (from 1514+/-250 ml/min to 1015+/-163; P<0.001). THF and FHF were strictly correlated in the whole population (r = 0.871; P<0.001) and both correlated with age (r = -0.510 and r = -0.596; P<0.005). CONCLUSION: With ageing there is a reduction of hepatic blood flow without any additional intrahepatic shunting.

Transient spontaneous regression of hepatocellular carcinoma.

We report on 2 patients with liver cirrhosis and biopsy-proven hepatocellular carcinoma who underwent spontaneous regression. In 1 case the tumor became undetectable at ultrasonography, while, in the other, the liver lesions decreased in size and showed inner calcifications. In both patients, alpha-fetoprotein, which was high at first diagnosis, returned to normal values. After a tumor-free period of 4 years and 17 months, respectively, liver cancer reappeared and patients died from complications. We advance the hypothesis that tumor regression, when it occurs in cirrhotic patients, is always transient, with chronic liver disease being the oncogenic triggering factor.

Plasma catecholamines in pre- and in postmenopausal women with mild to moderate essential hypertension.

The sympathetic nervous system (SNS) is thought to play an important role in the pathogenesis of essential hypertension and many studies have established a relationship between plasma levels of norepinephrine (NE) and epinephrine (E) and sympathetic nervous activity (SNA). Furthermore, it has been suggested that climacteric women are more exposed to psychosocial stress which can produce a transient rise in blood pressure (BP) and, with time, determine a hypertensive state. Plasma NE and E levels were measured at rest and after physiological stimulation (head-up tilt test) in 20 hypertensive (BP: 146 +/- 13/101 +/- 4 mm Hg) and in 20 normotensive women (BP: 132 +/- 7/85 +/- 4 mm Hg). Women in each of these two groups were further subdivided according to their climacteric status (10 premenopausal and 10 postmenopausal women). No difference in NE values at rest was found between groups and subgroups. During head-up tilt test, Ln NE plasma values increased in normotensive and hypertensive groups; the rise was significantly higher in hypertensive than in normotensive women (P < 0.01). In climacteric subgroups, Ln NE appeared markedly increased above resting levels in pre- and postmenopausal hypertensive women when their position was changed from supine to upright (P < 0.01). Since high plasma NE levels after stimulation (head-up tilt) are associated with sympathetic overactivity, we conclude that SNA is involved in the pathogenesis of essential hypertension in climacteric women.

Efficacy of a surveillance program for early detection of hepatocellular carcinoma.

BACKGROUND: Contrasting data have so far been reported on the utility and efficacy of screening patients with cirrhosis for early detection of hepatocellular carcinoma (HCC). The goal of this study was to evaluate the efficacy of a regular ultrasonographic and laboratory follow-up for the early detection of small HCC, and to identify parameters correlated with a higher risk of developing HCC. METHODS: One hundred and sixty-four consecutive patients with liver cirrhosis living in Emilia Romagna, Italy, were enrolled in the period 1989-1991. All patients underwent clinical, biochemical, and ultrasonographic evaluations at entry and at 3- and 6-month intervals during follow-up. RESULTS: By April 1995, 34 patients had developed HCC. In 76% of the patients, ultrasonography identified HCC when it was still single and small (< 4 cm). At discriminant, logistic regression and univariate analyses, sex and the entry concentration of alkaline phosphatase, alpha-fetoprotein, gamma-glutamyl transpeptidase, and albumin were associated with a higher risk of developing HCC, whereas at multivariate analysis (Cox's model), only sex and the entry concentration of alkaline phosphatase, albumin, and alpha-fetoprotein were independently and significantly related to the appearance of HCC. CONCLUSIONS: A regular ultrasonographic follow-up, timed at 3- to 6-month intervals according to the risk of HCC development in patients with cirrhosis, allows the detection of liver carcinoma at an early stage in a high proportion of patients, possibly improving the prognosis of the disease.

Physical examination of the liver: is it still worth it?

OBJECTIVES: The aim of this study was to evaluate the actual role of physical examination of the liver in normal subjects and in cirrhotic patients. METHODS: One hundred healthy subjects and 100 patients with liver cirrhosis underwent a physical and an ultrasonographic evaluation of the liver by independent operators. Physical examination was performed by means of percussion and palpation to determine total liver span, liver span below the costal margin, and liver consistency. Total liver span, liver span below the costal margin, and liver volume were also determined by means of ultrasonography. RESULTS: The agreement between physical and ultrasonographic assessment of the liver span below the costal margin was poor in controls (chance corrected agreement index = 0.13) and excellent in patients (chance corrected agreement index = 0.93). Physical and ultrasonographic total liver span were correlated in patients with cirrhosis (r = 0.592) but not in controls (r = 0.205). Echo-measured liver span significantly correlated with the actual volume of the organ in both groups, whereas physical liver span significantly correlated with liver volume in cirrhosis but not in controls. The difference between actual liver volume and the value predicted by liver span was large. The cirrhotic liver was slightly reduced in size in comparison with that of healthy subjects and differed by an increase in consistency and a thickened edge. CONCLUSIONS: The bedside examination of the liver does not provide any accurate information regarding the actual volume of the organ. Its major role remains to define the characteristics of lower edge, mainly consistency, which may help in clinical diagnosis. Liver volume proved to predict prognosis in patients with cirrhosis, but its measurement needs quantitative, reproducible methods, which can be obtained only by imaging techniques.

Thyroid involvement in patients with active inflammatory bowel diseases.

Previous studies have documented an association between systemic diseases and disorders of the thyroid gland, expressed by an enlargement of the thyroid and by the presence of anti-thyroid antibodies. Chronic inflammatory bowel diseases (IBD, ulcerative colitis and Crohn's disease) may also present a multi-organ involvement, including the biliary tree, joints and uvea. To detect a possible subclinical thyroid involvement, thyroid volume and function were assessed in 31 patients with IBD in active phase and in 50 control subjects. Thyroid volume was calculated by ultrasonography on the basis of the three maximum diameters of the 2 lobes. A blood sample was taken to determine free thyroid hormones, TSH, and anti-thyroid antibodies. In patients with IBD, thyroid volume was increased on average by 35%, and the prevalence of thyroid enlargements (antero-posterior diameter > 20 mm) was 3 times higher (45% vs 16%). Free thyroxine was increased by nearly 50%, but only 10% of patients had anti-thyroid antibodies. Alterations of thyroid volume and function are present in IBD, even in the absence of clinically-detectable thyroid disease. The association of IBD with thyroid disorders, as well as the involvement of various organs, confirms the view that IBD is a systemic disease.

[Ultrasonographic evaluation of gallbladder and gastric emptying after ingestion of water with various saline compositions]. / Valutazione ultrasonografica dello svuotamento colecistico e gastrico dopo assunzione di acque a diversa composizione salina.

OBJECTIVE: Evaluation of gallbladder and gastric emptying after ingestion of a saline enriched water ("Acqua Santa" di Chianciano) in comparison with a commercial oligomineral water. STUDY DESIGN: A 40-minute blind prospective study. LOCATION: The study was performed at the Terme of Chianciano (Siena) for subjects of group A and at the Institute of Clinica Medica Generale and Terapia Medica of the University of Bologna for subjects of group B. PATIENTS OR PARTICIPANTS: Two groups of healthy subjects were studied. Each group consisted of 12 subjects without gallbladder disease. EXPERIMENTAL PROTOCOL: Fasting subjects of group A ingested alternatively, for two consecutive mornings, 400 ml of the saline enriched water at the natural temperature of 33 degrees C or 400 ml of oligomineral water warmed to the same temperature. Subjects of group B ingested the same waters at 18 degrees C. METHODS: Gastric and gallbladder emptying were evaluated, after ingestion of the different waters, by means of ultrasonography. RESULTS: In both groups gallbladder emptying was significantly higher after ingestion of the saline enriched water. On the other hand gastric emptying was similar with both waters. CONCLUSIONS: This study demonstrated that saline enriched water determines a greater emptying of the gallbladder in comparison with an oligomineral water. This effects is not related to gastric emptying but rather it is due to a higher concentration of saline components and thus to their possible effect on gallbladder motility.