Survival of patients with early hepatocellular carcinoma treated by percutaneous alcohol injection.

BACKGROUND: Once small (<10 mm) nodules, suspicious for hepatocellular carcinoma, are detected in cirrhotics, the European Association for the Study of the Liver guidelines recommend to delay histological confirmation and treatment until they increase in size. AIM: To validate this policy by evaluating survival of 450 cirrhotics in Child-Pugh class A or B with unifocal 'early' hepatocellular carcinoma treated by percutaneous alcohol injection. METHODS: Patients were sorted by nodular size into three groups: < or =10 mm (n = 36, group A), >10 to < or = 20 mm (n = 142, group B) and >20 to < or = 30 mm (n = 272, group C). Overall and tumour-free survivals were estimated by Kaplan-Meier method. RESULTS: In groups A, B and C, mean follow-up was 33 +/- 26, 34 +/- 22 and 35 +/- 25 months (P = 0.89), mean survival time was 63 +/- 54, 57 +/- 48 and 62 +/- 66 months (P = 0.69) and mean tumour-free survival was 44 +/- 47, 46 +/- 58 and 41 +/- 68 months (P = 0.51), respectively. When patients were sorted by Child status, mean survival time was 76 +/- 82 and 38 +/- 29 months in Child A and B (P < 0.0001). CONCLUSIONS: The comparable survival of percutaneous alcohol injection-treated patients with single, early hepatocellular carcinoma sorted by nodular size supports the European Association for the Study of the Liver 'wait-and-see' policy for patients with lesions <10 mm, and suggests that allowing the nodules to grow prior to taking further diagnostic or therapeutic actions would not harm these patients.

Ultrasonographic and biochemical parameters in the non-invasive evaluation of liver fibrosis in hepatitis C virus chronic hepatitis.

BACKGROUND: Prior studies suggest that platelet counts of <140 000/microL can discriminate patients with different stages of fibrosis. AIM: To determine the added value of abdominal ultrasound analysis of morphological liver features in increasing the diagnostic accuracy of platelet counts for the prediction of liver fibrosis at histology. METHODS: In a retrospective study, clinical records of 1143 chronic hepatitis C patients at their first presentation, naives to both liver biopsy and anti-viral treatment, were reviewed. Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios of following indices were evaluated singularly or in combination: platelet counts <140 000/microL; nodular liver surface, spleen and portal vein size. RESULTS: All indices had specificity rate of > or =90% in excluding bridging fibrosis/cirrhosis, whereas sensitivity was acceptable (51%) for only platelet counts <140 000/microL. None of the ultrasonographic parameters singularly evaluated and reached an acceptable sensitivity rate. For ruling cirrhosis in or out, specificity rate was > or =82% for all tests, with the highest value reported by portal vein size. Low platelet counts plus nodular liver surface had the best sensitivity. CONCLUSIONS: No additional significant predictive value was given by adding ultrasonographic parameters to low platelet counts, whereas only a mild non-significant improvement in sensitivity was obtained combining platelet counts <140 000/microL with the presence of nodular liver surface. The platelet counts <140 000/microL showed the best predictive value for including both significant fibrosis and cirrhosis.

Causes of portal venous thrombosis in cirrhotic patients: the role of genetic and acquired factors.

OBJECTIVE AND METHODS: We compared frequencies of three common prothrombotic mutations (factor V Leiden, the G20210A mutation of the prothrombin gene, and homozygosity for C677T methylenetetrahydrofolate reductase) in 219 cirrhotic patients, 43 with and 176 without portal vein thrombosis (PVT). The following variables were related to PVT: prothrombin levels, platelet count, Child-Pugh classification, previous abdominal surgery, number of decompensation events, size of varices, red markers on varices, and sclerotherapy. All patients were followed up for a mean period of 18 months (range 10-30). RESULTS: Prothrombotic mutations were detected in 64 of the 219 cirrhotic patients (29.2%), at equal frequency in patients with or without PVT. At univariate analysis, PVT was associated with Child-Pugh classes B and C, signs of liver decompensation, large varices with red markings, sclerotherapy, and abdominal surgery. At multivariate analysis, PVT was associated with sclerotherapy [odds ratio (OR) 4.9, 95% confidence interval (CI) 2.2-11] and previous surgery (OR 2.8, 95% CI 1.2-6.3). The combination of the two acquired factors increased the risk of PVT, whereas the combination of local with genetic defects did not. Only a single patient with genetic thrombophilia and without PVT at inclusion developed the complication during follow-up, concomitantly with the development of hepatocellular carcinoma. CONCLUSION: In cirrhotic patients prothrombotic mutations by themselves are not causative of PVT. Sclerotherapy and previous abdominal surgery favour the development of two-thirds of cases of PVT; in the remaining cases the pathogenesis remains elusive.

Re-treatment of patients with anti-HBe-positive chronic hepatitis B who relapsed after an initial course of lamivudine.

AIM: To evaluate the efficacy of a long-term course of lamivudine monotherapy in patients with anti-HBe-positive chronic hepatitis B who relapsed after the first course of either lamivudine/interferon (n = 16; Group 1) or lamivudine (n = 20; Group 2). METHODS: Biochemical and virological tests were performed every 3 months. At baseline and breakthrough, the region coding for the YMDD amino acid motif was sequenced. RESULTS: The length of re-treatment averaged 24 months. The virological response peaked at 6 months (94.4%), and declined to 66.7% and 50% at 12 and 24 months, respectively. The rates of breakthrough were 2.9%, 31.4% and 48.6% at 6, 12 and 24 months, respectively. By the second year, responders amounted to 62.5% and 40% in Groups 1 and 2, respectively (P = 0.10). The 18 responders at month 24 are still on therapy after 25-51 months of treatment: 14 still maintain a response, nine from Group 1 and five from Group 2. CONCLUSIONS: Re-treatment with lamivudine can control viral replication. This effect is maintained for the initial 12 months in two-thirds of patients, but afterwards the duration of response lessens due to the development of viral resistance.

Clearance of hepatitis B surface antigen in chronic carriers of hepatitis delta antibodies.

BACKGROUND/AIMS: We evaluated the rate of seroclearance of the hepatitis B surface antigen (HBsAg) and its clinical significance in patients with chronic hepatitis delta virus (HDV). METHODS: Antibody to HDV was tested in HBsAg-positive subjects admitted to our Hospital from 1991 to 1995. In 1997, a biochemical and virologic study was performed in the surviving anti-HD-positive patients who had not undergone transplantation. As a control, a cohort of 106 HBsAg-positive, anti-HD-negative patients was studied. RESULTS: One hundred and forty-one subjects were originally positive for anti-HD. After 4 years of follow-up, six of the 60 patients who underwent re-evaluation (10%) had cleared the HBsAg: three of the six patients had minimal changes at the initial liver histology and normal ALT, whereas in the remaining three patients with chronic active hepatitis ALT normalized during the observation. Anti-HD persisted in five of the six patients. Only one patient had raised anti-HBs. In contrast, three of 106 HBsAg carriers without HDV infection (2.8%) cleared the HBsAg within the same time and seroconverted to anti-HBs (p=0.002). CONCLUSION: HBsAg clearance is increased over the years in HDV patients compared to ordinary HBsAg carriers, and is often associated with improvement of HDV disease without seroconversion to anti-HBs.

Pharmacologic treatment can prevent pancreatic injury after ERCP: a meta-analysis.

BACKGROUND: The identification of therapeutic agents that can prevent the pancreatic injury after endoscopic retrograde cholangiopancreatography (ERCP) is of considerable importance. METHODS: We performed a meta-analysis including 28 clinical trials on the use of somatostatin (12 studies), octreotide (10 studies), and gabexate mesilate (6 studies) after ERCP. Outcome measures evaluated were the incidence of acute pancreatitis, hyperamylasemia, and pancreatic pain. Three analyses were run separately: for all available studies, for randomized trials only, and for only those studies published as complete reports. RESULTS: When all available studies were analyzed, somatostatin and gabexate mesilate were significantly associated with improvements in all three outcomes. Odds ratios (OR) for gabexate mesilate were 0.27 (95% CI [0.13, 0. 57], p = 0.001) for acute pancreatitis, 0.66 (95% CI [0.48, -0.89], p = 0.007) for hyperamylasemia, and 0.33 (95% CI [0.18, 0.58], p = 0. 0005) for post-procedural pain. Somatostatin reduced acute pancreatitis (OR 0.38: 95% CI [0.22, 0.65], p < 0.001), pain (OR 0. 24: 95% CI [0.14, 0.42], p < 0.001), and hyperamylasemia (OR 0.65: 95% CI [0.48, 0.90], p = 0.008). Octreotide was associated only with a reduced risk of post-ERCP hyperamylasemia (OR 0.51: 95% CI [0.31, 0.83], p = 0.007) but had no effect on acute pancreatitis and pain. The statistical significance of data did not change after analyzing randomized trials only or studies published as complete reports. For each considered outcome, the publication bias assessment and the number of patients that need to be treated to prevent one adverse effect were, respectively, higher and lower for somatostatin than for gabexate mesilate. CONCLUSIONS: The pancreatic injury after ERCP can be prevented with the administration of either somatostatin or gabexate mesilate, but the former agent is more cost-effective. Additional studies comparing the efficacy of short-term infusion of somatostatin versus gabexate mesilate in patients at high risk for post-ERCP complications seem warranted.

Anticardiolipin antibodies in patients with liver disease.

OBJECTIVE: Our aim was to test the hypothesis that anticardiolipin antibodies (aCL) may cause an antiphospholipid syndrome and thrombotic events in patients with liver disease. METHODS: aCL were measured in 116 healthy controls and 372 patients with liver disease of different stage and etiology: 136 cases secondary to hepatitis C virus (HCV) infection, 139 due to hepatitis B virus (HBV) infection, 69 with alcoholic liver damage, and 28 cryptogenic in origin. Prior thrombotic events were recorded. The results were related to age, gender, stage, severity, and etiology of the liver disease, as well as to the occurrence of organ- and nonorgan-specific autoantibodies. RESULTS: aCL were positive in 4.4% of controls and in 18.8% of patients (p < 0.0002). Patients with aCL were more frequently men with an advanced cirrhosis and simultaneous occurrence of anti-smooth-muscle antibodies (ASMA) in serum (p < 0.0006); their liver damage was often secondary to HBV (37.3%) or alcohol abuse (18.5%). At conditional logistic regression analysis, only the presence of ASMA (odds ratio [OR] = 3.02, 95% confidence interval [CI] 1.7-5.5, p = 0.0003), HBV (OR = 3.4, 95% CI 1.6-7.2, p = 0.0013), or alcoholic liver disease (OR = 5.3, 95% CI 2.3-12.2, p = 0.0001) were independently associated with aCL. Thrombosis was encountered in 24 patients (6.4%). At conditional logistic regression analysis, thrombosis was significantly associated with advanced age (OR = 1.07, 95% CI 1.0-1.1, p = 0.0094), development of hepatocellular carcinoma (OR = 17.8, 95% CI 1.6-196.0, p = 0.01), HBV etiology (OR = 6.3, 95% CI, 1.6-24.6, p = 0.0076), or cryptogenic liver disease (OR = 54.8, 95% CI 5-599.9, p = 0.001). Of the five patients with newly documented portal thrombosis during the follow-up, only one tested positive for aCL. CONCLUSIONS: In patients with nonautoimmune liver disease, aCL production is an epiphenomenon of the liver damage and is not associated with thrombotic complications. These data do not support the hypothesis that HCV is a cause of the antiphospholipid syndrome.

Intrafamilial transmission of hepatitis delta virus: molecular evidence.

BACKGROUND/AIMS: Epidemiologic studies have suggested that transmission of hepatitis delta virus (HDV) occurs by intrafamilial routes in some populations in southern Italy, where HDV infection is endemic. To further evaluate intrafamilial transmission of HDV, we obtained the partial sequence of the viral genome from HDV-RNA positive members of families in which two or more immediate family members were positive for HDV-RNA. METHODS: The region analyzed was the semi-conserved region from nucleotides 908 to 1265. Sequences obtained from family members were compared with those obtained from a control group of 20 unrelated patients. RESULTS: The mean genetic divergence among HDV isolates was 2.8 +/- 1.7% within the 9 families analyzed, and 7.6 +/- 2.2% among the control group of unrelated individuals (p < 0.0001). A Receiver Operating Characteristic curve and Youden Index were used to define a cut-off value of 3.5% to discriminate sequence variations calculated within families and in the control group. CONCLUSIONS: The data indicate that in most family units, HDV-infected members harbored nearly identical strains of HDV, and provide molecular support that HDV infection can be transmitted within the family. Such spreading among family members highlights the role of inapparent transmission through personal contacts.

Splenic abscess secondary to penetrating gastric ulcer.

Splenic abscess is a rare disease whose diagnosis is difficult, though the use of modern imaging methods has increased diagnosed cases in recent years. We report a case of splenic abscess whose aetiology is unusual, namely, a gastric ulcer penetrating into the splenic artery and causing arterial thrombosis and septic embolism. Ultrasonography and ultrasound-guided puncture resolved any diagnostic doubt, and subsequent surgery confirmed the diagnosis. Pathogenesis, clinical picture, diagnostic methods, and treatment are discussed with reference to the literature.

Metastatic melanoma: endoscopy as aid to earlier in vivo diagnosis of gastrointestinal involvement. A case report.

Autopsy frequently reveals gastrointestinal involvement in patients that have died from melanoma, whereas little evidence of the latter emerges in ante-mortem diagnosis and, even then, largely in connection with emergency situations: obstructions, bleeding or perforation. Moreover, the frequently asymptomatic character of gastrointestinal melanoma explains why it largely eludes detection. The present report concerns a case of metastatic melanoma of the stomach, duodenum and liver, where symptoms were scarcely in evidence, and underlines the usefulness of digestive endoscopy both in the staging of the disease and even more so in follow-up.

Percutaneous biopsy in diffuse liver disease: increasing diagnostic yield and decreasing complication rate by routine ultrasound assessment of puncture site.

OBJECTIVE: To evaluate the usefulness of routine ultrasound assessment of puncture site before performing percutaneous biopsy in diffuse liver disease. Seven hundred fifty-three consecutive patients were studied retrospectively. METHODS: Serial scanning of the last intercostal spaces allowed us to establish the most suitable access to the thicker liver parenchyma (assessing the most favorable angulation of the needle too), avoiding the puncture of adjacent organs; no more than 1 min was necessary for such a determination. RESULTS: In 99.4% of patients, a definitive or indicative pathological diagnosis of chronic liver disease was obtained. Only one hemorrhagic complication (0.13%) occurred, requiring no surgical treatment or blood transfusion. Three cases of vasovagal reaction occurred (0.40%): two of these recovered spontaneously, while the other one needed i.v. administration of atropine. Mortality was 0 in our series. CONCLUSIONS: Routine ultrasound of the puncture site is a quick method of assessment, allowing one to increase the diagnostic yield of percutaneous liver biopsy and to maintain low complication rates for such a procedure.

Free-hand technique with ordinary antisepsis in abdominal US-guided fine-needle punctures: three-year experience.

PURPOSE: To evaluate the adequacy of ordinary antisepsis in ultrasound (US)-guided free-hand fine-needle puncture. MATERIALS AND METHODS: Diagnostic and therapeutic procedures (n = 573) were performed in 456 patients. No puncture attachments, sterile gloves, or drapes or covers were used. Before each procedure the transducer was cleaned with a solution of water and 70% alcohol. No needles were contaminated. Patients were monitored for 5 days to exclude sepsis. Subsequently, the patients underwent follow-up blood and laboratory testing, including testing for for hepatitis B and C markers and human immunodeficiency virus antibodies, every 3 months for 6 months. The operators underwent the same follow-up for the first 6 months and for an additional 6 months. RESULTS: No patient or operator presented with fever or sepsis or with negative viral or hepatitis markers that became positive during follow-up. CONCLUSION: Use of this free-hand US-guided technique with ordinary antisepsis is safe for patients and operators, and it allows savings in time and the cost of materials.

Hepatic hydrothorax. Diagnosis and management.

Twelve cases of right hepatic hydrothorax are reported. Tc-99m SC that was injected intraperitoneally and intrapleurally provided evidence of a one-way flow of fluid from the peritoneal to the pleural cavity. Eight patients, whose hydrothorax was refractory to sodium restriction, diuretics and repeated thoracenteses, were treated by endopleural tetracycline instillation. The pathogenetic role of the diaphragmatic defect and the diagnostic usefulness of radionuclide imaging are stressed.

[Evaluation of two treatment schedules with different doses of interferon in chronic HBsAg+ anti-HBe+ hepatitis]. / Valutazione di due schemi terapeutici di interferone nell'epatite cronica HBsAg+ anti-HBe+.

Twenty-three patients with hepatitis B were treated with recombinant interferon-alpha-2a. Twelve patients were given 6 MU three times a week for 6 months (Group A); eleven patients were given 9 MU three times a week for an initial 4-month course and subsequently for a further 3-month course after 6 months of no therapy (group B). Eight patients in the group A (66.7%) and seven patients in the group B became negative for HBV-DNA and normalized their ALT, compared to 31% of controls. Relapses were noticed in 75% of the responders in the group A and in 71.4% of the responders in the group B within 12 months after interferon discontinuation. The Authors are consequently of opinion that it is appropriate to try longer treatments with moderate doses of interferon in order to maintain the response as long as possible.

[Peptic ulcer in liver cirrhosis]. / La malattia peptica nella cirrosi epatica.

The frequency of peptic ulcer and the role of ulcerogenic risk factors in cirrhotic patients were evaluated in a retrospective study. Peptic disease was observed in 18.2% of the cirrhotic patients examined. When compared to the prevalence of ulcerative lesions in the general population, this finding suggests that cirrhotic patients have the same probability of being affected by peptic ulcer as non-cirrhotic subjects. The analysis of ulcerogenic risk factors highlighted the importance of alcohol and smoking. The etiology of cirrhosis and portal hypertension were not found to be important. In conclusion, peptic disease is not more frequent in cirrhotic patients than in the general population.

[Solitary rectal ulcer syndrome. 8 case reports]. / La sindrome dell'ulcera solitaria del retto. Osservazione di 8 casi.

Following a brief review of the various names in routine use to indicate solitary ulcer of the rectum syndrome, stress is laid on its variable anatomoclinical expressions, presenting personally observed cases and discussing the pathogenetic mechanisms and the diagnostic and therapeutic implications.

Evaluation of the use of ultrasonography in the study of liquid gastric emptying.

Gastric emptying of two different test liquid meals (500 ml isotonic saline and 500 ml skimmed milk, 1.8% fat) has been measured in 10 (saline) and in 19 (milk) normal volunteers by means of real-time ultrasonography (RUS) and scintigraphy, employed simultaneously. In each subject, saline and milk contained 37 MBq of diethylenetriaminopentacetic acid (DPTA) marked with 99mTc. Determinations were made thereafter every 5 min up to 45 min with saline and every 30 min up to a maximum of 220 min with milk. The determination of gastric emptying by RUS was obtained indirectly through the measurement of gastric dimensions, with a single scan performed at the epigastrium, while the subject was kept in a standing position. At each observation, the percent decrease of gastric measurements and the decay in radioactivity over the gastric region were calculated, blind, by two independent examiners. Linear regression and correlation coefficient were subsequently computed for gastric measurements and decay in radioactivity. The results show that the values obtained with RUS do not differ grossly from the ones obtained with scintigraphy. This suggests that the ultrasonographic determination of gastric dimensions with a single section of the stomach may be a valuable method for use in the evaluation of gastric emptying of liquids.

Granular cell tumor of the esophagus.

Granular cell tumor (GCT) of the esophagus is a rarely-met-with neoplasm. It is almost invariably benign in character and is of still-disputed histogenesis. Small lesions are asymptomatic. Those over 1 cm in diameter may be accompanied by painful swallowing or retrosternal discomfort. Local resection is the treatment of choice for lesions that are accompanied by symptoms, or that are larger than 1 cm. A tumor incidentally encountered in an asymptomatic patient may be safely followed endoscopically. A successful endoscopic removal of such a lesion is described.