Small (

PURPOSE: We prospectively compared gadoliniumenhanced magnetic resonance imaging (dynamic MRI), superparamagnetic iron oxide (SPIO) (ferucarbotran) MRI and multidetector-row computed tomography (MDCT) and the combination of dynamic MRI plus MDCT vs. dynamic MRI plus SPIO-MRI (double-contrast MRI: DC-MRI) for the detection of small (1 cm and the highest specificity (83.3%) superior to dynamic MRI (p<0.0001). In the per-lesion analysis, SPIO-MRI demonstrated a positive predictive value higher than dynamic MRI (p=0.0059) and than both the combinations dynamic MRI/MDCT and DC-MRI (p=0.0021 and p=0.0087, respectively). DC-MRI showed the highest sensitivity (97.7%) and accuracy (78.9%), detecting hypovascular and atypical HCCs >1 cm. Furthermore its per-patient negative predictive value was the highest (100%), and significantly higher than all the other methods. CONCLUSIONS: DC-MRI is the most sensitive and accurate method and can be confidently used as a single-step procedure for the detection of small HCCs, with the exception of lesions <1 cm.

Meta-analysis: the efficacy of proton pump inhibitors for laryngeal symptoms attributed to gastro-oesophageal reflux disease.

BACKGROUND: Many investigators have proposed an association between gastro-oesophageal reflux disease and laryngo-pharyngeal symptoms, suggesting that medical or surgical therapy for reflux may be useful. AIM: To perform a meta-analysis assessing the effectiveness of medical or surgical therapy for reflux disease in adult patients with laryngeal or pharyngeal symptoms presumed to be due to gastro-oesophageal reflux disease. METHODS: Randomized controlled trials comparing medical or surgical treatments for gastro-oesophageal reflux disease against placebo were identified by searching MEDLINE (1966-September 2005), EMBASE (1974-September 2005), the CCRCT (until September 2005) and abstracts from gastroenterology and ENT meetings. The relative risks of reporting symptomatic improvement or resolution of symptoms was evaluated using a random-effects model. RESULTS: Five studies using high-dose proton pump inhibitor as intervention met the inclusion criteria and were included in the meta-analysis. No surgical studies met inclusion criteria. The pooled relative risk was 1.18 (95% confidence interval: 0.81-1.74). There was no heterogeneity between studies but evidence of significant publication bias. Sub-group analysis performed evaluating Jadad scores and symptom type, did not change the relative risk. CONCLUSIONS: Therapy with a high-dose proton pump inhibitor is no more effective than placebo in producing symptomatic improvement or resolution of laryngo-pharyngeal symptoms. Further studies are necessary to identify the characteristics of patients that may respond to proton pump inhibitor therapy.

Serum lipid and lipoprotein patterns in patients with liver cirrhosis and chronic active hepatitis.

BACKGROUND: An impaired lipid metabolism is often found in patients with chronic liver diseases. Unfortunately, few studies are available concerning serum lipid and lipoprotein levels in patients with liver cirrhosis and chronic active hepatitis (CAH). OBJECTIVES: To evaluate low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and total cholesterol serum levels in patients with cirrhosis and CAH and control patients and to relate the findings to the severity of the cirrhosis (Child classification). METHODS: We measured the serum lipid pattern in 34 consecutive patients with liver cirrhosis (15 men and 19 women; mean [+/-SD] age, 55 +/- 14 years; Child classes: 14 in A, 9 in B, 11 in C; patients with biliary cirrhosis were excluded), 34 patients with CAH, and 34 control patients. The 3 groups were matched for sex and age. Total serum, HDL cholesterol, and triglyceride levels were measured by enzymatic methods; serum LDL and VLDL levels were calculated. RESULTS: In patients with cirrhosis, there was a significant decrease in LDL, HDL, and total cholesterol serum levels compared with both the patients with CAH and the control patients, while the VLDL cholesterol level in patients with cirrhosis was significantly lower compared with the control patients alone. A significant decrease in total cholesterol levels was also observed in the CAH group when compared with the control patients. In patients with cirrhosis, levels of LDL, HDL, and total serum cholesterol were progressively lower when comparing patients in Child class A with patients in class C. CONCLUSIONS: In this study, the striking decrease in the level of serum LDL cholesterol in patients with liver disease was related to the increasing severity of the disease. Accordingly, the assessment of the serum LDL cholesterol level is important for an effective treatment and prognostic evaluation of patients with chronic liver disease.

Protease activities, as well as plasminogen activators, contribute to the "lytic" state during orthotopic liver transplantation.

High levels of tissue plasminogen activator (t-PA) have been reported to be the main component of the high fibrinolytic activity measured in patients during orthotopic liver transplantation. However, a previous study of our group suggested that specific t-PA may not completely account for the massive fibrinolytic activities recorded. In the present study we investigated the fibrinolytic patterns in 10 consecutive liver cirrhosis patients undergoing OLT. Euglobulin fibrinolytic activity, measured either on physiologic (fibrin plates) or amidolytic substrates, increased as expected during anhepatic and reperfusion phases, but largely exceeded the specific activity of t-PA, as proved by quenching procedures using anti-t-PA antibodies. The presence of plasmin- and trypsin-like amidolytic activities was detected in native plasmas at the end of anhepatic and reperfusion phases, together with decreased levels of protease inhibitors, especially alpha 1 Antitrypsin. In conclusion, the hyperfibrinolytic pattern recorded in the central OLT phases is not only attributable to an increased t-PA concentration, and is better described as a complex "lytic" state also including the presence of free proteases (plasmin- and trypsin-like), with limited participation of u-PA. Although t-PA increase is probably the main mechanism of stimulation of the fibrinolytic system during OLT, actual and not just potential proteolytic activities can be found in this condition independent of the occurrence of major hemorrhagic complications.

Effect of deoxycholic, chenodeoxycholic, and cholic acids on intestinal absorption of cholesterol in humans.

The effect of administration of primary and secondary bile acids on absorption of cholesterol was investigated in 15 volunteers. Eight Caucasians with radiolucent gallstones were studied before and after administration of chenodeoxycholic acid (all eight) and cholic acid (eight before, six after treatment) for 3 months, and seven healthy subjects were studied before and five were studied after administration of deoxycholic acid for 6 weeks. The hourly absorption of [3H]cholesterol was measured for 24 hours in a 20-cm duodenal segment by use of an intestinal perfusion technique. Fasting serum cholesterol and triglyceride levels were also measured before and after administration of bile acid. In patients with gallstones, absorption of cholesterol in the duodenum, expressed as the mean (+/- SEM) percentage of [3H]cholesterol absorbed hourly for 24 hours, was not significantly different after administration of chenodeoxycholic (22.5 +/- 4.4%) or cholic (25.6 +/- 5.9%) acid when compared with the pretreatment value (21.1 +/- 4.3%). Moreover, administration of chenodeoxycholic and cholic acid did not affect serum lipid levels. In contrast, administration of deoxycholic acid to healthy volunteers suppressed [3H]cholesterol absorption (13.2 +/- 3.2%) compared with that of the pretreatment period (26.5 +/- 3.8%) and decreased serum cholesterol levels by 15%. Our results suggest that chenodeoxycholic acid decreases the concentration of cholesterol in bile and dissolves gallstones by a mechanism other than inhibition of absorption of cholesterol. The data also indicate that the hypocholesterolemic effect of deoxycholic acid is due to the inhibition of intestinal absorption of cholesterol.

A radioimmunoassay for lithocholic acid conjugates in human serum and liver tissue.

A sensitive and specific radioimmunoassay for glycine and taurine conjugates of lithocholic acid (CLCA) has been developed. 3H-glycolithocholic acid (S.A. = 17Ci/mmol) was used as tracer. Separation of free from antibody-bound bile acid was carried out using ammonium sulphate (saturated solution). The antiserum showed high specificity for both glyco and tauro conjugated lithocholate (100% cross reaction) and lithocholic acid (25% cross reaction). The sensitivity of the assay (1 pmole/tube), was adequate for measuring CLCA in peripheral blood and hepatic tissue in man.

Reversal of primary liver graft non-function using prostaglandins.

Primary graft non-function remains one of the most life-threatening problems after liver transplantation. Its etiology is still unclear. Liver retransplantation is the only therapeutic alternative to this problem. The PGE1 series of prostaglandins have recently been successfully used in the treatment of transplanted organ dysfunction. In this paper we describe a case of primary graft non-function successfully treated with continuous infusion of prostaglandin PGE1, and we briefly discuss the pathogenetic and therapeutic hypotheses.

A new hemodialysis monitoring device using filtrate concentrations: a comparison with standard serum techniques.

A new device allowing sampling to be performed at any time, and using the filtrate obtained during hemodialysis is described. The device was used in 27 patients undergoing regular dialysis. Urea, creatinine and potassium were measured in samples taken both from arterial blood and from the device at 10, 40, 120 and 230 minutes after the beginning of the dialysis. The results were compared. A constant bias of about 10% was noted between the two sets of results but statistical analysis showed this was correctable.

[Medical treatment of cholesterol cholelithiasis using chemodeoxycholic acid in man]. / Il trattamento medico della calcolosi biliare colesterolica nell'uomo con acido chenodesossicolico.

The results of a tiral using chenodeoxycholic acid in 400 patients with cholesterol gallstones are reported. The "qualifying points" of such treatment are compared with the literature data in clinical and laboratory terms. 54% of 300 in clinical and laboratory terms. 54% of 300 patients who received less than 12 mg/kg/day achieved dissolution in a mean time of 11 months, while 64% of the remainder (12-15 mg/kg/day) did so in an average of 8 months. Microcalculi proved most sensitive to treatment (65% of positive results). Lithiasis over 5 years standing and over-weight (10% over the ideal figure) were factors that imposed more protracted treatment. Careful selection of candidates was proved important by the results of quarterly liver and intestine performance examinations. These were more extensive and more clearly aimed than those proposed by other workers. They showed that the acid is neither hepato nor enterotoxic. Indeed, no serious side-effects were noted.

[Changes in bile and blood lipid levels following chenodeoxycholic acid therapy]. / Modificazioni dell'assetto lipidico biliare ed ematico dopo terapia con acido chenodesossicolico.

Original and known methods and ordinary routine tests were used to evaluate changes in bile salts, phospholipids and cholesterol and in serum lipids induced in 50 patients during treatment with chenodeoxycholic acid (2-12 mg/Kg/day) for about 15 months. No significant differences in serum lipids, though a clear fall in triglycerides was noted in those who received 7-12 mg/Kg/day as opposed to 2-7 mg/Kg/day. There was a marked fall in the molar percentage of biliary cholesterol, followed by a significant reduction in the saturation index of Metzger. Once again, greater reduction was noted in patients receiving the higher dose range. A correlation between the dose used and the percentage of cholesterol in the bile was thus evident. After treatment, chenodeoxycholic acid was the main bile acid and there was a significant fall in cholic and deoxycholic acid. The desired drug effect can be obtained with low doses (7-12 mg/Kg/day) and a biliary chenodeoxycholic value well below 90%.

[Results of chenic acid therapy in patients with cholesterol calculi]. / Risultati della terapia con acido chenico nei pazienti portatori di calcoli di colesterolo.

58 patients suffering from cholesterol gallstones were treated with chenodesoxycholic acid at a dose of 2-15 mg/Kg/die for about 15 months so as to determine its effettiveness and establish a minimum effective dose. 8 of these patients presented stones in the common bile duct. The results showed: a complete dissolution of the stones in 16 of the 50 patients considered to be suffering from cholecystic lithiasis; partial dissolution in 15; no change in the remaining 19. Of the 8 patients with bile duct stones, 3 presented complete dissolution, 2 partial, and 3 no change. An improvement in digestive function was observed in most cases. The liver function tests carried out in each patient before, during and after treatment with chenodesoxycholic acid were completely normal.

[Correlation of malabsorption of bile acids, bile lipid composition and calculi]. / Correlazione tra il malassorbimento degli acidi biliari, la composizione lipidica biliare e i calcoli.

The relation between malabsorption of bile acids, the bile lipid composition, and biliary stones was examined in 8 patients subjected to ileal resection (particularly for Crohn's disease), 6 with ileal bypass for morbid obesity, and 10 healthy controls. The 1-14C-cholylglycine breath test was employed to detect of the absorption and deconjugation of bile acids. Bile lipid composition was expressed according with Metzger's saturation index. Healthy subjects gave normal findings in all respects, whereas ileal resection was accompanied by malabsorption, increased deconjugation, and faecal loss of 14C. These changes, particularly malabsorption, were more evident after ileal bypass. Preoperative saturation values rose to more than 1 in all cases, especially after resection. Liver disease (steatosis and cirrhosis) 6 months after bypass, together with cholesterol lithiasis in 2/6 patients.

[Hepatic and pancreatic disease in patients with acquired immunodeficiency syndrome (AIDS)]. / Patologie epatiche e pancreatiche in pazienti con sindromi da immunodeficienza acquisita (AIDS).

AIDS is frequently expressed through gastrointestinal o abdominal symptoms. In addition, patients with AIDS or ARC frequently have hepatic and biliary symptoms, while pancreatic alterations are found in 4-30% of patients hospitalised for AIDS. Since AIDS patients are immunodepressed, they are subject to opportunistic infection often multifocal and the pathological processes can be present simultaneously. About 2/3 of patients have enlarged liver, steatosis, splenomegaly, lymphoadenopathy, cholecystic and biliary tract abnormalities, alterations of liver function tests, and abdominal discomfort in the upper right quadrant. Jaundice is rare and hepatic failure is not common. Hepatic biopsy is often necessary to establish the diagnosis. The hepatic localisation of an opportunistic pathogenic agent is generally a sign of systemic dissemination which is expressed as granulomatous hepatitis (atypical mycobacteria, frequently mycobacterium avium, or M. tuberculosis representing the reactivation of latent diseases), peliosis hepatis, infection from CMV, HSV, EBV, Pneumocystis carinii, and mycotic infections. Coinfections with the hepatic virus (HBV, HDV, HCV) are also often present. Pharmacological damage may also be present (mainly caused by antibiotic therapies). Neoplasia are rare (hepatic Kaposi's sarcoma associated with cutaneous and gastrointestinal manifestations, or generally metastatic lymphoma). Damage of the biliary tract usually develops after other manifestations of the illness; the most frequent pictures are cholestatic syndromes and cholangitis, while cholecystitis and jaundice are rare. Pancreatic lesions are generally asymptomatic. They are diagnosed during autopsy and are caused principally by opportunistic agents.

[Therapy of cholesterol lithiasis with chenodeoxycholic acid (Chenoxyl)]. / La terapia della litiasi colesterolica con acido chenodesossicolico (Chenossil)

Chenodesoxycholic acid (500-750 mg/day Chenoxyl) was employed over a period of 9 months in the treatment of 40 patients with radiotransparent calculi in a functioning gallbladder and 8 with choledochal lithiasis. Radiological examination and complete hepatological exploration were carried out before and after the treatment in all cases. Complete dissolution was obtained in 6 and 2 cases respectively, with reduction of size in 13 and 2, and no change in 21 and 4. No significant variations were notes in the blood lipid picture or in liver function. There were no cases of diarrhoea.

[The Boario project. A study of the prevalence of lithiasis in a spa population]. / Progetto boario. Studio della frequenza della malattia litiasica in una popolazione termale.

In order to better evaluate some epidemiological findings observed during previous studies on large samples of free living populations we carried out a case-control study on a randomly selected group of subjects in a health spa, Boario Terme. Seven-hundred and thirty subjects, aged 40-69 years, participated in the study. The study protocol included an ultrasonographic examination of the upper abdomen, a physical examination, a questionnaire, and a blood sample. Prevalence of gallstone disease was two times higher in females (37.2%) than in males (19.7%) (RRMH = 1.88). Fifty out of the 80 gallstone subjects were not aware of the disease prior the study (62.5%), and 60 did not experience any specific biliary symptom (colic) in the 5 years prior the study. The so-called "nonspecific symptoms" were not found related to gallstone disease. Gallstone disease was positively related to number of pregnancies, obesity, and economical status. In conclusion the present study confirmed some results observed during previous epidemiological studies. In regards to symptoms present data suggest that biliary colic is the only specific symptom for gallstone disease. In addition, the high number of asymptomatic gallstones observed in this study suggests the need of more investigations on high-risk populations in order to make earlier diagnosis and eventually to prevent the disease.