Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon.

BACKGROUND: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. AIM: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. METHODS: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. RESULTS: TTR by Kaplan-Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. CONCLUSION: In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used.

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.

Multiple intrahepatic vascular shunts causing hyperammoniaemic encephalopathy in a patient without liver cirrhosis.

The very rare case of a non-cirrhotic patient with multiple intrahepatic portosystemic and arteriosystemic vascular shunts, presenting with hyperammoniaemic type B encephalopathy and hypoalbuminaemia due to proteinuria, is reported. The correct diagnosis, suspected by abdominal ultrasound and colour-Doppler imaging, was confirmed by hepatic and superior mesenteric angiography. A comparison with the few similar cases existing in the literature is offered.

Comparison between alcohol- and hepatitis C virus-related hepatocellular carcinoma: clinical presentation, treatment and outcome.

BACKGROUND: Hepatitis C virus (HCV) and alcohol abuse are the main risk factors for hepatocellular carcinoma (HCC) in Western countries. AIM: To investigate the role of alcoholic aetiology on clinical presentation, treatment and outcome of HCC as well as on each Barcelona Clinic Liver Cancer (BCLC) stage, as compared to HCV-related HCCs. METHODS: A total of 1642 HCV and 573 alcoholic patients from the Italian Liver Cancer (ITA.LI.CA) database, diagnosed with HCC between January 2000 and December 2012 were compared for age, gender, type of diagnosis, tumour burden, portal vein thrombosis (PVT), oesophageal varices, liver function tests, alpha-fetoprotein, BCLC, treatment and survival. Aetiology was tested as predictor of survival in multivariate Cox regression models and according to HCC stages. RESULTS: Cirrhosis was present in 96% of cases in both groups. Alcoholic patients were younger, more likely male, with HCC diagnosed outside surveillance, in intermediate/terminal BCLC stage and had worse liver function. After adjustment for the lead-time, median (95% CI) overall survival (OS) was 27.4 months (21.5-33.2) in alcoholic and 33.6 months (30.7-36.5) in HCV patients (P = 0.021). The prognostic role of aetiology disappeared when survival was assessed in each BCLC stage and in the Cox regression multivariate models. CONCLUSIONS: Alcoholic aetiology affects survival of HCC patients through its negative effects on secondary prevention and cancer presentation but not through a greater cancer aggressiveness or worse treatment result. In fact, survival adjusted for confounding factors was similar in alcoholic and HCV patients.

Years of life that could be saved from prevention of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour ≥ 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost.

Ultrasonography and echo-guided fine-needle biopsy in the diagnosis of focal fatty liver change.

The usefulness of ultrasound and echo-guided fine-needle biopsy (FNB) in the diagnosis of focal fatty liver change (FFLC) is stressed, on the basis of a retrospective series of 21 patients (8 of whom with a past history of primary cancer), followed-up for a mean period of 13.7 months. FFLC presented with various echographic patterns, shapes, dimensions and localizations. In 17 patients the diagnosis of FFLC was made by FNB, yielding cytologic and/or histological samples with steatotic, but also normal, hepatocytes. In another 4 patients the diagnosis was made by echographic follow-up. In all patients, clinical, hematological and echographic follow-up excluded the onset of neoplastic disease, confirming the high specificity of FNB in diagnosing FFLC. The possibility of changing appearance over time, and the inconstant correlation of FFLC with known causes of hepatic steatosis are discussed, as well as the hypothesis that the focal defect seen with ultrasound, could be an area of normal hepatic tissue in a fatty liver. The authors affirm the necessity to perform FNB on each doubtful lesion, but certainly when the patient has a history of malignancy.

Utility of alpha-fetoprotein (AFP) in the screening of patients with virus-related chronic liver disease: does different viral etiology influence AFP levels in HCC? A study in 350 western patients.

BACKGROUND/AIMS: Dosage of serum AFP (alpha-fetoprotein) is widely used for HCC screening in patients with chronic liver disease. Virus-related chronic liver disease is the main cause of cirrhosis and HCC in Western and Far Eastern countries, but the relationship between viral etiology and AFP levels in HCC is still unclear. The aim of this study was to verify, in Western patients with post-viral chronic liver disease, the usefulness of AFP dosage for the detection of HCC, and the influence of viral etiology on AFP levels in HCC. METHODOLOGY: The study population included 350 patients with post viral chronic liver disease that underwent liver biopsy, serum AFP determination and ultrasound liver evaluation. Seven patients had normal liver histology, 197 had chronic hepatitis, 72 had cirrhosis, and 74 had cirrhosis and HCC. ROC (receiver operating characteristic) analysis was used to assess the best diagnostic AFP threshold value for HCC detection. Logistic regression analysis was performed to individuate independent predictors of HCC diagnosis. RESULTS: No difference was observed in AFP levels between HCV- and HBV-positive patients, neither in the whole population nor in the HCC patients only. ROC area under curve for AFP was 0.801 (95% CI: 0.721-0.867). The analysis individuated a best accurate AFP threshold value for HCC diagnosis of 50 ng/mL. HCC was detected with specificity > or = 95% only for AFP > 100 ng/mL. The sensitivity however was poor (25%). Male sex, age > 60, and AFP were independent predictors of HCC diagnosis. CONCLUSIONS: Serum AFP levels in HCC patients are not influenced by virus B or C hepatitis pattern. AFP dosage should not be used for HCC diagnosis in non-cirrhotic patients. Male patients with cirrhosis should be regarded with a more "aggressive" screening program compared to females.

Nodular lesions of the liver in multiple myeloma: a role for cytoadhesion molecules?

Two patients with multiple myeloma and in vivo macroscopic nodular lesions of the liver are presented. The clinical aspects of this very unusual condition are briefly reviewed. In particular, the expression on neoplastic plasma cells of the cytoadhesion molecules CD56 and CD11a, which are involved in the cellular process of recirculation and homing, suggests a possible role for such markers in this atypical localization of the disease.

[Acute adult respiratory distress in a gram-negative infection. Clinical contribution]. / Stress respiratorio acuto dell'adulto in corso di sepsi da gram-negativi. Contributo clinico.

The adult respiratory distress syndrome in major complication of hospitalized patients. The therapeutic role of intravenous albumin, diuretics, corticosteroids and oxygen administration is yet doubtful. The Authors, after a description of pathogenetic, histological and clinical aspects of the syndrome, report a case occurred at their observation; it is showed the important role of intravascular coagulopathy and reversible ECG alterations, and the therapeutic valve of positive end-expiratory pressures (PEEP).

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.

[Ureteral jet during medical treatment of benign prostatic hypertrophy]. / Il "jet" ureterale in corso di trattamento medico dell'ipertrofia prostatica benigna.

By Color-Doppler ultrasound it's possible to visualize urine flow from ureter into the bladder. Aim of the study was to image these ureteral jets in patients with benign prostatic hyperplasia (BPH) before and after therapy. Seven patients were studied, whose age ranged from 52 to 69 years; they were not affected by methabolic, hepatic, renal diseases and by prostate inflammation. A duplex scanner (Toshiba SSA 270 A) with a convex probe of 3.5 MHz was used. A transabdominal ultrasound study was performed, measuring prostatic volume and imaging ureteral jet before and along a treatment (at four months intervals) with Finasteride 5 mg/die (Finastid, Neopharmed) and at the end of treatment. We found that the mean velocity of jets in patient affected by was higher than in healthy subjects (80 cm/sec vs 60 cm/sec) bur during treatment it decreased along with symptom improvements and decreasing volume at US. We concluded that analysis of ureteral jets with Color-Doppler P.W. may add useful informations to real-time us in the study of patients affected by BPH undergoing treatment with Finasteride.

[Echo-Doppler evaluation of the renal arterial flow in hepatic cirrhosis]. / Valutazione mediante eco-Doppler del flusso arteriolare renale in corso di cirrosi epatica.

In liver cirrhosis the sodium retention depends on a decreased renal perfusion by arteriolar vasoconstriction. To evaluate the usefulness of echo-Doppler in detecting such hemodynamic impairment, we studied 16 cirrhotic patients and 16 healthy subjects as control group. We measured Pulsatility Index (P.I.) and Resistivity Index (R.I.). Both parameters resulted to be statistically higher in cirrhotic patients than in controls; moreover they resulted to be higher in cirrhotics with ascites than in those without. Therefore echo-Doppler can detect intraparenchymal renal vasoconstriction in cirrhosis, this impaired perfusion is already evident before ascites formation.

Nodular regenerative hyperplasia of the liver: coral atoll-like lesions on ultrasound are characteristic in predisposed patients.

Nodular regenerative hyperplasia (NRH) is an uncommon liver disease characterised histologically by numerous small hyperplastic nodules that are not separated by fibrotic tissue. It is thought to be the result of obliterative vasculopathy, and it has been associated with chronic use of medications, toxic substances and a wide variety of systemic diseases. Imaging diagnosis of early-stage NRH remains problematic. The nodules are rarely discerned and their appearance and behaviour before and after contrast medium administration are heterogeneous and not specific. A review of the literature shows that ultrasound has succeeded on occasion in revealing small focal liver lesions in patients with NRH. To our knowledge, there has been no published data on the performance in this setting of last-generation ultrasound scanners and techniques such as contrast-enhanced ultrasound (CEUS). The question is an important one because abdominal ultrasound is widely used as a first-line imaging technique for the evaluation of liver disease, and this makes it particularly suitable as a potential tool for the early diagnosis of NRH. Owing to the prolonged subclinical period and the limited help provided by imaging, the diagnosis in vivo of NRH is currently frequently missed, and it is still made exclusively on the basis of liver biopsy. In conclusion, this report describes 4 cases of biopsy-proven NRH that have been diagnosed over the past 2 years by our group. All were characterised by known comorbidities that confer a predisposition to NRH and by a peculiar parenchymal ultrasound pattern that we refer to as the "atoll sign".

Impact of evidence-based medicine on the treatment of patients with unresectable hepatocellular carcinoma.

BACKGROUND: A randomized controlled trial performed by the Barcelona Clinic Liver Cancer (BCLC) published in 2002 demonstrated that transcatheter arterial chemoembolisation (TACE) is an effective treatment for well-selected patients with unresectable hepatocellular carcinoma (HCC). AIM: To access whether this information has modified the use of TACE in clinical practice. METHODS: From 2042 HCC patients included in the Italian Liver Cancer database, we selected 336 cases diagnosed over two 4-year periods (1999-2002, n = 161 and 2003-2006, n = 175), fulfilling the inclusion criteria of the BCLC study. These groups were compared for TACE application rate, patient characteristics and survival. RESULTS: Patients undergoing TACE increased in the 2003-2006 period (from 62% to 73%, P = 0.035), with an increase in of Child-Pugh class A (from 64% to 77%, P = 0.048) and advanced HCC patients (from 54% to 69%, P = 0.041). In the 1999-2002 period, there was no significant difference in survival between TACE-treated and untreated patients, while in the 2003-2006 period, TACE-treated patients survived longer (P < 0.0001). CONCLUSIONS: Following the publication of studies providing evidence of a survival benefit of TACE in selected patients with unresectable HCC, significantly more patients with well-compensated cirrhosis underwent TACE within this very homogenous population, leading to an increased survival despite a more advanced tumour stage.

Cruveilhier-Baumgarten syndrome without esophageal varices: ultrasonographic diagnosis and echo-Doppler study.

Two cases of Cruveilhier-Baumgarten syndrome not clinically evident and without esophageal varices in patients with liver cirrhosis and portal hypertension are presented. The diagnosis was made by real-time ultrasonography, which showed echographic caput medusae with large afferent umbilical veins and efferent inferior superficial epigastric veins. Doppler flowmetry documented high blood flow rates in these collateral portal-systemic circulations, and this explained the absence of large varices at endoscopy. The role of massive spontaneous portal-systemic shunts in preventing the formation of other shunts and particularly esophageal variceal bleeding is discussed.