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ABSTRACT: This study prospectively aimed at having better information about the natural history of serum cytokines in cirrhotic patients undergoing liver transplant surgery and at assessing their ability to set-up an appropriate dynamic relationship between pro and anti-inflammation. The levels of six cytokines (TNF-α, IL-1, IL-2, IL-6, IL-8, IL-10) were measured in blood samples collected at different time-points before, during and after (48hours) the transplant procedure from the radial artery of 62 consecutive cirrhotic patients who underwent orthotopic liver transplantation. IL-1 always stayed within the normal range; IL-2 showed elevated baseline levels but decreased up to half at the end of the study ( p<0.0001). IL-6 peaked at the end of surgery and returned to baseline 48hours afterwards. The same happened to IL-8 concentrations. IL-10 levels shown above the normal threshold at baseline, peaked at the end of surgery (p<0.0001) and halved at the end of the study (p<0.0001). TNF-α peaked at the end of surgery without, however, being different from baseline levels (p=0.6). The physiologic pattern of cytokines release and their dynamic relationship was found to be preserved with a quick return to a balance between pro and anti-inflammation as shown by the IL-6/IL-10 and TNF-α/IL10 ratios (used to assess the inflammatory balance). A correlation was found between perioperative pro-inflammatory cytokines levels and the severity of the liver disease necessitating OLT. In summary, cirrhotic patients can achieve a balanced inflammatory response to surgery which is considered a primary requirement for uneventful grafts and patients postoperative recovery.
Transplant Immunology 04/2013; · 1.46 Impact Factor
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Marco Bugliani,
Farooq Syed,
Matilde Masini,
Lorella Marselli,
Mara Suleiman,
Michela Novelli, Franco Filipponi,
Ugo Boggi,
Pellegrino Masiello,
Vincenzo De Tata,
Piero Marchetti
Acta Diabetologica 03/2013; · 2.78 Impact Factor
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ABSTRACT: PURPOSE: To retrospectively evaluate agreement between modified RECIST (mRECIST) assessed at Computed Tomography (CT) and pathology in a large series of patients with hepatocellular carcinoma (HCC) who were transplanted after transarterial chemoembolization (TACE). MATERIALS AND METHODS: IRB approval was obtained. The study included 178 patients (M/F=155/23; mean age 55.8±6.3 years) with HCC who were transplanted after TACE from January 1996 to December 2010 and with at least one CT examination before liver transplantation (LT). Two blinded independent readers retrospectively reviewed CT examinations, to assess tumor response to TACE according to mRECIST. Patients were classified in responders (complete and partial response) and non-responders (stable and progressive disease). On the explanted livers, percentage of tumor necrosis was classified as 100, >50 and <50%. RESULTS: The mean interval between latest CT and LT was 57.4±39.8 days. At latest CT examination, the objective response rate was 78.1% (139/178), with 86 cases (48.3%) of complete response (CR). A good intra- (k=0.75 and 0.86) and inter-observer (k=0.81) agreement was obtained. On a per-patient basis, agreement between mRECIST and pathology was obtained in 120 patients (67.4%), with 19 cases (10.7%) of underestimation and 39 cases (21.9%) of overestimation of tumor response at CT. CT sensitivity and specificity in differentiating between responders and non-responders were 93 and 82.9%, respectively. Out of 302 nodules, sensitivity and specificity of CT in detecting complete necrosis were 87.5 and 68.9%, respectively. CONCLUSIONS: CT can overestimate tumor response after TACE. Nonetheless, mRECIST assessed at CT after TACE are reproducible and reliable in differentiating responders and non-responders.
European journal of radiology 01/2013; · 2.65 Impact Factor
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Marco Bugliani,
Robin Liechti,
Hwanju Cheon,
Mara Suleiman,
Lorella Marselli,
Clare Kirkpatrick, Franco Filipponi,
Ugo Boggi,
Ioannis Xenarios,
Farooq Syed,
Laurence Ladiere,
Claes Wollheim,
Myung-Shik Lee,
Piero Marchetti
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ABSTRACT: To shed light on islet cell molecular phenotype in human type 2 diabetes (T2D), we studied the trascriptome of non-diabetic (ND) and T2D islets to then focus on the ubiquitin-proteasome system (UPS), the major protein degradation pathway. We assessed gene expression, amount of ubiquitinated proteins, proteasome activity, and the effects of proteasome inhibition and prolonged exposure to palmitate. Microarray analysis identified more than one thousand genes differently expressed in T2D islets, involved in many structures and functions, with consistent alterations of the UPS. Quantitative RT-PCR demonstrated downregulation of selected UPS genes in T2D islets and beta cell fractions, with greater ubiquitin accumulation and reduced proteasome activity. Chemically induced reduction of proteasome activity was associated with lower glucose-stimulated insulin secretion, which was partly reproduced by palmitate exposure. These results show the presence of many changes in islet transcriptome in T2D islets and underline the importance of the association between UPS alterations and beta cell dysfunction in human T2D.
Molecular and Cellular Endocrinology 12/2012; · 4.19 Impact Factor
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ABSTRACT: PURPOSE: To analyze Gd-EOB-DTPA-enhanced magnetic resonance (MR) findings of nodules (low-grade dysplastic nodules-LGDNs; high-grade dysplastic nodules-HGDN, and hepatocellular carcinoma-HCC), histologically identified on cirrhotic, explanted livers. METHODS: IRB approval was obtained for this study. Thirty-four patients underwent Gd-EOB-DTPA-enhanced MR examinations (1.5T system), that included 20-min delayed hepatobiliary (HB) phase imaging, before undergoing orthotopic liver transplantation (OLT; mean time MR-OLT: 2.7 months). A total of 102 hepatic nodules were identified and analyzed at histopathological examination, and classified as LGDN, HGDN, and HCC. Two radiologists by consensus performed a quantitative (enhancement ratios, ERs) and a qualitative analyses of signal intensities of identified nodules on vascular dynamic phases (30-35 s after injection-arterial phase; 180-190 s after injection late phase) and on HB phases. Correlation between nodules MR patterns and histological classification was analyzed by means of dedicated statistical software. RESULTS: No differences were appreciable among ERs of HGDN and HCCs on HB phase (P > 0.001). Lesions' enhancement on vascular dynamic and on HB phases significantly correlated to histological classification of nodules (P < 0.0001). Nodular hyperintensity on arterial phase and hypointensity on late phase were highly predictive for HCC (PPV 100%), with a moderate sensitivity (72.5%). Nodular hypointensity on HB phase was detected on 39/40 HCCs (sensitivity 97.5%) and in 21/30 HGDNs, whereas no LGDN showed it. CONCLUSIONS: Hyperenhancement on arterial phase and hypointensity on late phase are the most specific clues for the diagnosis of HCC. Hypointensity on HB phase shows a PPV of 100% in suggesting nodular premalignancy/malignancy, independently from nodular dynamic vascular enhancement.
Abdominal Imaging 09/2012; · 1.73 Impact Factor
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Davide Ghinolfi,
Paolo De Simone,
Gabriele Catalano,
Stefania Petruccelli,
Laura Coletti,
Paola Carrai,
Josep Marti,
Giovanni Tincani,
Antonio Cicorelli,
Roberto Cioni, Franco Filipponi
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ABSTRACT: Ghinolfi D, De Simone P, Catalano G, Petruccelli S, Coletti L, Carrai P, Marti J, Tincani G, Cicorelli A, Cioni R, Filipponi F. Transjugular intrahepatic portosystemic shunt for hepatitis C virus-related portal hypertension after liver transplantation. Abstract: This is a single center retrospective review of 19 consecutive liver transplant (LT) patients with hepatitis C virus (HCV)-related graft recurrent hepatitis who underwent transjugular intrahepatic portosystemic shunt (TIPS) at a median interval of 21 months (range: 5-50) from LT. Indications were refractory ascites in 11 patients (57.9%), hydrothorax in six (31.6%), and both in two (10.5%). TIPS was successful in 94.7% of cases (18/19) with only one procedure-related mortality (5.3%) owing to sepsis on day 35. At a median follow-up of 23 months (range: one month-nine yr), TIPS allowed for symptoms resolution in 16 patients (84.2%), with ascites resolving in all cases and hydrothorax persisting in 2. Post-TIPS patient survival at six months, one yr, and three yr was 84.2%, 73.7%, and 56.8%, respectively. We compared these results with a control group of 29 patients with HCV recurrence but without unresponsive ascites or hydrothorax. Patients in the control group had better survival than patients undergoing TIPS placement. However, survival of TIPS patients with a MELD score lower than or equal to 12 was similar to that of the control group. We conclude that TIPS may be used to treat complications secondary to HCV.
Clinical Transplantation 02/2012; 26(5):699-705. · 1.67 Impact Factor
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ABSTRACT: Patients with hepatic cirrhosis frequently show idiopathic hyperventilation at rest, despite no concomitant cardiopulmonary disease. The aim of the study was to determine whether altered chemosensitivity either to hypoxia or hypercapnia could underlie inappropriate hyperventilation in cirrhotic patients.
We consecutively recruited 30 biopsy proven cirrhotic patients equally distributed in the three Child's classes A, B and C (age 54 ± 8 years, mean ± SD). All patients underwent evaluation of chemosensitivity to hypoxia and to hypercapnia and blood sampling for brain natriuretic peptide, norepinephrine and progesterone, besides full clinical characterization. We also recruited 10 age- and gender-matched healthy controls (age 55 ± 7 years).
Overall, 18 patients (60%) showed an increased chemosensitivity to carbon dioxide (CO(2)), while 8 patients (27%) showed enhanced chemosensitivity to hypoxia. Child's class C patients had lower arterial partial pressure of CO(2) (PaCO(2)), higher rest ventilation, increased chemosensitivity to hypercapnia, plasma level of norepinephrine and serum progesterone levels when compared to class A patients and controls (all p < 0.05). Rest ventilation was positively related to pH (R = 0.41, p = 0.023), chemosensitivity to hypercapnia (R = 0.54, p = 0.002), and progesterone (R = 0.53, p = 0.016) and negatively to PaCO(2) (R = 0.61, p < 0.001), but not to hemoglobin level and chemosensitivity to hypoxia. Chemosensitivity to hypercapnia was positively related to PaCO(2) (R = 0.74, p < 0.001), serum progesterone (R = 0.50, p = 0.016), and to plasma norepinephrine (R = 0.57, p = 0.004).
Enhanced chemosensitivity to hypercapnia was found in more decompensated cirrhotic patients and was associated with sympathetic overactivity and elevated serum progesterone, likely representing a key mechanism underlying the "unexplained" hyperventilation observed in such patients.
International journal of cardiology 01/2012; 154(1):22-6. · 7.08 Impact Factor
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Mariella Tancredi,
Lorella Marselli,
Cristina Lencioni,
Matilde Masini,
Marco Bugliani,
Mara Suleiman,
Pellegrino Masiello,
Ugo Boggi, Franco Filipponi,
Francesco Dotta,
Piero Marchetti,
Graziano Di Cianni
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ABSTRACT: Gestational diabetes (GD) results from insufficient endogenous insulin supply. No information is available on features of islet cells in human GD. Herein, we describe several properties of islets from a woman with GD. Immunohistochemical stainings and EM analyses were performed on pancreatic samples. Islet isolation was achieved by enzymatic dissociation and density gradient centrifugation. Ex vivo insulin secretion was studied in response to fuel secretagogues. Control islets were obtained from matched non-pregnant, non-diabetic women. Total insulin positive area was lower in GD, mainly due to the presence of smaller islets. β-cell apoptosis and the presence of Ki67 positive islet cells were similar in GD and controls, whereas the amount of insulin positive cells in or close to the ducts was decreased in GD. Ex vivo insulin secretion did not differ between GD and non-pregnant, non-diabetic islets. These findings suggest that in this case of human GD there might mainly be a defect of β-cell amount, not due to increased apoptosis, but possibly to insufficient regeneration.
Islets 09/2011; 3(5):231-3.
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ABSTRACT: Reliable cardiac output monitoring is particularly useful in the cirrhotic patient undergoing liver transplant surgery, because cirrhosis of the liver is associated with a vasodilated and high output state, known as cirrhotic cardiomyopathy, that challenges the reliability of pulse contour cardiac output technology. The contractility of the ventricle in cirrhosis is impaired, which is tolerated even though the ejection fraction and cardiac output are elevated because of the low peripheral resistance. However, during surgery the cirrhotic patient can decompensate because of the physiological changes and stress of surgery. Recently, we showed that the FloTrac/Vigileo™ failed to perform in cirrhotic patients undergoing transplant surgery. In response, the company upgraded their software. Therefore, we have assessed the accuracy and reliability of this new third-generation (version 3.02) FloTrac/Vigileo algorithm software in the same setting.
The cardiac index was measured simultaneously by single-bolus thermodilution (CI(TD)), using a pulmonary artery catheter, and pulse contour analysis, using the FloTrac/Vigileo (CI(V)). Readings were made at 10 time points during and after liver transplant surgery in 21 patients. Comparisons with data from our 2009 study, which used second-generation (version 01.10) software, were also made.
Our new data show that version 3.02 software significantly reduced the adverse effect on pulse contour cardiac output reading bias in low peripheral resistance states, and thus improves the overall precision and trending ability of the system. Regression analysis between CI(TD) and CI(V) showed that the correlation was moderate (r =0.67, 95% confidence interval, 0.40 to 0.86). The Bland and Altman analysis showed that bias was 0.4 L.min(-1) · m(-2), and the percentage error was 52% (95% confidence interval, 49% to 55%). Trending ability of the new software also was improved but was still well below the current benchmarks.
The new software (version 3.02) provided substantial improvements over the previous versions with better overall precision and trending ability. Further algorithm refinements will increase this technology's reliability to be extensively used in the highly complex setting of cirrhotic patients undergoing liver transplantation.
Anesthesia and analgesia 06/2011; 113(3):515-22. · 3.08 Impact Factor
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ABSTRACT: Multiligand receptor for advanced glycation end products (RAGE) is expressed in a wide variety of tissues, including the liver. Interactions with its ligands lead to cellular activation and thus prolonged inflammation and apoptosis. RAGE also exists in a soluble, truncated isoform called soluble RAGE, which has the same ligand-binding specificity as membrane-RAGE; acting as decoy, it can contribute to the removal/neutralization of circulating ligands and the resultant reduction of signaling pathway activation. Experimental and clinical studies have highlighted the idea that the RAGE-ligand axis is involved in the development of liver fibrosis, inflammation, and regeneration after a massive injury and in the setting of liver transplantation. The involvement of the RAGE-ligand axis in vascular disease, diabetes, cancer, and neurodegeneration is well established, but it still needs to be clarified in the setting of liver diseases. We present a review of the recent literature on this receptor in surgical and clinical settings involving the liver, and we highlight the open issues and possible directions of future research.
Liver Transplantation 03/2011; 17(6):633-40. · 3.39 Impact Factor
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ABSTRACT: To investigate the feasibility, safety, and efficacy of single-session ethanol ablation with multipronged needles in the treatment of early-stage hepatocellular carcinoma (HCC).
A pilot clinical study enrolled 20 patients with Child-Pugh A-B cirrhosis (15 men and 5 women 53-84 years old [mean 70.3 years old ± 8.3, median 72 years old]) and with 25 HCC tumors 1.2-3.8 cm in longest diameter (mean 2.3 cm ± 0.6) located in unfavorable locations for radiofrequency (RF) ablation. Ethanol ablation was performed under moderate sedation using a multipronged injection needle (Quadra-Fuse; REX Medical, Conshohocken, Pennsylvania) and ultrasound guidance. Follow-up period ranged from 12-24 months (mean 15.9 months ± 4.6, median 16 months) and included contrast-enhanced computed tomography (CT) or magnetic resonance (MR) imaging performed 1 month after treatment and at 3-month intervals thereafter.
The treatment protocol was successfully completed in all patients (technical success rate 100%). No major complications were observed. A single treatment session with injection of 5-26 mL of ethanol (mean 9.5 mL ± 5.5) resulted in complete tumor ablation at 1 month CT or MR imaging in 21 (84%) of 25 tumors. A second treatment session increased the number of tumors with complete response (CR) to 23 of 25 (primary effectiveness rate 92%). Tumor progression was observed in three cases during the follow-up period, for a rate of confirmed CR of 80% (20 of 25).
Ethanol ablation performed with a multipronged injection needle was not associated with any major complications and resulted in a high rate of confirmed CR. This technique offers an alternative to RF ablation for single-session treatment of early-stage HCC.
Journal of vascular and interventional radiology: JVIR 10/2010; 21(10):1533-8. · 1.81 Impact Factor
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Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 09/2010; 21(6):611. · 1.25 Impact Factor
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ABSTRACT: To assess the diagnostic value of magnetic resonance cholangiography (MRC) when evaluating biliary complications in a large series of liver transplants.
One hundred and twenty-nine patients prospectively underwent magnetic resonance (MR) imaging and MR cholangiography at 1.5-T device after orthotopic liver transplantation (OLT). After the preliminary acquisition of axial T1- and T2-weighted images, MRC involved respiratory-triggered, thin-slab (2 mm), heavily T2-weighted fast spin-echo and breath-hold, thick-slab (10-50 mm), single-shot T2-weighted sequences. MR images were blindly evaluated by two experienced readers in conference to determine the biliary anatomy and the presence of complications, whose final diagnosis was based on endoscopic retrograde cholangiography, percutaneous trans-hepatic cholangiography, and by integrating clinical follow-up with ultrasound and/or MR findings.
Biliary complications were found in 60 patients (46.5%) and were represented by ischemic-type biliary lesions (n=21); anastomotic strictures (n=13); non-anastomotic strictures (n=5); anastomotic strictures associated to lithiasis (n=6); lithiasis (n=6); papillary dysfunctions (n=9). The sensitivity, specificity, positive predictive value, and negative predictive value of the reviewers for the detection of all types of biliary complications in patients with OLT were 98%, 94%, 94%, and 98%, respectively.
MRC is a reliable technique for detecting post-OLT biliary complications and should be recommended before planning therapeutic interventions.
Clinical Transplantation 07/2010; 24(4):E82-7. · 1.67 Impact Factor
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ABSTRACT: Loco-regional interventional treatments continue to evolve and to play a major role in the therapeutic management of hepatocellular carcinoma (HCC). Image-guided ablation is established as the treatment of choice for patients with early-stage HCC when transplantation or resection is precluded. Recent refinements in technique have substantially increased the ability of radiofrequency ablation to achieve sustained complete response of target tumors in properly selected patients, and new alternate thermal and nonthermal methods for local tumor treatment are currently under investigation. Transarterial chemoembolization (TACE) is the standard of care for patients with multinodular disease at the intermediate stage. The introduction of drug-eluting beads--that enhance drug delivery to the tumor and reduce systemic exposure--appears to improve anticancer activity and safety profile of TACE compared with conventional regimens. Despite these advances, the long-term outcomes of patients treated with loco-regional therapies remain unsatisfactory because of the high rate of tumor recurrence. The introduction of molecular targeted therapies that inhibit tumor proliferation and angiogenesis has opened new prospects in this regard. Clinical trials focused on combining interventional treatment with systemically active drugs are ongoing. The outcomes of such studies are eagerly awaited, as they have the potential to revolutionize treatment of HCC.
Transplant International 07/2010; 23(7):698-703. · 2.92 Impact Factor
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ABSTRACT: To retrospectively evaluate the clinical outcome of patients with hepatocellular carcinoma (HCC) who exceeded the Milan criteria, who underwent transarterial chemoembolization (TACE) before orthotopic liver transplantation (OLT), to determine the value of computed tomography (CT)-based tumor response to TACE as a preoperative selection criterion for OLT.
The study included 33 patients with HCC who exceeded the Milan criteria and underwent OLT after TACE. Informed written consent was obtained before TACE and OLT. Institutional review board approval was not required. Tumor response to TACE was evaluated at 1 month with CT according to amended Response Evaluation Criteria in Solid Tumours (RECIST) guidelines. In the explanted liver, degree of tumor necrosis (> or = 90%, 50%-89%, or < 50%), residual tumor stage and grade, and presence of microvascular invasion were assessed. Follow-up after OLT ranged from 1 to 143 months.
After TACE, CT showed complete tumor response (CR) in 18 (55%) patients. On the explanted liver, tumor necrosis was rated 90% or greater in 20 (61%) patients, with a good correlation with CT. Microvascular invasion was observed in nine (27%) of 33 patients; none of them were reported to have a CR at CT. The 5-year cumulative survival rate after OLT was 72.5%; it was significantly (P = .003) higher in patients with a CR (94.4%) compared with patients with a partial response (PR) (45.4%) and stable disease (50%). The 5-year cumulative recurrence-free rate after OLT was 74.4%; it was not affected by the tumor nodule size and number, whereas it was significantly (P = .008) higher in patients with a CR (94.4%) compared with patients with a PR (46.7%) and stable disease (50%).
In patients with HCC who exceeded the Milan criteria, a CR after TACE, on the basis of amended RECIST guidelines, is associated with excellent posttransplantation outcomes. Therefore, 1-month response to TACE assessed at CT may represent a valid selection criterion for OLT.
Radiology 04/2010; 255(1):289-300. · 5.73 Impact Factor
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Valentina D'Aleo,
Silvia Del Guerra,
Manuela Martano,
Barbara Bonamassa,
Donatella Canistro,
Antonio Soleti,
Luca Valgimigli,
Moreno Paolini, Franco Filipponi,
Ugo Boggi,
Stefano Del Prato,
Roberto Lupi
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ABSTRACT: Chronic exposure to high free fatty acids (FFA) can lead to irreversible damage of beta-cell accounting for impaired insulin secretion. Multiple mechanisms concur in generating the damage, but activation of oxidative stress may contribute to the final toxic effect. To better understand the phenomenon of lipotoxicity in human beta-cells, we evaluated the effects of 24-h pre-culture with 1.0 mmol/l FFA on the function, survival and mRNA expression of several enzymes involved in the generation and scavenging of reactive oxygen species (ROS).
Human islets, prepared by collagenase digestion and density gradient purification from 9 pancreases of multiorgan donors, were incubated for 24-h in the presence 1.0 mmol/l long-chain mixture (oleate:palmitate, 2:1) FFA, with or without 100 micromol/l IAC, a non-peptidyl low molecular weight radical scavenger. At the end of incubation period, insulin secretion was measured by static incubation, and mRNA expression of insulin, Cu/Zn-SOD, Mn-SOD, Catalase, Glutathione peroxidase (GSH-px) and HO-1 by quantitative Real-Time RT-PCR. Nitrotyrosine levels were determined by an ELISA technique.
As compared to control incubation (Ctrl, no FFA), exposure to FFA was associated with impaired insulin release and reduced insulin mRNA expression. The presence of IAC in the incubation medium increased insulin release significantly and prevented changes in mRNA expression. Exposure to FFA was associated with oxidative stress as indicated by a significant accumulation of nitrotyrosine and IAC restrained such an increase. mRNA expression of Cu/Zn-SOD, Mn-SOD, Catalase, GSH-Px, and HO-1 were all modified after FFA exposure. These changes were partially prevented in the presence of IAC.
In human islets 24-h exposure to high FFA causes oxidative stress associated with changes of several enzymes involved in ROS scavenging. These effects were prevented by the use of an antioxidant molecule.
Molecular and Cellular Endocrinology 06/2009; 309(1-2):63-6. · 4.19 Impact Factor
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Gianluca Masi,
Fotios Loupakis,
Luca Pollina,
Enrico Vasile,
Samanta Cupini,
Sergio Ricci,
Isa Maura Brunetti,
Roberta Ferraldeschi,
Giuseppe Naso, Franco Filipponi,
Andrea Pietrabissa,
Orlando Goletti,
Giacomo Baldi,
Lorenzo Fornaro,
Michele Andreuccetti,
Alfredo Falcone
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ABSTRACT: The GONO-FOLFOXIRI regimen improved the rate of R0 secondary resection of metastases in initially unresectable metastatic colorectal cancer. The objective of this study was to evaluate the long-term outcome of resected patients and the impact of FOLFOXIRI on perioperative morbidities, mortality, and chemotherapy induced hepatotoxicity.
Overall, 196 patients with initially unresectable metastatic colorectal cancer were treated with FOLFOXIRI in 2 phase II and 1 phase III trial. This regimen was associated with an elevated response rate (70.4%) and 37 patients (19%) could undergo a secondary R0 surgery on metastases. This study was registered with the Australian New Zealand Clinical Trials Registry Database at http://www.anzctr.org.au/Statistics.aspx and has ID number ACTRN12608000615381.
Main characteristics of the 37 radically resected patients were: median age 64 years (45-73), Eastern Cooperative Oncology Group Performance Status (ECOG) PS > or = 1 in 30%, synchronous metastases in 65%, multiple sites of disease in 22%, and metastases confined to the liver in 68%. Preoperative FOLFOXIRI was administered for a median of 5.5 months. There was no perioperative mortality and all morbidities (27% of patients) resolved without sequelae. After a median follow up of 67 months, 5-year and 8-year survival are 42% and 33% respectively. At 5 years, 29% of patients are free of disease. The analysis of treatment-induced liver injury showed neither G3 vascular toxicity nor G4 steatosis, and steato-hepatitis in only 5% of patients.
The GONO-FOLFOXIRI regimen allow an R0 surgery in approximately 1 out of 5 unselected patients with initially unresectable metastatic colorectal cancer, and the long-term survival of resected patients is considerable. Neoadjuvant FOLFOXIRI for 3-6 months is safe and not associated with severe liver injury.
Annals of surgery 03/2009; 249(3):420-5. · 7.90 Impact Factor
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Paolo De Simone,
Paola Carrai,
Arianna Precisi,
Stefania Petruccelli,
Lidiana Baldoni,
Emanuele Balzano,
Juri Ducci,
Francesco Caneschi,
Laura Coletti,
Daniela Campani, Franco Filipponi
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ABSTRACT: We present the 12-month results of a prospective trial of conversion from calcineurin inhibitors (CNI) to everolimus (EVL) in maintenance liver transplant (LT) recipients. Forty (M:F = 28:12; 54.9 +/- 11 years) patients were enrolled at a mean interval of 45.5 +/- 31.2 months from transplantation. Conversion was with EVL at a dosage of 0.75 mg b.i.d., withdrawal of antimetabolites, and a 50%-per-week reduction of CNI to a complete stop within 4 weeks. The treatment success was conversion to EVL monotherapy at 12 months while failure was presence of CNI, death, and graft loss. Indication to conversion was deteriorating renal function in 36 (90%). At 12 months, patient- and graft survival were 100% and the success rate was 75% (30/40). Ten patients (25%) were failures: four (10%) for acute rejection; three hepatitis C virus-RNA positive patients (7.5%) for hypertransaminasemia; one (2.5%) for acute cholangitis; and two (5%) due to persistent pruritus and oral ulcers. In patients on EVL monotherapy, at 12 months the mean change of calculated creatinine clearance (cCrCl) was 4.03 +/- 12.6 mL/min and the only variable correlated with the probability of improvement was baseline cCrCl (P < 0.0001). Conversion from CNI to EVL is feasible in 75% of the cases and associated with improvement in renal function for patients with higher baseline cCrCl.
Transplant International 01/2009; 22(3):279-86. · 2.92 Impact Factor
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Lucio Urbani,
Alessandro Mazzoni,
Lucia Bindi,
Gianni Biancofiore,
Massimo Bisà,
Luca Meacci,
Massimo Esposito,
Roberto Mozzo,
Piero Colombatto,
Irene Bianco, [......],
Gabriele Catalano,
Umberto Montin,
Giovanni Tincani,
Emanuele Balzano,
Stefania Petruccelli,
Paola Carrai,
Carlo Tascini,
Francesco Menichetti,
Fabrizio Scatena, Franco Filipponi
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ABSTRACT: The aim of the present work was to assess the incidence of neuro-nephrotoxicity after a single-staggered dose of calcineurin inhibitors (CI) with different immunosuppressive approaches. From January to December 2006, all liver transplantation (LT) recipients at risk of renal or neurological complications treated with extracorporeal photopheresis (ECP) + mycophenolate mofetil + steroids and staggered introduction of CI (ECP group) were compared with a historical control group on standard CI-based immunosuppression. The ECP group included 24 patients with a mean model for end-stage liver disease (MELD) score of 19.9 +/- 11.1. The control group consisted of 18 patients with a mean MELD score of 12.5 +/- 5.2 (p = 0.012). In the ECP group CI were introduced at a mean of 9.2 +/- 6.2 d (4-31 d) after LT. Five patients in the ECP group presented acute neuro-nephrotoxicity after the first CI administration on post-transplant d 4, 5, 6, 6, and 14. Overall patient survival at one, six, and 12 months was 100%, 95.8%, and 95.8% in the ECP group vs. 94.4%, 77.7%, and 72.2% in the control group (p < 0.001). In conclusion, we showed that CI toxicity may occur after a single-staggered dose administration, ECP seems to be a valuable tool for managing CI-related morbidity regardless of the concomitant immunosuppressive regimen, being associated with a lower mortality rate in the early post-transplant course.
Clinical Transplantation 01/2009; 23(6):853-60. · 1.67 Impact Factor
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ABSTRACT: Donor's age and immunosuppression influence the severity of hepatitis C virus (HCV) recurrence. We analyzed the 18-month mortality in 302 consecutive HCV recipients, divided into three groups, with homogeneous immunosuppression and preemptive antiviral therapy in the last group.
Group 1: one hundred thirty-three patients (1996-2000) mainly received a triple therapy (steroids- cyclosporine A [CyA]-azathioprine); first line treatment of biopsy-proven acute rejection (BPAR) was with steroid boluses; second-line with OKT3. Group 2: ninety-one patients (2001-2003) mainly received a double therapy (steroids-CyA) and induction with anti-CD25 antibody; first-line BPAR treatment was increased dose/switch of the calcineurin inhibitor; second-line steroid boluses; third-line extracorporeal photopheresis (ECP). Group 3: seventy-eight patients (2004-June 2006) mainly received a monotherapy (CyA) associated with ECP and induction with anti-CD25 antibody; first-line BPAR treatment was increased dose/switch of calcineurin inhibitor with increased ECP frequency, second-line steroid boluses, and third-line retransplantation.
Median donor's age increased from 54 (13-84) years in group 1 to 60 (10-93) years in group 2 and 66 (17-84) years in group 3 (P<0.001). Overall mortality in groups 1, 2, and 3 decreased from 28.6% to 22% and 10.2% respectively (P = 0.003); HCV-related mortality from 7.5% and 12.1% to 1.3%, respectively (P = 0.029). BPAR were 33.8% in group 1 and 9.0% in group 3. Applicability of the preemptive antiviral therapy in group 3 was 69.2%. Sustained viral clearance occurred in 38.9% of 36 patients who completed the protocol. At multivariate analysis, a single-drug immunosuppressive regimen was the only variable independently associated with survival (P=0.05).
Low and steady immunosuppression combined with preemptive antiviral therapy significantly improved the short-term mortality of HCV recipients transplanted with aged organs. Prolonged follow-up will assess whether this benefit is maintained in the long run.
Transplantation 12/2008; 86(12):1666-71. · 4.00 Impact Factor
