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AimsTo perform a cost-effectiveness analysis (CEA) comparing personalised dosimetry with standard dosimetry in the context of selective internal radiation therapy (SIRT) with TheraSphere for the management of adult patients with locally advanced hepatocellular carcinoma (HCC) from the Italian Healthcare Service perspective.Materials and methodsA partition survival model was developed to project costs and the quality-adjusted life years (QALYs) over a lifetime horizon. Clinical inputs were retrieved from a published randomised controlled trial. Health resource utilisation inputs were extracted from the questionnaires administered to clinicians in three oncology centres in Italy, respectively. Cost parameters were based on Italian official tariffs.ResultsOver a lifetime horizon, the model estimated the average QALYs of 1.292 and 0.578, respectively, for patients undergoing personalised and standard dosimetry approaches. The estimated mean costs per patient were €23,487 and €19,877, respectively. The incremental cost-utility ratio (ICUR) of personalised versus standard dosimetry approaches was €5,056/QALY.ConclusionsPersonalised dosimetry may be considered a cost-effective option compared to standard dosimetry for patients undergoing SIRT for HCC in Italy. These findings provide evidence for clinicians and payers on the value of personalised dosimetry as a treatment option for patients with HCC.

UNLABELLED A 75-year-old Caucasian woman with alcohol-related cirrhosis was admitted to our Unit in October 2012 for the diagnostic evaluation of a focal liver lesion detected by regular surveillance ultrasound. The subsequent dynamic CT and MR led to a diagnosis of infiltrative hepatocellular carcinoma (HCC) of 5 cm in the hepatic segment IV with neoplastic infiltration of the left branch of the portal vein, in absence of extrahepatic metastases. Therapy with sorafenib 400 mg bid was started and the subsequent dynamic CT performed at the 10th month of therapy showed a complete response according to RECIST criteria and mRECIST, while seriated dosages of α-fetoprotein levels showed a progressive reduction up to normalization. After 18 months of therapy, Sorafenib was discontinued due to a grade 3 adverse event. Nonetheless, all subsequent radiological controls, performed over the following two years confirmed a complete off-therapy response despite withdrawal of Sorafenib. After three years the patient is asymptomatic, with a preserved liver function and undetectable solid tumor lesions at dynamic CT. This case represents one of the few examples of complete response to anti-angiogenic drugs and, to our knowledge, the only case of sustained response, even after the discontinuation of Sorafenib, described so far in the literature. KEY WORDS hepatocellular carcinoma - HCC - BCLC - sorafenib - complete response. ABBREVIATIONS AFP: alpha-fetoprotein; AE: adverse event; BCLC: Barcelona Clinic Liver Cancer; CT: computed tomography; HCC: hepatocellular carcinoma; mRECIST: modified response evaluation criteria in solid tumors; PS: Performance status; RCTs: randomized controlled trials.

BACKGROUND α-Fetoprotein (AFP) is a biomarker commonly used in the management of patients with hepatocellular carcinoma (HCC), although the possible determinants of its serum levels in these patients have not been adequately explored. For this study, the authors evaluated the relevance of demographic, clinical, and oncologic factors to the presence of elevated AFP levels in large cohort of patients with HCC. METHODS In 4123 patients with HCC who were managed by the Italian Liver Cancer Group, AFP levels were assessed along with their association with demographic, biochemical, clinical, and oncologic characteristics. Patients were subdivided according to the presence of elevated AFP (ie, >10 ng/mL). RESULTS AFP levels were elevated in 62.4% of patients with HCC. Multivariate logistic regression analysis indicated that being a woman (odds ratio [OR], 1.497; 95% confidence interval [95%CI], 1.250-1.793; P 2 cm (OR, 1.346; 95% CI, 1.135-2.596; P = .001), multinodular HCC (OR, 1.641; 95% CI, 1.403-1.920; P

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death with an increasing prevalence worldwide. Early diagnosis of HCC is important since observational studies have reported that, in patients undergoing surveillance, cancer is diagnosed at an earlier stage with increased chances of curative therapies. Anyway, despite the extensive use of screening for HCC, its effectiveness is still a controversial topic since supporting evidence is not unequivocal and some issues need to be explored. Areas covered: The aim of this paper is to review main literature data supporting performance and effectiveness of screening for early detection of hepatocellular carcinoma. Expert commentary: Clinical benefit of screening for HCC is controversial and there are no sufficient data supporting its effectiveness in reducing cancer specific mortality. Since it is unlikely that RCTs will be performed in the future, surveillance should be still reasonably recommended in all at-risk population, until potential data against its effectiveness will be provided. In the future additional and more effective non-invasive tests will be needed, as well as proper surveillance intervals and risk threshold for surveillance enrollment must be assessed and refined by prospective studies.

In cases of morbid obesity, obstructive sleep apnea (OSA) was associated with biopsy-proven liver damage. The role of non-invasive techniques to monitor liver changes during OSA treatment with continuous positive airway pressure (CPAP) is unknown. We used non-invasive ultrasound techniques to assess liver steatosis and fibrosis in severe OSA patients at diagnosis and during long-term CPAP treatment. Fifteen consecutive patients with severe OSA (apnea hypopnea index 52.5 ± 19.1/h) were studied by liver ultrasound and elastography (Fibroscan) at 6-mo (n = 3) or 1-y (n = 12) follow-up. Mean age was 49.3 ± 11.9 y, body mass index (BMI) was 35.4 ± 6.4 kg/m(2). Adherence to CPAP was ≥5 h/night. At baseline, most patients had severe liver steatosis independent of BMI; at follow-up, liver steatosis was not statistically different, but a relationship between severity of steatosis and BMI became apparent (Spearman's rho: 0.53, p = 0.03). Significant fibrosis as assessed by Fibroscan was absent at diagnosis or follow-up (failure or unreliable measurements in four markedly obese patients). Therefore, ultrasound liver assessment is feasible in most OSA patients, and CPAP treatment may positively affect liver steatosis.

Background. Although band ligation is now recommended for prevention of rebleeding from oesophageal varices in cirrhosis, sclerotherapy is still widely used. Patients submitted to chronic sclerotherapy undergo several endoscopies and experience a large number of serious complications. However, long-term outcome is poorly defined. Aims. To assess the clinical course and prognostic indicators of patients undergoing chronic sclerotherapy for prevention of variceal rebleeding as a basis for future evaluation of long-term band ligation outcome. Methods. Prospective cohort study prognostic analysis by the Cox proportional hazards model. Results. A total of 218 consecutive cirrhotic patients (37 Child class A, 154 B, 27 CJ were enrolled in the study. Varices were obliterated in 139 (64%) patients in a mean of 5 (±2.6) sessions and recurred in 58 139 (41.7%) within one year. A total of 132 (60%) patients experienced 283 rebleeding episodes and 73 (33%) died. Bleeding from oesophageal ulcers was the most serious complication causing 14% of all rebleeding episodes. Significant prognostic indicators of sclerotherapy outcome were: Child-Pugh class for variceal obliteration; gastric varices and platelet count for recurrence of varices; failure to obliterate varices, variceal size and gastric varices for rebleeding; blood urea nitrogen and failure to obliterate varices for death. Presence of gastric varices was the only prognostic indicator for death in the 79 patients not achieving variceal obliteration. A mean of 10 endoscopies and of 6 hospital admissions were needed per each patient with an estimated cost of US$ 7154 per patient during the first two years of therapy. Conclusions. Sclerotherapy is a very demanding and costly treatment, and is associated with frequent and serious side-effects. The probability of treatment failure is significantly higher in Child C patients with gastric varices. Alternative treatments should be considered for these patients.

One hundred and forty-seven patients with Child's A cirrhosis and no evidence of hepatocellular carcinoma were followed up in an 8-year prospective surveillance program with testing by ultrasound and alphafetoprotein every 6 months. Eighteen of 147 patients were HBsAg positive. Anti-hepatitis C virus antibodies were found in 103 out of 133 cases tested. Sixteen patients had a history of heavy drinking. Thirty hepatocellular carcinomas were detected during follow up. At the time of diagnosis, ultrasound detected focal lesions in all the patients whereas alphafetoprotein was below diagnostic levels. The hepatocellular carcinoma was single in 26 patients and multiple in four. The overall 8-year cumulative tumor-free rate was 69% (95% confidence interval = 58-73). The yearly hepatocellular carcinoma incidence from 1985 to 1992 was respectively 2%, 1.5%, 2%, 3%, 5%, 4.8%, 7% and 10%. The initial value of AFP50 ng/ml and400 ng/ml was significantly related to the development of hepatocellular carcinoma. This series shows that the cumulative incidence of hepatocellular carcinoma in cirrhosis in Italy is higher than previously reported, but lower than that observed in Asiatic areas. A 6-month interval for ultrasound is reasonable to detect treatable tumors. Alphafetoprotein has no value for early diagnosis, although its intermediate values (50 and400 ng/ml) may indicate the presence of undetectable cancer which will appear during the follow up, and suggests that ultrasound should be employed more frequently in patients with these values.

The most common extraintestinal manifestations of Crohn's disease concern joints, skin, and eyes; however other organs such as liver, pancreas, kidneys, heart, lungs or brain can also be affected. Aseptic abscesses are an emergent entity in patients with inflammatory bowel disease and despite medical treatment the surgical approach may represent an alternative therapy. We report a case of a young woman with splenic aseptic abscesses as complication of Crohn's disease. After steroid sparing and antibiotic failure the patient underwent successful splenectomy.

The role of prognostic variables in the treatment of hepatocellular carcinoma (HCC) by transarterial chemoembolisation (TACE) is controversial.To evaluate the survival of patients with HCC on cirrhosis treated with TACE and to analyse the prognostic factors affecting survival.From 1996 to 2006, 580 consecutive patients with HCC in cirrhosis were observed. Of these 194 patients underwent TACE. The primary end-point was survival. Independent predictors of survival were identified using the Cox model.The cumulative 1-year, 3-year, and 5-year survival rates were 96%, 60%, and 41%, respectively. The multivariate analysis showed significant reduction of survival among patients with serum bilirubin values2mg/dl compared to patients with values2mg/dl (Hazard ratio 3.84; CI 95% 1.70-8.66; p-value=0.001). Multivariate analysis performed in the group of patients treated with TACE alone showed that elevated serum bilirubin (Hazard ratio 2.96; CI 95% 1.20-7.3; p-value 0.02) and incomplete tumour response (Hazard ratio 2.88; CI 95% 1.18-7.05; p-value 0.02) are correlated with a worse outcome.TACE was well tolerated and overall survival rate was 41% after 5 years. Complete tumour response and serum bilirubin2mg/dl were identified as predictors of survival.

Dear Sir, It is still questioned the use of combination therapy with biologics and immunosuppressants in the management of severe or steroid-dependent Crohn's Disease (CD). The main concern is about the risk that a prolonged therapy may increase the incidence of lymphoproliferative disorders.1 A 46 year-old man with ileocolonic CD diagnosed at the age of twenty year-old was admitted, on January 2012, to our unit for the abrupt onset of obstructive jaundice, associated with weight loss. The previous clinical course of CD was indolent in the last 20 years, and the patient maintained long periods of remission after short courses of steroids and metronidazole up to 2004, when he moved to USA for work. In USA the patient …

OBJECTIVE: Percutaneous ethanol injection may prolong the survival of patients with small hepatocellular carcinoma associated with cirrhosis. The aim was to identify prognostic factors of survival and of local recurrence, as well as separate new lesions. METHODS: We performed Cox regression analysis in 115 consecutive patients with hepatocellular carcinoma (81 Child-Pugh class A, 34 Child-Pugh class B) treated by percutaneous ethanol injection. The validity of the model was tested by comparing predicted and observed survival in 105 independent patients from an external series. RESULTS: Overall survival rates were 89%, 63%, and 43% at 1, 2, and 3 yr, respectively. The 1-, 2-, and 3-yr survival rates were 96%, 78%, and 63%, respectively, for Child-Pugh class A patients and were 73%, 35%, 12%, respectively, for Child-Pugh class B. The albumin level was the only independent variable significantly associated with survival (p < 0.0001). The 3-yr rate of appearance of separate new lesions and local recurrence were 41% and 23%, respectively. The survival predicted by the model agreed with that observed in the independent patients. CONCLUSIONS: Survival of patients with hepatocellular carcinoma treated by percutaneous ethanol injection is related to baseline albumin level. The high rate of recurrence (both local and distant) points out the palliative role of this therapy.

Ethanol injection has been reported to be effective in the treatment of hepatocellular carcinoma, but no controlled randomized trials have been performed. We therefore performed a trial comparing ethanol injection with an untreated, matched historical comparison group in the treatment of hepatocellular carcinoma.From 1992 to 1993, 35 patients (14 Child's A and 21 Child's B cirrhosis) with small (4 cm) hepatocellular carcinoma associated with cirrhosis were treated by ethanol injection. Each patient was matched with an untreated case (followed up during the period 1984-89) for variables known to have independent prognostic value (age, Child's classification, number of lesions, alpha-fetoprotein, and modality of diagnosis).The 1-, 2-, and 3-year survival rates of ethanol-treated patients were 86% (95% confidence interval (CI), 69-94), 53% (95% CI, 34-68), and 33% (95% CI, 15-52), whereas the survival rates of the comparison group were 75% (95% CI, 56-85), 26% (95% CI, 13-41), and 14% (95% CI, 5-27) (P = 0.01). The 1-, 2-, and 3-year survival rates of Child's A were 100%. 87% (95% CI, 30-97), 71% (95 CI, 33-90), 71% (95% CI, 33-90) in the ethanol-treated patients and 92 (95% CI, 59-99), 43% (95% CI, 23-73), and 21% (95% CI, 23-72) in untreated patients. The 1-, 2-, and 3-year survival of Child's B patients were 76% (95% CI, 59-97), 32% (95% CI, 13-53), and 9% (95% CI, 0.8-33) in the treated group and 61% (95% CI, 40-83), 14% (95% CI, 3-32), and 9% (95% CI, 1-26) in the treated group.These data suggest that ethanol injection prolongs the life of patients with hepatocellular carcinoma associated with Child's A cirrhosis but seems not to influence the survival of Child's B patients.

Fifty patients with 81 abdominal hydatid cysts were followed with ultrasound during and after treatment with albendazole. In 61 cysts (75%), regressive changes were observed after treatment. Detachment of the membrane and change to a solid pattern in anechoic cysts were observed. Disappearance of septa or change to a solid pattern in anechoic cysts with intracystic septation were also found. There was an increase of hyperechoic structures in cysts with a mixed pattern. Follow-up ultrasound examination showed disappearance of 7 cysts, while anechoic structures reappeared in five cases. In anechoic cysts, regressive changes due to albendazole seem to be permanent, but in cysts with a mixed pattern recurrences are sometimes observed.

The present study deals with the natural history of 37 asymptomatic patients with cirrhosis and hepatocellular carcinoma, 25 with 2-9-cm tumors who were not surgically treated (first group) and 12 with tumors smaller than 4 cm who underwent resection (second group). All patients were in Child's A class. Two-year survival (according to life-table analysis by the Kaplan-Meier method) was 50% in the first group and 39% in the second group. This difference was not significant. In the first group no relation was found between survival and initial tumor size or alpha-fetoprotein levels. Ultrasound examinations at 3-mo intervals revealed the following patterns of tumor growth: (a) no significant growth during the follow-up (9 patients); (b) significant growth (tumor size at least doubling) only in the final stage of the disease (11 patients); (c) initial significant growth followed by a period of no increase in size (5 patients). These findings show that in our geographical area (a) 2-yr survival of untreated asymptomatic patients with hepatocellular carcinoma associated with cirrhosis does not differ from that of similar patients undergoing resection and (b) the tumor can exhibit long periods of no growth alternating with periods of exponential growth.

Ascitic fluid pH and arterial-ascitic fluid pH gradient were compared to ascitic fluid polymorphonuclear cell count in 84 patients with cirrhotic ascites and in 12 with malignant ascites to assess their role as diagnostic tests for spontaneous bacterial peritonitis and to clarify the relationship between ascitic fluid pH and lactate. Ascitic fluid pH was significantly lower (pH 7.30) in spontaneous bacterial peritonitis (n = 18) and probable spontaneous bacterial peritonitis (n = 12) than in sterileascites (pH 7.41; n = 54). Since blood pH levels were not different in the presence of infection, arterial-ascitic fluid pH gradient was significantly higher in spontaneous bacterial peritonitis and probable spontaneous bacterial peritonitis than in sterile ascites (0.12 vs. 0.02). The close correlations between arterial-ascitic pH gradient and lactate (r = 0.77, p < 0.0001), lactate and bicarbonate gradient(r = 0.64, p = 0.003) and arterial-ascitic pH gradient and pCO2 gradient (r = —0.90, p < 0.0001) suggest that the low ascitic fluid pH may be due to an increase in lactate and CO2. Patients with Escherichia coli-induced spontaneous bacterial peritonitis had significantly lower ascitic fluid pH and higher lactate than those with spontaneous bacterial peritonitisbyother organisms. Values of ascitic fluid pH, lactate and arterial-ascitic fluid pH gradient in malignant ascites were similar to those of spontaneous bacterial peritonitis and probable spontaneous bacterial peritonitis. Cutoff points, selected by receiver operating characteristic curves analysis, of 450 per mm3 for polymorphonuclear cells and of 0.07 for arterial-ascitic fluid pH gradient, allow high positive and negative predictive values for spontaneous bacterial peritonitis. The polymorphonuclear cell count has the highest sensitivity and specificity. The use of both testscan be useful in the early diagnosis of spontaneous bacterial peritonitis or to confirmspontaneous bacterial peritonitis when bacteriological cultures are negative, if conditions associated with neutrocytic ascites or malignancy are excluded.

Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Background & Aims: Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Methods: One-thousand three-hundred and eighty Child–Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n = 850), annual surveillance (n = 234) or when patients came when symptomatic (n = 296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm. Results: The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p