F. Borzio - Academia.edu (original) (raw)
Papers by F. Borzio
Gastroenterology, 1997
The preneoplastic role of macroregenerative nodules in cirrhosis is still debated. Thirty-two con... more The preneoplastic role of macroregenerative nodules in cirrhosis is still debated. Thirty-two consecutive ultrasonography-detected macronodules were followed up to evaluate whether and which lesions are the actual precursors of hepatocellular carcinoma, if histology can identify preneoplastic macronodules, and whether additional parameters are related to neoplastic evolution. Macroregenerative nodule classification was based on recently proposed histological criteria. Extranodular liver cell dysplasia was also evaluated. The follow-up included ultrasonography and serum alpha-fetoprotein level determination every 3 months. Twenty-two macronodules (78%) were classified as typical and 7 (22%) as atypical. Twenty-one were hypoechoic, and 11 were hyperechoic. Extranodular dysplasia was more frequently associated with atypical than typical macronodules (5 of 7 vs. 6 of 22). After 28 +/- 15 months, neoplastic transformation occurred in 8 macronodules (25%) and was more frequent in atypical than in typical (5 of 7 vs. 3 of 25), in hyperechoic than in hypoechoic (5 of 11 vs. 3 of 21), and in extranodular dysplasia-associated macronodules than in extranodular dysplasia-free macronodules (5 of 11 vs. 2 of 18). Five hepatocellular carcinomas appeared outside the original macronodule. Atypical macroregenerative nodules can be considered precursors of hepatocellular carcinoma. Histology is useful in identifying preneoplastic macronodules, and hyperechoic pattern and extranodular dysplasia are additional risk factors for neoplastic transformation.
American Journal of Gastroenterology, 2012
Letters to the Editor may be associated with symptoms of IBS, CVS, atopic dermatitis, fi bromyalg... more Letters to the Editor may be associated with symptoms of IBS, CVS, atopic dermatitis, fi bromyalgia, and chronic fatigue (6). Th e diagnosis of a mitochondrial-based disorder is supported by a matrilineal family history, with his mother Susannah and her mother Sarah both having chronic illness for most of their later lives. Susannah ' s brother Tom suff ered headaches, abdominal pain, and seasickness, and had marked cold sensitivity. As well as Susannah and Tom, Sarah had two other children who were probably affl icted. Richard died in infancy with a gastrointestinal complaint; Mary Ann was of short stature and retarded. She suff ered from epilepsy, episodes of blindness, and paralysis. She died at the age of eight with symptoms typical of the MELAS syndrome. An A3243G mitochondrial DNA mutation explains the illnesses of Darwin, of his mother, his maternal uncle, his maternal grandmother, and other relations. Whitehead et al. postulate that IBS and its comorbidity disorders may have shared pathophysiological mechanisms (3). It is proposed that mitochondrial dysfunction may be one such mechanism.
Minerva Chirurgica, 1999
BACKGROUND AND AIMS The use of steroids was recently extended to the various forms of ulcerative ... more BACKGROUND AND AIMS The use of steroids was recently extended to the various forms of ulcerative rectocolitis by the introduction of topical formulations, above all steroids with an hepatic "first pass" devoid of systemic interference. The aim of this study was to evaluate the efficacy and tolerability of Beclomethasone dipropionate (BDP) in a rectal foam formulation, in the treatment of patients suffering from ulcerative colitis. METHODS The experimental protocol took the form of a 28-day open prospective trial using BDP rectal foam in patients suffering from ulcerative colitis. Endoscopic, histological, clinical and tolerability parameters were evaluated. The centres taking part in the trial collected data for 60 cases out of a total of 80 patients enrolled in the study, of both sexes and aged between 20 and 81 years old, suffering from proctosigmoiditis (46.7%) and ulcerative rectocolitis (53.3%). RESULTS Endoscopic parameters showed an improvement after 28 days of trea...
Liver international : official journal of the International Association for the Study of the Liver, Jan 10, 2018
Metabolic disorders are well known risk factors for HCC. Conversely, their impact on the natural ... more Metabolic disorders are well known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its etiology. We analyzed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analyzed: BMI, diabetes, arterial hypertension, hypercholesterolemia and hypertriglyceridemia. According to these features, patients were divided into 3 groups: 0{\hyphen}1, 2 and 3{\hyphen}5 metabolic features. As compared with patients with 0{\hyphen}1 metabolic features, patients with 3{\hyphen}5 features showed lower percentage of HCC diagnosis on surveillance (p{\equal}0.021), larger tumors (p{\equal}0.038), better liver function (higher percentage of Child{\hyphen}Pugh class A [p{\equal}0.007] and MELD{\lt}10 [p{\equal}0.003]), higher percentage of metastasis (p{\equal}0.02...
Alimentary pharmacology & therapeutics, Jan 11, 2016
Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its ... more Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. To assess how many years of life are lost after HCC diagnosis. Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when ...
Minerva gastroenterologica e dietologica, 1999
The authors assessed the efficacy and tolerability of BDP in an open protocol using rectal enemas... more The authors assessed the efficacy and tolerability of BDP in an open protocol using rectal enemas and suppositories and in a double-blind protocol vs mesalazine using rectal enemas. A total of 47 patients suffering from ulcerous rectocolitis were enrolled in the study and treated for 42 days while undergoing endoscopic, histologic and clinical controls. In conclusion, the authors affirm that BDP may represent a useful new therapeutic instrument in the treatment of slight to moderately severe forms of inflammatory intestinal disease.
Minerva chirurgica, 1999
The use of steroids was recently extended to the various forms of ulcerative rectocolitis by the ... more The use of steroids was recently extended to the various forms of ulcerative rectocolitis by the introduction of topical formulations, above all steroids with an hepatic "first pass" devoid of systemic interference. The aim of this study was to evaluate the efficacy and tolerability of Beclomethasone dipropionate (BDP) in a rectal foam formulation, in the treatment of patients suffering from ulcerative colitis. The experimental protocol took the form of a 28-day open prospective trial using BDP rectal foam in patients suffering from ulcerative colitis. Endoscopic, histological, clinical and tolerability parameters were evaluated. The centres taking part in the trial collected data for 60 cases out of a total of 80 patients enrolled in the study, of both sexes and aged between 20 and 81 years old, suffering from proctosigmoiditis (46.7%) and ulcerative rectocolitis (53.3%). Endoscopic parameters showed an improvement after 28 days of treatment in 74.5% of patients; a clinic...
Recenti progressi in medicina, 1989
We report a case of intestinal schistosomiasis; secondary hepatic involvement is particularly des... more We report a case of intestinal schistosomiasis; secondary hepatic involvement is particularly described, with a very distinctive ecographic feature of portal hypertension and a bioptic picture stressing a granulomatous periportal inflammation. In the work we emphasize the importance of a multidisciplinary approach (physicians working in the fields of internal medicine, infectious disease, gastrointestinal diseases, radiologist, pathologist) in the course of diagnostic investigation. Finally, we confirm the effectiveness of praziquantel against Schistosoma mansoni.
Hepatology, 2014
The prognosis of untreated patients with hepatocellular carcinoma (HCC) is heterogeneous, and sur... more The prognosis of untreated patients with hepatocellular carcinoma (HCC) is heterogeneous, and survival data were mainly obtained from control arms of randomized studies. Clinical practice data on this topic are urgently needed, so as to help plan studies and counsel patients. We assessed the prognosis of 600 untreated patients with HCC managed by the Italian Liver Cancer Group. Prognosis was evaluated by subdividing patients according to the Barcelona Clinic Liver Cancer (BCLC) classification. We also assessed the main demographic, clinical, and oncological determinants of survival in the subgroup of patients with advanced HCC (BCLC C). Advanced (BCLC C: n 5 138; 23.0%) and end-stage HCC (BCLC D; n 5 210; 35.0%) represented the majority of patients. Overall median survival was 9 months, and the principal cause of death was tumor progression (n 5 279; 46.5%). Patients' median survival progressively and significantly decreased as BCLC stage worsened (BCLC 0: 38 months; BCLC A: 25 months; BCLC B: 10 months; BCLC C: 7 months; BCLC D: 6 months; P < 0.0001). Female gender (hazard ratio [HR] 5 0.55; 95% confidence interval [CI] 5 0.33-0.90; P 5 0.018), ascites (HR 5 1.81; 95% CI 5 1.21-2.71; P 5 0.004), and multinodular (>3) HCC (HR 5 1.79; 95% CI 5 1.21-2.63; P 5 0.003) were independent predictors of survival in patients with advanced HCC (BCLC C). Conclusion: BCLC adequately predicts the prognosis of untreated HCC patients. In untreated patients with advanced HCC, female gender, clinical decompensation of cirrhosis, and multinodular tumor are independent prognostic predictors and should be taken into account for patient stratification in future therapeutic studies.
Seminars in Oncology, 2014
Background. Standard liver function parameter levels and tumor indices were analyzed using Networ... more Background. Standard liver function parameter levels and tumor indices were analyzed using Network Phenotyping Strategy (NPS), a graph-theory based approach, which compares personal patterns of complete relationships between clinical data to reference patterns with significant association to disease outcome. We previously applied NPS to Taiwan hepatocellular cancer (HCC) patients and recognized two clinical phenotypes, S and L, differing in the size and tumor nodule numbers. Aims. To validate the applicability of the NPS-based HCC S/L classification on an independent European HCC cohort, for which survival information was additionally available. Results. Patients with S and L phenotypes, recognized by the same data processing as previously, had 1.5x larger mean tumor masses in L relative to S, p=6x10-16. S-phenotype patients had typically 1.7x longer survival compared to L-phenotype. NPS integrated liver-and tumor factors. Cirrhosis associated thrombocytopenia was typical for smaller S-tumors. Hepatic inflammation and tumor factors contributed to more aggressive L tumors, with parenchymal destruction and shorter survival. Summary. NPS provides integrative interpretation for HCC behavior, identifying by clinical parameter patterns two tumor and survival phenotypes. The NPS classifier was implemented as an application for web browsers and is available upon request
The Lancet Oncology, 2011
Background Allocation of deceased-donor livers to patients with chronic liver failure is improved... more Background Allocation of deceased-donor livers to patients with chronic liver failure is improved by prioritising patients by 5-year liver transplantation survival benefi t. The Barcelona Clinic Liver Cancer (BCLC) staging has been proposed as the standard means to assess for prognosis of patients with hepatocellular carcinoma. We aimed to create a prediction model linking the BCLC stage of patients with hepatocellular carcinoma to their 5-year liver transplant benefi t. Methods A large cohort of consecutive patients with hepatocellular carcinoma (n=1328) from the ITA.LI.CA database (n=2951) were judged as potentially eligible for liver transplantation according to the following criteria: absence of macroscopic vascular invasion or metastases, age 70 years or younger, and absence of relevant extra-hepatic comorbidities. To assess the correlation between BCLC staging and non-liver transplantation survival, we did Cox univariate and multivariate analyses including the following covariates: BCLC stage, year of diagnosis, age, sex, cause of cirrhosis, model for end-stage liver disease score, α-fetoprotein concentrations, and treatment. Liver-transplantation survival benefi t for patients was calculated, using Monte Carlo simulation analysis, as the patient's 5-year life expectancy with liver transplantation (estimated by the Metroticket model) minus the 5-year life expectancy without liver transplantation according to BCLC stage. Findings 83 (6%) of 1328 patients had BCLC 0 stage disease, 614 (46%) had BCLC A, 500 (38%) had BCLC B-C, and 131 (10%) had BCLC D. In the Cox non-liver transplantation survival multivariate model, hazard ratios associated with increasing BCLC stages were 1•530 (95% CI 1•107-2•116) for BCLC A versus BCLC 0, 1•572 (1•350-1•830) for BCLC B-C versus BCLC A, and 1•470 (1•164-1•856) for BCLC D versus BCLC B-C. Results of the Monte Carlo simulation analysis confi rmed the signifi cant eff ect of BCLC classifi cation on transplant benefi t; in the adjusted model, a median 5-year transplant benefi t of 11•19 months (IQR 10•73-11•67) for BCLC 0, 13•49 months (11•51-15•57) for BCLC A, 17•36 months (15•06-19•28) for BCLC B-C, and 28•46 months (26•38-30•34) for BCLC D. Interpretation Liver transplantation could result in survival benefi t for patients with hepatocellular carcinoma and advanced liver cirrhosis (BCLC stage D) and in those with intermediate tumours (BCLC stages B-C), regardless of the nodule number-size criteria (ie, Milan criteria), provided that macroscopic vascular invasion and extra-hepatic disease are absent.
Journal of Hepatology, 2009
Background and Aim: Prognosis of HCC is not entirely predictable because both liver failure and c... more Background and Aim: Prognosis of HCC is not entirely predictable because both liver failure and cancer progression affect survival by complex interactions. Aim of our study was to construct a prognostic index called NAPI tailored for cirrhotic patients with treatable HCC. Methods: We prospectively evaluated 282 patients with Child-Pugh 7 cirrhosis and HCC within Milan criteria seen at our Liver Unit (training cohort). Survival was estimated by the Kaplan-Meier method, and differences between groups assessed by the log-rank test. Potential risk factors for death were identified by Cox proportional-hazards analysis and, to develop a practical prognostic score, we assigned these factors weighted points proportional to the b-regression coefficient values. The system was validated in 171 consecutive patients selected from the database of another hospital (validation cohort) and was compared with the CLIP and BCLC systems. Results: During a median follow-up of 34 months, 163 patients in the training cohort died. Four independent prognostic factors were identified: no HCC treatment or incomplete treatment effect (4 points), 3.3 g/dL (3 points), MELD albumin >11 (2 points), and abnormal serum alkaline phosphatase (2 points). Risk score for each patient was calculated and the population divided in three groups: low-risk (0 points), intermediaterisk (2−5 points), and high-risk (6−11 points). In the training cohort, the median survival for these groups was 108, 42, and 25 months respectively. In the validation cohort, the corresponding median survival was 77, 45, and 24 months. Considering the 5-year mortality risk, the C-statistic was 0.786 in the training cohort and 0.716 in the validation cohort. The corresponding C-statistics for the BCLC and the CLIP staging systems were 0.679 and 0.736 in the training cohort, and 0.476 and 0.517 in the validation cohort respectively. Conclusions: A new risk score for predicting death in cirrhotic patients with treatable HCC was developed and validated in an independent cohort. This score performed better than the two score systems more diffusely used in clinical practice. NAPI score may be an useful tool in clinical practice to optimize the therapeutic strategy.
Journal of Hepatology, 1994
To evaluate the diagnostic accuracy of fine-needle aspiration, fine-needle biopsy and extranodula... more To evaluate the diagnostic accuracy of fine-needle aspiration, fine-needle biopsy and extranodular fine needle biopsy in identifying focal lesions in cirrhosis, 100 consecutive ultrasound detected nodules were studied. Seventy-three were hepatocellular carcinomas (31 were well-differentiated hepatocellular carcinomas), 23 were benign lesions (one angioma and 22 large regenerative nodules) and two were metastases. The lesions were divided according to maximum diameter as follows: &amp;amp;amp;lt; 20 mm in 36, &amp;amp;amp;gt; 20 &amp;amp;amp;lt; 30 mm in 27, and &amp;amp;amp;gt; 30 mm in 33. In four cases there were multiple nodules of different sizes. Fine needle aspiration, intranodular fine needle biopsy and extranodular fine needle biopsy were obtained in each lesion. The sensitivity, specificity and diagnostic accuracy of each procedure were evaluated separately by three independent pathologists. Seven fine needle aspirations and three intranodular fine needle biopsies were considered inadequate. The highest diagnostic accuracy (96%) was obtained by the combined analysis of fine needle aspiration plus intranodular and extranodular fine needle biopsy, and this superiority was confirmed in each group of lesions. Fine needle aspiration showed a lower accuracy (48%) than intranodular fine needle biopsy (67%). When fine needle aspiration and intranodular fine needle biopsy were evaluated together, an accuracy of 91% was found. Intralesional fine needle biopsy plus extranodular fine needle biopsy analysis gave an accuracy of 78% and, particularly relevant, a specificity of 95%. These results indicate that, in patients with cirrhosis with nodular lesions &amp;amp;amp;lt; 30 mm, fine needle biopsy is superior to fine needle aspiration and that the combined evaluation of fine needle aspiration plus intranodular and extranodular fine needle biopsy is the most accurate approach.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Hepatology, 2003
Background/Aims: The natural outcome of ultrasound-detected macronodules in cirrhosis is still po... more Background/Aims: The natural outcome of ultrasound-detected macronodules in cirrhosis is still poorly understood. In this study we assessed the incidence and predictors of malignant transformation in a prospective study of 90 consecutive ultrasound-detected macronodules in cirrhosis. Methods: Macronodules classification was based on recently proposed histological criteria. Extranodular large (LCC) and small cell changes were also evaluated. The follow-up included ultrasound and serum alfa-fetoprotein determination every 3 months. Independent predictors of hepatocellular carcinoma were evaluated by Cox proportional hazards regression analysis. Results: During a mean follow-up of 33 months, 28 (31%) nodules transformed into hepatocellular carcinoma. The incidence of hepatocellular carcinoma per 100 person-years of follow-up was 11.3%, with a malignant transformation rate of 3.5, 15.5, 31 and 48.5% at 1, 2, 3, and 5 years respectively. High-grade dysplastic nodules (HGDN) (hazard risk 5 2.4; CI 95% 5 1.1-5.0) and LCC (hazard risk 5 3.1; CI 95% 5 1.2-7.8) were independent predictors of malignant transformation. Eight additional hepatocellular carcinomas developed outside the original lesions raising the overall malignant transformation rate to 40% while 15 macronodules (17%) became undetectable at ultrasound (US). Conclusions: Macronodules characterize a cirrhotic subpopulation with high risk of hepatocellular carcinoma. HGDN and LCC are strong predictors of malignant transformation; subjects with simultaneous presence of both these two conditions are at highest risk of cancer development. The management of cirrhotics with macronodules should be based on morphologic features detected on liver microsamples.
Hormone and Metabolic Research, 1983
Anomalies du taux des hormones pituitaires chez des patients cirrhotiques. Elles sont probablemen... more Anomalies du taux des hormones pituitaires chez des patients cirrhotiques. Elles sont probablement liees a une modification de divers neurotransmetteurs dont la dopamine et la serotonine, en raison d'une accumulation de faux neurotransmetteurs
Hepatology, 2012
11 for the Italian Liver Cancer (ITA.LI.CA) group Alpha-fetoprotein is a tumor marker that has be... more 11 for the Italian Liver Cancer (ITA.LI.CA) group Alpha-fetoprotein is a tumor marker that has been used for surveillance and diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. The prognostic capability of this marker in patients with HCC has not been clearly defined. In this study our aim was to evaluate the prognostic usefulness of serum alpha-fetoprotein in patients with well-compensated cirrhosis, optimal performance status, and small HCC identified during periodic surveillance ultrasound who were treated with curative intent. Among the 3,027 patients included in the Italian Liver Cancer study group database, we selected 205 Child-Pugh class A and Eastern Cooperative Group Performance Status 0 patients with cirrhosis with a single HCC 3 cm of diameter diagnosed during surveillance who were treated with curative intent (hepatic resection, liver transplantation, percutaneous ethanol injection, radiofrequency thermal ablation). Patients were subdivided according to alpha-fetoprotein serum levels (i.e., normal 20 ng/mL; mildly elevated 21-200 ng/mL; markedly elevated >200 ng/mL). Patient survival, as assessed by the Kaplan-Meier method, was not significantly different among the three alpha-fetoprotein classes (P 5 0.493). The same result was obtained in the subgroup of patients with a single HCC 2 cm (P 5 0.714). An alpha-fetoprotein serum level of 100 ng/mL identified by receiver operating characteristic curve had inadequate accuracy (area under the curve 5 0.536, 95% confidence interval 5 0.465-0.606) to discriminate between survivors and deceased patients. Conclusion: Alphafetoprotein serum levels have no prognostic meaning in well-compensated cirrhosis patients with single, small HCC treated with curative intent.
Gastroenterology, 1995
The authors thank Professor Roberto De Franchis for his extensive and dedicated editorial review,... more The authors thank Professor Roberto De Franchis for his extensive and dedicated editorial review, as well as for his support and encouragement.
European Journal of Gastroenterology & Hepatology, 2002
Hepatocellular carcinogenesis in cirrhosis is a multistage process that includes large regenerati... more Hepatocellular carcinogenesis in cirrhosis is a multistage process that includes large regenerative nodules, dysplastic nodules, and hepatocarcinoma. The aim of this study was to establish whether contrast-enhanced Doppler ultrasonography (US) is able to distinguish between early hepatocellular carcinoma (HCC) and small nonmalignant nodules in cirrhosis. Between January 1998 and December 1999, 500 cirrhotic patients with no previous history of HCC or evidence of hepatic focal lesions were enrolled and prospectively followed-up with US every 6 months until December 2000. Sixty-one patients developed focal lesions, 12 multifocal, and 49 monofocal. Biopsy of focal lesions, contrast-enhanced Doppler US, and spiral computed tomography (CT) were performed in 41 consecutive patients with small (<3 cm) monofocal lesions. Twenty nodules were diagnosed as HCC and 21 as nonmalignant (14 large regenerative nodules, 3 low-grade, and 4 high-grade dysplastic nodules) by liver biopsy. Intratumoral arterial blood flow was detected in 19 of 20 (95%) HCC and 6 of 21 (28%) nonmalignant nodules by contrast-enhanced Doppler US (P<.0001). The mean peak resistance and pulsatility indices were 0.82 +/- 0.09 and 1.56 +/- 0.2 in HCC and 0.62 +/- 0.08 and 0.82 +/- 0.08 in dysplastic lesions (P =.002 and.0001), respectively. Spiral CT revealed arterial perfusion in 19 of 20 HCC and in 4 of 21 nonmalignant nodules (high-grade dysplastic nodules). Four of the apparently false-positive nodules at enhanced Doppler US were high-grade dysplastic nodules and 2 evolved to HCC during follow-up. In conclusion, contrast-enhanced Doppler US is a noninvasive, very sensitive technique in differentiating malignant and premalignant lesions from nonmalignant focal lesions in the liver.
European Journal of Gastroenterology & Hepatology, 1996
approximately 3%. 3,4 Early detection of HCC in cirrhotic pa-A prospective study was performed to... more approximately 3%. 3,4 Early detection of HCC in cirrhotic pa-A prospective study was performed to establish tients can usually be achieved by screening with noninvasive whether infection with specific hepatitis C virus (HCV) techniques, such as ultrasound (US) scan and serum a-fetogenotypes was associated with an increased risk of protein (AFP) concentration. 5,6 development of hepatocellular carcinoma (HCC) in cir-Over the years, several lines of experimental evidence indirhosis. A cohort of 163 consecutive hepatitis C virus anticated that male sex, age, and alcohol consumption 4,7,8 were body (anti-HCV)-positive cirrhotic patients was proclosely associated with the development of HCC in cirrhotic spectively evaluated for the development of HCC at patients. The identification of additional variables associated 6-month intervals by ultrasound (US) scan and awith an increased risk of developing HCC would be particufetoprotein (AFP) concentration. HCV genotypes were larly important to optimize preventive medical programs in determined according to Okamoto. Risk factors associthis setting. Recent studies suggested a possible role for HCV ated with cancer development were analyzed by univarigenotype in chronic liver disease outcome and, specifically, ate and multivariate statistics. At enrollment, 101 pa-HCV type 1 was more frequently found in advanced liver tients (62%) were infected with type 1b, 48 (29.5%) were disease, such as cirrhosis and HCC, 9-11 and was associated infected with type 2a/c, 2 (1.2%) were infected with type with a more rapid deterioration of liver histology in chronic 3a, 1 (0.6%) was infected with type 1a, 3 (1.8%) had a hepatitis. 12 We have studied the distribution of HCV genomixed-type infection, and, in 8 patients (4.9%), genotype types in a cohort of patients with cirrhosis prospectively folcould not be assigned. After a 5-to 7-year follow-up (melowed for early detection of HCC, and we performed multivardian, 68 months), HCC developed in 22 of the patients, iate analysis to evaluate the independent risk for tumor 19 infected with type 1b and 3 with type 2a/c (P õ .005). development associated with specific HCV types and with Moreover, HCC developed more frequently in males (P other variables, including interferon treatment, which has õ .01), patients with excessive alcohol intake (P õ .01), been recently reported to reduce the cancer risk in HCVthose over 60 years of age (P õ .02), and in patients who induced cirrhosis. 13 did not receive interferon treatment (P õ .02). Multivariate analysis showed that type 1b was the most important PATIENTS AND METHODS risk factor associated with tumor development (odds ra-Patients. Between January 1989 and December 1990, all cirrhotic tio 6.14, 1.77-21.37 95% confidence interval). Other indepatients (nÅ 501) attending the outpatient clinic were enrolled in a pendent risk factors were older age and male sex. Cirprospective study aimed at early recognition of HCC. Of these, 109 rhotic patients infected with HCV type 1b carry a were patients already included in a follow-up program, and 392 were significantly higher risk of developing HCC than panew referrals. The diagnosis of cirrhosis was confirmed histologically tients infected by other HCV types. The latter may reor based on clinical signs of portal hypertension as esophageal or quire a less intensive clinical surveillance for the early gastric varices, ascites, and splenomegaly. At enrollment, complete detection of neoplasia. (HEPATOLOGY 1997;25:754-758.) medical history and physical examination were obtained for each patient, and serological and biochemical screenings were performed, which included standard liver function tests, AFP, and hepatitis B Hepatitis C virus (HCV) is a major etiological agent associand delta virus markers. The Child-Turcotte score, modified by Pugh, ated with the development of cirrhosis. 1 HCV infection alone was also calculated. Aliquots of sera collected at entry were stored accounts for over 25% of all cases of cirrhosis in Italy, 2 a at 030ЊC for further serological and molecular analysis. When hepacondition that is associated with an increased risk of hepatotitis C virus antibody (anti-HCV) serology became available, sera cellular carcinoma (HCC), with a yearly incidence rate of from 472 of 501 patients were tested by second-generation enzyme immunoassay (Ortho Diagnostic Systems, Raritan, NJ), and 240 subjects (51%) were found to be anti-HCV-positive. Seventy-seven anti-HCV-positive patients were further excluded from the study Abbreviations: HCV, hepatitis C virus; HCC, hepatocellular carcinoma; US, ultrasound; according to the following criteria: 1) evidence for, or suspicion of, AFP, a-fetoprotein; anti-HCV, hepatitis C virus antibodies.
Acta Endocrinologica, 1981
Increased serum growth hormone (GH) and prolactin (Prl) levels and abnormal responses to some sti... more Increased serum growth hormone (GH) and prolactin (Prl) levels and abnormal responses to some stimuli have been reported in patients with chronic liver disease. Serum GH and Prl concentrations were measured in 11 cirrhotic patients and in sex and age matched healthy controls in basal conditions and after administration of L-dopa alone (500 mg), and L-dopa (100 mg) with carbidopa (35 mg) following pre-treatment with carbidopa (50 mg every 6 h for one day), a regimen which results in selective activation of brain dopaminergic pathways. Basal GH and Prl levels were significantly higher in cirrhotics than in controls; serum GH did not increase significantly and serum Prl was subnormally inhibited in patients after both tests. A patient with clearcut hyperprolactinaemia unresponsive to dopaminergic stimulation showed normal basal Prl levels and suppression by L-dopa following clinical improvement, while her elevated GH levels remained unchanged and did not increase after L-dopa. These data confirm the existence of abnormalities in the regulation of GH and Prl release in liver cirrhosis and suggest that dopaminergic dysfunction may be responsible. The subnormal Prl suppression induced by L-dopa, which stimulates both brain and peripheral dopaminergic receptors, suggests that dopaminergic dysfunction is not confined to the central nervous system in liver cirrhosis. It appears that serum Prl concentration may be of value in monitoring decompensated liver disease and that abnormalities of Prl secretion are reversible with clinical improvement.
Gastroenterology, 1997
The preneoplastic role of macroregenerative nodules in cirrhosis is still debated. Thirty-two con... more The preneoplastic role of macroregenerative nodules in cirrhosis is still debated. Thirty-two consecutive ultrasonography-detected macronodules were followed up to evaluate whether and which lesions are the actual precursors of hepatocellular carcinoma, if histology can identify preneoplastic macronodules, and whether additional parameters are related to neoplastic evolution. Macroregenerative nodule classification was based on recently proposed histological criteria. Extranodular liver cell dysplasia was also evaluated. The follow-up included ultrasonography and serum alpha-fetoprotein level determination every 3 months. Twenty-two macronodules (78%) were classified as typical and 7 (22%) as atypical. Twenty-one were hypoechoic, and 11 were hyperechoic. Extranodular dysplasia was more frequently associated with atypical than typical macronodules (5 of 7 vs. 6 of 22). After 28 +/- 15 months, neoplastic transformation occurred in 8 macronodules (25%) and was more frequent in atypical than in typical (5 of 7 vs. 3 of 25), in hyperechoic than in hypoechoic (5 of 11 vs. 3 of 21), and in extranodular dysplasia-associated macronodules than in extranodular dysplasia-free macronodules (5 of 11 vs. 2 of 18). Five hepatocellular carcinomas appeared outside the original macronodule. Atypical macroregenerative nodules can be considered precursors of hepatocellular carcinoma. Histology is useful in identifying preneoplastic macronodules, and hyperechoic pattern and extranodular dysplasia are additional risk factors for neoplastic transformation.
American Journal of Gastroenterology, 2012
Letters to the Editor may be associated with symptoms of IBS, CVS, atopic dermatitis, fi bromyalg... more Letters to the Editor may be associated with symptoms of IBS, CVS, atopic dermatitis, fi bromyalgia, and chronic fatigue (6). Th e diagnosis of a mitochondrial-based disorder is supported by a matrilineal family history, with his mother Susannah and her mother Sarah both having chronic illness for most of their later lives. Susannah ' s brother Tom suff ered headaches, abdominal pain, and seasickness, and had marked cold sensitivity. As well as Susannah and Tom, Sarah had two other children who were probably affl icted. Richard died in infancy with a gastrointestinal complaint; Mary Ann was of short stature and retarded. She suff ered from epilepsy, episodes of blindness, and paralysis. She died at the age of eight with symptoms typical of the MELAS syndrome. An A3243G mitochondrial DNA mutation explains the illnesses of Darwin, of his mother, his maternal uncle, his maternal grandmother, and other relations. Whitehead et al. postulate that IBS and its comorbidity disorders may have shared pathophysiological mechanisms (3). It is proposed that mitochondrial dysfunction may be one such mechanism.
Minerva Chirurgica, 1999
BACKGROUND AND AIMS The use of steroids was recently extended to the various forms of ulcerative ... more BACKGROUND AND AIMS The use of steroids was recently extended to the various forms of ulcerative rectocolitis by the introduction of topical formulations, above all steroids with an hepatic "first pass" devoid of systemic interference. The aim of this study was to evaluate the efficacy and tolerability of Beclomethasone dipropionate (BDP) in a rectal foam formulation, in the treatment of patients suffering from ulcerative colitis. METHODS The experimental protocol took the form of a 28-day open prospective trial using BDP rectal foam in patients suffering from ulcerative colitis. Endoscopic, histological, clinical and tolerability parameters were evaluated. The centres taking part in the trial collected data for 60 cases out of a total of 80 patients enrolled in the study, of both sexes and aged between 20 and 81 years old, suffering from proctosigmoiditis (46.7%) and ulcerative rectocolitis (53.3%). RESULTS Endoscopic parameters showed an improvement after 28 days of trea...
Liver international : official journal of the International Association for the Study of the Liver, Jan 10, 2018
Metabolic disorders are well known risk factors for HCC. Conversely, their impact on the natural ... more Metabolic disorders are well known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its etiology. We analyzed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analyzed: BMI, diabetes, arterial hypertension, hypercholesterolemia and hypertriglyceridemia. According to these features, patients were divided into 3 groups: 0{\hyphen}1, 2 and 3{\hyphen}5 metabolic features. As compared with patients with 0{\hyphen}1 metabolic features, patients with 3{\hyphen}5 features showed lower percentage of HCC diagnosis on surveillance (p{\equal}0.021), larger tumors (p{\equal}0.038), better liver function (higher percentage of Child{\hyphen}Pugh class A [p{\equal}0.007] and MELD{\lt}10 [p{\equal}0.003]), higher percentage of metastasis (p{\equal}0.02...
Alimentary pharmacology & therapeutics, Jan 11, 2016
Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its ... more Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. To assess how many years of life are lost after HCC diagnosis. Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when ...
Minerva gastroenterologica e dietologica, 1999
The authors assessed the efficacy and tolerability of BDP in an open protocol using rectal enemas... more The authors assessed the efficacy and tolerability of BDP in an open protocol using rectal enemas and suppositories and in a double-blind protocol vs mesalazine using rectal enemas. A total of 47 patients suffering from ulcerous rectocolitis were enrolled in the study and treated for 42 days while undergoing endoscopic, histologic and clinical controls. In conclusion, the authors affirm that BDP may represent a useful new therapeutic instrument in the treatment of slight to moderately severe forms of inflammatory intestinal disease.
Minerva chirurgica, 1999
The use of steroids was recently extended to the various forms of ulcerative rectocolitis by the ... more The use of steroids was recently extended to the various forms of ulcerative rectocolitis by the introduction of topical formulations, above all steroids with an hepatic "first pass" devoid of systemic interference. The aim of this study was to evaluate the efficacy and tolerability of Beclomethasone dipropionate (BDP) in a rectal foam formulation, in the treatment of patients suffering from ulcerative colitis. The experimental protocol took the form of a 28-day open prospective trial using BDP rectal foam in patients suffering from ulcerative colitis. Endoscopic, histological, clinical and tolerability parameters were evaluated. The centres taking part in the trial collected data for 60 cases out of a total of 80 patients enrolled in the study, of both sexes and aged between 20 and 81 years old, suffering from proctosigmoiditis (46.7%) and ulcerative rectocolitis (53.3%). Endoscopic parameters showed an improvement after 28 days of treatment in 74.5% of patients; a clinic...
Recenti progressi in medicina, 1989
We report a case of intestinal schistosomiasis; secondary hepatic involvement is particularly des... more We report a case of intestinal schistosomiasis; secondary hepatic involvement is particularly described, with a very distinctive ecographic feature of portal hypertension and a bioptic picture stressing a granulomatous periportal inflammation. In the work we emphasize the importance of a multidisciplinary approach (physicians working in the fields of internal medicine, infectious disease, gastrointestinal diseases, radiologist, pathologist) in the course of diagnostic investigation. Finally, we confirm the effectiveness of praziquantel against Schistosoma mansoni.
Hepatology, 2014
The prognosis of untreated patients with hepatocellular carcinoma (HCC) is heterogeneous, and sur... more The prognosis of untreated patients with hepatocellular carcinoma (HCC) is heterogeneous, and survival data were mainly obtained from control arms of randomized studies. Clinical practice data on this topic are urgently needed, so as to help plan studies and counsel patients. We assessed the prognosis of 600 untreated patients with HCC managed by the Italian Liver Cancer Group. Prognosis was evaluated by subdividing patients according to the Barcelona Clinic Liver Cancer (BCLC) classification. We also assessed the main demographic, clinical, and oncological determinants of survival in the subgroup of patients with advanced HCC (BCLC C). Advanced (BCLC C: n 5 138; 23.0%) and end-stage HCC (BCLC D; n 5 210; 35.0%) represented the majority of patients. Overall median survival was 9 months, and the principal cause of death was tumor progression (n 5 279; 46.5%). Patients' median survival progressively and significantly decreased as BCLC stage worsened (BCLC 0: 38 months; BCLC A: 25 months; BCLC B: 10 months; BCLC C: 7 months; BCLC D: 6 months; P < 0.0001). Female gender (hazard ratio [HR] 5 0.55; 95% confidence interval [CI] 5 0.33-0.90; P 5 0.018), ascites (HR 5 1.81; 95% CI 5 1.21-2.71; P 5 0.004), and multinodular (>3) HCC (HR 5 1.79; 95% CI 5 1.21-2.63; P 5 0.003) were independent predictors of survival in patients with advanced HCC (BCLC C). Conclusion: BCLC adequately predicts the prognosis of untreated HCC patients. In untreated patients with advanced HCC, female gender, clinical decompensation of cirrhosis, and multinodular tumor are independent prognostic predictors and should be taken into account for patient stratification in future therapeutic studies.
Seminars in Oncology, 2014
Background. Standard liver function parameter levels and tumor indices were analyzed using Networ... more Background. Standard liver function parameter levels and tumor indices were analyzed using Network Phenotyping Strategy (NPS), a graph-theory based approach, which compares personal patterns of complete relationships between clinical data to reference patterns with significant association to disease outcome. We previously applied NPS to Taiwan hepatocellular cancer (HCC) patients and recognized two clinical phenotypes, S and L, differing in the size and tumor nodule numbers. Aims. To validate the applicability of the NPS-based HCC S/L classification on an independent European HCC cohort, for which survival information was additionally available. Results. Patients with S and L phenotypes, recognized by the same data processing as previously, had 1.5x larger mean tumor masses in L relative to S, p=6x10-16. S-phenotype patients had typically 1.7x longer survival compared to L-phenotype. NPS integrated liver-and tumor factors. Cirrhosis associated thrombocytopenia was typical for smaller S-tumors. Hepatic inflammation and tumor factors contributed to more aggressive L tumors, with parenchymal destruction and shorter survival. Summary. NPS provides integrative interpretation for HCC behavior, identifying by clinical parameter patterns two tumor and survival phenotypes. The NPS classifier was implemented as an application for web browsers and is available upon request
The Lancet Oncology, 2011
Background Allocation of deceased-donor livers to patients with chronic liver failure is improved... more Background Allocation of deceased-donor livers to patients with chronic liver failure is improved by prioritising patients by 5-year liver transplantation survival benefi t. The Barcelona Clinic Liver Cancer (BCLC) staging has been proposed as the standard means to assess for prognosis of patients with hepatocellular carcinoma. We aimed to create a prediction model linking the BCLC stage of patients with hepatocellular carcinoma to their 5-year liver transplant benefi t. Methods A large cohort of consecutive patients with hepatocellular carcinoma (n=1328) from the ITA.LI.CA database (n=2951) were judged as potentially eligible for liver transplantation according to the following criteria: absence of macroscopic vascular invasion or metastases, age 70 years or younger, and absence of relevant extra-hepatic comorbidities. To assess the correlation between BCLC staging and non-liver transplantation survival, we did Cox univariate and multivariate analyses including the following covariates: BCLC stage, year of diagnosis, age, sex, cause of cirrhosis, model for end-stage liver disease score, α-fetoprotein concentrations, and treatment. Liver-transplantation survival benefi t for patients was calculated, using Monte Carlo simulation analysis, as the patient's 5-year life expectancy with liver transplantation (estimated by the Metroticket model) minus the 5-year life expectancy without liver transplantation according to BCLC stage. Findings 83 (6%) of 1328 patients had BCLC 0 stage disease, 614 (46%) had BCLC A, 500 (38%) had BCLC B-C, and 131 (10%) had BCLC D. In the Cox non-liver transplantation survival multivariate model, hazard ratios associated with increasing BCLC stages were 1•530 (95% CI 1•107-2•116) for BCLC A versus BCLC 0, 1•572 (1•350-1•830) for BCLC B-C versus BCLC A, and 1•470 (1•164-1•856) for BCLC D versus BCLC B-C. Results of the Monte Carlo simulation analysis confi rmed the signifi cant eff ect of BCLC classifi cation on transplant benefi t; in the adjusted model, a median 5-year transplant benefi t of 11•19 months (IQR 10•73-11•67) for BCLC 0, 13•49 months (11•51-15•57) for BCLC A, 17•36 months (15•06-19•28) for BCLC B-C, and 28•46 months (26•38-30•34) for BCLC D. Interpretation Liver transplantation could result in survival benefi t for patients with hepatocellular carcinoma and advanced liver cirrhosis (BCLC stage D) and in those with intermediate tumours (BCLC stages B-C), regardless of the nodule number-size criteria (ie, Milan criteria), provided that macroscopic vascular invasion and extra-hepatic disease are absent.
Journal of Hepatology, 2009
Background and Aim: Prognosis of HCC is not entirely predictable because both liver failure and c... more Background and Aim: Prognosis of HCC is not entirely predictable because both liver failure and cancer progression affect survival by complex interactions. Aim of our study was to construct a prognostic index called NAPI tailored for cirrhotic patients with treatable HCC. Methods: We prospectively evaluated 282 patients with Child-Pugh 7 cirrhosis and HCC within Milan criteria seen at our Liver Unit (training cohort). Survival was estimated by the Kaplan-Meier method, and differences between groups assessed by the log-rank test. Potential risk factors for death were identified by Cox proportional-hazards analysis and, to develop a practical prognostic score, we assigned these factors weighted points proportional to the b-regression coefficient values. The system was validated in 171 consecutive patients selected from the database of another hospital (validation cohort) and was compared with the CLIP and BCLC systems. Results: During a median follow-up of 34 months, 163 patients in the training cohort died. Four independent prognostic factors were identified: no HCC treatment or incomplete treatment effect (4 points), 3.3 g/dL (3 points), MELD albumin >11 (2 points), and abnormal serum alkaline phosphatase (2 points). Risk score for each patient was calculated and the population divided in three groups: low-risk (0 points), intermediaterisk (2−5 points), and high-risk (6−11 points). In the training cohort, the median survival for these groups was 108, 42, and 25 months respectively. In the validation cohort, the corresponding median survival was 77, 45, and 24 months. Considering the 5-year mortality risk, the C-statistic was 0.786 in the training cohort and 0.716 in the validation cohort. The corresponding C-statistics for the BCLC and the CLIP staging systems were 0.679 and 0.736 in the training cohort, and 0.476 and 0.517 in the validation cohort respectively. Conclusions: A new risk score for predicting death in cirrhotic patients with treatable HCC was developed and validated in an independent cohort. This score performed better than the two score systems more diffusely used in clinical practice. NAPI score may be an useful tool in clinical practice to optimize the therapeutic strategy.
Journal of Hepatology, 1994
To evaluate the diagnostic accuracy of fine-needle aspiration, fine-needle biopsy and extranodula... more To evaluate the diagnostic accuracy of fine-needle aspiration, fine-needle biopsy and extranodular fine needle biopsy in identifying focal lesions in cirrhosis, 100 consecutive ultrasound detected nodules were studied. Seventy-three were hepatocellular carcinomas (31 were well-differentiated hepatocellular carcinomas), 23 were benign lesions (one angioma and 22 large regenerative nodules) and two were metastases. The lesions were divided according to maximum diameter as follows: &amp;amp;amp;lt; 20 mm in 36, &amp;amp;amp;gt; 20 &amp;amp;amp;lt; 30 mm in 27, and &amp;amp;amp;gt; 30 mm in 33. In four cases there were multiple nodules of different sizes. Fine needle aspiration, intranodular fine needle biopsy and extranodular fine needle biopsy were obtained in each lesion. The sensitivity, specificity and diagnostic accuracy of each procedure were evaluated separately by three independent pathologists. Seven fine needle aspirations and three intranodular fine needle biopsies were considered inadequate. The highest diagnostic accuracy (96%) was obtained by the combined analysis of fine needle aspiration plus intranodular and extranodular fine needle biopsy, and this superiority was confirmed in each group of lesions. Fine needle aspiration showed a lower accuracy (48%) than intranodular fine needle biopsy (67%). When fine needle aspiration and intranodular fine needle biopsy were evaluated together, an accuracy of 91% was found. Intralesional fine needle biopsy plus extranodular fine needle biopsy analysis gave an accuracy of 78% and, particularly relevant, a specificity of 95%. These results indicate that, in patients with cirrhosis with nodular lesions &amp;amp;amp;lt; 30 mm, fine needle biopsy is superior to fine needle aspiration and that the combined evaluation of fine needle aspiration plus intranodular and extranodular fine needle biopsy is the most accurate approach.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Hepatology, 2003
Background/Aims: The natural outcome of ultrasound-detected macronodules in cirrhosis is still po... more Background/Aims: The natural outcome of ultrasound-detected macronodules in cirrhosis is still poorly understood. In this study we assessed the incidence and predictors of malignant transformation in a prospective study of 90 consecutive ultrasound-detected macronodules in cirrhosis. Methods: Macronodules classification was based on recently proposed histological criteria. Extranodular large (LCC) and small cell changes were also evaluated. The follow-up included ultrasound and serum alfa-fetoprotein determination every 3 months. Independent predictors of hepatocellular carcinoma were evaluated by Cox proportional hazards regression analysis. Results: During a mean follow-up of 33 months, 28 (31%) nodules transformed into hepatocellular carcinoma. The incidence of hepatocellular carcinoma per 100 person-years of follow-up was 11.3%, with a malignant transformation rate of 3.5, 15.5, 31 and 48.5% at 1, 2, 3, and 5 years respectively. High-grade dysplastic nodules (HGDN) (hazard risk 5 2.4; CI 95% 5 1.1-5.0) and LCC (hazard risk 5 3.1; CI 95% 5 1.2-7.8) were independent predictors of malignant transformation. Eight additional hepatocellular carcinomas developed outside the original lesions raising the overall malignant transformation rate to 40% while 15 macronodules (17%) became undetectable at ultrasound (US). Conclusions: Macronodules characterize a cirrhotic subpopulation with high risk of hepatocellular carcinoma. HGDN and LCC are strong predictors of malignant transformation; subjects with simultaneous presence of both these two conditions are at highest risk of cancer development. The management of cirrhotics with macronodules should be based on morphologic features detected on liver microsamples.
Hormone and Metabolic Research, 1983
Anomalies du taux des hormones pituitaires chez des patients cirrhotiques. Elles sont probablemen... more Anomalies du taux des hormones pituitaires chez des patients cirrhotiques. Elles sont probablement liees a une modification de divers neurotransmetteurs dont la dopamine et la serotonine, en raison d'une accumulation de faux neurotransmetteurs
Hepatology, 2012
11 for the Italian Liver Cancer (ITA.LI.CA) group Alpha-fetoprotein is a tumor marker that has be... more 11 for the Italian Liver Cancer (ITA.LI.CA) group Alpha-fetoprotein is a tumor marker that has been used for surveillance and diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. The prognostic capability of this marker in patients with HCC has not been clearly defined. In this study our aim was to evaluate the prognostic usefulness of serum alpha-fetoprotein in patients with well-compensated cirrhosis, optimal performance status, and small HCC identified during periodic surveillance ultrasound who were treated with curative intent. Among the 3,027 patients included in the Italian Liver Cancer study group database, we selected 205 Child-Pugh class A and Eastern Cooperative Group Performance Status 0 patients with cirrhosis with a single HCC 3 cm of diameter diagnosed during surveillance who were treated with curative intent (hepatic resection, liver transplantation, percutaneous ethanol injection, radiofrequency thermal ablation). Patients were subdivided according to alpha-fetoprotein serum levels (i.e., normal 20 ng/mL; mildly elevated 21-200 ng/mL; markedly elevated >200 ng/mL). Patient survival, as assessed by the Kaplan-Meier method, was not significantly different among the three alpha-fetoprotein classes (P 5 0.493). The same result was obtained in the subgroup of patients with a single HCC 2 cm (P 5 0.714). An alpha-fetoprotein serum level of 100 ng/mL identified by receiver operating characteristic curve had inadequate accuracy (area under the curve 5 0.536, 95% confidence interval 5 0.465-0.606) to discriminate between survivors and deceased patients. Conclusion: Alphafetoprotein serum levels have no prognostic meaning in well-compensated cirrhosis patients with single, small HCC treated with curative intent.
Gastroenterology, 1995
The authors thank Professor Roberto De Franchis for his extensive and dedicated editorial review,... more The authors thank Professor Roberto De Franchis for his extensive and dedicated editorial review, as well as for his support and encouragement.
European Journal of Gastroenterology & Hepatology, 2002
Hepatocellular carcinogenesis in cirrhosis is a multistage process that includes large regenerati... more Hepatocellular carcinogenesis in cirrhosis is a multistage process that includes large regenerative nodules, dysplastic nodules, and hepatocarcinoma. The aim of this study was to establish whether contrast-enhanced Doppler ultrasonography (US) is able to distinguish between early hepatocellular carcinoma (HCC) and small nonmalignant nodules in cirrhosis. Between January 1998 and December 1999, 500 cirrhotic patients with no previous history of HCC or evidence of hepatic focal lesions were enrolled and prospectively followed-up with US every 6 months until December 2000. Sixty-one patients developed focal lesions, 12 multifocal, and 49 monofocal. Biopsy of focal lesions, contrast-enhanced Doppler US, and spiral computed tomography (CT) were performed in 41 consecutive patients with small (<3 cm) monofocal lesions. Twenty nodules were diagnosed as HCC and 21 as nonmalignant (14 large regenerative nodules, 3 low-grade, and 4 high-grade dysplastic nodules) by liver biopsy. Intratumoral arterial blood flow was detected in 19 of 20 (95%) HCC and 6 of 21 (28%) nonmalignant nodules by contrast-enhanced Doppler US (P<.0001). The mean peak resistance and pulsatility indices were 0.82 +/- 0.09 and 1.56 +/- 0.2 in HCC and 0.62 +/- 0.08 and 0.82 +/- 0.08 in dysplastic lesions (P =.002 and.0001), respectively. Spiral CT revealed arterial perfusion in 19 of 20 HCC and in 4 of 21 nonmalignant nodules (high-grade dysplastic nodules). Four of the apparently false-positive nodules at enhanced Doppler US were high-grade dysplastic nodules and 2 evolved to HCC during follow-up. In conclusion, contrast-enhanced Doppler US is a noninvasive, very sensitive technique in differentiating malignant and premalignant lesions from nonmalignant focal lesions in the liver.
European Journal of Gastroenterology & Hepatology, 1996
approximately 3%. 3,4 Early detection of HCC in cirrhotic pa-A prospective study was performed to... more approximately 3%. 3,4 Early detection of HCC in cirrhotic pa-A prospective study was performed to establish tients can usually be achieved by screening with noninvasive whether infection with specific hepatitis C virus (HCV) techniques, such as ultrasound (US) scan and serum a-fetogenotypes was associated with an increased risk of protein (AFP) concentration. 5,6 development of hepatocellular carcinoma (HCC) in cir-Over the years, several lines of experimental evidence indirhosis. A cohort of 163 consecutive hepatitis C virus anticated that male sex, age, and alcohol consumption 4,7,8 were body (anti-HCV)-positive cirrhotic patients was proclosely associated with the development of HCC in cirrhotic spectively evaluated for the development of HCC at patients. The identification of additional variables associated 6-month intervals by ultrasound (US) scan and awith an increased risk of developing HCC would be particufetoprotein (AFP) concentration. HCV genotypes were larly important to optimize preventive medical programs in determined according to Okamoto. Risk factors associthis setting. Recent studies suggested a possible role for HCV ated with cancer development were analyzed by univarigenotype in chronic liver disease outcome and, specifically, ate and multivariate statistics. At enrollment, 101 pa-HCV type 1 was more frequently found in advanced liver tients (62%) were infected with type 1b, 48 (29.5%) were disease, such as cirrhosis and HCC, 9-11 and was associated infected with type 2a/c, 2 (1.2%) were infected with type with a more rapid deterioration of liver histology in chronic 3a, 1 (0.6%) was infected with type 1a, 3 (1.8%) had a hepatitis. 12 We have studied the distribution of HCV genomixed-type infection, and, in 8 patients (4.9%), genotype types in a cohort of patients with cirrhosis prospectively folcould not be assigned. After a 5-to 7-year follow-up (melowed for early detection of HCC, and we performed multivardian, 68 months), HCC developed in 22 of the patients, iate analysis to evaluate the independent risk for tumor 19 infected with type 1b and 3 with type 2a/c (P õ .005). development associated with specific HCV types and with Moreover, HCC developed more frequently in males (P other variables, including interferon treatment, which has õ .01), patients with excessive alcohol intake (P õ .01), been recently reported to reduce the cancer risk in HCVthose over 60 years of age (P õ .02), and in patients who induced cirrhosis. 13 did not receive interferon treatment (P õ .02). Multivariate analysis showed that type 1b was the most important PATIENTS AND METHODS risk factor associated with tumor development (odds ra-Patients. Between January 1989 and December 1990, all cirrhotic tio 6.14, 1.77-21.37 95% confidence interval). Other indepatients (nÅ 501) attending the outpatient clinic were enrolled in a pendent risk factors were older age and male sex. Cirprospective study aimed at early recognition of HCC. Of these, 109 rhotic patients infected with HCV type 1b carry a were patients already included in a follow-up program, and 392 were significantly higher risk of developing HCC than panew referrals. The diagnosis of cirrhosis was confirmed histologically tients infected by other HCV types. The latter may reor based on clinical signs of portal hypertension as esophageal or quire a less intensive clinical surveillance for the early gastric varices, ascites, and splenomegaly. At enrollment, complete detection of neoplasia. (HEPATOLOGY 1997;25:754-758.) medical history and physical examination were obtained for each patient, and serological and biochemical screenings were performed, which included standard liver function tests, AFP, and hepatitis B Hepatitis C virus (HCV) is a major etiological agent associand delta virus markers. The Child-Turcotte score, modified by Pugh, ated with the development of cirrhosis. 1 HCV infection alone was also calculated. Aliquots of sera collected at entry were stored accounts for over 25% of all cases of cirrhosis in Italy, 2 a at 030ЊC for further serological and molecular analysis. When hepacondition that is associated with an increased risk of hepatotitis C virus antibody (anti-HCV) serology became available, sera cellular carcinoma (HCC), with a yearly incidence rate of from 472 of 501 patients were tested by second-generation enzyme immunoassay (Ortho Diagnostic Systems, Raritan, NJ), and 240 subjects (51%) were found to be anti-HCV-positive. Seventy-seven anti-HCV-positive patients were further excluded from the study Abbreviations: HCV, hepatitis C virus; HCC, hepatocellular carcinoma; US, ultrasound; according to the following criteria: 1) evidence for, or suspicion of, AFP, a-fetoprotein; anti-HCV, hepatitis C virus antibodies.
Acta Endocrinologica, 1981
Increased serum growth hormone (GH) and prolactin (Prl) levels and abnormal responses to some sti... more Increased serum growth hormone (GH) and prolactin (Prl) levels and abnormal responses to some stimuli have been reported in patients with chronic liver disease. Serum GH and Prl concentrations were measured in 11 cirrhotic patients and in sex and age matched healthy controls in basal conditions and after administration of L-dopa alone (500 mg), and L-dopa (100 mg) with carbidopa (35 mg) following pre-treatment with carbidopa (50 mg every 6 h for one day), a regimen which results in selective activation of brain dopaminergic pathways. Basal GH and Prl levels were significantly higher in cirrhotics than in controls; serum GH did not increase significantly and serum Prl was subnormally inhibited in patients after both tests. A patient with clearcut hyperprolactinaemia unresponsive to dopaminergic stimulation showed normal basal Prl levels and suppression by L-dopa following clinical improvement, while her elevated GH levels remained unchanged and did not increase after L-dopa. These data confirm the existence of abnormalities in the regulation of GH and Prl release in liver cirrhosis and suggest that dopaminergic dysfunction may be responsible. The subnormal Prl suppression induced by L-dopa, which stimulates both brain and peripheral dopaminergic receptors, suggests that dopaminergic dysfunction is not confined to the central nervous system in liver cirrhosis. It appears that serum Prl concentration may be of value in monitoring decompensated liver disease and that abnormalities of Prl secretion are reversible with clinical improvement.