Ilario de Sio | Università della Campania Luigi Vanvitelli (original) (raw)

Papers by Ilario de Sio

Research paper thumbnail of Serum γ-Glutamyltransferase Isoform Complexed to LDL in the Diagnosis of Small Hepatocellular Carcinoma

Research paper thumbnail of HCV infection in symptom-free patients

Research in Virology, 1997

Research paper thumbnail of Decision-making model for a non-invasive diagnosis of compensated liver cirrhosis

The Italian journal of gastroenterology, 1993

Liver biopsy is used as a gold standard in the diagnosis of chronic liver disease. However, this ... more Liver biopsy is used as a gold standard in the diagnosis of chronic liver disease. However, this procedure is not without risk to the patients. This study was aimed to evaluate whether clinical, ultrasonographic, and biochemical variables may discriminate between well-compensated liver cirrhosis and non-cirrhotic chronic liver disease. Logistic regression analysis was used to assess the independent predictive value of each variable. Moreover, the post-test probability of the diagnostic variables was converted into "weights" which positively correlated with the likelihood of diagnosis of liver cirrhosis. We applied a decisional rule based on the diagnostic "weight" of each variable to 412 patients, 278 with well-compensated liver cirrhosis and 134 with non-cirrhotic chronic liver disease, diagnosed by liver biopsy with/without laparoscopy. By adding the diagnostic "weights" of each variable, liver cirrhosis and non-cirrhotic chronic liver disease were co...

Research paper thumbnail of Ultrasound-Guided Fine Needle Biopsy of Pancreatic Masses: Results of a Multicenter Study

American Journal of Gastroenterology, 1998

The aim of this study was to investigate the results of ultrasound-guided fine needle biopsy of p... more The aim of this study was to investigate the results of ultrasound-guided fine needle biopsy of pancreatic masses in a large multicenter series. This study collected the data of 510 patients who had a final diagnosis available and who had undergone ultrasound-guided fine needle biopsy of the pancreas. Retrieval rate, sensitivity, specificity, and overall diagnostic accuracy of the whole series, by three different bioptic procedures (cytology, histology, and cytology plus histology) were evaluated. The reliability of ultrasound-guided fine needle biopsy to allow a correct diagnosis in the different pancreatic pathologies was calculated. Finally, any complications were collected. For cytology, histology, and cytology plus histology, retrieval rate values were: 94%, 96%, and 97%; sensitivity was: 87%, 94%, and 94%, specificity: 100%; and diagnostic accuracy: 91%, 90%, and 95%, respectively. Ultrasound-guided fine-needle biopsy correctly diagnosed all the cases of pancreatic metastases or non-Hodgkin's lymphoma (23 of 510 cases as 5%; in eight of 23 it led to the first diagnosis of the primary tumor) and all the cases of abscesses, 97% of the cases of pseudocysts, 86% of pancreatic adenocarcinomas, 62% of cystic neoplasms, 35% of the cases of chronic pancreatitis (in this case, the bioptic procedures were reviewed), and 33% of neuroendocrine tumors. There were complications in one case of asymptomatic peripancreatic hematoma, three cases of vaso-vagal reactions, and 21 cases of pain. Ultrasound-guided fine needle biopsy of the pancreas is efficacious, without any difference between the various bioptic modalities (with the exception of chronic pancreatitis, in which histology is better). The technique is safe. Moreover, the procedure allows the identification of patients affected by pancreatic tumors other than adenocarcinoma (in our survey 5% of the total); in about one third of these patients it leads to the diagnosis of the primary tumor, thus avoiding inappropriate treatments.

Research paper thumbnail of Diagnosis of chronic liver disease: reproducibility and validation of liver biopsy

The American Journal of Gastroenterology, 2002

raised homocysteine is a point mutation (C to T substitution at nucleotide 677) in the coding reg... more raised homocysteine is a point mutation (C to T substitution at nucleotide 677) in the coding region of the gene for methylenetetrahydrofolate reductase (MTHFR), which is involved in the remethylation pathway of homocysteine. Recently, we performed a study in a population of 64 IBD patients in whom vitamin B 12 and folic acid levels were determined together with the prevalence of the MTHFR genotypes. Among the 11 IBD patients carrying the TT MTHFR genotype, six had hyperhomocysteinemia, of whom five had concurrent folate and/or vitamin B 12 deficiency. The relative risk of developing hyperhomocysteinemia was 5.3-fold (95% CI ϭ 2.9-9.6) in IBD patients with the TT MTHFR genotype associated with folate and/or vitamin B 12 deficiency, in comparison to individuals with CC or CT MTHFR genotypes and adequate levels of folate and/or vitamin B 12. Furthermore, in patients' homozygotic for the C677T MTHFR gene mutation there is an increased folate requirement to mantain plasma homocysteine within normal levels (5). Thus, the IBD patients with this genetic background are at increased risk to develop hyperhomocysteinemia and may need vitamin B 12 and folate supplementation. In conclusion, we suggest that determination of both the MTHFR genotype and vitamin status may predict the risk of developing hyperhomocysteinemia in IBD patients.

Research paper thumbnail of Liver failure in an obese middle-aged woman after biliointestinal bypass

World Journal of Clinical Cases, 2013

Cotticelli G and de Sio I made substantial contributions to the conception and design of the stud... more Cotticelli G and de Sio I made substantial contributions to the conception and design of the study; Funaro A, Sgambato D, Del Prete A, de Sio C and Romano L were involved in the acquisition, analysis and interpretation of data; Federico A, Gravina A and Miranda A were involved in drafting the manuscript and critically revising it for important intellectual content; Loguercio C and Romano M approved the final version for publication.

Research paper thumbnail of CASE REPORT: Occurrence of HCC in Asymptomatic HCV-Related Chronic Hepatitis

Digestive Diseases and Sciences, 2002

Hepatocellular carcinoma (HCC) is one of the most feared complications of liver cirrhosis regardl... more Hepatocellular carcinoma (HCC) is one of the most feared complications of liver cirrhosis regardless of its etiology. The incidence rate of HCC in Italy is estimated at around 3–5% per year (1). The literature, however, contains rare reports of HCC in noncirrhotic liver (2–3). Experimental evidence in the literature has implicated the hepatitis C virus as a possible independent risk

Research paper thumbnail of Survival of cirrhotic patients with early hepatocellular carcinoma treated by percutaneous ethanol injection or liver transplantation

Liver Transplantation, 2004

For "early" hepatocellular carcinoma (HCC), surgery, orthotopic liver transplantation (OLT) and p... more For "early" hepatocellular carcinoma (HCC), surgery, orthotopic liver transplantation (OLT) and percutaneous ethanol injection (PEI) improve the natural history of the disease. We performed a retrospective study to evaluate the outcome of patients with cirrhosis and early HCC treated by PEI (n ‫؍‬ 417) or OLT (n ‫؍‬ 172). Overall, 589 patients with cirrhosis were studied. The proportion of patients in Child-Turcotte-Pugh (CTP) classes A, B, and C was 52.5%, 33.6%, and 13.9%, respectively. Most patients (78.9%) had solitary HCC. Overall 5-year and 10-year cumulative survival rates were 36.1% and 15.5% after PEI, and 66.3% and 49.1% after OLT, respectively (P < .0001). Overall 5-year and 10-year cumulative tumor-free survival rates were 25.3% and 18.0% after PEI, and 84.6% and 82.2% after OLT, respectively (P < .0001). When patients were sorted according to the severity of cirrhosis, mean survival times in PEI and OLT patients were 67 and 80 months in CTP class A (P ‫؍‬ .05), 38 and 90 months in class B (P < .0001), and 31 and 95 months in class C (P ‫؍‬ .0004). Similarly, mean tumorfree survival times in the 2 series of patients were 49 and 98 months in CTP class A (P < .0001), 39 and 121 months in class B (P < .0001), and 35 and 139 months in class C (P < .0001). In conclusion, this study challenges the therapeutic efficacy of PEI for patients with cirrhosis and early HCC, when compared to OLT: the proportion of both long-term survivors and tumor-free survivors was increased by OLT over PEI. The benefit of OLT extends to all patients, regardless of the degree of liver impairment.

Research paper thumbnail of 254 SINGLE HEPATOCELLULAR CARCINOMA SMALLER THAN 2 cm: ARE PERCUTANEOUS ETHANOL INJECTION AND RADIOFREQUENCY ABLATION EQUALLY EFFECTIVE?

Journal of Hepatology, 2013

ABSTRACT The impact of radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) on ... more ABSTRACT The impact of radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) on survival in patients with small hepatocellular carcinoma (HCC) is unclear. We compared their efficacy in cirrhotics with single HCC ≤2 cm. Two hundred forty-four cirrhotics with single HCC ≤2 cm treated with PEI (108 cases) or RFA (136 cases) were enrolled in the study. Eighty-one patients in each group were selected for propensity score matching analysis. The five-year survival was not significantly different (64.7% in PEI and 72.9% in RFA group) but the 5-year recurrence (73.3% in PEI and 49% in RFA group, p=0.023) and local tumor progression (49% in PEI and 30.1% in RFA group, p=0.018) were higher in the PEI group. PEI and RFA are equally effective in treating HCCs smaller than 2 cm in terms of 5-year survival, despite higher cumulative and local recurrence rates, in patients treated with PEI. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Research paper thumbnail of 671 Clinical Features of Non Alcoholic Steatohepatitis (Nash)-Related Hepatocellular Carcinoma (HCC) in Italy: A Multicenter Prospective Survey

Journal of Hepatology, 2013

Research paper thumbnail of US-guided fine-needle biopsy of early HCC: Multicenter Italian study

Journal of Hepatology, 2003

Research paper thumbnail of Ultrasound-guide biopsy for the diagnosis of hepatocellular carcinoma — a study base on 420 patients

Journal of Hepatology, 1997

Huang et al. (1) reported their experience in the ultrasound-guided biopsy of hepatocellular carc... more Huang et al. (1) reported their experience in the ultrasound-guided biopsy of hepatocellular carcinoma (HCC) using very large cutting needles (with an outer diameter of 1.8 or 2.1 mm). In their study the sensitivity of the procedure was 86% (with 14% false negatives), with neoplastic seeding occurring in the chest wall in nine cases (2%) and post-biopsy internal bleeding in five cases (1.2%). Between January 1987 and January 1996, we performed 471 ultrasound-guided biopsies of focal liver lesions in 417 patients with liver cirrhosis (LC), using fine needles; in 336 cases we used an aspiration biopsy needle (AB) with an outer diameter of 0.7 mm; in 135 cases we used a cutting biopsy needle (CB) with an outer diameter of 0.8 mm, and in 58 cases both types of needle (AB+CB). The data obtained in terms of sensitivity @ENS), specificity (SPEC), overall diagnostic accuracy (ODA) and complications (COMPL) are shown in Table 1. Our data confirm, as previously reported (2-6), the high diagnostic accuracy of ultrasound-guided fine-needle biopsy in the diagnosis of HCC in LC. Sensitivity and overall diagnostic accuracy were higher when we used CB needles compared with AB needles; the use of double biopsy (AB+CB needles) in our series did not increase the sensitivity and the overall diagnostic accuracy compared with the CB needle. We did not find any differences in specificity and complications between the three groups, nor was needle-tract seeding observed in any of the patients. We agree with Huang et al. that fine needle biopsy may not be able to discriminate a well-differentiated HCC from an adenomatous hyperplastic nodule. However, cytology and/or microhistology samples taken from tumoral and non-tumoral areas have been reported to allow a diagnosis of well-differentiated HCC in nearly 100% of cases (7).

Research paper thumbnail of Predictive factors of survival and intrahepatic recurrence of hepatocellular carcinoma in cirrhosis after percutaneous ethanol injection: analysis of 71 patients

Journal of Hepatology, 1997

Background/Aims: This study was undertaken to determine the factors predicting survival and intra... more Background/Aims: This study was undertaken to determine the factors predicting survival and intrahepatic recurrence in hepatocellular carcinoma patients treated with percutaneous ethanol injection. Methods: Seventy-one patients with cirrhosis and hepatocelhdar carcinoma underwent percutaneous ethanol injection (54 males/l7 females; median age 66 years; Child A 54/R 17). Fifty-two patients had a single nodule 15 cm and 19 had multiple nodules, up to three, each one ~4 cm. Follow-up ranged from 2-63 months (median 26). Results: Overall survival rates were 89%, 54% and 24% and new lesions recurrence rates 32%, 73% and 81% at 1, 3 and 5 years, respectively. At univariate analysis, monofocal tumor (p<O.O5), absence of ascites (p<O.O5), complete tumor necrosis at CT-scan or MRI (p<O.Ol), post-treatment a-fetoprotein 110 ng/ml (pCO.05) and Child A class in patients with a single nodule Q~0.05) were associated with higher survival. Presence of tumor capsule at imaging (p<O.O5), complete tumor necrosis at CT-scan or MRI (pCO.01) and post-treatment a-fetoprotein ~10 N RECENT years, percutaneous ethanol injection I (PEI) has been widely used in the treatment of patients with hepatocellular carcinoma (HCC) in liver cirrhosis (LC). Ten years after the first report from Livraghi et al. (l), a number of studies on large series of patients has shown that PEI is a valuable treatment of HCC in patients with cirrhosis; 5-year survival rates comparable to those of patients who had undergone resection were reported (2-7). In recent years, with the increased use of routine ultra

Research paper thumbnail of Natural history of focal nodular hyperplasia of the liver: An ultrasound study

Journal of Clinical Ultrasound, 1996

Sixteen cases of focal nodular hyperplasia (FNH) of the liver were followed by ultrasound (US) fo... more Sixteen cases of focal nodular hyperplasia (FNH) of the liver were followed by ultrasound (US) for a mean of 33 months (range 6-81). In 69% of the cases, the diagnosis was incidental. On US the lesions were single in 75% of the cases, localized in the right lobe in 75%, and subcapsular in 50%. No specific US-pattern could be identified. A central scar was found in 19% of the patients. At the end of the follow-up, the size was reduced in 7/16 cases, and in 1/16 the lesion disappeared. The spontaneous reduction of nodules in FNH must be considered in the management of this pseudotumor.

Research paper thumbnail of Which Clinical and Sonographic Parameters May Be Useful to Discriminate NASH from Steatosis?

Journal of Clinical Gastroenterology, 2011

Background: The natural history of nonalcoholic steatohepatitis (NASH) includes the passage throu... more Background: The natural history of nonalcoholic steatohepatitis (NASH) includes the passage through steatosis. Goal: To retrospectively evaluate the usefulness of sonographic parameters compared to histological diagnosis when differentiating steatosis from NASH. Study: This retrospective study reviewed records of patients with steatosis from databases of our Departments, selecting only those who had been diagnosed by sonography and liver biopsy [64 males (63.82%); 30 females (36.18%)].

Research paper thumbnail of Biopsy diagnosis of hepatocellular carcinoma

Research paper thumbnail of Tumor dissemination after radiofrequency ablation of hepatocellular carcinoma

Hepatology, 2003

The high incidence of tumor seeding along the needle tract, reported by Llovet et al., 1 has not ... more The high incidence of tumor seeding along the needle tract, reported by Llovet et al., 1 has not been reported as a complication of radiofrequency (RF) ablation of hepatocellular carcinoma (HCC) with the cooled needle in studies that date from 1996 and include several hundred patients. 2-7 It was recently reported in preliminary form only for treatment of metastases. 8 The authors did not provide a convincing explanation for the discrepancy between their data and other series. The duration of the follow-up or a lack of accurate ultrasound (US) or computed tomography (CT) monitoring cannot account for the difference, because most studies were published more than 2 years ago and the follow-up is now far longer than that of the Barcelona experience. In our center, we started performing ethanol injection in 1986, laser thermal ablation in 1997, and RF thermal ablation with the cooled needle in 1999. To date, we have used RF in 63 patients with a total of 77 nodules; the follow-up averages 16 months (range, 1-42 months). Follow-up is performed with US every 3 months and spiral CT every 6 months. Among various minor and major complications including 1 death, we never saw tumor seeding along the needle tract. The absence of this complication in our and other experiences, in contrast with the Barcelona results, is probably due to the avoidance of direct puncture of subcapsular tumors, a criterion adopted by us and by other centers. Subcapsular HCC were reported previously to give a high incidence of complications at echoguided biopsy, 9 mainly hemorrhage and hemoperitoneum, and these complications were related to the size of the needle. Some cases of seeding were also reported after fine needle biopsy 10,11 and ethanol injection 12 of subcapsular HCC. Therefore, standard practice is to avoid their puncture, particularly when the needle cannot be introduced through a layer of nontumoral liver tissue. In fact, in the 4 HCC cases of the Barcelona group that showed seeding after the procedure, the authors state that it was not possible to perform thermocoagulation when retiring the needle, a procedure that is mandatory for avoiding neoplastic seeding. We are surprised at the high percentage of subcapsular HCC treated in the series of Llovet et al. (11 out of 32 patients!), considering that these tumors are the most favorable for resection. The conclusion that we draw from this study is that puncture of subcapsular HCC (and not only for RF ablation, which utilizes large-caliber needles) entails a high risk of hemoperitoneum, may facilitate neoplastic dissemination outside the liver capsule, and should be avoided. We agree that RF ablation should be considered an experimental procedure until further studies ascertain whether it is cost effective in comparison with ethanol injection or other local-regional treatments.

Research paper thumbnail of Massive gastric ulceration after transarterial chemoembolization for hepatocellular carcinoma

Gastrointestinal Endoscopy, 2006

1. Gastrointest Endosc. 2006 Apr;63(4):718-20. Massive gastric ulceration after transarterial che... more 1. Gastrointest Endosc. 2006 Apr;63(4):718-20. Massive gastric ulceration after transarterial chemoembolization for hepatocellular carcinoma. Morante A, Romano M, Cuomo A, de Sio I, Cozzolino A, Mucherino C, Salerno R, Blanco Cdel V, Romano M. ...

Research paper thumbnail of Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: A randomized controlled trial

Free Radical Biology and Medicine, 2012

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyl... more The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with

Research paper thumbnail of Excellent prognosis and prevalence of HCV infection of primary hepatic and splenic non-Hodgkin’s lymphoma

European Journal of Haematology, 2008

Primary Hepatic (PHL) and Primary Splenic (PSL) non-Hodgkin&amp;amp;amp;amp;amp;amp;amp;amp;a... more Primary Hepatic (PHL) and Primary Splenic (PSL) non-Hodgkin&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Lymphoma are rare entities. Small series of PHL and PSL have been reported, suggesting a non-fortuitous association with Hepatitis C Virus (HCV) infection. The prognosis is believed to be dismal, with early recurrence and short survival. We retrospectively reviewed all PHL and PSL patients diagnosed at our institution between 1990 and 2005. Twenty-five adult patients were identified, six with PHL and 19 with PSL. Twenty-four patients had a B-cell lymphoma, defined as Diffuse Large B-cell lymphoma in 18. The prevalence of HCV infection was 68% among PSL and 66% among PHL. Combination chemotherapy was the mainstay of treatment for PHL and PSL; all but one patient with PSL underwent splenectomy before chemotherapy. Complete remission was achieved in all the cases after frontline therapy; only four patients relapsed but responded to additional chemotherapy courses. Most patients presented with aggressive histological subtypes; 92% were alive at a median follow up of 79 months. HCV infection did not appear to influence the results of therapy. Our study confirms the rarity of PHL and PSL, shows a high prevalence of HCV infection, and demonstrates that the outcome of patients with PHL and PSL may be favourable.

Research paper thumbnail of Serum γ-Glutamyltransferase Isoform Complexed to LDL in the Diagnosis of Small Hepatocellular Carcinoma

Research paper thumbnail of HCV infection in symptom-free patients

Research in Virology, 1997

Research paper thumbnail of Decision-making model for a non-invasive diagnosis of compensated liver cirrhosis

The Italian journal of gastroenterology, 1993

Liver biopsy is used as a gold standard in the diagnosis of chronic liver disease. However, this ... more Liver biopsy is used as a gold standard in the diagnosis of chronic liver disease. However, this procedure is not without risk to the patients. This study was aimed to evaluate whether clinical, ultrasonographic, and biochemical variables may discriminate between well-compensated liver cirrhosis and non-cirrhotic chronic liver disease. Logistic regression analysis was used to assess the independent predictive value of each variable. Moreover, the post-test probability of the diagnostic variables was converted into "weights" which positively correlated with the likelihood of diagnosis of liver cirrhosis. We applied a decisional rule based on the diagnostic "weight" of each variable to 412 patients, 278 with well-compensated liver cirrhosis and 134 with non-cirrhotic chronic liver disease, diagnosed by liver biopsy with/without laparoscopy. By adding the diagnostic "weights" of each variable, liver cirrhosis and non-cirrhotic chronic liver disease were co...

Research paper thumbnail of Ultrasound-Guided Fine Needle Biopsy of Pancreatic Masses: Results of a Multicenter Study

American Journal of Gastroenterology, 1998

The aim of this study was to investigate the results of ultrasound-guided fine needle biopsy of p... more The aim of this study was to investigate the results of ultrasound-guided fine needle biopsy of pancreatic masses in a large multicenter series. This study collected the data of 510 patients who had a final diagnosis available and who had undergone ultrasound-guided fine needle biopsy of the pancreas. Retrieval rate, sensitivity, specificity, and overall diagnostic accuracy of the whole series, by three different bioptic procedures (cytology, histology, and cytology plus histology) were evaluated. The reliability of ultrasound-guided fine needle biopsy to allow a correct diagnosis in the different pancreatic pathologies was calculated. Finally, any complications were collected. For cytology, histology, and cytology plus histology, retrieval rate values were: 94%, 96%, and 97%; sensitivity was: 87%, 94%, and 94%, specificity: 100%; and diagnostic accuracy: 91%, 90%, and 95%, respectively. Ultrasound-guided fine-needle biopsy correctly diagnosed all the cases of pancreatic metastases or non-Hodgkin&#39;s lymphoma (23 of 510 cases as 5%; in eight of 23 it led to the first diagnosis of the primary tumor) and all the cases of abscesses, 97% of the cases of pseudocysts, 86% of pancreatic adenocarcinomas, 62% of cystic neoplasms, 35% of the cases of chronic pancreatitis (in this case, the bioptic procedures were reviewed), and 33% of neuroendocrine tumors. There were complications in one case of asymptomatic peripancreatic hematoma, three cases of vaso-vagal reactions, and 21 cases of pain. Ultrasound-guided fine needle biopsy of the pancreas is efficacious, without any difference between the various bioptic modalities (with the exception of chronic pancreatitis, in which histology is better). The technique is safe. Moreover, the procedure allows the identification of patients affected by pancreatic tumors other than adenocarcinoma (in our survey 5% of the total); in about one third of these patients it leads to the diagnosis of the primary tumor, thus avoiding inappropriate treatments.

Research paper thumbnail of Diagnosis of chronic liver disease: reproducibility and validation of liver biopsy

The American Journal of Gastroenterology, 2002

raised homocysteine is a point mutation (C to T substitution at nucleotide 677) in the coding reg... more raised homocysteine is a point mutation (C to T substitution at nucleotide 677) in the coding region of the gene for methylenetetrahydrofolate reductase (MTHFR), which is involved in the remethylation pathway of homocysteine. Recently, we performed a study in a population of 64 IBD patients in whom vitamin B 12 and folic acid levels were determined together with the prevalence of the MTHFR genotypes. Among the 11 IBD patients carrying the TT MTHFR genotype, six had hyperhomocysteinemia, of whom five had concurrent folate and/or vitamin B 12 deficiency. The relative risk of developing hyperhomocysteinemia was 5.3-fold (95% CI ϭ 2.9-9.6) in IBD patients with the TT MTHFR genotype associated with folate and/or vitamin B 12 deficiency, in comparison to individuals with CC or CT MTHFR genotypes and adequate levels of folate and/or vitamin B 12. Furthermore, in patients' homozygotic for the C677T MTHFR gene mutation there is an increased folate requirement to mantain plasma homocysteine within normal levels (5). Thus, the IBD patients with this genetic background are at increased risk to develop hyperhomocysteinemia and may need vitamin B 12 and folate supplementation. In conclusion, we suggest that determination of both the MTHFR genotype and vitamin status may predict the risk of developing hyperhomocysteinemia in IBD patients.

Research paper thumbnail of Liver failure in an obese middle-aged woman after biliointestinal bypass

World Journal of Clinical Cases, 2013

Cotticelli G and de Sio I made substantial contributions to the conception and design of the stud... more Cotticelli G and de Sio I made substantial contributions to the conception and design of the study; Funaro A, Sgambato D, Del Prete A, de Sio C and Romano L were involved in the acquisition, analysis and interpretation of data; Federico A, Gravina A and Miranda A were involved in drafting the manuscript and critically revising it for important intellectual content; Loguercio C and Romano M approved the final version for publication.

Research paper thumbnail of CASE REPORT: Occurrence of HCC in Asymptomatic HCV-Related Chronic Hepatitis

Digestive Diseases and Sciences, 2002

Hepatocellular carcinoma (HCC) is one of the most feared complications of liver cirrhosis regardl... more Hepatocellular carcinoma (HCC) is one of the most feared complications of liver cirrhosis regardless of its etiology. The incidence rate of HCC in Italy is estimated at around 3–5% per year (1). The literature, however, contains rare reports of HCC in noncirrhotic liver (2–3). Experimental evidence in the literature has implicated the hepatitis C virus as a possible independent risk

Research paper thumbnail of Survival of cirrhotic patients with early hepatocellular carcinoma treated by percutaneous ethanol injection or liver transplantation

Liver Transplantation, 2004

For "early" hepatocellular carcinoma (HCC), surgery, orthotopic liver transplantation (OLT) and p... more For "early" hepatocellular carcinoma (HCC), surgery, orthotopic liver transplantation (OLT) and percutaneous ethanol injection (PEI) improve the natural history of the disease. We performed a retrospective study to evaluate the outcome of patients with cirrhosis and early HCC treated by PEI (n ‫؍‬ 417) or OLT (n ‫؍‬ 172). Overall, 589 patients with cirrhosis were studied. The proportion of patients in Child-Turcotte-Pugh (CTP) classes A, B, and C was 52.5%, 33.6%, and 13.9%, respectively. Most patients (78.9%) had solitary HCC. Overall 5-year and 10-year cumulative survival rates were 36.1% and 15.5% after PEI, and 66.3% and 49.1% after OLT, respectively (P < .0001). Overall 5-year and 10-year cumulative tumor-free survival rates were 25.3% and 18.0% after PEI, and 84.6% and 82.2% after OLT, respectively (P < .0001). When patients were sorted according to the severity of cirrhosis, mean survival times in PEI and OLT patients were 67 and 80 months in CTP class A (P ‫؍‬ .05), 38 and 90 months in class B (P < .0001), and 31 and 95 months in class C (P ‫؍‬ .0004). Similarly, mean tumorfree survival times in the 2 series of patients were 49 and 98 months in CTP class A (P < .0001), 39 and 121 months in class B (P < .0001), and 35 and 139 months in class C (P < .0001). In conclusion, this study challenges the therapeutic efficacy of PEI for patients with cirrhosis and early HCC, when compared to OLT: the proportion of both long-term survivors and tumor-free survivors was increased by OLT over PEI. The benefit of OLT extends to all patients, regardless of the degree of liver impairment.

Research paper thumbnail of 254 SINGLE HEPATOCELLULAR CARCINOMA SMALLER THAN 2 cm: ARE PERCUTANEOUS ETHANOL INJECTION AND RADIOFREQUENCY ABLATION EQUALLY EFFECTIVE?

Journal of Hepatology, 2013

ABSTRACT The impact of radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) on ... more ABSTRACT The impact of radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) on survival in patients with small hepatocellular carcinoma (HCC) is unclear. We compared their efficacy in cirrhotics with single HCC ≤2 cm. Two hundred forty-four cirrhotics with single HCC ≤2 cm treated with PEI (108 cases) or RFA (136 cases) were enrolled in the study. Eighty-one patients in each group were selected for propensity score matching analysis. The five-year survival was not significantly different (64.7% in PEI and 72.9% in RFA group) but the 5-year recurrence (73.3% in PEI and 49% in RFA group, p=0.023) and local tumor progression (49% in PEI and 30.1% in RFA group, p=0.018) were higher in the PEI group. PEI and RFA are equally effective in treating HCCs smaller than 2 cm in terms of 5-year survival, despite higher cumulative and local recurrence rates, in patients treated with PEI. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Research paper thumbnail of 671 Clinical Features of Non Alcoholic Steatohepatitis (Nash)-Related Hepatocellular Carcinoma (HCC) in Italy: A Multicenter Prospective Survey

Journal of Hepatology, 2013

Research paper thumbnail of US-guided fine-needle biopsy of early HCC: Multicenter Italian study

Journal of Hepatology, 2003

Research paper thumbnail of Ultrasound-guide biopsy for the diagnosis of hepatocellular carcinoma — a study base on 420 patients

Journal of Hepatology, 1997

Huang et al. (1) reported their experience in the ultrasound-guided biopsy of hepatocellular carc... more Huang et al. (1) reported their experience in the ultrasound-guided biopsy of hepatocellular carcinoma (HCC) using very large cutting needles (with an outer diameter of 1.8 or 2.1 mm). In their study the sensitivity of the procedure was 86% (with 14% false negatives), with neoplastic seeding occurring in the chest wall in nine cases (2%) and post-biopsy internal bleeding in five cases (1.2%). Between January 1987 and January 1996, we performed 471 ultrasound-guided biopsies of focal liver lesions in 417 patients with liver cirrhosis (LC), using fine needles; in 336 cases we used an aspiration biopsy needle (AB) with an outer diameter of 0.7 mm; in 135 cases we used a cutting biopsy needle (CB) with an outer diameter of 0.8 mm, and in 58 cases both types of needle (AB+CB). The data obtained in terms of sensitivity @ENS), specificity (SPEC), overall diagnostic accuracy (ODA) and complications (COMPL) are shown in Table 1. Our data confirm, as previously reported (2-6), the high diagnostic accuracy of ultrasound-guided fine-needle biopsy in the diagnosis of HCC in LC. Sensitivity and overall diagnostic accuracy were higher when we used CB needles compared with AB needles; the use of double biopsy (AB+CB needles) in our series did not increase the sensitivity and the overall diagnostic accuracy compared with the CB needle. We did not find any differences in specificity and complications between the three groups, nor was needle-tract seeding observed in any of the patients. We agree with Huang et al. that fine needle biopsy may not be able to discriminate a well-differentiated HCC from an adenomatous hyperplastic nodule. However, cytology and/or microhistology samples taken from tumoral and non-tumoral areas have been reported to allow a diagnosis of well-differentiated HCC in nearly 100% of cases (7).

Research paper thumbnail of Predictive factors of survival and intrahepatic recurrence of hepatocellular carcinoma in cirrhosis after percutaneous ethanol injection: analysis of 71 patients

Journal of Hepatology, 1997

Background/Aims: This study was undertaken to determine the factors predicting survival and intra... more Background/Aims: This study was undertaken to determine the factors predicting survival and intrahepatic recurrence in hepatocellular carcinoma patients treated with percutaneous ethanol injection. Methods: Seventy-one patients with cirrhosis and hepatocelhdar carcinoma underwent percutaneous ethanol injection (54 males/l7 females; median age 66 years; Child A 54/R 17). Fifty-two patients had a single nodule 15 cm and 19 had multiple nodules, up to three, each one ~4 cm. Follow-up ranged from 2-63 months (median 26). Results: Overall survival rates were 89%, 54% and 24% and new lesions recurrence rates 32%, 73% and 81% at 1, 3 and 5 years, respectively. At univariate analysis, monofocal tumor (p<O.O5), absence of ascites (p<O.O5), complete tumor necrosis at CT-scan or MRI (p<O.Ol), post-treatment a-fetoprotein 110 ng/ml (pCO.05) and Child A class in patients with a single nodule Q~0.05) were associated with higher survival. Presence of tumor capsule at imaging (p<O.O5), complete tumor necrosis at CT-scan or MRI (pCO.01) and post-treatment a-fetoprotein ~10 N RECENT years, percutaneous ethanol injection I (PEI) has been widely used in the treatment of patients with hepatocellular carcinoma (HCC) in liver cirrhosis (LC). Ten years after the first report from Livraghi et al. (l), a number of studies on large series of patients has shown that PEI is a valuable treatment of HCC in patients with cirrhosis; 5-year survival rates comparable to those of patients who had undergone resection were reported (2-7). In recent years, with the increased use of routine ultra

Research paper thumbnail of Natural history of focal nodular hyperplasia of the liver: An ultrasound study

Journal of Clinical Ultrasound, 1996

Sixteen cases of focal nodular hyperplasia (FNH) of the liver were followed by ultrasound (US) fo... more Sixteen cases of focal nodular hyperplasia (FNH) of the liver were followed by ultrasound (US) for a mean of 33 months (range 6-81). In 69% of the cases, the diagnosis was incidental. On US the lesions were single in 75% of the cases, localized in the right lobe in 75%, and subcapsular in 50%. No specific US-pattern could be identified. A central scar was found in 19% of the patients. At the end of the follow-up, the size was reduced in 7/16 cases, and in 1/16 the lesion disappeared. The spontaneous reduction of nodules in FNH must be considered in the management of this pseudotumor.

Research paper thumbnail of Which Clinical and Sonographic Parameters May Be Useful to Discriminate NASH from Steatosis?

Journal of Clinical Gastroenterology, 2011

Background: The natural history of nonalcoholic steatohepatitis (NASH) includes the passage throu... more Background: The natural history of nonalcoholic steatohepatitis (NASH) includes the passage through steatosis. Goal: To retrospectively evaluate the usefulness of sonographic parameters compared to histological diagnosis when differentiating steatosis from NASH. Study: This retrospective study reviewed records of patients with steatosis from databases of our Departments, selecting only those who had been diagnosed by sonography and liver biopsy [64 males (63.82%); 30 females (36.18%)].

Research paper thumbnail of Biopsy diagnosis of hepatocellular carcinoma

Research paper thumbnail of Tumor dissemination after radiofrequency ablation of hepatocellular carcinoma

Hepatology, 2003

The high incidence of tumor seeding along the needle tract, reported by Llovet et al., 1 has not ... more The high incidence of tumor seeding along the needle tract, reported by Llovet et al., 1 has not been reported as a complication of radiofrequency (RF) ablation of hepatocellular carcinoma (HCC) with the cooled needle in studies that date from 1996 and include several hundred patients. 2-7 It was recently reported in preliminary form only for treatment of metastases. 8 The authors did not provide a convincing explanation for the discrepancy between their data and other series. The duration of the follow-up or a lack of accurate ultrasound (US) or computed tomography (CT) monitoring cannot account for the difference, because most studies were published more than 2 years ago and the follow-up is now far longer than that of the Barcelona experience. In our center, we started performing ethanol injection in 1986, laser thermal ablation in 1997, and RF thermal ablation with the cooled needle in 1999. To date, we have used RF in 63 patients with a total of 77 nodules; the follow-up averages 16 months (range, 1-42 months). Follow-up is performed with US every 3 months and spiral CT every 6 months. Among various minor and major complications including 1 death, we never saw tumor seeding along the needle tract. The absence of this complication in our and other experiences, in contrast with the Barcelona results, is probably due to the avoidance of direct puncture of subcapsular tumors, a criterion adopted by us and by other centers. Subcapsular HCC were reported previously to give a high incidence of complications at echoguided biopsy, 9 mainly hemorrhage and hemoperitoneum, and these complications were related to the size of the needle. Some cases of seeding were also reported after fine needle biopsy 10,11 and ethanol injection 12 of subcapsular HCC. Therefore, standard practice is to avoid their puncture, particularly when the needle cannot be introduced through a layer of nontumoral liver tissue. In fact, in the 4 HCC cases of the Barcelona group that showed seeding after the procedure, the authors state that it was not possible to perform thermocoagulation when retiring the needle, a procedure that is mandatory for avoiding neoplastic seeding. We are surprised at the high percentage of subcapsular HCC treated in the series of Llovet et al. (11 out of 32 patients!), considering that these tumors are the most favorable for resection. The conclusion that we draw from this study is that puncture of subcapsular HCC (and not only for RF ablation, which utilizes large-caliber needles) entails a high risk of hemoperitoneum, may facilitate neoplastic dissemination outside the liver capsule, and should be avoided. We agree that RF ablation should be considered an experimental procedure until further studies ascertain whether it is cost effective in comparison with ethanol injection or other local-regional treatments.

Research paper thumbnail of Massive gastric ulceration after transarterial chemoembolization for hepatocellular carcinoma

Gastrointestinal Endoscopy, 2006

1. Gastrointest Endosc. 2006 Apr;63(4):718-20. Massive gastric ulceration after transarterial che... more 1. Gastrointest Endosc. 2006 Apr;63(4):718-20. Massive gastric ulceration after transarterial chemoembolization for hepatocellular carcinoma. Morante A, Romano M, Cuomo A, de Sio I, Cozzolino A, Mucherino C, Salerno R, Blanco Cdel V, Romano M. ...

Research paper thumbnail of Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: A randomized controlled trial

Free Radical Biology and Medicine, 2012

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyl... more The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with

Research paper thumbnail of Excellent prognosis and prevalence of HCV infection of primary hepatic and splenic non-Hodgkin’s lymphoma

European Journal of Haematology, 2008

Primary Hepatic (PHL) and Primary Splenic (PSL) non-Hodgkin&amp;amp;amp;amp;amp;amp;amp;amp;a... more Primary Hepatic (PHL) and Primary Splenic (PSL) non-Hodgkin&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Lymphoma are rare entities. Small series of PHL and PSL have been reported, suggesting a non-fortuitous association with Hepatitis C Virus (HCV) infection. The prognosis is believed to be dismal, with early recurrence and short survival. We retrospectively reviewed all PHL and PSL patients diagnosed at our institution between 1990 and 2005. Twenty-five adult patients were identified, six with PHL and 19 with PSL. Twenty-four patients had a B-cell lymphoma, defined as Diffuse Large B-cell lymphoma in 18. The prevalence of HCV infection was 68% among PSL and 66% among PHL. Combination chemotherapy was the mainstay of treatment for PHL and PSL; all but one patient with PSL underwent splenectomy before chemotherapy. Complete remission was achieved in all the cases after frontline therapy; only four patients relapsed but responded to additional chemotherapy courses. Most patients presented with aggressive histological subtypes; 92% were alive at a median follow up of 79 months. HCV infection did not appear to influence the results of therapy. Our study confirms the rarity of PHL and PSL, shows a high prevalence of HCV infection, and demonstrates that the outcome of patients with PHL and PSL may be favourable.