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Matteo Fassan,
Marco Pizzi,
Stefano Realdon,
Mariangela Balistreri,
Vincenza Guzzardo,
Vittorina Zagonel,
Carlo Castoro,
Luca Mastracci, Fabio Farinati,
Donato Nitti,
Giovanni Zaninotto,
Massimo Rugge
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ABSTRACT: A subset of gastric (intestinal-type) and esophageal (Barrett) adenocarcinoma features HER2 protein overexpression. Consistent evidence demonstrates that microRNAs have a major role in HER2 (dys)regulation. MiR-125a-5p and miR125b expressions were tested in the spectrum of lesions in the gastroesophageal carcinogenic cascade, also correlating miR-125a-5p/125b levels with HER2 status. MiR-125a-5p and miR-125b expression (quantitative reverse transcriptase polymerase chain reaction [qRT-PCR]) and HER2 status (immunohistochemistry [IHC] and chromogenic in situ hybridization [CISH]) were assessed in a series of 90 biopsy samples spanning the whole histologic spectrum of gastric and esophageal carcinogenesis. To support the obtained results, the qRT-PCR levels of microRNAs and their expression (in situ hybridization) were tested in an adjunctive series of gastric and esophageal adenocarcinoma, including (IHC/CISH validated) HER2-negative and HER2-positive cases. Both miR-125a-5p and miR-125b levels were significantly down-regulated throughout the gastric and esophageal carcinogenic cascade. HER2 status (IHC and CISH) correlated inversely with miR-125 expression (qRT-PCR and in situ hybridization). Dysregulation of miR-125a-5p/125b and HER2 is an early event in the gastric (intestinal-type) and esophageal (Barrett) oncogenesis. In both oncogenetic cascades, miR-125 expression correlates inversely with HER2 status. MiR-125a-5p/125b can be considered among the therapeutic targets in HER2-positive esophageal and gastric adenocarcinoma.
Human pathology 04/2013; · 3.03 Impact Factor
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Hepatology 03/2013; · 11.66 Impact Factor
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ABSTRACT: The aim of this study was to demonstrate the safety and efficacy of laparoscopic ablation for cirrhotic HCC patients. Between January 2004 and December 2009, laparoscopic ablation was applied prospectively in 169 consecutive HCC patients (median age 62 years, 43% hepatitis C positive) considered ineligible for liver resection and/or percutaneous ablation. There was clinically relevant portal hypertension in 72% of cases. A significant proportion of subjects (50%) had multinodular tumors or nodules larger than 25 mm. The main ablation techniques used were radiofrequency in 103 patients (61%), microwave ablation in 8 (5%), and ethanol injection in 58 (34%). The primary endpoint was 3-year survival. There was no perioperative mortality. The overall morbidity rate was 25%. The median postoperative hospital stay was 3 days (range 1-19 days). Patients survived a median 33 months with a 3-year survival rate of 47%. Cox's multivariate analysis identified patient age, presence of diabetes, albumin ≤37 g/l, and alpha-fetoprotein >400 µg/l as significant preoperative predictors of survival, while the chance to undergo liver transplantation and postoperative ascites were the only independent postoperative predictor of survival. Laparoscopic ablation is a safe and effective therapeutic option for selected HCC patients ineligible for liver resection and/or percutaneous ablation.
PLoS ONE 01/2013; 8(2):e57249. · 4.09 Impact Factor
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ABSTRACT: BACKGROUND: Coffee is associated with a reduced risk of hepatocellular carcinoma in patients with chronic C hepatitis. This prospective trial was aimed at assessing the mechanisms underlying coffee-related protective effects. METHODS: Forty patients with chronic hepatitis C were randomized into two groups: the first consumed 4 cups of coffee/day for 30 days, while the second remained coffee "abstinent". At day 30, the groups were switched over for a second month. RESULTS: At baseline, aspartate aminotransferase and alanine aminotransferase were lower in patients drinking 3-5 (Group B) than 0-2 cups/day (Group A) (56±6 vs 74±11/60±3 vs 73±7U/L p=0.05/p=0.04, respectively). HCV-RNA levels were significantly higher in Group B [(6.2±1.5)×10(5)vs (3.9±1.0)×10(5)UI/mL, p=0.05]. During coffee intake, 8-hydroxydeoxyguanosine and collagen levels were significantly lower than during abstinence (15±3 vs 44±16 8-hydroxydeoxyguanosine/10(5)deoxyguanosine, p=0.05 and 56±9 vs 86±21ng/mL, p=0.04). Telomere length was significantly higher in patients during coffee intake (0.68±0.06 vs 0.48±0.04 Arbitrary Units, p=0.006). Telomere length and 8-hydroxydeoxyguanosine were inversely correlated. CONCLUSION: In chronic hepatitis C coffee consumption induces a reduction in oxidative damage, correlated with increased telomere length and apoptosis, with lower collagen synthesis, factors that probably mediate the protection exerted by coffee with respect to disease progression.
Digestive and Liver Disease 12/2012; · 3.05 Impact Factor
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Massimo Rugge,
Giovanni Zaninotto,
Paola Parente,
Lisa Zanatta,
Francesco Cavallin,
Bastianello Germanà,
Ettore Macrì,
Ermenegildo Galliani,
Paolo Iuzzolino,
Francesco Ferrara, [......], Fabio Farinati,
Giorgio Battaglia,
Giorgio Diamantis,
Stefano Realdon,
Ennio Guido,
Gaetano Mastropaolo,
Daniele Canova,
Antonello Guerini,
Marilisa Franceschi,
Maurizio Zirillo
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ABSTRACT: OBJECTIVE:: To establish the incidence and risk factors for progression to high-grade intraepithelial neoplasia (HG-IEN) or Barrett's esophageal adenocarcinoma (BAc) in a prospective cohort of patients with esophageal intestinal metaplasia [(BE)]. BACKGROUND:: BE is associated with an increased risk of BAc unless cases are detected early by surveillance. No consistent data are available on the prevalence of BE-related cancer, the ideal surveillance schedule, or the risk factors for cancer. METHODS:: In 2003, a regional registry of BE patients was created in north-east Italy, establishing the related diagnostic criteria (endoscopic landmarks, biopsy protocol, histological classification) and timing of follow-up (tailored to histology) and recording patient outcomes. Thirteen centers were involved and audited yearly. The probability of progression to HG-IEN/BAc was calculated using the Kaplan-Meier method; the Cox regression model was used to calculate the risk of progression. RESULTS:: HG-IEN (10 cases) and EAc (7 cases) detected at the index endoscopy or in the first year of follow-up were considered to be cases of preexisting disease and excluded; 841 patients with at least 2 endoscopies {median, 3 [interquartile range (IQR): 2-4); median follow-up = 44.6 [IQR: 24.7-60.5] months; total 3083 patient-years} formed the study group [male/female = 646/195; median age, 60 (IQR: 51-68) years]. Twenty-two patients progressed to HG-IEN or BAc (incidence: 0.72 per 100 patient-years) after a median of 40.2 (26.9-50.4) months. At multivariate analysis, endoscopic abnormalities, that is, ulceration or nodularity (P = 0.0002; relative risk [RR] = 7.6; 95% confidence interval, 2.63-21.9), LG-IEN (P = 0.02, RR = 3.7; 95% confidence interval, 1.22-11.43), and BE length (P = 0.01; RR = 1.16; 95% confidence interval, 1.03-1.30) were associated with BE progression. Among the LG-IEN patients, the incidence of HG-IEN/EAc was 3.17 patient-years, that is, 6 times higher than in BE patients without LG-IEN. CONCLUSIONS:: These results suggest that in the absence of intraepithelial neoplastic changes, BE carries a low risk of progression to HG-IEN/BAc, and strict surveillance (or ablative therapy) is advisable in cases with endoscopic abnormalities, LG-IEN or long BE segments.
Annals of surgery 11/2012; 256(5):788-795. · 7.90 Impact Factor
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Edoardo G Giannini,
Simona Marenco,
Linda Bruzzone,
Vincenzo Savarino, Fabio Farinati,
Paolo Del Poggio,
Gian Ludovico Rapaccini,
Maria Anna Di Nolfo,
Luisa Benvegnù,
Marco Zoli,
Franco Borzio,
Eugenio Caturelli,
Maria Chiaramonte,
Franco Trevisani
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ABSTRACT: BACKGROUND: In the Western world, hepatocellular carcinoma seldom develops in patients without cirrhosis, and reports describing the characteristics of non-cirrhotic patients with hepatocellular carcinoma are rather infrequent. METHODS: We evaluated the main clinical characteristics, treatment options, and survival of patients with hepatocellular carcinoma developed in non-cirrhotic liver among the 3027 consecutive cases of hepatocellular carcinoma accrued in the Italian Liver Cancer database during the last 20 years. RESULTS: We identified 52 patients with hepatocellular carcinoma in non-cirrhotic livers (1.7% of all hepatocellular carcinomas), 42 with (80.8%) and 10 without (19.2%) chronic liver disease. In patients without chronic liver disease, median tumour diameter was greater compared to patients with chronic liver disease (7.8 versus 4.0cm, P=0.046). Curative treatment was feasible in 20 patients (38.5%). Median overall survival was 26 months and 5-year survival rate was 23.7%. Detection of hepatocellular carcinoma outside surveillance (P=0.036), advanced hepatocellular carcinoma stage (P<0.0001), and non-curative treatment (P=0.007) were associated with worse prognosis, but tumour stage was the only independent predictor of survival. CONCLUSIONS: In Italy, less than 2% of hepatocellular carcinomas develop in a non-cirrhotic liver, and almost never in a normal liver. These patients frequently present with advanced tumours, have low eligibility rates for curative treatment, and have a dismal prognosis despite their preserved liver function.
Digestive and Liver Disease 10/2012; · 3.05 Impact Factor
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Edoardo G Giannini, Fabio Farinati,
Paolo Del Poggio,
Gian Ludovico Rapaccini,
Maria Anna Di Nolfo,
Luisa Benvegnù,
Marco Zoli,
Franco Borzio,
Eugenio Caturelli,
Maria Chiaramonte,
Franco Trevisani
The American Journal of Gastroenterology 10/2012; 107(10):1588-9. · 7.28 Impact Factor
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ABSTRACT: Dysregulation of autophagy is important in the pathogenesis of many diseases, including cancer. Several aspects of the biological role of autophagy are however still unclear and the relationship between apoptosis and autophagy, particularly in the liver has yet to be thoroughly explored. In this study we evaluated the expression of Beclin 1 (one of the main autophagocytic agents, which bridges autophagy, apoptosis and both differentiation), and both pro- (Bad, Bax) and anti-apoptotic (Bcl-2, Bcl-xL) factors in liver samples from patients with different stages of liver disease.
The study concerned 93 patients from 49 cases of chronic hepatitis (CH) (30 HCV and 19 HBV-related), 13 of cirrhosis (CIRR) (10 HCV and 3 HBV-related), 21 of hepatocellular carcinoma (both HCC and peritumoral tissues [PHCC]), and 10 controls (CONTR). Real-time PCR and Western blotting were used to measure mRNA and protein expression levels.
Beclin 1 mRNA levels were lower in HCC than in CH (P = 0.010) or CIRR (P = 0.011), and so were the Bcl-xL transcripts (P < 0.0001). Bad mRNA levels were higher in CH and CIRR than in CONTR, while Bax transcripts were increased in all tissues (P = 0.036). PHCC expressed the highest Bcl-2 mRNA levels. HBV-related CH tissues showed significantly higher Bcl-xL and Bad mRNA levels than HCV-related CH (P = 0.003 and P = 0.016, respectively).
High Beclin 1, Bcl-xL and Bad levels in CH and CIRR tissues suggest an interaction between autophagy and apoptosis in the early and intermediate stages of viral hepatitis. In HCC these processes seem to be downregulated, probably enabling the survival and growth of neoplastic hepatocytes.
BMC Gastroenterology 08/2012; 12:118. · 2.42 Impact Factor
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ABSTRACT: Chronic atrophic gastritis, a precancerous change for gastric cancer, shows a loss of appropriate glands, Helicobacter pylori infection and autoimmune gastritis being the two main etiologic factors. While H. pylori eradication is the mandatory treatment for the former, no etiologic treatment is available for the latter, in which a Th1-type response, modulated by Tregs and Th17 cells, is involved. H. pylori-related atrophic gastritis is a risk factor for gastric adenocarcinoma, while autoimmune atrophic gastritis is also linked to a substantial risk of gastric type I carcinoid, related to the chronic stimulus exerted by hypergastrinemia on enterochromaffin-like cells. Several studies have been published on gastric cancer treatment through an active specific immunotherapy, aimed at improving the immunoregulatory response and increasing the circulating tumor-specific T cells. No study on immunotherapy of carcinoids is available but, in our experience, the administration of an antigastrin 17 vaccine induced carcinoid regression in two out of three patients treated.
Immunotherapy 06/2012; 4(6):587-99. · 1.85 Impact Factor
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Cardin Romilda,
Piciocchi Marika,
Sinigaglia Alessandro,
Lavezzo Enrico,
Bortolami Marina,
Kotsafti Andromachi,
Cillo Umberto,
Zanus Giacomo,
Mescoli Claudia,
Rugge Massimo, Farinati Fabio
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ABSTRACT: MicroRNAs expression has been extensively studied in hepatocellular carcinoma but little is known regarding the relationship, if any, with inflammation, production of reactive oxygen species (ROS), host's repair mechanisms and cell immortalization. This study aimed at assessing the extent of oxidative DNA damage (8-hydroxydeoxyguanosine - 8-OHdG) in different phases of the carcinogenetic process, in relation to DNA repair gene polymorphism, telomeric dysfunction and to the expression of several microRNAs, non-coding genes involved in post-transcriptional regulation, cell proliferation, differentiation and death.
Tissue samples obtained either at surgery, [neoplastic (HCC) and adjacent non-cancerous cirrhotic tissues (NCCT)] at percutaneous or laparoscopic biopsy (patients with HCV or HBV-related hepatitis or patients undergoing cholecystectomy) were analysed for 8-OHdG (HPLC-ED), OGG1 (a DNA repair gene) polymorphism (PCR-RFLP), telomerase activity, telomere length (T/S, by RT-PCR), Taqman microRNA assay and Bad/Bax mRNA (RT-PCR). Fifty-eight samples from 29 HCC patients (obtained in both neoplastic and peritumoral tissues), 22 from chronic hepatitis (CH) and 10 controls (cholecystectomy patients - CON) were examined.
Eight-OHdG levels were significantly higher in HCC and NCCT than in CH and CON (p=0.001). Telomerase activity was significantly higher in HCC than in the remaining subgroups (p=0.002); conversely T/S was significantly lower in HCC (p=0.05). MiR-199a-b, -195, -122, -92a and -145 were down-regulated in the majority of HCCs while miR-222 was up-regulated. A positive correlation was observed among 8-OHdG levels, disease stage, telomerase activity, OGG1 polymorphisms and ALT/GGT levels. In HCC, miR-92 expression correlated positively with telomerase activity, 8-OHdG levels and Bad/Bax mRNA.
The above findings confirm the accumulation, in the progression of chronic liver damage to HCC, of a ROS-mediated oxidative DNA damage, and suggest that this correlates with induction of telomerase activity and, as a novel finding, with over-expression of miR-92, a microRNA that plays a role in both the apoptotic process and in cellular proliferation pathways.
BMC Cancer 05/2012; 12:177. · 3.01 Impact Factor
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ABSTRACT: Gastric intraepithelial neoplasia (IEN; formerly dysplasia) is an advanced precancerous lesion. Lesions indefinite for IEN mimic the IEN phenotype but lack some morphologic attributes of IEN. Indefinite for IEN lesions may arise in native foveolae (atypical foveolar hyperproliferation [aFH]) or intestinalized glands (hyperproliferative intestinal metaplasia [HIM]). The clinicopathologic outcome of such lesions is debated. We retrospectively studied the clinicopathologic behavior of 129 consecutive indefinite for IEN lesions (HIM, 98; aFH, 31; median follow-up, 31 months) and correlated outcome with the extent and topography of mucosal atrophy (assessed by OLGA staging) at the initial endoscopy/biopsy. At enrollment, aFH never coexisted with severe/extensive atrophy (all cases were in low-risk OLGA stages [0-II]), whereas HIM was associated with low- and high-risk OLGA stages (0-II, 73; III-IV, 25). At follow-up, IEN was never documented among cases enrolled as aFH, while follow-up endoscopy/biopsy documented 6 neoplastic intraepithelial lesions among 98 cases of HIM (6%, all had high-risk OLGA stages at initial biopsy). OLGA staging can stratify indefinite for IEN lesions into different risk classes, potentially contributing to decisions for a patient-specific follow-up strategy.
American Journal of Clinical Pathology 05/2012; 137(5):727-32. · 2.60 Impact Factor
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Edoardo G Giannini,
Simona Marenco,
Giacomo Borgonovo,
Vincenzo Savarino, Fabio Farinati,
Paolo Del Poggio,
Gian Ludovico Rapaccini,
Maria Anna Di Nolfo,
Luisa Benvegnù,
Marco Zoli,
Franco Borzio,
Eugenio Caturelli,
Maria Chiaramonte,
Franco Trevisani
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ABSTRACT: 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 = 0.493). The same result was obtained in the subgroup of patients with a single HCC ≤2 cm (P = 0.714). An alpha-fetoprotein serum level of 100 ng/mL identified by receiver operating characteristic curve had inadequate accuracy (area under the curve = 0.536, 95% confidence interval = 0.465-0.606) to discriminate between survivors and deceased patients. Conclusion: Alpha-fetoprotein serum levels have no prognostic meaning in well-compensated cirrhosis patients with single, small HCC treated with curative intent. (HEPATOLOGY 2012).
Hepatology 04/2012; 56(4):1371-1379. · 11.66 Impact Factor
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Journal of Hepatology 01/2012; 57(1):221-2. · 9.26 Impact Factor
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Alessandro Cucchetti,
Franco Trevisani,
Matteo Cescon,
Giorgio Ercolani, Fabio Farinati,
Paolo Del Poggio,
Gianludovico Rapaccini,
Maria Anna Di Nolfo,
Luisa Benvegnù,
Marco Zoli,
Franco Borzio,
Edoardo Giovanni Giannini,
Eugenio Caturelli,
Maria Chiaramonte,
Antonio Daniele Pinna
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ABSTRACT: It was recently shown that semi-annual surveillance for hepatocellular carcinoma (HCC) in cirrhotic patients provides a prognostic advantage over the annual program; however, its cost-effectiveness (CE) in the general cirrhotic population still needs to be defined.
A Markov model was built to compare CE of these two strategies, considering literature results and treatment modalities of 918 cirrhotic patients from the Italian Liver Cancer (ITA.LI.CA) database.
Results from the Markov model suggest that, compared to annual surveillance, semi-annual surveillance leads to a gain in quality-adjusted life expectancy, in an unselected cirrhotic population, of 1.35 quality-adjusted life-months (QALMs) over 10 years since surveillance start in compensated patients, and of 0.73 QALMs in decompensated patients. Semi-annual surveillance was more cost-effective in compensated than in decompensated cirrhosis, with an incremental CE ratio (ICER) of 1997 and 3814€/QALM, respectively. In compensated cirrhosis, semi-annual surveillance was more cost-effective than the annual program when the annual HCC incidence was ≥3.2% and the relative survival gain after cancer diagnosis was ≥20% with respect to the annual program. In decompensated cirrhosis, semi-annual surveillance was cost-effective in patients amenable to liver transplantation. In both groups, CE of semi-annual surveillance improved with the increase of annual incidence and the survival benefit obtainable with HCC treatment.
Both surveillance strategies for HCC in cirrhotic patients can be recommended, according to the individual risk profile for HCC occurrence and the expected survival gain obtainable after tumor diagnosis and therapy.
Journal of Hepatology 01/2012; 56(5):1089-96. · 9.26 Impact Factor
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ABSTRACT: Therapeutic options in advanced stage hepatocellular carcinoma have been very poor until the discovery of new therapeutic agents that target the molecular pathways involved in hepatocarcinogenesis. In this paper we try to review the most important molecular agents in development, with a specific focus on sorafenib's role and safety profile, especially in the treatment of patients with suboptimal liver function.
Digestive Diseases 01/2012; 30(3):284-8. · 2.37 Impact Factor
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ABSTRACT: Gastric cancer (GC) is still a leading cause of cancer-related death worldwide, and environmental, genetic, and epigenetic DNA changes are involved in the process of gastric carcinogenesis. The objective of this study was to establish the extent of DNA methylation at various CpG islands in GC and in precancerous changes [gastric noninvasive neoplasia (NIN)]. Eighty-one gastric samples were analyzed using methylation-specific PCR at several CpG islands. Thirty-eight samples were obtained at surgery [19 neoplastic (GC) and 19 nonneoplastic cancer-surrounding tissues (sGC)] and 43 at endoscopy (biopsies in 23 NIN patients and 20 controls). Hypermethylation of TPEF (a growth inhibitor), PTGER3 (a prostaglandin receptor isoform), and MINT31 (a promoter locus regulating calcium channels that is involved in p53 mutation) discriminated NIN and GC from normal mucosa, suggesting an early role as initiating events, whereas hypermethylation at ARGHAP20 developed with the progression from NIN to GC. MINT31 hypermethylation predicted persistence or worsening of NIN and cancer development. In conclusion, these data support a progressive accumulation of aberrant methylations in NIN and GC at various CpG islands with distinct time courses. With hypermethylation, the genes involved in regulating the balance between apoptosis and cell proliferation may become silenced and trigger gastric tumorigenesis. Hypermethylation of MINT31 predicted NIN persistence, as well as progression to higher grade or to GC, and might be used as a marker of GC risk.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 12/2011; 21(5):442-8. · 2.21 Impact Factor
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Fabio Farinati,
Anna Giacomin,
Veronica Vanin,
Adriana Sergio,
Patrizia Burra,
Umberto Cillo,
Annamaria Di Nolfo,
Paolo Del Poggio,
Luisa Benvegnu,
Marco Zoli,
Franco Borzio,
Edoardo G Giannini,
Eugenio Caturelli,
Nora Cazzagon,
Gian Ludovico Rapaccini,
Franco Trevisani
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ABSTRACT: Hepatocellular carcinoma (HCC) is an established indication for liver transplantation (LT), but the selection criteria and priority are still debated.
To ascertain the number and features of patients with HCC who undergo transplantation in a Western country, the number of patients eligible for LT according to the American Association for the Study of Liver Diseases (AASLD) guidelines, the number of patients who actually undergo transplantation and whether adherence affects survival.
This is a retrospective analysis from a multicentre Italian database of 2042 cases of HCC, recruited prospectively and consecutively. Kaplan-Meier (log rank) and Cox multivariate analysis estimated survival.
Patients who had undergone transplantation (50, 2.5%, with no change over time) had a median survival of 133 months, significantly influenced by the number of lesions and alpha-fetoprotein levels, which were found to be independent predictors of survival on multivariate analysis. Milan criteria were fulfilled in 68%, impacting on survival, whereas 48% fulfilled AASLD guidelines, without such an impact. Two hundred and twenty-eight (11%) patients were eligible for LT according to AASLD; in this group, alpha-fetoprotein levels and Child-Pugh class were independent predictors of survival.
Among patients with HCC, those undergoing LT represent a small minority; even fewer (1%) are those who undergo transplantation according to AASLD guidelines, adherence to which only marginally affects survival. Overall, LT impact on HCC patients' treatment is very limited.
European journal of gastroenterology & hepatology 11/2011; 24(2):195-202. · 1.66 Impact Factor
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Giovanni Zaninotto,
Paola Parente,
Renato Salvador, Fabio Farinati,
Chiara Tieppo,
Nicola Passuello,
Lisa Zanatta,
Matteo Fassan,
Francesco Cavallin,
Mario Costantini,
Claudia Mescoli,
Giorgio Battaglia,
Alberto Ruol,
Ermanno Ancona,
Massimo Rugge
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ABSTRACT: Barrett's esophagus (BE) is the most serious complication of GERD. In BE patients, this observational study compares the effects of antireflux surgery versus antisecretory medical therapy.
Overall, 89 BE patients (long BE = 45; short BE = 44) were considered: 45 patients underwent antireflux surgery and 44 underwent medical therapy. At both initial and follow-up endoscopy, symptoms were assessed using a detailed questionnaire; BE phenotypic changes [intestinal metaplasia (IM) presence/type, Cdx2 expression] were assessed by histology (H&E), histochemistry (HID), and immunohistochemistry. Surgical failures were defined as follows: (1) abnormal 24-h pH monitoring results after surgery, (2) endoscopically evident recurrent esophagitis, and (3) recurrent hiatal hernia or slipped fundoplication on endoscopy or barium swallow.
Reversion of IM was observed in 12/44 SSBE and 0/45 LSBE patients (p < 0.01). Reversion was more frequently observed after effective antireflux surgery than after medical treatment (p = 0.04). In patients with no further evidence of IM after therapy, Cdx2 expression was also absent (p = 0.02). The extent of IM was reduced, and the IM phenotype improved in SSBE patients after surgery.
Patients with short BE (but not those with long BE) may benefit from surgically reducing the esophagus' exposure to GE reflux; among these patients, successful surgery carries a higher IM reversion rate than medical treatment.
Journal of Gastrointestinal Surgery 11/2011; 16(1):7-14; discussion 14-5. · 2.83 Impact Factor
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Cancer Chemotherapy and Pharmacology 11/2011; 68(6):1639-40; author reply 1641-2. · 2.83 Impact Factor
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ABSTRACT: To compare the reliability of gastritis staging systems in ranking gastritis-associated cancer risk in a large series of consecutive patients.
Gastric mucosal atrophy is the precancerous condition in which intestinal-type gastric cancer (GC) most frequently develops. The operative link for gastritis assessment (OLGA) staging system ranks the GC risk according to both the topography and the severity of gastric atrophy (as assessed histologically on the basis of the Sydney protocol for gastric mucosal biopsy). Both cross-sectional and long-term follow-up trials have consistently associated OLGA stages III-IV with a higher risk of GC. A recently-proposed modification of the OLGA staging system (OLGIM) basically incorporates the OLGA frame, but replaces the atrophy score with an assessment of intestinal metaplasia (IM) alone. A series of 4552 consecutive biopsy sets (2007-2009) was retrieved and reassessed according to both the OLGA and the OLGIM staging systems. A set of at least 5 biopsy samples was available for all the cases considered.
In 4460 of 4552 cases (98.0%), both the high-risk stages (III + IV) and the low-risk stages (0 +I + II) were assessed applying the OLGA and OLGIM criteria. Among the 243 OLGA high-risk stages, 14 (5.8%) were down-staged to a low risk using OLGIM. The 67 (1.5%) incidentally-found neoplastic lesions (intraepithelial or invasive) were consistently associated with high-risk stages, as assessed by both OLGA and OLGIM (P < 0.001 for both). Two of 34 intestinal-type GCs coexisting with a high-risk OLGA stage (stage III) were associated with a low-risk OLGIM stage (stage II).
Gastritis staging systems (both OLGA and OLGIM) convey prognostically important information on the gastritis-associated cancer risk. Because of its clinical impact, the stage of gastritis should be included as a conclusive message in the gastritis histology report. Since it focuses on IM alone, OLGIM staging is less sensitive than OLGA staging in the identification of patients at high risk of gastric cancer.
World Journal of Gastroenterology 11/2011; 17(41):4596-601. · 2.47 Impact Factor
