33 results on '"Simonetti RG"'
Search Results
2. Review: antioxidant supplementation does not reduce gastrointestinal cancer
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Bjelakovic, G, Nikolova, D, Simonetti, RG, and Mariano, Claudia
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Gastrointestinal cancer -- Risk factors ,Gastrointestinal cancer -- Research ,Gastrointestinal cancer -- Care and treatment ,Antioxidants -- Causes of ,Antioxidants -- Care and treatment ,Antioxidants -- Risk factors ,Antioxidants -- Research ,Health - Published
- 2005
3. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis.
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Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C, Bjelakovic, Goran, Nikolova, Dimitrinka, Gluud, Lise Lotte, Simonetti, Rosa G, and Gluud, Christian
- Abstract
Context: Antioxidant supplements are used for prevention of several diseases.Objective: To assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention trials. DATA SOURCES AND TRIAL SELECTION: We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials.Data Extraction: We included 68 randomized trials with 232 606 participants (385 publications).Data Synthesis: When all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.04[corrected]-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality.Conclusions: Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study. [ABSTRACT FROM AUTHOR]- Published
- 2007
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4. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis.
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Bjelakovic G, Nikolova D, Simonetti RG, and Gluud C
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- 2004
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5. Antioxidant supplements for prevention of gastrointestinal cancers.
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Correa P, Fontham E, Bravo LE, Mera R, Czernichow S, Galan P, Hercberg S, Bjelakovic G, Nikolova D, Simonetti RG, Gluud C, Moreno-Reyes R, Boelaert M, and Meuris S
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- 2005
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6. An Unusual Presentation of Zollinger-Ellison Syndrome
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Emanuele Sinagra, Marco Messina, Maria Rosa Rizzuto, C. Linea, Georgios Amvrosiadis, Ambrogio Orlando, Aroldo Rizzo, R. G. Simonetti, Andrea Scalisi, Mario Cottone, L.M. Montalbano, Giovanni Perricone, Stefania Plano, Claudia Romano, Sinagra E, Perricone G, Linea C, Montalbano L, Plano S, Simonetti RG, Orlando A,Romano C ,Amvrosiadis G, Messina M, Scalisi A, Rizzuto MR, Rizzo A, and Cottone M
- Subjects
Positron emission tomography ,Pathology ,medicine.medical_specialty ,Settore MED/09 - Medicina Interna ,Octreotide ,Zollinger-Ellison syndrome ,Published online: January, 2013 ,medicine ,lcsh:RC799-869 ,Gastrin ,Somatostatin receptor ,business.industry ,Gastroenterology ,Zollinger ellison. severe esophagitis ,medicine.disease ,medicine.anatomical_structure ,Octreoscan ,Radionuclide therapy ,Gastric acid ,lcsh:Diseases of the digestive system. Gastroenterology ,Esophageal strictures ,Pancreas ,business ,Esophagitis ,medicine.drug - Abstract
Zollinger-Ellison syndrome is an often progressive, persistent and frequently life-threatening disease, described for the first time as characterized by ulceration of the upper jejunum, hypersecretion of gastric acid and non-beta islet cell tumors of the pancreas; this syndrome is due to the hypersecretion of gastrin. We report a case of Zollinger-Ellison syndrome presenting as severe esophagitis evolving in stenosis, which demonstrates how a delayed diagnosis may induce risk of disease spreading. In this setting new diagnostic approaches, such as somatostatin receptor scanning and positron emission tomography with 68 Ga-labeled octreotide, could be particularly useful, as well as further new therapeutic options, such as molecular targeted treatments and peptide receptor radionuclide therapy, though surgery is currently the only form of curative treatment, and the role of the therapeutic options mentioned needs to be clarified by forthcoming studies
- Published
- 2013
7. Portosystemic shunts versus endoscopic intervention with or without medical treatment for prevention of rebleeding in people with cirrhosis.
- Author
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Simonetti RG, Perricone G, Robbins HL, Battula NR, Weickert MO, Sutton R, and Khan S
- Subjects
- Bias, Cause of Death, Esophageal and Gastric Varices prevention & control, Gastrointestinal Hemorrhage epidemiology, Gastrointestinal Hemorrhage prevention & control, Hepatic Encephalopathy epidemiology, Hepatic Encephalopathy etiology, Humans, Intention to Treat Analysis, Portasystemic Shunt, Surgical adverse effects, Portasystemic Shunt, Transjugular Intrahepatic adverse effects, Randomized Controlled Trials as Topic, Secondary Prevention, Splenorenal Shunt, Surgical adverse effects, Endoscopy methods, Esophageal and Gastric Varices therapy, Gastrointestinal Hemorrhage therapy, Liver Cirrhosis complications, Portasystemic Shunt, Surgical methods
- Abstract
Background: People with liver cirrhosis who have had one episode of variceal bleeding are at risk for repeated episodes of bleeding. Endoscopic intervention and portosystemic shunts are used to prevent further bleeding, but there is no consensus as to which approach is preferable., Objectives: To compare the benefits and harms of shunts (surgical shunts (total shunt (TS), distal splenorenal shunt (DSRS), or transjugular intrahepatic portosystemic shunt (TIPS)) versus endoscopic intervention (endoscopic sclerotherapy or banding, or both) with or without medical treatment (non-selective beta blockers or nitrates, or both) for prevention of variceal rebleeding in people with liver cirrhosis., Search Methods: We searched the CHBG Controlled Trials Register; CENTRAL, in the Cochrane Library; MEDLINE Ovid; Embase Ovid; LILACS (Bireme); Science Citation Index - Expanded (Web of Science); and Conference Proceedings Citation Index - Science (Web of Science); as well as conference proceedings and the references of trials identified until 22 June 2020. We contacted study investigators and industry researchers., Selection Criteria: Randomised clinical trials comparing shunts versus endoscopic interventions with or without medical treatment in people with cirrhosis who had recovered from a variceal haemorrhage., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. When possible, we collected data to allow intention-to-treat analysis. For each outcome, we estimated a meta-analysed estimate of treatment effect across trials (risk ratio for binary outcomes). We used random-effects model meta-analysis as our main analysis and as a means of presenting results. We reported differences in means for continuous outcomes without a meta-analytic estimate due to high variability in their assessment among all trials. We assessed the certainty of evidence using GRADE., Main Results: We identified 27 randomised trials with 1828 participants. Three trials assessed TSs, five assessed DSRSs, and 19 trials assessed TIPSs. The endoscopic intervention was sclerotherapy in 16 trials, band ligation in eight trials, and a combination of band ligation and either sclerotherapy or glue injection in three trials. In eight trials, endoscopy was combined with beta blockers (in one trial plus isosorbide mononitrate). We judged all trials to be at high risk of bias. We assessed the certainty of evidence for all the outcome review results as very low (i.e. the true effects of the results are likely to be substantially different from the results of estimated effects). The very low evidence grading is due to the overall high risk of bias for all trials, and to imprecision and publication bias for some outcomes. Therefore, we are very uncertain whether portosystemic shunts versus endoscopy interventions with or without medical treatment have effects on all-cause mortality (RR 0.99, 95% CI 0.86 to 1.13; 1828 participants; 27 trials), on rebleeding (RR 0.40, 95% CI 0.33 to 0.50; 1769 participants; 26 trials), on mortality due to rebleeding (RR 0.51, 95% CI 0.34 to 0.76; 1779 participants; 26 trials), and on occurrence of hepatic encephalopathy, both acute (RR 1.60, 95% CI 1.33 to 1.92; 1649 participants; 24 trials) and chronic (RR 2.51, 95% CI 1.38 to 4.55; 956 participants; 13 trials). No data were available regarding health-related quality of life. Analysing each modality of portosystemic shunts individually (i.e. TS, DSRS, and TIPS) versus endoscopic interventions with or without medical treatment, we are very uncertain if each type of shunt has effect on all-cause mortality: TS, RR 0.46, 95% CI 0.19 to 1.13; 164 participants; 3 trials; DSRS, RR 0.93, 95% CI 0.65 to 1.33; 352 participants; 4 trials; and TIPS, RR 1.10, 95% CI 0.92 to 1.31; 1312 participants; 19 trial; on rebleeding: TS, RR 0.28, 95% CI 0.14 to 0.56; 127 participants; 2 trials; DSRS, RR 0.26, 95% CI 0.11 to 0.65; 330 participants; 5 trials; and TIPS, RR 0.44, 95% CI 0.36 to 0.55; 1312 participants; 19 trials; on mortality due to rebleeding: TS, RR 0.25, 95% CI 0.06 to 0.96; 164 participants; 3 trials; DSRS, RR 0.31, 95% CI 0.13 to 0.74; 352 participants; 5 trials; and TIPS, RR 0.65, 95% CI 0.40 to 1.04; 1263 participants; 18 trials; on acute hepatic encephalopathy: TS, RR 1.66, 95% CI 0.70 to 3.92; 115 participants; 2 trials; DSRS, RR 1.70, 95% CI 0.94 to 3.08; 287 participants; 4 trials, TIPS, RR 1.61, 95% CI 1.29 to 1.99; 1247 participants; 18 trials; and chronic hepatic encephalopathy: TS, Fisher's exact test P = 0.11; 69 participants; 1 trial; DSRS, RR 4.87, 95% CI 1.46 to 16.23; 170 participants; 2 trials; and TIPS, RR 1.88, 95% CI 0.93 to 3.80; 717 participants; 10 trials. The proportion of participants with shunt occlusion or dysfunction was overall 37% (95% CI 33% to 40%). It was 3% (95% CI 0.8% to 10%) following TS, 7% (95% CI 3% to 13%) following DSRS, and 47.1% (95% CI 43% to 51%) following TIPS. Shunt dysfunction in trials utilising polytetrafluoroethylene-covered stents was 17% (95% CI 11% to 24%). Length of inpatient hospital stay and cost were not comparable across trials. Funding was unclear in 16 trials; 11 trials were funded by government, local hospitals, or universities., Authors' Conclusions: Evidence on whether portosystemic shunts versus endoscopy interventions with or without medical treatment in people with cirrhosis and previous hypertensive portal bleeding have little or no effect on all-cause mortality is very uncertain. Evidence on whether portosystemic shunts may reduce bleeding and mortality due to bleeding while increasing hepatic encephalopathy is also very uncertain. We need properly conducted trials to assess effects of these interventions not only on assessed outcomes, but also on quality of life, costs, and length of hospital stay., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)
- Published
- 2020
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8. Plasma expanders for people with cirrhosis and large ascites treated with abdominal paracentesis.
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Simonetti RG, Perricone G, Nikolova D, Bjelakovic G, and Gluud C
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- Humans, Quality of Life, Randomized Controlled Trials as Topic, Ascites etiology, Ascites therapy, Liver Cirrhosis complications, Paracentesis, Plasma Substitutes therapeutic use
- Abstract
Background: Plasma volume expanders are used in connection to paracentesis in people with cirrhosis to prevent reduction of effective plasma volume, which may trigger deleterious effect on haemodynamic balance, and increase morbidity and mortality. Albumin is considered the standard product against which no plasma expansion or other plasma expanders, e.g. other colloids (polygeline , dextrans, hydroxyethyl starch solutions, fresh frozen plasma), intravenous infusion of ascitic fluid, crystalloids, or mannitol have been compared. However, the benefits and harms of these plasma expanders are not fully clear., Objectives: To assess the benefits and harms of any plasma volume expanders such as albumin, other colloids (polygeline, dextrans, hydroxyethyl starch solutions, fresh frozen plasma), intravenous infusion of ascitic fluid, crystalloids, or mannitol versus no plasma volume expander or versus another plasma volume expander for paracentesis in people with cirrhosis and large ascites., Search Methods: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CNKI, VIP, Wanfang, Science Citation Index Expanded, and Conference Proceedings Citation Index until January 2019. Furthermore, we searched FDA, EMA, WHO (last search January 2019), www.clinicaltrials.gov/, and www.controlled-trials.com/ for ongoing trials., Selection Criteria: Randomised clinical trials, no matter their design or year of publication, publication status, and language, assessing the use of any type of plasma expander versus placebo, no intervention, or a different plasma expander in connection with paracentesis for ascites in people with cirrhosis. We considered quasi-randomised, retrieved with the searches for randomised clinical trials only, for reports on harms., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. We calculated the risk ratio (RR) or mean difference (MD) using the fixed-effect model and the random-effects model meta-analyses, based on the intention-to-treat principle, whenever possible. If the fixed-effect and random-effects models showed different results, then we made our conclusions based on the analysis with the highest P value (the more conservative result). We assessed risks of bias of the individual trials using predefined bias risk domains. We assessed the certainty of the evidence at an outcome level, using GRADE, and constructed 'Summary of Findings' tables for seven of our review outcomes., Main Results: We identified 27 randomised clinical trials for inclusion in this review (24 published as full-text articles and 3 as abstracts). Five of the trials, with 271 participants, assessed plasma expanders (albumin in four trials and ascitic fluid in one trial) versus no plasma expander. The remaining 22 trials, with 1321 participants, assessed one type of plasma expander, i.e. dextran, hydroxyethyl starch, polygeline, intravenous infusion of ascitic fluid, crystalloids, or mannitol versus another type of plasma expander, i.e. albumin in 20 of these trials and polygeline in one trial. Twenty-five trials provided data for quantitative meta-analysis. According to the Child-Pugh classification, most participants were at an intermediate to advanced stage of liver disease in the absence of hepatocellular carcinoma, recent gastrointestinal bleeding, infections, and hepatic encephalopathy. All trials were assessed as at overall high risk of bias. Ten trials seemed not to have been funded by industry; twelve trials were considered unclear about funding; and five trials were considered funded by industry or a for-profit institution.We found no evidence of a difference in effect between plasma expansion versus no plasma expansion on mortality (RR 0.52, 95% CI 0.06 to 4.83; 248 participants; 4 trials; very low certainty); renal impairment (RR 0.32, 95% CI 0.02 to 5.88; 181 participants; 4 trials; very low certainty); other liver-related complications (RR 1.61, 95% CI 0.79 to 3.27; 248 participants; 4 trials; very low certainty); and non-serious adverse events (RR 1.04, 95% CI 0.32 to 3.40; 158 participants; 3 trials; very low certainty). Two of the trials stated that no serious adverse events occurred while the remaining trials did not report on this outcome. No trial reported data on health-related quality of life.We found no evidence of a difference in effect between experimental plasma expanders versus albumin on mortality (RR 1.03, 95% CI 0.82 to 1.30; 1014 participants; 14 trials; very low certainty); serious adverse events (RR 0.89, 95% CI 0.10 to 8.30; 118 participants; 2 trials; very low certainty); renal impairment (RR 1.17, 95% CI 0.71 to 1.91; 1107 participants; 17 trials; very low certainty); other liver-related complications (RR 1.10, 95% CI 0.82 to 1.48; 1083 participants; 16 trials; very low certainty); and non-serious adverse events (RR 1.37, 95% CI 0.66 to 2.85; 977 participants; 14 trials; very low certainty). We found no data on heath-related quality of life and refractory ascites., Authors' Conclusions: Our systematic review and meta-analysis did not find any benefits or harms of plasma expanders versus no plasma expander or of one plasma expander such as polygeline, dextrans, hydroxyethyl starch, intravenous infusion of ascitic fluid, crystalloids, or mannitol versus albumin on primary or secondary outcomes. The data originated from few, small, mostly short-term trials at high risks of systematic errors (bias) and high risks of random errors (play of chance). GRADE assessments concluded that the evidence was of very low certainty. Therefore, we can neither demonstrate or discard any benefit of plasma expansion versus no plasma expansion, and differences between one plasma expander versus another plasma expander.Larger trials at low risks of bias are needed to assess the role of plasma expanders in connection with paracentesis. Such trials should be conducted according to the SPIRIT guidelines and reported according to the CONSORT guidelines.
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- 2019
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9. An unusual cause of acute mesenteric ischaemia.
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Perricone G and Simonetti RG
- Abstract
Competing Interests: Competing interests: None declared.
- Published
- 2019
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10. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.
- Author
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Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, and Gluud C
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- Female, Humans, Male, Antioxidants administration & dosage, Mortality, Primary Prevention methods, Secondary Prevention methods
- Published
- 2015
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11. Vitamin D supplementation for prevention of mortality in adults.
- Author
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Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, and Gluud C
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- Adolescent, Adult, Aged, Aged, 80 and over, Cause of Death, Dietary Supplements, Female, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic, Young Adult, Calcitriol therapeutic use, Cholecalciferol therapeutic use, Ergocalciferols therapeutic use, Hydroxycholecalciferols therapeutic use, Mortality, Vitamins therapeutic use
- Abstract
Background: Available evidence on the effects of vitamin D on mortality has been inconclusive. In a recent systematic review, we found evidence that vitamin D3 may decrease mortality in mostly elderly women. The present systematic review updates and reassesses the benefits and harms of vitamin D supplementation used in primary and secondary prophylaxis of mortality., Objectives: To assess the beneficial and harmful effects of vitamin D supplementation for prevention of mortality in healthy adults and adults in a stable phase of disease., Search Methods: We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index-Expanded and Conference Proceedings Citation Index-Science (all up to February 2012). We checked references of included trials and pharmaceutical companies for unidentified relevant trials., Selection Criteria: Randomised trials that compared any type of vitamin D in any dose with any duration and route of administration versus placebo or no intervention in adult participants. Participants could have been recruited from the general population or from patients diagnosed with a disease in a stable phase. Vitamin D could have been administered as supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol)) or as an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol))., Data Collection and Analysis: Six review authors extracted data independently. Random-effects and fixed-effect meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RRs). To account for trials with zero events, we performed meta-analyses of dichotomous data using risk differences (RDs) and empirical continuity corrections. We used published data and data obtained by contacting trial authors.To minimise the risk of systematic error, we assessed the risk of bias of the included trials. Trial sequential analyses controlled the risk of random errors possibly caused by cumulative meta-analyses., Main Results: We identified 159 randomised clinical trials. Ninety-four trials reported no mortality, and nine trials reported mortality but did not report in which intervention group the mortality occurred. Accordingly, 56 randomised trials with 95,286 participants provided usable data on mortality. The age of participants ranged from 18 to 107 years. Most trials included women older than 70 years. The mean proportion of women was 77%. Forty-eight of the trials randomly assigned 94,491 healthy participants. Of these, four trials included healthy volunteers, nine trials included postmenopausal women and 35 trials included older people living on their own or in institutional care. The remaining eight trials randomly assigned 795 participants with neurological, cardiovascular, respiratory or rheumatoid diseases. Vitamin D was administered for a weighted mean of 4.4 years. More than half of the trials had a low risk of bias. All trials were conducted in high-income countries. Forty-five trials (80%) reported the baseline vitamin D status of participants based on serum 25-hydroxyvitamin D levels. Participants in 19 trials had vitamin D adequacy (at or above 20 ng/mL). Participants in the remaining 26 trials had vitamin D insufficiency (less than 20 ng/mL).Vitamin D decreased mortality in all 56 trials analysed together (5,920/47,472 (12.5%) vs 6,077/47,814 (12.7%); RR 0.97 (95% confidence interval (CI) 0.94 to 0.99); P = 0.02; I(2) = 0%). More than 8% of participants dropped out. 'Worst-best case' and 'best-worst case' scenario analyses demonstrated that vitamin D could be associated with a dramatic increase or decrease in mortality. When different forms of vitamin D were assessed in separate analyses, only vitamin D3 decreased mortality (4,153/37,817 (11.0%) vs 4,340/38,110 (11.4%); RR 0.94 (95% CI 0.91 to 0.98); P = 0.002; I(2) = 0%; 75,927 participants; 38 trials). Vitamin D2, alfacalcidol and calcitriol did not significantly affect mortality. A subgroup analysis of trials at high risk of bias suggested that vitamin D2 may even increase mortality, but this finding could be due to random errors. Trial sequential analysis supported our finding regarding vitamin D3, with the cumulative Z-score breaking the trial sequential monitoring boundary for benefit, corresponding to 150 people treated over five years to prevent one additional death. We did not observe any statistically significant differences in the effect of vitamin D on mortality in subgroup analyses of trials at low risk of bias compared with trials at high risk of bias; of trials using placebo compared with trials using no intervention in the control group; of trials with no risk of industry bias compared with trials with risk of industry bias; of trials assessing primary prevention compared with trials assessing secondary prevention; of trials including participants with vitamin D level below 20 ng/mL at entry compared with trials including participants with vitamin D levels equal to or greater than 20 ng/mL at entry; of trials including ambulatory participants compared with trials including institutionalised participants; of trials using concomitant calcium supplementation compared with trials without calcium; of trials using a dose below 800 IU per day compared with trials using doses above 800 IU per day; and of trials including only women compared with trials including both sexes or only men. Vitamin D3 statistically significantly decreased cancer mortality (RR 0.88 (95% CI 0.78 to 0.98); P = 0.02; I(2) = 0%; 44,492 participants; 4 trials). Vitamin D3 combined with calcium increased the risk of nephrolithiasis (RR 1.17 (95% CI 1.02 to 1.34); P = 0.02; I(2) = 0%; 42,876 participants; 4 trials). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18 (95% CI 1.17 to 8.68); P = 0.02; I(2) = 17%; 710 participants; 3 trials)., Authors' Conclusions: Vitamin D3 seemed to decrease mortality in elderly people living independently or in institutional care. Vitamin D2, alfacalcidol and calcitriol had no statistically significant beneficial effects on mortality. Vitamin D3 combined with calcium increased nephrolithiasis. Both alfacalcidol and calcitriol increased hypercalcaemia. Because of risks of attrition bias originating from substantial dropout of participants and of outcome reporting bias due to a number of trials not reporting on mortality, as well as a number of other weaknesses in our evidence, further placebo-controlled randomised trials seem warranted.
- Published
- 2014
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12. An unusual presentation of zollinger-ellison syndrome.
- Author
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Sinagra E, Perricone G, Linea C, Montalbano L, Plano S, Simonetti RG, Orlando A, Romano C, Amvrosiadis G, Messina M, Scalisi A, Rizzuto MR, Rizzo AG, and Cottone M
- Abstract
Zollinger-Ellison syndrome is an often progressive, persistent and frequently life-threatening disease, described for the first time as characterized by ulceration of the upper jejunum, hypersecretion of gastric acid and non-beta islet cell tumors of the pancreas; this syndrome is due to the hypersecretion of gastrin. We report a case of Zollinger-Ellison syndrome presenting as severe esophagitis evolving in stenosis, which demonstrates how a delayed diagnosis may induce risk of disease spreading. In this setting new diagnostic approaches, such as somatostatin receptor scanning and positron emission tomography with 68 Ga-labeled octreotide, could be particularly useful, as well as further new therapeutic options, such as molecular targeted treatments and peptide receptor radionuclide therapy, though surgery is currently the only form of curative treatment, and the role of the therapeutic options mentioned needs to be clarified by forthcoming studies.
- Published
- 2013
- Full Text
- View/download PDF
13. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.
- Author
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Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, and Gluud C
- Subjects
- Antioxidants adverse effects, Ascorbic Acid administration & dosage, Ascorbic Acid adverse effects, Female, Health Status, Humans, Male, Randomized Controlled Trials as Topic, Selenium administration & dosage, Selenium adverse effects, Vitamin A administration & dosage, Vitamin A adverse effects, Vitamin E administration & dosage, Vitamin E adverse effects, beta Carotene administration & dosage, beta Carotene adverse effects, Antioxidants administration & dosage, Mortality, Primary Prevention methods, Secondary Prevention methods
- Abstract
Background: Our systematic review has demonstrated that antioxidant supplements may increase mortality. We have now updated this review., Objectives: To assess the beneficial and harmful effects of antioxidant supplements for prevention of mortality in adults., Search Methods: We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science to February 2011. We scanned bibliographies of relevant publications and asked pharmaceutical companies for additional trials., Selection Criteria: We included all primary and secondary prevention randomised clinical trials on antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention., Data Collection and Analysis: Three authors extracted data. Random-effects and fixed-effect model meta-analyses were conducted. Risk of bias was considered in order to minimise the risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors. Random-effects model meta-regression analyses were performed to assess sources of intertrial heterogeneity., Main Results: Seventy-eight randomised trials with 296,707 participants were included. Fifty-six trials including 244,056 participants had low risk of bias. Twenty-six trials included 215,900 healthy participants. Fifty-two trials included 80,807 participants with various diseases in a stable phase. The mean age was 63 years (range 18 to 103 years). The mean proportion of women was 46%. Of the 78 trials, 46 used the parallel-group design, 30 the factorial design, and 2 the cross-over design. All antioxidants were administered orally, either alone or in combination with vitamins, minerals, or other interventions. The duration of supplementation varied from 28 days to 12 years (mean duration 3 years; median duration 2 years). Overall, the antioxidant supplements had no significant effect on mortality in a random-effects model meta-analysis (21,484 dead/183,749 (11.7%) versus 11,479 dead/112,958 (10.2%); 78 trials, relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05) but significantly increased mortality in a fixed-effect model (RR 1.03, 95% CI 1.01 to 1.05). Heterogeneity was low with an I(2)- of 12%. In meta-regression analysis, the risk of bias and type of antioxidant supplement were the only significant predictors of intertrial heterogeneity. Meta-regression analysis did not find a significant difference in the estimated intervention effect in the primary prevention and the secondary prevention trials. In the 56 trials with a low risk of bias, the antioxidant supplements significantly increased mortality (18,833 dead/146,320 (12.9%) versus 10,320 dead/97,736 (10.6%); RR 1.04, 95% CI 1.01 to 1.07). This effect was confirmed by trial sequential analysis. Excluding factorial trials with potential confounding showed that 38 trials with low risk of bias demonstrated a significant increase in mortality (2822 dead/26,903 (10.5%) versus 2473 dead/26,052 (9.5%); RR 1.10, 95% CI 1.05 to 1.15). In trials with low risk of bias, beta-carotene (13,202 dead/96,003 (13.8%) versus 8556 dead/77,003 (11.1%); 26 trials, RR 1.05, 95% CI 1.01 to 1.09) and vitamin E (11,689 dead/97,523 (12.0%) versus 7561 dead/73,721 (10.3%); 46 trials, RR 1.03, 95% CI 1.00 to 1.05) significantly increased mortality, whereas vitamin A (3444 dead/24,596 (14.0%) versus 2249 dead/16,548 (13.6%); 12 trials, RR 1.07, 95% CI 0.97 to 1.18), vitamin C (3637 dead/36,659 (9.9%) versus 2717 dead/29,283 (9.3%); 29 trials, RR 1.02, 95% CI 0.98 to 1.07), and selenium (2670 dead/39,779 (6.7%) versus 1468 dead/22,961 (6.4%); 17 trials, RR 0.97, 95% CI 0.91 to 1.03) did not significantly affect mortality. In univariate meta-regression analysis, the dose of vitamin A was significantly associated with increased mortality (RR 1.0006, 95% CI 1.0002 to 1.001, P = 0.002)., Authors' Conclusions: We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing.
- Published
- 2012
- Full Text
- View/download PDF
14. Vitamin D supplementation for prevention of mortality in adults.
- Author
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Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, and Gluud C
- Subjects
- Adult, Aged, Aged, 80 and over, Cause of Death, Dietary Supplements, Female, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic, Calcitriol therapeutic use, Cholecalciferol therapeutic use, Ergocalciferols therapeutic use, Hydroxycholecalciferols therapeutic use, Mortality, Vitamins therapeutic use
- Abstract
Background: The available evidence on vitamin D and mortality is inconclusive., Objectives: To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults., Search Strategy: We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science (to January 2011). We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials., Selection Criteria: We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention. Vitamin D could have been administered as supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol))., Data Collection and Analysis: Six authors extracted data independently. Random-effects and fixed-effect model meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RR). To account for trials with zero events, meta-analyses of dichotomous data were repeated using risk differences (RD) and empirical continuity corrections. Risk of bias was considered in order to minimise risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors., Main Results: Fifty randomised trials with 94,148 participants provided data for the mortality analyses. Most trials included elderly women (older than 70 years). Vitamin D was administered for a median of two years. More than one half of the trials had a low risk of bias. Overall, vitamin D decreased mortality (RR 0.97, 95% confidence interval (CI) 0.94 to 1.00, I(2) = 0%). When the different forms of vitamin D were assessed separately, only vitamin D(3) decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I(2) = 0%; 74,789 participants, 32 trials) whereas vitamin D(2), alfacalcidol, or calcitriol did not. Trial sequential analysis supported our finding regarding vitamin D(3), corresponding to 161 individuals treated to prevent one additional death. Vitamin D(3) combined with calcium increased the risk of nephrolithiasis (RR 1.17, 95% CI 1.02 to 1.34, I(2) = 0%). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to 8.68, I(2) = 17%). Data on health-related quality of life and health economics were inconclusive., Authors' Conclusions: Vitamin D in the form of vitamin D(3) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care. Vitamin D(2), alfacalcidol, and calcitriol had no statistically significant effect on mortality. Vitamin D(3) combined with calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol significantly increased hypercalcaemia.
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- 2011
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15. Systematic review: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements.
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Bjelakovic G, Nikolova D, Simonetti RG, and Gluud C
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- Adolescent, Adult, Aged, Aged, 80 and over, Ascorbic Acid therapeutic use, Bias, Carotenoids therapeutic use, Drug Therapy, Combination, Female, Gastrointestinal Neoplasms epidemiology, Humans, Male, Middle Aged, Oxidative Stress drug effects, Randomized Controlled Trials as Topic, Selenium therapeutic use, Vitamin E therapeutic use, Young Adult, Antioxidants therapeutic use, Dietary Supplements, Gastrointestinal Neoplasms prevention & control
- Abstract
Background: The evidence on whether antioxidant supplements prevent gastrointestinal cancers is contradictory., Aim: To assess the beneficial and harmful effects of antioxidant supplements in preventing gastrointestinal cancers., Methods: Using the Cochrane Collaboration methodology, we reviewed the randomized trials comparing antioxidant supplements with placebo or no intervention on the occurrence of gastrointestinal cancers. We searched electronic databases and reference lists until October, 2007. Our outcome measures were gastrointestinal cancers, overall mortality and adverse events. Outcomes were reported as relative risks (RR) with 95% confidence intervals (CI) based on random-effects and fixed-effect models meta-analyses., Results: We identified 20 randomized trials (211,818 participants) assessing beta-carotene, vitamin A, vitamin C, vitamin E, and selenium. The trial quality was generally high. The antioxidant supplements were without a significant effect on the occurrence of gastrointestinal cancers (RR 0.94, 95% CI 0.83-1.06, I(2) = 54.0%). The heterogeneity seemed to be explained by bias risk (low-bias risk trials RR 1.04, 95% CI 0.96-1.13 compared to high-bias risk trials RR 0.59, 95% CI 0.43-0.80, test of interaction P < 0.0005) and type of antioxidant supplement (beta-carotene potentially increasing and selenium potentially decreasing cancer risk). Antioxidant supplements had no significant effect on mortality in a random-effects model meta-analysis (RR 1.02, 95% CI 0.97-1.07, I(2) = 53.5%) but significantly increased mortality in a fixed-effect model meta-analysis (RR 1.04, 95% CI 1.02-1.07)., Conclusions: We could not find evidence that the studied antioxidant supplements prevented gastrointestinal cancers. On the contrary, they seem to increase overall mortality.
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- 2008
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16. Antioxidant supplements for preventing gastrointestinal cancers.
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Bjelakovic G, Nikolova D, Simonetti RG, and Gluud C
- Subjects
- Antioxidants adverse effects, Gastrointestinal Neoplasms mortality, Humans, Liver Neoplasms mortality, Pancreatic Neoplasms mortality, Randomized Controlled Trials as Topic, Antioxidants administration & dosage, Dietary Supplements adverse effects, Gastrointestinal Neoplasms prevention & control, Liver Neoplasms prevention & control, Pancreatic Neoplasms prevention & control
- Abstract
Background: Oxidative stress may cause gastrointestinal cancers. The evidence on whether antioxidant supplements are effective in preventing gastrointestinal cancers is contradictory., Objectives: To assess the beneficial and harmful effects of antioxidant supplements in preventing gastrointestinal cancers., Search Strategy: We identified trials through the trials registers of the four Cochrane Review Groups on gastrointestinal diseases, The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2007), MEDLINE, EMBASE, LILACS, SCI-EXPANDED, and The Chinese Biomedical Database from inception to October 2007. We scanned reference lists and contacted pharmaceutical companies., Selection Criteria: Randomised trials comparing antioxidant supplements to placebo/no intervention examining occurrence of gastrointestinal cancers., Data Collection and Analysis: Two authors (GB and DN) independently selected trials for inclusion and extracted data. Outcome measures were gastrointestinal cancers, overall mortality, and adverse effects. Outcomes were reported as relative risks (RR) with 95% confidence interval (CI) based on random-effects and fixed-effect model meta-analysis. Meta-regression assessed the effect of covariates across the trials., Main Results: We identified 20 randomised trials (211,818 participants), assessing beta-carotene (12 trials), vitamin A (4 trials), vitamin C (8 trials), vitamin E (10 trials), and selenium (9 trials). Trials quality was generally high. Heterogeneity was low to moderate. Antioxidant supplements were without significant effects on gastrointestinal cancers (RR 0.94, 95% CI 0.83 to 1.06). However, there was significant heterogeneity (I(2) = 54.0%, P = 0.003). The heterogeneity may have been explained by bias risk (low-bias risk trials RR 1.04, 95% CI 0.96 to 1.13 compared to high-bias risk trials RR 0.59, 95% CI 0.43 to 0.80; test of interaction P < 0.0005), and type of antioxidant supplement (beta-carotene potentially increasing and selenium potentially decreasing cancer risk). The antioxidant supplements had no significant effects on mortality in a random-effects model meta-analysis (RR 1.02, 95% CI 0.97 to 1.07, I(2) = 53.5%), but significantly increased mortality in a fixed-effect model meta-analysis (RR 1.04, 95% CI 1.02 to 1.07). Beta-carotene in combination with vitamin A (RR 1.16, 95% CI 1.09 to 1.23) and vitamin E (RR 1.06, 95% CI 1.02 to 1.11) significantly increased mortality. Increased yellowing of the skin and belching were non-serious adverse effects of beta-carotene. In five trials (four with high risk of bias), selenium seemed to show significant beneficial effect on gastrointestinal cancer occurrence (RR 0.59, 95% CI 0.46 to 0.75, I(2) = 0%)., Authors' Conclusions: We could not find convincing evidence that antioxidant supplements prevent gastrointestinal cancers. On the contrary, antioxidant supplements seem to increase overall mortality. The potential cancer preventive effect of selenium should be tested in adequately conducted randomised trials.
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- 2008
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17. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.
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Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, and Gluud C
- Subjects
- Antioxidants adverse effects, Ascorbic Acid administration & dosage, Ascorbic Acid adverse effects, Humans, Randomized Controlled Trials as Topic, Selenium administration & dosage, Selenium adverse effects, Vitamin A administration & dosage, Vitamin A adverse effects, Vitamin E administration & dosage, Vitamin E adverse effects, beta Carotene administration & dosage, beta Carotene adverse effects, Antioxidants administration & dosage, Health Status, Mortality, Primary Prevention methods
- Abstract
Background: Animal and physiological research as well as observational studies suggest that antioxidant supplements may improve survival., Objectives: To assess the effect of antioxidant supplements on mortality in primary or secondary prevention randomised clinical trials., Search Strategy: We searched The Cochrane Library (Issue 3, 2005), MEDLINE (1966 to October 2005), EMBASE (1985 to October 2005), and the Science Citation Index Expanded (1945 to October 2005). We scanned bibliographies of relevant publications and wrote to pharmaceutical companies for additional trials., Selection Criteria: We included all primary and secondary prevention randomised clinical trials on antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. Included participants were either healthy (primary prevention trials) or had any disease (secondary prevention trials)., Data Collection and Analysis: Three authors extracted data. Trials with adequate randomisation, blinding, and follow-up were classified as having a low risk of bias. Random-effects and fixed-effect meta-analyses were performed. Random-effects meta-regression analyses were performed to assess sources of intertrial heterogeneity., Main Results: Sixty-seven randomised trials with 232,550 participants were included. Forty-seven trials including 180,938 participants had low risk of bias. Twenty-one trials included 164,439 healthy participants. Forty-six trials included 68111 participants with various diseases (gastrointestinal, cardiovascular, neurological, ocular, dermatological, rheumatoid, renal, endocrinological, or unspecified). Overall, the antioxidant supplements had no significant effect on mortality in a random-effects meta-analysis (relative risk [RR] 1.02, 95% confidence interval [CI] 0.99 to 1.06), but significantly increased mortality in a fixed-effect model (RR 1.04, 95% CI 1.02 to 1.06). In meta-regression analysis, the risk of bias and type of antioxidant supplement were the only significant predictors of intertrial heterogeneity. In the trials with a low risk of bias, the antioxidant supplements significantly increased mortality (RR 1.05, 95% CI 1.02 to 1.08). When the different antioxidants were assessed separately, analyses including trials with a low risk of bias and excluding selenium trials found significantly increased mortality by vitamin A (RR 1.16, 95% CI 1.10 to 1.24), beta-carotene (RR 1.07, 95% CI 1.02 to 1.11), and vitamin E (RR 1.04, 95% CI 1.01 to 1.07), but no significant detrimental effect of vitamin C (RR 1.06, 95% CI 0.94 to 1.20). Low-bias risk trials on selenium found no significant effect on mortality (RR 0.91, 95% CI 0.76 to 1.09)., Authors' Conclusions: We found no evidence to support antioxidant supplements for primary or secondary prevention. Vitamin A, beta-carotene, and vitamin E may increase mortality. Future randomised trials could evaluate the potential effects of vitamin C and selenium for primary and secondary prevention. Such trials should be closely monitored for potential harmful effects. Antioxidant supplements need to be considered medicinal products and should undergo sufficient evaluation before marketing.
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- 2008
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18. Meta-analysis: antioxidant supplements for primary and secondary prevention of colorectal adenoma.
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Bjelakovic G, Nagorni A, Nikolova D, Simonetti RG, Bjelakovic M, and Gluud C
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- Adult, Aged, Aged, 80 and over, Colorectal Neoplasms diet therapy, Dietary Supplements, Female, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic, Treatment Outcome, Antioxidants therapeutic use, Colorectal Neoplasms prevention & control
- Abstract
Background: Colorectal cancer may be prevented by reducing the development of adenomatous polyps., Aim: To assess the benefits and harms of antioxidant supplements in preventing colorectal adenoma., Methods: Using the Cochrane Collaboration methodology we reviewed all randomized clinical trials comparing antioxidant supplements with placebo or no intervention. We searched electronic databases and the reference lists until October 2005. Outcome measures were development of colorectal adenoma adverse events. We analysed dichotomous outcomes with fixed- and random-effects model meta-analyses and calculated the relative risk with 95% confidence interval., Results: We identified eight randomized trials (17 620 participants). Neither fixed-effect (relative risk: 0.93, 95% CI: 0.81-1.1) nor random-effect model meta-analyses (0.82, 0.60-1.1) showed statistically significant effects of supplementation with beta-carotene, vitamins A, C, E and selenium alone or in combination. Antioxidant supplements seemed to increase the development of colorectal adenoma in three low-bias risk trials (1.2, 0.99-1.4) and significantly decrease its development in five high-bias risk trials (0.59, 0.47-0.74). The estimates difference is significant (P < 0.0001). There was no significant difference between the intervention groups regarding adverse events, including mortality (0.82, 0.47-1.4)., Conclusion: We found no convincing evidence that antioxidant supplements have significant beneficial effect on primary or secondary prevention of colorectal adenoma.
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- 2006
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19. Treatment of small hepatocellular carcinoma with percutaneous ethanol injection: a validated prognostic model.
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Orlando A, D'Antoni A, Cammà C, Albanese M, Livraghi T, Torzilli G, Virdone R, Sciarrino E, Simonetti RG, Maringhini A, Pagliaro L, and Cottone M
- Subjects
- Aged, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Ethanol adverse effects, Female, Follow-Up Studies, Humans, Injections, Intralesional, Liver Cirrhosis complications, Liver Cirrhosis pathology, Liver Function Tests, Liver Neoplasms mortality, Liver Neoplasms pathology, Male, Middle Aged, Serum Albumin metabolism, Survival Rate, Carcinoma, Hepatocellular drug therapy, Ethanol administration & dosage, Liver Neoplasms drug therapy
- Abstract
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.
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- 2000
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20. Characteristics of hepatocellular carcinoma in Italy.
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Stroffolini T, Andreone P, Andriulli A, Ascione A, Craxi A, Chiaramonte M, Galante D, Manghisi OG, Mazzanti R, Medaglia C, Pilleri G, Rapaccini GL, Simonetti RG, Taliani G, Tosti ME, Villa E, and Gasbarrini G
- Subjects
- Adult, Age Distribution, Aged, Aged, 80 and over, Carcinoma, Hepatocellular epidemiology, Carcinoma, Hepatocellular etiology, Female, Hepatitis B Surface Antigens blood, Hepatitis C Antibodies blood, Hepatitis Viruses isolation & purification, Humans, Italy epidemiology, Liver Cirrhosis complications, Liver Neoplasms epidemiology, Liver Neoplasms etiology, Logistic Models, Male, Middle Aged, Prevalence, Regression Analysis, Sex Distribution, alpha-Fetoproteins analysis, Carcinoma, Hepatocellular diagnosis, Liver Neoplasms diagnosis
- Abstract
Background/aims: This study aimed to assess the main features of hepatocellular carcinoma at the time of diagnosis in Italy, particularly in relation to the presence or absence of underlying cirrhosis, hepatitis virus marker patterns, age of the subjects and alpha-foetoprotein values., Methods: A total of 1148 patients with hepatocellular carcinoma seen at 14 Italian hospitals in the 1-year period from May 1996 to May 1997 were the subjects of this prevalence study. Both newly diagnosed cases (incident cases) and cases diagnosed before May 1996 but still attending the hospitals during the study period (prevalent cases) were included., Results: We found that 71.1% of cases were positive for hepatitis C virus antibodies but negative for HBsAg; in contrast, 11.5% were negative for anti-HCV but positive for HBsAg; 5.3% were positive for both markers; and 12.1% were negative for both viruses. The mean age of detection was over 60 years, with a younger mean age in HBsAg-positive compared to anti-HCV-positive patients (59.3 years vs. 65.6 years, p<0.01). The male-to-female ratio among HBsAg-positive patients was 10.4:1, in contrast to 2.8:1 among anti-HCV-positive patients (p<0.01). The majority of cases (93.1%) had underlying cirrhosis. Cirrhotic patients were more likely to be anti-HCV positive than non-cirrhotic cases (73.2% vs 43.9%; p<0.01); conversely, absence of hepatitis virus markers was more frequently observed in the non-cirrhotic than in the cirrhotic population (40.9% vs. 10.0%; p<0.01). Overall, the alpha-foetoprotein level was altered (>20 ng/ml) in 57.9% of patients; only 18% of cases presented diagnostic (>400 ng/ml) values. Anti-HCV positivity (O.R. 2.0; CI 95%=1.3-3.1) but not HBsAg positivity (O.R. 1.0; CI 95%=0.6-1.8) was shown to be an independent predictor of the likelihood of altered alpha-foetoprotein values by multivariate analysis., Conclusions: These findings point to differences in the characteristics of the populations infected by hepatitis B and hepatitis C. Factors other than the hepatitis viruses are important in non-cirrhotic patients. A change in the relative prevalence of hepatitis virus markers among hepatocellular carcinoma cases was demonstrated, reflecting a significant change in the rate of HBV endemicity in the Italian population. Finally, the increased trend in the mortality rate from liver cancer in Italy from 4.8 per 100,000 in 1969 to 10.9 in 1994 may reflect the large cohort of subjects infected with HCV via the iatrogenic route during 1950s and 1960s when glass syringes were commonly used for medical treatment.
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- 1998
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21. Treatment of small hepatocellular carcinoma associated with cirrhosis by percutaneous ethanol injection. A trial with a comparison group.
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Orlando A, Cottone M, Virdone R, Parisi P, Sciarrino E, Maringhini A, Caltagirone M, Simonetti RG, and Pagliaro L
- Subjects
- Carcinoma, Hepatocellular mortality, Case-Control Studies, Ethanol administration & dosage, Female, Humans, Liver Cirrhosis mortality, Liver Neoplasms mortality, Male, Middle Aged, Solvents administration & dosage, Survival Rate, Carcinoma, Hepatocellular complications, Carcinoma, Hepatocellular therapy, Ethanol therapeutic use, Liver Cirrhosis complications, Liver Neoplasms complications, Liver Neoplasms therapy, Solvents therapeutic use
- Abstract
Background: 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., Methods: 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)., Results: 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., Conclusions: 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.
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- 1997
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22. Treatment of hepatocellular carcinoma: a systematic review of randomized controlled trials.
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Simonetti RG, Liberati A, Angiolini C, and Pagliaro L
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Hepatocellular therapy, Clinical Trials, Phase III as Topic, Embolization, Therapeutic, Humans, Immunotherapy, Male, Randomized Controlled Trials as Topic, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
- Abstract
Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. Many treatments have been proposed but considerable uncertainty still remains about their effectiveness. In this review we evaluated the quality, clinical coherence, consistency and results of Randomized Controlled Trials (RCT) of non-surgical treatments for HCC., Methods: Thirty-seven RCTs examining the effect of different treatments were retrieved using MEDLINE (November 1978 to December 1995) and a review of reference lists. Selected aspects of the quality of design, conduct and reporting were examined. The odds ratio for the probability of surviving up to one year was calculated according to the Mantel Haenszel Peto method and displayed using l'Abbe plots., Results: The 37 RCTs overall included 2803 patients (median 56, range 20-289). Patients prognosis varied widely across studies which also failed to report on important information about their characteristics. Only 10 RCTs had an untreated control group; the remaining 27 compared different regimens of intravenous or intraarterial chemotherapy with or without embolization of hepatic artery, hormono- and immunotherapy regimens. Some evidence of a moderate benefit emerged only from RCTs using tamoxifen and transcatheter arterial embolization vs. no treatment in unresectable patients: pooled odds ratio for 1-year survival were, respectively, 2.0 (95% confidence intervals (CI) 1.1-3.6) and 2.0 (95% CI 1.1-3.6). At 2 years, however, pooled odds ratio were no longer statistically significant for tamoxifen 1.2 (95% CI 0.6-2.6) but was significant for embolization 2.3 (95% CI 1.2-4.6). No evidence of efficacy was detected for embolization as adjuvant therapy in resected or transplanted patients nor for chemotherapy added to intraarterial embolization., Conclusions: This systematic review of RCTs on HCC, mostly in non resectable patients, indicate that the non-surgical current treatments are ineffective or minimally and uncertainly effective. The three treatment modalities minimally and uncertainly effective (i.e., embolization, tamoxifen and IFN) can deserve further assessment by larger and methodologically more sound randomized trials.
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- 1997
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23. Screening for hepatocellular carcinoma in patients with Child's A cirrhosis: an 8-year prospective study by ultrasound and alphafetoprotein.
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Cottone M, Turri M, Caltagirone M, Parisi P, Orlando A, Fiorentino G, Virdone R, Fusco G, Grasso R, and Simonetti RG
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- Aged, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular etiology, Female, Humans, Incidence, Liver Cirrhosis blood, Liver Cirrhosis classification, Liver Neoplasms diagnostic imaging, Liver Neoplasms etiology, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Survival Analysis, Ultrasonography, Carcinoma, Hepatocellular epidemiology, Liver Cirrhosis complications, Liver Neoplasms epidemiology, Mass Screening methods, alpha-Fetoproteins analysis
- Abstract
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 AFP > 50 ng/ml and < 400 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 and < 400 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.
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- 1994
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24. Hepatitis C viremia in chronic liver disease: relationship to interferon-alpha or corticosteroid treatment.
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Magrin S, Craxi A, Fabiano C, Simonetti RG, Fiorentino G, Marino L, Diquattro O, Di Marco V, Loiacono O, and Volpes R
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- Adult, Alanine Transaminase blood, Carcinoma, Hepatocellular blood, Chronic Disease, DNA, Viral blood, Female, Hepacivirus genetics, Hepatitis C drug therapy, Humans, Interferon alpha-2, Liver Cirrhosis blood, Liver Cirrhosis drug therapy, Liver Neoplasms blood, Male, Middle Aged, Polymerase Chain Reaction, RNA, Viral blood, Recombinant Proteins, Retrospective Studies, Viremia drug therapy, Hepatitis C blood, Interferon-alpha therapeutic use, Prednisone therapeutic use, Viremia blood
- Abstract
We assessed the pattern of hepatitis C viremia in chronic liver disease by studying 100 hepatitis C virus antibody-positive patients: 48 with chronic hepatitis, 21 with cirrhosis and 31 with hepatocellular carcinoma and cirrhosis. Serum hepatitis C virus RNA was detected by means of both the conventional nested polymerase chain reaction and a newly developed assay based on branched DNA that can also quantify viremia. Hepatitis C virus RNA was found in 94 of 100 patients with polymerase chain reaction and in 71 of 100 patients with branched-DNA (p < 0.001). Mean viremia level (x 10(3) genome equivalents/ml +/- S.D.), as assessed with the branched-DNA test, was 5,700 +/- 7,618 in the 48 patients with chronic hepatitis, 3,340 +/- 3,633 in the 21 patients with cirrhosis and 1,768 +/- 2,770 in the 31 patients with hepatocellular carcinoma (p < 0.02). We also analyzed retrospectively the relationship between viremia and treatment. Fifty-five patients (41 chronic hepatitis, 14 cirrhosis) underwent interferon-alpha treatment. Mean viremia level was comparable among the 30 responders (5,644 +/- 8,207) and the 25 nonresponders (5,519 +/- 6,208) to interferon, but it was significantly lower (1,841 +/- 1,864) in the 12 of 30 responders (11 chronic hepatitis, 1 cirrhosis) who maintained remission up to 1 yr after cessation of interferon treatment. Fourteen patients (7 chronic hepatitis, 7 cirrhosis) with autoantibodies (12 antinuclear, 2 anti-liver-kidney microsomal) were treated with prednisone. The mean viremia level significantly increased after 3 mo of treatment, even in face of ALT decrease.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
25. Hepatitis C virus infection, HBsAg carrier state and hepatocellular carcinoma: relative risk and population attributable risk from a case-control study in Italy.
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Stroffolini T, Chiaramonte M, Tiribelli C, Villa E, Simonetti RG, Rapicetta M, Stazi MA, Bertin T, Crocè SL, and Trande P
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular microbiology, Case-Control Studies, Enzyme-Linked Immunosorbent Assay, Hepatitis C diagnosis, Humans, Italy, Liver Neoplasms microbiology, Middle Aged, Risk Factors, Carcinoma, Hepatocellular etiology, Carrier State, Hepatitis B Surface Antigens blood, Hepatitis C complications, Liver Neoplasms etiology
- Abstract
In 1990, a case-control study was conducted in Italy to investigate the possible association between HCV infection and hepatocellular carcinoma (HCC). Serum samples from 65 subjects with newly diagnosed hepatocellular carcinoma and 99 hospital control subjects were tested for the presence of anti-HCV by second-generation ELISA test; positive sera were assayed by RIBA anti-HCV second-generation test. In addition, samples were tested for hepatitis B surface antigen (HBsAg), antibodies to the hepatitis B core antigen (anti-HBc), and antibodies to HBsAg (anti-HBs). The presence of HCV and/or HBsAg serologic markers was significantly associated with hepatocellular carcinoma risk: the relative risk (RR) of HCC was 21.3 (95% CI = 8.8-51.5) for anti-HCV positivity in the absence of HBsAg; the relative risk of HCC was 13.3 (95% CI = 5.5-32.2) for the presence of HBsAg in the absence of anti-HCV. A higher risk (77.0) was observed when both markers were present. These findings indicate that HCV and HBsAg are independent risk factors for HCC. The results of multivariate analysis showed that the adjusted RR linking anti-HCV and HCC was 26.9 (95% CI = 9.9-72.5), the adjusted RR linking HBsAg and HCC was 11.4 (95% CI = 3.1-41.4), whereas no association (RR 1.5; 95% CI = 0.6-3.6) was found to link HCC with anti-HBc and/or anti-HBs positivity. Through the computation of population attributable risk we estimate that 25% of HCC cases occurring in Italy could be attributed to anti-HCV positivity alone and 20% to HBsAg carrier state alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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- 1992
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26. Hepatitis C virus infection as a risk factor for hepatocellular carcinoma in patients with cirrhosis. A case-control study.
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Simonetti RG, Cammà C, Fiorello F, Cottone M, Rapicetta M, Marino L, Fiorentino G, Craxì A, Ciccaglione A, and Giuseppetti R
- Subjects
- Aged, Case-Control Studies, Female, Hepacivirus immunology, Hepatitis Antibodies blood, Hepatitis B Antibodies blood, Hepatitis B Core Antigens immunology, Hepatitis B Surface Antigens blood, Humans, Male, Middle Aged, Prevalence, Risk Factors, Sicily, Carcinoma, Hepatocellular etiology, Hepatitis C complications, Liver Cirrhosis complications, Liver Neoplasms etiology
- Abstract
Objective: To determine whether chronic hepatitis C virus (HCV) infection is an independent risk factor for hepatocellular carcinoma and whether it increases the cirrhosis-related risk for hepatocellular carcinoma., Design: Two pair-matched case-control studies., Setting: A referral-based hospital., Patients: In study I, 212 patients with hepatocellular carcinoma (197 of whom had known underlying cirrhosis) were compared with controls who had chronic nonhepatic diseases. In study II, the 197 patients with hepatocellular carcinoma and cirrhosis were compared with 197 pair-matched controls who had cirrhosis but not hepatocellular carcinoma., Measurements: Levels of antibody to HCV (anti-HCV), hepatitis B surface antigen (HBsAg), and antibody to hepatitis B core antigen (anti-HBc) were assayed, and alcohol abuse was assessed by history., Main Results: In study I, 151 patients (71%) with hepatocellular carcinoma were anti-HCV positive compared with 11 controls (5%) with chronic nonhepatic diseases (odds ratio, 42; 95% CI, 22 to 95). Multivariate analysis showed that anti-HCV was an independent risk factor for hepatocellular carcinoma (odds ratio, 69; CI, 15 to 308). The analysis also showed that HBsAg (odds ratio, 8.7; CI, 1.5 to 50) and anti-HBc (odds ratio, 4.2 (CI, 1.7 to 11) were risk factors for hepatocellular carcinoma. No statistically significant interaction was found between anti-HCV and the markers of HBV infection. In study II, 146 patients (74%) with hepatocellular carcinoma and cirrhosis were anti-HCV positive compared with 122 patients (62%) with cirrhosis alone (odds ratio, 1.8; CI, 1.1 to 2.8). Multivariate analysis confirmed that anti-HCV (odds ratio, 2.0; CI, 1.3 to 32) and HBsAg (odds ratio, 2.0; CI, 1.0 to 4.2) were independent risk factors for hepatocellular carcinoma., Conclusions: Hepatitis C virus infection is a risk factor for hepatocellular carcinoma, apparently by inducing cirrhosis and, to a lesser extent, by enhancing the risk in patients with cirrhosis. Hepatitis C virus infection acts independently of HBV infection (another risk factor) and of alcohol abuse, age, or gender.
- Published
- 1992
- Full Text
- View/download PDF
27. Hepatocellular carcinoma. A worldwide problem and the major risk factors.
- Author
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Simonetti RG, Cammà C, Fiorello F, Politi F, D'Amico G, and Pagliaro L
- Subjects
- Carcinoma, Hepatocellular etiology, Female, Humans, Incidence, Liver Neoplasms etiology, Male, Risk Factors, Carcinoma, Hepatocellular epidemiology, Global Health, Liver Neoplasms epidemiology
- Abstract
Male sex, age, cirrhosis, and HBsAg are the major risk factors for hepatocellular carcinoma (HCC). The geographic distribution of HCC is highly uneven, such that three distinct incidence areas are recognized. To clarify the reason(s) for this geographic variability of HCC, the risk factors in each incidence area were assessed. In parallel with the geographic distribution of HCC, HBsAg prevalence was highest in both HCC patients and in general population in Africa and Asia, where mothers of HCC patients are frequently HBsAg-positive, suggesting that hepatitis B virus hyperendemicity and perinatal infection account for the high HCC incidence in these areas. Cirrhosis, which is found on autopsy in 80% of the cases of HCC patients worldwide, is the most prevalent risk factor for HCC in areas where hepatitis B virus infection is less common. However, HBsAg carriage adds to the HCC risk carried by cirrhosis and explains the higher incidence of HCC in cirrhotics from Africa and Asia as well as elsewhere. Available data suggest that chronic HCV infection is a risk factor for cirrhosis and HCC. HBV vaccination should decrease HCC incidence rates worldwide; however, HCC prevention in regions where HBsAg carriage is infrequent may also require prevention of the other causes of cirrhosis in order for HCC rates to decline.
- Published
- 1991
- Full Text
- View/download PDF
28. The clinical value of serum ferritin in hepatocellular carcinoma.
- Author
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Simonetti RG, Craxi A, Dardanonì G, Lanzarone F, Barbaria F, Cottone M, and Pagliaro L
- Subjects
- Adult, Aged, Carcinoma, Hepatocellular drug therapy, Doxorubicin therapeutic use, Humans, Liver Cirrhosis blood, Liver Cirrhosis drug therapy, Liver Neoplasms drug therapy, Middle Aged, alpha-Fetoproteins metabolism, Carcinoma, Hepatocellular blood, Ferritins blood, Liver Neoplasms blood
- Abstract
Serum ferritin is often elevated in patients with hepatocellular carcinoma (HCC). Its use as a disease marker has been proposed. We have measured serum ferritin levels in 85 patients with HCC and in 62 comparable subjects with cirrhosis. Abnormal values (greater than or equal to 300 ng/ml) were found in 54% of the patients with HCC and in 35% of those with cirrhosis (median 323 and 204 ng/ml, respectively). The overlap of the range of concentration in HCC and cirrhosis was so great that no discriminant level could be chosen. No relationship was found between alpha-fetoprotein and ferritin concentrations. Among 61 patients who received Adriamycin treatment, no discernible fall in ferritin levels was observed, while alpha-fetoprotein increased progressively during the follow-up. Serum ferritin has no role in diagnosing and/or monitoring the response to treatment of patients with HCC.
- Published
- 1985
29. Tissue markers of hepatitis B virus infection in hepatocellular carcinoma and cirrhosis.
- Author
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Craxi A, Pasqua P, Giannuoli G, Di Stefano R, Simonetti RG, and Pagliaro L
- Subjects
- Antibodies, Monoclonal, Carcinoma, Hepatocellular complications, Female, Fluorescent Antibody Technique, Hepatitis B complications, Hepatitis B Antibodies analysis, Humans, Liver Cirrhosis complications, Liver Neoplasms complications, Male, Middle Aged, Carcinoma, Hepatocellular immunology, Hepatitis B immunology, Hepatitis B Core Antigens analysis, Hepatitis B Surface Antigens analysis, Liver Cirrhosis immunology, Liver Neoplasms immunology
- Abstract
In order to assess the prevalence of tissue markers of HBV infections (HBsAg and HBcAg) in HBsAg seropositive and seronegative hepatocellular carcinoma (HCC) as compared with other advanced liver diseases (inactive cirrhosis, IC, and active cirrhosis, AC), we studied 49 patients with HCC (13 HBsAg+), 52 patients with IC (5 HBsAg+) and 53 patients with AC (14 HBsAg+). Among HBsAg seropositive patients, intrahepatic HBsAg was frequently found (26/32 cases), while HBcAg was present more rarely (5/32 cases) and correlated with serological features of high-level viral replication. HBsAg seronegative, anti-HBc +/- anti-HBs positive subjects had intrahepatic HBsAg in 8/34 cases, and HBcAg in liver cell nuclei in 14/34 cases. HBcAg was more frequent in cirrhosis than in HCC. No other differences in the intrahepatic display of HBV markers was observed, nor was a specific pattern identified for HCC. Viral components were never found in the liver in the absence of serum HBsAg or anti-HBc. Neoplastic hepatocytes did not usually support the synthesis of HBsAg or HBcAg.
- Published
- 1984
30. Adriamycin treatment for hepatocellular carcinoma. Experience with 109 patients.
- Author
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Sciarrino E, Simonetti RG, Le Moli S, and Pagliaro L
- Subjects
- Aged, Alopecia chemically induced, Carcinoma, Hepatocellular etiology, Carcinoma, Hepatocellular mortality, Doxorubicin administration & dosage, Doxorubicin adverse effects, Female, Heart Diseases chemically induced, Hepatitis B complications, Hepatitis B Surface Antigens analysis, Humans, Injections, Intravenous, Liver Neoplasms etiology, Liver Neoplasms mortality, Male, Middle Aged, Prognosis, alpha-Fetoproteins analysis, Carcinoma, Hepatocellular drug therapy, Doxorubicin therapeutic use, Liver Neoplasms drug therapy
- Abstract
One hundred nine patients with hepatocellular carcinoma were treated with intravenous (IV) Adriamycin (doxorubicin). Cumulative survival rate was 34% at 6 months and 13% at 1 year. Survival was positively related to a good performance status and to alpha-fetoprotein less than 50 ng/ml, not influenced by hepatitis B surface antigen (HBsAg) and by presence of clear cells in the tumor. Partial response (alpha-fetoprotein decrease by greater than or equal to 50% of the initial value) was observed in 10 patients and complete response in 1 patient, always within the fourth dose, with a 10% response rate. Twenty of 75 symptomatic patients (27%) achieved improvement in performance and/or pain reduction. Withdrawal of treatment became necessary for side effects in six patients. In conclusion, IV Adriamycin in hepatocellular carcinoma has only limited efficacy. Because of its early activity, treatment can be stopped after three doses if there is no evidence of response.
- Published
- 1985
- Full Text
- View/download PDF
31. Prevalence of antibodies to hepatitis C virus in hepatocellular carcinoma.
- Author
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Simonetti RG, Cottone M, Craxi' A, Pagliaro L, Rapicetta M, Chionne P, and Costantino A
- Subjects
- Female, Humans, Male, Prevalence, Antibodies, Viral analysis, Carcinoma, Hepatocellular microbiology, Hepatitis C microbiology, Hepatitis Viruses immunology, Hepatitis, Viral, Human microbiology, Liver Neoplasms microbiology
- Published
- 1989
- Full Text
- View/download PDF
32. Spontaneous bacterial peritonitis: a prospective investigation in predominantly nonalcoholic cirrhotic patients.
- Author
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Pinzello G, Simonetti RG, Craxì A, Di Piazza S, Spanò C, and Pagliaro L
- Subjects
- Aged, Ascites complications, Ascites diagnosis, Ascites microbiology, Bacterial Infections microbiology, Bacterial Infections mortality, Female, Humans, Liver Cirrhosis diagnosis, Liver Cirrhosis microbiology, Male, Middle Aged, Peritonitis microbiology, Peritonitis mortality, Prospective Studies, Bacterial Infections diagnosis, Liver Cirrhosis complications, Peritonitis diagnosis
- Published
- 1983
- Full Text
- View/download PDF
33. Ultrasound in monitoring patients with hepatocellular carcinoma treated with adriamycin.
- Author
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Sciarrino E, Cottone M, Dardanoni G, La Seta F, Le Moli S, Marcenò MP, Maringhini A, Simonetti RG, and Pagliaro L
- Subjects
- Carcinoma, Hepatocellular drug therapy, Humans, Liver Neoplasms drug therapy, Time Factors, Carcinoma, Hepatocellular pathology, Doxorubicin therapeutic use, Liver Neoplasms pathology, Ultrasonography
- Published
- 1985
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