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Research paper thumbnail of Reply to: "Sorafenib or 90Y loaded resin microsphere radioembolization for locally-advanced hepatocellular carcinoma, what should we trust?

Liver international : official journal of the International Association for the Study of the Liver, Jan 16, 2015

There is no doubt that resin and glass (90) Y-loaded microspheres have different specific activit... more There is no doubt that resin and glass (90) Y-loaded microspheres have different specific activities (Bq per sphere) and, hence, the total amount of spheres needed to ensure an adequate radiobiological effect is different. Therefore, we may agree to the semantic issue put forward by Dr. Garin et al. However, we disagree with the argument that the use of the term radioembolization would generate a misinterpretation of the substantial (clinical) message we provided by comparing selective internal radiation therapy (SIRT) with systemic therapy based on sorafenib administration. Indeed, to the best of our knowledge, there is no evidence that one type of microspheres (glass or resin) is superior to the other one for the outcomes we considered, i.e. tumor response, toxicity and patient survival. This article is protected by copyright. All rights reserved.

Research paper thumbnail of Orthotopic liver transplantation (OLT): Contribution of imaging and interventional radiology in preparing the transplantation and managing complications. Part 2: Post-OLT complications and their treatment

Research paper thumbnail of Detection of hydroxyl radical (OH) using salicylate (SA) as a trapping agent in rat liver exposed to hypoxia-reoxygenation injury

Research paper thumbnail of Bone mass and metabolism in non cholestatic liver cirrhosis

Research paper thumbnail of Vitamin E deficiency and autonomic neuropathy in liver cirrhosis before and after liver transplant

Research paper thumbnail of Effect of nutritional status on the ischemia-reperfusion injury experienced by rat fatty livers

Research paper thumbnail of Prospective down-staging protocol for HCC not meeting the Milan criteria

Research paper thumbnail of The Optimal Immunosuppression Regimen for Delaying Fibrosis Progression in HCV After Liver Transplantation

Research paper thumbnail of Influence of HBsAg and anti-HCV status on the diagnostic accuracy of alpha (1)-fetoprotein (AFP) in patients with chronic liver disease

Research paper thumbnail of Improvement of autonomic neuropathy after successful liver transplantation (LTR) in cirrhosis

Research paper thumbnail of Alcohol consumption influences the survival of patients with hepatocellular carcinoma treated with endoarterial therapy

Research paper thumbnail of What is the probability of being too old for salvage transplantation after hepatocellular carcinoma resection?

The strategy of salvage transplantation for patients with hepatocellular carcinoma is based on th... more The strategy of salvage transplantation for patients with hepatocellular carcinoma is based on the premise that tumour recurrence will be still transplantable at the time of recurrence. However, patients can not only present non-transplantable recurrence but can also be over the age limit accepted for transplantation. To measure the risk of being too old for salvage transplantation of patients resected for hepatocellular carcinoma within Milan criteria. A Markov simulation model was developed on the basis of published literature. The risk of being too old for salvage transplantation depends on the time-span between age at hepatic resection and age limit, and the expected median waiting-time. Patients resected at an age 2 or 3 years below the age limit carry a risk of being too old that overcomes the probability of receiving transplantation. Salvage strategy can cause harm that depends on the tumour characteristics and degree of portal hypertension, becoming maximal for patients with multiple tumours, clinical signs of portal hypertension and increased bilirubin levels. The best strategy to adopt should be balanced between the risk of being too old and the expected transplant benefit, but salvage strategy could be pursued if it did not turn into significant harm in comparison to primary transplantation.

Research paper thumbnail of Refining sorafenib therapy: lessons from clinical practice

Future Oncology, 2014

Understanding the best use of sorafenib is essential in order to maximize clinical benefit in hep... more Understanding the best use of sorafenib is essential in order to maximize clinical benefit in hepatocellular carcinoma. Based on Phase III and noninterventional study data, as well as our extensive experience, we discuss dose modification in order to manage adverse events, disease response evaluation and how to maximize treatment benefit. Sorafenib should be initiated at the approved dose (400 mg twice daily) and reduced/ interrupted as appropriate in order to manage adverse events. Dose modification should be considered before discontinuation. Appropriate tumor response assessment is critical. Focusing on radiologic response may result in premature sorafenib discontinuation; symptomatic progression should also be considered. If second-line therapies or trials are unavailable, continuing sorafenib beyond radiologic progression may provide a clinical benefit. Our recommendations enable the maximization of treatment duration, and hence clinical benefit, for patients.

Research paper thumbnail of Current concepts in hepatic resection for hepatocellular carcinoma in cirrhotic patients

World Journal of Gastroenterology, 2012

Hepatocellular carcinoma (HCC) is one of the most frequent neoplasms worldwide and in most cases ... more Hepatocellular carcinoma (HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with liver cirrhosis. Liver resection is considered the most potentially curative therapy for HCC patients when liver transplantation is not an option or is not immediately accessible. This review is aimed at investigating the current concepts that drive the surgical choice in the treatment of HCC in cirrhotic patients; Eastern and Western perspectives are highlighted. An extensive literature review of the last two decades was performed, on topics covering various aspects of hepatic resection. Early post-operative and long-term outcome measures adopted were firstly analyzed in an attempt to define an optimal standardization useful for research comparison. The need to avoid the development of post-hepatectomy liver failure represents the "conditio sine qua non" of surgical choice and the role of the current tools available for the assessment of liver function reserve were investigated. Results of he-patic resection in relationship with tumor burden were compared with those of available competing strategies, namely, radiofrequency ablation for early stages, and trans-arterial chemoembolization for intermediate and advanced stages. Finally, the choice for anatomical versus non-anatomical, as well as the role of laparoscopic approach, was overviewed. The literature review suggests that partial hepatectomy for HCC should be considered in the context of multi-disciplinary evaluation of cirrhotic patients. Scientific research on HCC has moved, in recent years, from surgical therapy toward non-surgical approaches and most of the literature regarding topics debated in the present review is represented by observational studies, whereas very few well-designed randomized controlled trials are currently available; thus, no robust recommendations can be derived.

Research paper thumbnail of Partial Necrosis on Hepatocellular Carcinoma Nodules Facilitates Tumor Recurrence after Liver Transplantation

Transplantation, 2004

The presence of partial necrosis in hepatocellular carcinoma (HCC) nodules is a common histologic... more The presence of partial necrosis in hepatocellular carcinoma (HCC) nodules is a common histologic finding after liver transplantation, but its correlation with tumor recurrence has never been investigated. we retrospectively reviewed the outcome of 54 patients with a single histologically proven HCC after liver transplantation. All cases had a survival of more than 6 months, and patients treated preoperatively had a transarterial chemoembolization (TACE) procedure. Since 1996, our center has applied the Milan criteria. Correlations between tumor recurrences and clinicopathologic variables, including the presence of partial necrosis, were performed. Etiologic factors for HCC partial necrosis were also investigated. Sixteen of 54 (29.6%) HCC nodules presented partial necrosis, and 4 (25%) of them developed HCC recurrence compared with 1 of 38 (2.6%) cases without this histologic finding (P<0.05). Partial necrosis was related to TACE procedure (P<0.05), patient age less than 50 years (P<0.05), and tumor diameter greater than 2 cm (P<0.05). Multivariate analysis showed only TACE as an independent variable. The other variables related to the five (9.3%) tumor recurrences were HCC diameter greater than 2 cm (P<0.05), year of liver transplantation before 1996 (P<0.05), and the presence of satellite nodules (P<0.05). The Cox regression analysis showed the presence of partial necrosis as an independent variable related to tumor recurrence. The analysis of the recurrence-free survival confirmed the results of the recurrence rate. Partial necrosis was a risk factor for tumor recurrence after liver transplantation. Patients and procedures should be selected while also bearing in mind the side-effect of incomplete necrosis of the nodules.

Research paper thumbnail of Metronomic Capecitabine in Advanced Hepatocellular Carcinoma Patients: A Phase II Study

Research paper thumbnail of Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: Meta-Analysis of Randomized Controlled Trials1

Research paper thumbnail of Hepatocellular Carcinoma Responding to Superselective Transarterial Chemoembolization: An Issue of Nodule Dimension?

Journal of Vascular and Interventional Radiology, 2013

To evaluate the per-nodule efficacy of superselective transarterial chemoembolization of hepatoce... more To evaluate the per-nodule efficacy of superselective transarterial chemoembolization of hepatocellular carcinomas (HCCs). From 2006-2009, 271 cirrhotic patients with 635 nodules underwent a first superselective transarterial chemoembolization, repeated "on demand" after local recurrences (LR) or partial responses (PR). Complete response (CR), time to nodule progression (TTnP), and local recurrence rate (LRR), according to three size classes (≤ 2 cm, 2.1-5 cm, and>5 cm) were evaluated. After the first superselective transarterial chemoembolization, the CR was 64%, sustained over time in 77%, higher in small (68%) and intermediate-size (64%) nodules than in large nodules (25%; P<.001). The LRR was 23%:20% in small, 27% in intermediate, and 67% in large HCCs (P<.05). The median TTnP of large HCCs was 4 months versus 7-9 months for small and intermediate HCCs. The second superselective transarterial chemoembolization achieved a higher CR (63% in LR, 52% in PR) than the third superselective transarterial chemoembolization (32%). Median TTnP after the second superselective transarterial chemoembolization for LR and PR (8 months and 6 months) was longer than after the third superselective transarterial chemoembolization (3.5 months). Nodules ≤ 5 cm had a CR after the first superselective transarterial chemoembolization (66%) and the second superselective transarterial chemoembolization for LR (64%) or PR (55%) higher than after the third superselective transarterial chemoembolization (40%); nodules>5 cm had a CR of 25% after the first superselective transarterial chemoembolization, LR of 50% and PR of 25%, and after the second and third superselective transarterial chemoembolizations, PR of 0%. Effectiveness of superselective transarterial chemoembolization has a clear cutoff above and below 5-cm nodules, with better results in smaller nodules. In HCCs ≤ 5 cm, the efficacy of the first and second superselective transarterial chemoembolizations performed for LR was higher than the second superselective transarterial chemoembolization for PR and the third superselective transarterial chemoembolization. For HCCs>5 cm, retreatment of PR is of little value, and the third cycle is ineffective.

Research paper thumbnail of A reappraisal of the Barcelona Clinic Liver Cancer model: natural history of untreated 'intermediate stage' hepatocellular carcinoma

Journal of Internal Medicine, 2004

Research paper thumbnail of The use of donor fatty liver for liver transplantation: a challenge or a quagmire?

Journal of Hepatology, 1996

Research paper thumbnail of Reply to: "Sorafenib or 90Y loaded resin microsphere radioembolization for locally-advanced hepatocellular carcinoma, what should we trust?

Liver international : official journal of the International Association for the Study of the Liver, Jan 16, 2015

There is no doubt that resin and glass (90) Y-loaded microspheres have different specific activit... more There is no doubt that resin and glass (90) Y-loaded microspheres have different specific activities (Bq per sphere) and, hence, the total amount of spheres needed to ensure an adequate radiobiological effect is different. Therefore, we may agree to the semantic issue put forward by Dr. Garin et al. However, we disagree with the argument that the use of the term radioembolization would generate a misinterpretation of the substantial (clinical) message we provided by comparing selective internal radiation therapy (SIRT) with systemic therapy based on sorafenib administration. Indeed, to the best of our knowledge, there is no evidence that one type of microspheres (glass or resin) is superior to the other one for the outcomes we considered, i.e. tumor response, toxicity and patient survival. This article is protected by copyright. All rights reserved.

Research paper thumbnail of Orthotopic liver transplantation (OLT): Contribution of imaging and interventional radiology in preparing the transplantation and managing complications. Part 2: Post-OLT complications and their treatment

Research paper thumbnail of Detection of hydroxyl radical (OH) using salicylate (SA) as a trapping agent in rat liver exposed to hypoxia-reoxygenation injury

Research paper thumbnail of Bone mass and metabolism in non cholestatic liver cirrhosis

Research paper thumbnail of Vitamin E deficiency and autonomic neuropathy in liver cirrhosis before and after liver transplant

Research paper thumbnail of Effect of nutritional status on the ischemia-reperfusion injury experienced by rat fatty livers

Research paper thumbnail of Prospective down-staging protocol for HCC not meeting the Milan criteria

Research paper thumbnail of The Optimal Immunosuppression Regimen for Delaying Fibrosis Progression in HCV After Liver Transplantation

Research paper thumbnail of Influence of HBsAg and anti-HCV status on the diagnostic accuracy of alpha (1)-fetoprotein (AFP) in patients with chronic liver disease

Research paper thumbnail of Improvement of autonomic neuropathy after successful liver transplantation (LTR) in cirrhosis

Research paper thumbnail of Alcohol consumption influences the survival of patients with hepatocellular carcinoma treated with endoarterial therapy

Research paper thumbnail of What is the probability of being too old for salvage transplantation after hepatocellular carcinoma resection?

The strategy of salvage transplantation for patients with hepatocellular carcinoma is based on th... more The strategy of salvage transplantation for patients with hepatocellular carcinoma is based on the premise that tumour recurrence will be still transplantable at the time of recurrence. However, patients can not only present non-transplantable recurrence but can also be over the age limit accepted for transplantation. To measure the risk of being too old for salvage transplantation of patients resected for hepatocellular carcinoma within Milan criteria. A Markov simulation model was developed on the basis of published literature. The risk of being too old for salvage transplantation depends on the time-span between age at hepatic resection and age limit, and the expected median waiting-time. Patients resected at an age 2 or 3 years below the age limit carry a risk of being too old that overcomes the probability of receiving transplantation. Salvage strategy can cause harm that depends on the tumour characteristics and degree of portal hypertension, becoming maximal for patients with multiple tumours, clinical signs of portal hypertension and increased bilirubin levels. The best strategy to adopt should be balanced between the risk of being too old and the expected transplant benefit, but salvage strategy could be pursued if it did not turn into significant harm in comparison to primary transplantation.

Research paper thumbnail of Refining sorafenib therapy: lessons from clinical practice

Future Oncology, 2014

Understanding the best use of sorafenib is essential in order to maximize clinical benefit in hep... more Understanding the best use of sorafenib is essential in order to maximize clinical benefit in hepatocellular carcinoma. Based on Phase III and noninterventional study data, as well as our extensive experience, we discuss dose modification in order to manage adverse events, disease response evaluation and how to maximize treatment benefit. Sorafenib should be initiated at the approved dose (400 mg twice daily) and reduced/ interrupted as appropriate in order to manage adverse events. Dose modification should be considered before discontinuation. Appropriate tumor response assessment is critical. Focusing on radiologic response may result in premature sorafenib discontinuation; symptomatic progression should also be considered. If second-line therapies or trials are unavailable, continuing sorafenib beyond radiologic progression may provide a clinical benefit. Our recommendations enable the maximization of treatment duration, and hence clinical benefit, for patients.

Research paper thumbnail of Current concepts in hepatic resection for hepatocellular carcinoma in cirrhotic patients

World Journal of Gastroenterology, 2012

Hepatocellular carcinoma (HCC) is one of the most frequent neoplasms worldwide and in most cases ... more Hepatocellular carcinoma (HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with liver cirrhosis. Liver resection is considered the most potentially curative therapy for HCC patients when liver transplantation is not an option or is not immediately accessible. This review is aimed at investigating the current concepts that drive the surgical choice in the treatment of HCC in cirrhotic patients; Eastern and Western perspectives are highlighted. An extensive literature review of the last two decades was performed, on topics covering various aspects of hepatic resection. Early post-operative and long-term outcome measures adopted were firstly analyzed in an attempt to define an optimal standardization useful for research comparison. The need to avoid the development of post-hepatectomy liver failure represents the "conditio sine qua non" of surgical choice and the role of the current tools available for the assessment of liver function reserve were investigated. Results of he-patic resection in relationship with tumor burden were compared with those of available competing strategies, namely, radiofrequency ablation for early stages, and trans-arterial chemoembolization for intermediate and advanced stages. Finally, the choice for anatomical versus non-anatomical, as well as the role of laparoscopic approach, was overviewed. The literature review suggests that partial hepatectomy for HCC should be considered in the context of multi-disciplinary evaluation of cirrhotic patients. Scientific research on HCC has moved, in recent years, from surgical therapy toward non-surgical approaches and most of the literature regarding topics debated in the present review is represented by observational studies, whereas very few well-designed randomized controlled trials are currently available; thus, no robust recommendations can be derived.

Research paper thumbnail of Partial Necrosis on Hepatocellular Carcinoma Nodules Facilitates Tumor Recurrence after Liver Transplantation

Transplantation, 2004

The presence of partial necrosis in hepatocellular carcinoma (HCC) nodules is a common histologic... more The presence of partial necrosis in hepatocellular carcinoma (HCC) nodules is a common histologic finding after liver transplantation, but its correlation with tumor recurrence has never been investigated. we retrospectively reviewed the outcome of 54 patients with a single histologically proven HCC after liver transplantation. All cases had a survival of more than 6 months, and patients treated preoperatively had a transarterial chemoembolization (TACE) procedure. Since 1996, our center has applied the Milan criteria. Correlations between tumor recurrences and clinicopathologic variables, including the presence of partial necrosis, were performed. Etiologic factors for HCC partial necrosis were also investigated. Sixteen of 54 (29.6%) HCC nodules presented partial necrosis, and 4 (25%) of them developed HCC recurrence compared with 1 of 38 (2.6%) cases without this histologic finding (P<0.05). Partial necrosis was related to TACE procedure (P<0.05), patient age less than 50 years (P<0.05), and tumor diameter greater than 2 cm (P<0.05). Multivariate analysis showed only TACE as an independent variable. The other variables related to the five (9.3%) tumor recurrences were HCC diameter greater than 2 cm (P<0.05), year of liver transplantation before 1996 (P<0.05), and the presence of satellite nodules (P<0.05). The Cox regression analysis showed the presence of partial necrosis as an independent variable related to tumor recurrence. The analysis of the recurrence-free survival confirmed the results of the recurrence rate. Partial necrosis was a risk factor for tumor recurrence after liver transplantation. Patients and procedures should be selected while also bearing in mind the side-effect of incomplete necrosis of the nodules.

Research paper thumbnail of Metronomic Capecitabine in Advanced Hepatocellular Carcinoma Patients: A Phase II Study

Research paper thumbnail of Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: Meta-Analysis of Randomized Controlled Trials1

Research paper thumbnail of Hepatocellular Carcinoma Responding to Superselective Transarterial Chemoembolization: An Issue of Nodule Dimension?

Journal of Vascular and Interventional Radiology, 2013

To evaluate the per-nodule efficacy of superselective transarterial chemoembolization of hepatoce... more To evaluate the per-nodule efficacy of superselective transarterial chemoembolization of hepatocellular carcinomas (HCCs). From 2006-2009, 271 cirrhotic patients with 635 nodules underwent a first superselective transarterial chemoembolization, repeated "on demand" after local recurrences (LR) or partial responses (PR). Complete response (CR), time to nodule progression (TTnP), and local recurrence rate (LRR), according to three size classes (≤ 2 cm, 2.1-5 cm, and>5 cm) were evaluated. After the first superselective transarterial chemoembolization, the CR was 64%, sustained over time in 77%, higher in small (68%) and intermediate-size (64%) nodules than in large nodules (25%; P<.001). The LRR was 23%:20% in small, 27% in intermediate, and 67% in large HCCs (P<.05). The median TTnP of large HCCs was 4 months versus 7-9 months for small and intermediate HCCs. The second superselective transarterial chemoembolization achieved a higher CR (63% in LR, 52% in PR) than the third superselective transarterial chemoembolization (32%). Median TTnP after the second superselective transarterial chemoembolization for LR and PR (8 months and 6 months) was longer than after the third superselective transarterial chemoembolization (3.5 months). Nodules ≤ 5 cm had a CR after the first superselective transarterial chemoembolization (66%) and the second superselective transarterial chemoembolization for LR (64%) or PR (55%) higher than after the third superselective transarterial chemoembolization (40%); nodules>5 cm had a CR of 25% after the first superselective transarterial chemoembolization, LR of 50% and PR of 25%, and after the second and third superselective transarterial chemoembolizations, PR of 0%. Effectiveness of superselective transarterial chemoembolization has a clear cutoff above and below 5-cm nodules, with better results in smaller nodules. In HCCs ≤ 5 cm, the efficacy of the first and second superselective transarterial chemoembolizations performed for LR was higher than the second superselective transarterial chemoembolization for PR and the third superselective transarterial chemoembolization. For HCCs>5 cm, retreatment of PR is of little value, and the third cycle is ineffective.

Research paper thumbnail of A reappraisal of the Barcelona Clinic Liver Cancer model: natural history of untreated 'intermediate stage' hepatocellular carcinoma

Journal of Internal Medicine, 2004

Research paper thumbnail of The use of donor fatty liver for liver transplantation: a challenge or a quagmire?

Journal of Hepatology, 1996