Lowered expression of microRNA-125a-5p in human hepatocellular carcinoma and up-regulation of its oncogenic targets sirtuin-7, matrix metalloproteinase-11, and c-Raf.

Human microRNA-125a-5p (miR-125a) is expressed in most tissues where it downregulates the expression of membrane receptors or intracellular transductors of mitogenic signals, thus limiting cell proliferation. Expression of this miRNA generally increases with cell differentiation whereas it is downregulated in several types of tumors, such as breast, lung, ovarian, gastric, colon, and cervical cancers, neuroblastoma, medulloblastoma, glioblastoma, and retinoblastoma. In this study, we focused on hepatocellular carcinoma and used real-time quantitative PCR to measure miR-125a expression in 55 tumor biopsies and in matched adjacent non-tumor liver tissues. This analysis showed a downregulation of miR-125a in 80 % of patients, with a mean decrease of 4.7-fold. Comparison of miRNA downregulation with clinicopathological parameters of patients didn't yield significant correlations except for serum bilirubin. We then evaluated the expression of known targets of miR-125a and found that sirtuin-7, matrix metalloproteinase-11, and c-Raf were up-regulated in tumor tissue by 2.2-, 3-, and 1.7-fold, respectively. Overall, these data support a tumor suppressor role for miR-125a and encourage further studies aimed at the comprehension of the molecular mechanisms governing its expression, eventually leading to treatments to restore its expression in tumor cells.

Occult HBV infection in HCC and cirrhotic tissue of HBsAg-negative patients: a virological and clinical study.

AIM: To evaluate the virological and clinical characteristics of occult HBV infection (OBI) in 68 consecutive HBsAg-negative patients with biopsy-proven cirrhosis and HCC. METHODS: HBV DNA was sought and sequenced in plasma, HCC tissue and non-HCC liver tissue by PCRs using primers for HBV core, surface and x regions. OBI was identified by the presence of HBV DNA in at least two different PCRs. RESULTS: OBI was detected in HCC tissue of 13 (20%) patients and in non-HCC liver tissue of 3 of these 13. OBI was detected in HCC tissue of 54.5% of 11 anti-HBs- negative/anti-HBc-positive patients, in 29.4% of 17 anti-HBs/anti-HBc-positive and in 5% of 40 anti-HBs/anti-HBc-negative (p < 0.0005). The 13 patients with OBI in HCC tissue more frequently than the 55 without showed Child-B or -C cirrhosis (53.9% vs. 5.5%, p < 0.0001) and BCLC-B or -C stages (46.1% vs. 1.8%, p < 0.0001). The pre-S1, pre-S2 and S region sequences in HCC tissue showed amino acid (AA) substitutions (F19L, P24L, S59F, T131I, Q129H) and deletions (in positions 4,8, 17 and 86) in the S region, AA substitutions (T40S, P124K, L54P, G76A, N222T and I273L) in pre-S1 region and AA substitutions in pre-S2 region (P41H and P66L). In the 3 patients showing OBI also in non-HCC liver tissue the S, pre-S1 and pre-S2 sequencing displayed patterns of mutations different. CONCLUSIONS: The study showed a significant correlation between OBI and the severity of liver damage, several patterns of mutations in the S, pre-S1 and pre-S2 regions in HCC tissue, some at their first description.

Sorafenib after RFA in HCC patients: a pilot study.

BACKGROUND/AIMS: To investigate the effectiveness and safety of sorafenib after radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC). METHODOLOGY: 44 intermediate or advanced HCC patients received sorafenib treatment after debulking with RFA therapy. Time to progression (TTP), response rate (RR), duration of sorafenib treatment and adverse effects were evaluated. An explorative comparison was performed with patients treated with sorafenib only. RESULTS: At 12 months, TTP was 10.3 months (range: 1-32). RR was 61% with 2 complete responses, and duration of sorafenib therapy was 10.9 months (1-32). No new safety concerns were report-ed. With sorafenib only, TTP was 7.2 months (range: 0-38) and RR was 40%, with one complete response; duration of therapy was 7.3 months (0-38). CONCLUSIONS: The sequence of RFA and sorafenib appears effective and safe in HCC patients. These findings could support the use of a sequential treatment with RFA and sorafenib in HCC patients.

Sonography and clinical outcome of viable hydatid liver cysts treated with double percutaneous aspiration and ethanol injection as first-line therapy: efficacy and long-term follow-up.

OBJECTIVE: The objective of our study was to report our 19-year experience with sonography and the clinical outcome of viable hydatid liver cysts treated with double percutaneous aspiration and ethanol injection as first-line therapy. CONCLUSION: Viable hydatid liver cysts can be safely and successfully managed with double percutaneous aspiration and ethanol injection as first-line-therapy.

Contrast-enhanced sonography in the characterization of small hepatocellular carcinomas in cirrhotic patients: comparison with contrast-enhanced ultrafast magnetic resonance imaging.

AIM: To evaluate the role of low mechanical index (MI) contrast-enhanced sonography (CEUS) for the characterization of small hepatocellular carcinomas (HCC) in cirrhotic patients by comparing the results to ultrafast dynamic gadolinium-enhanced magnetic resonance imaging (MRI) studies. MATERIALS AND METHODS: Between September 2003 and June 2004, 73 patients (49 male and 24 female; mean age, 63 years; age range, 40-84 years) with a single liver nodule (< or =30 mm) were selected to enter into the study. CEUS and MRI studies were performed in all patients on consecutive days. All lesions were histologically confirmed after both imaging studies. CEUS was performed at low MI after i.v. administration of the contrast agent SonoVue. The enhancement pattern related to tumor hypervascularity was analyzed. The Chi-square test was used for statistical analysis. RESULTS: HCCs < or =10 mm (11 cases): On CEUS, 3/11 HCCs were hypervascular, while 8/11 were not visible (sensitivity, 27.3%; specificity, 100%; positive predictive value, 100%; negative predictive value, 55.6%). MRI studies showed a typical pattern in eight HCCs (sensitivity, 72.7%; specificity, 90.0%; positive predictive value, 88.9%; negative predictive value, 75.0%). HCCs 11-30 mm (37 cases): On CEUS, 34/37 (91.9%) HCCs were hypervascular, 2/37 avascular, and 1/37 not visible (sensitivity, 91.9%; specificity, 93.3%; positive predictive value, 97.1%; negative predictive value, 82.4%). MRI studies showed a typical pattern in 35/37 HCCs (sensitivity, 94.6%; specificity, 86.7%; positive predictive value, 94.6%; negative predictive value, 86.7%). The overall concordance between CEUS and MRI results was 75.0%. CONCLUSION: CEUS is a promising technique for the characterization of small HCCs in cirrhotic patients. It could be complementary to conventional sonography in evaluating focal liver lesions larger than 10 mm.

Percutaneous needle aspiration of multiple pyogenic abscesses of the liver: 13-year single-center experience.

OBJECTIVE: The aim of this study was to report 13 years of experience in the management of multiple pyogenic liver abscesses with only percutaneous needle aspiration of the abscess cavities under sonographic guidance. MATERIALS AND METHODS: From December 1991 to October 2004, 39 consecutively registered patients (29 men and 10 women; age range, 37-82 years; mean age, 64 years) with 118 pyogenic liver abscesses were treated with sonographically guided percutaneous needle aspiration at our institution. The number of pyogenic liver abscesses per patient ranged from two to 15 (mean, 3.0). RESULTS: Eighty-seven percutaneous needle aspirations were performed on 39 patients with 118 pyogenic liver abscesses (range, 1-4 aspirations per patient; mean, 2.2 aspirations per patient). Because they were close to another aspirated abscess in the right lobe of the liver, 31 (26.3%) of 118 abscesses were aspirated without removal of the needle from the liver. Thirty-six (92.3%) of 39 patients were treated with a single aspiration of an abscess in a single session. The other three patients needed two aspiration sessions. No patient needed imaging-guided percutaneous catheter drainage or open surgical drainage. Complete reconstitution of liver parenchyma occurred within a maximum of 80 days. No abscesses recurred during the follow-up period, which ranged from 7 to 42 months (mean, 18 months). CONCLUSION: Percutaneous needle aspiration of multiple pyogenic abscesses under sonographic guidance is a safe, effective, and low-cost procedure. In our experience, percutaneous needle aspiration was acceptable to patients. Our data suggest that a trial of percutaneous needle aspiration should always be undertaken before catheter drainage or surgery.

Acute appendicitis mimicking infectious enteritis: diagnostic value of sonography.

OBJECTIVE: To verify the role of sonography in screening of acute appendicitis in patients admitted to an infectious disease unit for suspected acute infectious enteritis. METHODS: One hundred eighty consecutive patients (102 male and 78 female; age range, 5-72 years; mean age, 31 years) admitted for suspected infectious enteritis or typhoid fever were prospectively studied with abdominal sonography within 48 hours after admission. None of the patients had peritoneal irritation. Forty-six patients (25%) had white blood cell counts of more than 10,000/mm3 (range, 10,300-18,000/mm3). The diagnosis of acute appendicitis was made when a detectable appendix with an anteroposterior diameter of greater than 7 mm could be seen on sonography. RESULTS: Eleven (6%) of 180 patients had thickened appendixes (anteroposterior diameter range, 7-14 mm); 2 of them had periappendiceal abscesses. Four (36%) of 11 patients with acute appendicitis had high white blood cell counts. All sonographic diagnoses of acute appendicitis and periappendiceal abscesses were confirmed at surgery. Sonography ruled out acute appendicitis in 169 patients. In all of them, clinical and sonographic follow-up excluded the diagnosis of acute appendicitis. Normal appendixes were shown on sonography in 38 (22%) of 169 cases and were not detectable in 131 (78%) of 169. CONCLUSIONS: Sonography of the appendix is a useful method for early assessment of acute appendicitis in patients thought to have enteritis or typhoid fever.

Percutaneous sonographically guided saline-enhanced radiofrequency ablation of hepatocellular carcinoma.

OBJECTIVE: The purpose of our study was to analyze the efficacy, side effects, and short-term complications of saline-enhanced percutaneous radiofrequency ablation performed under sonographic guidance in a series of cirrhotic patients with hepatocellular carcinoma. SUBJECTS AND METHODS. Between September 2000 and June 2002, 84 patients (55 men and 29 women) with cirrhosis who ranged in age from 48 to 74 years (mean age, 64 years) and who had 95 hepatocellular carcinomas (seven patients had two tumors and two patients had three tumors) were treated with high frequency-induced thermotherapy. The diameters of the tumors ranged from 1.5 to 8.5 cm (mean, 3.6 cm). The efficacy of radiofrequency ablation was evaluated with triphasic contrast-enhanced CT performed 4 weeks after the procedure. RESULTS: Posttreatment CT showed complete necrosis in 73 (77%) of 95 hepatocellular carcinomas in 62 patients. Complete necrosis based on tumor size was seen in 40 (95%) of 42 tumors with diameters equal to or smaller than 3 cm, 32 (71%) of 45 tumors with diameters between 3.1 and 5.0 cm, and one (12%) of eight tumors with diameters larger than 5.0 cm. Twenty-two hepatocellular carcinomas showed incomplete necrosis. None of the patients experienced major complications. Four patients were lost to follow-up. The length of the follow-up period ranged from 4 to 22 months (mean, 10 months). One patient died 8 months after the radiofrequency ablation treatment. All the remaining patients are still alive. During the follow-up period, eight (10%) of 80 patients showed a local recurrence on sonography and CT. CONCLUSION: Our experience suggests that percutaneous radiofrequency ablation of hepatocellular carcinoma with high frequency-induced thermotherapy is safe and effective in the treatment of hepatocellular carcinomas equal to or smaller than 3 cm, fairly effective for hepatocellular carcinomas between 3 and 5 cm, and ineffective for tumors larger than 5 cm.

[Subphrenic abscess during the course of acute brucellosis: diagnosis and treatment with percutaneous sonographically-guided drainage]. / Ascesso sub-frenico in corso di brucellosi acuta: diagnosi e trattamento mediante drenaggio percutaneo eco-guidato.

Abscess formation during the course of acute brucellosis is a rare event. A case of subphrenic abscess, the first to our knowledge, is described. A 49 years-old male patient with fever and a mild increase in ALT and gamma-GT was referred to our Institution. Routine blood exams tested negative and antibodies against Brucella spp. Were also negative. CT examination of abdomen was normal. After 8 days, US examination showed a liquid area under the right diaphragma and US-guided puncture revealed an abscess; pus culture showed the presence of Brucella melitensis. Seven days later theWright reaction became positive. After percutaneous catheter drainage of the abscess, fever disappeared and US follow-up showed reconstitution of subphrenic space. Our study confirm that sonography is a valid method to demonstrate abdominal abscess and that US-guided percutaneous puncture and drainage are useful tools in diagnosis and treatment of fluid abdominal collections