Vincenzo Mazzaferro

Istituto Nazionale Tumori "Fondazione Pascale", Napoli, Campania, Italy

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Publications (244)1263.16 Total impact

  • Vincenzo Mazzaferro, Riccardo Lencioni, Pietro Majno
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    ABSTRACT: In the treatment of early hepatocellular carcinoma (HCC), resection ablation and transplantation have had excellent initial success. Choices have to be based on a broad and long-term vision integrating-besides patients' interests-the community's needs and resources. In this scenario, guidelines such as the Barcelona Clinic Liver Cancer (BCLC) staging system can be viewed as a hideous frame (symbolized by the myth of Procrustes, Poseidon's son who stretched or maimed travelers to fit into his bed), or as a useful structure against which personalized or innovative treatments must be reality checked. In this article, the latter view is taken: For resection, portal hypertension must still represent a powerful caveat, particularly because of poor long-term results. Expansion of the criteria may instead be explored for multiple tumors and vascular invasion, where good indications can consistently be selected in expert surgical centers. For ablation, competitive results can be obtained although a small, but appreciable proportion of patients with early vascular invasion (∼ 10%), as they could probably benefit from anatomical resections. Conversely, ablative techniques overcoming the location and size limitations are developing and may prove competitive. For transplantation, several equivalent careful expansions of Milan's Criteria can be accepted, but as more patients have access to the waiting list-often prioritized on non-HCC indications-current allocation models prove to be insufficient, if not plainly inequitable, and should be revised.
    Seminars in Liver Disease 11/2014; 34(4):415-26. · 8.27 Impact Factor
  • Jordi Bruix, Gregory Gores, Vincenzo Mazzaferro
    Gut 10/2014; · 10.73 Impact Factor
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  • Sherrie Bhoori, Vincenzo Mazzaferro
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    ABSTRACT: Liver transplantation (LT) is the best option of cure for hepatocellular carcinoma (HCC). Notwithstanding several alternatives, Milan Criteria remain the cornerstone for patient selection. Currently, expanded criteria patients are unsuitable for LT without taking downstaging approaches and response to therapies into consideration. Relative weight of HCC as indication to LT is increasing and that generates competition with MELD-described non-cancer indications. Allocation policies should be adjusted accordingly, considering principles of urgency and utility in the management of the waiting list and including transplant benefit to craft equitable criteria to deal with the limited resource of donated grafts. Maximization of cost-effectiveness of LT in HCC can be also pursued through changes in immunosuppression policies and multimodal management of post-transplant recurrences. This review is focused on those constantly mutating challenges that have to be faced by anyone dealing with the management of HCC in the context of liver transplantation.
    Baillière&#x027 s Best Practice and Research in Clinical Gastroenterology 10/2014; · 3.16 Impact Factor
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    ABSTRACT: Objective Search and review of available literature were made to define the indications for and timing of liver transplantation for neuroendocrine tumour (NET) liver metastases.Methods Electronic bibliographical databases were searched. Prospective and retrospective cohort studies and case–controlled studies were used for qualitative and quantitative synthesis of the systematic review. Reports of patients with liver transplantation alone for NET liver metastases of any origin or combined with resection of extrahepatic tumour deposits were recruited.ResultsThe number of patients who have undergone liver transplantation for NET liver metastases is 706. The post-transplant 5-year survival rate from the time of diagnosis was approximately 70%. NET patients with metastases confined to the liver and not poorly differentiated are favourable candidates for liver transplantation. Selection of patients based on evolution of tumours over 6 months is not recommended.Conclusion Non-resectable NET liver metastasis resistant to medical treatment and confined to the liver is an accepted indication for liver transplantation.
    HPB 08/2014; · 1.94 Impact Factor
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    ABSTRACT: In planning Yttrium-90 ((90)Y)-radioembolizations, strategy problems arise in tumours with multiple arterial supplies. We aim to demonstrate that tumours can be treated via one main feeding artery achieving flow redistribution by embolizing accessory vessels.
    Cardiovascular and interventional radiology. 06/2014;
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    ABSTRACT: Biliary tract cancer (BTC) is a highly lethal disease for which the best available therapy remains undetermined. The mammalian target of rapamycin (mTOR) pathway is upregulated in several cancers, including BTC, and preclinical evidence indicates that mTOR inhibition may be effective in the treatment of BTC. We sought to evaluate the activity and tolerability of the mTOR inhibitor RAD001 - everolimus - in patients with BTC progressing after prior chemotherapy. This was an open-label, single-arm, phase II study (EUDRACT 2008-007152-94) conducted in 8 sites in Italy. Patients with locally-advanced, metastatic, or recurrent BTC progressing despite previous chemotherapy received a daily oral dose of everolimus 10 mg administered continuously in 28-day cycles. The two primary endpoints were disease control rate (DCR) and objective response rate (ORR). Secondary endpoints were progression-free-survival (PFS), overall survival (OS) and time-to-progression (TTP). Thirty-nine patients were enrolled. The DCR was 44.7%, and the ORR was 5.1%. One patient showed a partial response at 2 months and one patient showed a complete response sustained up to 8 months. Median (95% CI) PFS was 3.2 (1.8-4.0) months, and median OS was 7.7 (5.5-13.2) months. Median TTP was 2.0 (1.7-3.7) months. Most common toxicities were asthenia (43.6%), thrombocytopenia (35.9%), pyrexia (30.8%) and erythema, mainly of mild-to-moderate severity. Two patients required dose reduction due to adverse events. Everolimus demonstrated a favourable toxicity profile and encouraging antitumour activity. Further trials are needed to establish the role of everolimus in the treatment of BTC.
    Annals of Oncology 05/2014; · 7.38 Impact Factor
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    ABSTRACT: PURPOSE: To evaluate the short-term safety and efficacy of the new generation of 70-150 µm drug-eluting beads (M1 DEB) in patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE) as a primary therapy or as a bridge to liver transplantation (LT). METHODS: Forty-five consecutive patients underwent TACE with M1 DEB loaded with doxorubicin (DEBDOX/M1). Clinical data were recorded at 12, 24, and 48 h, 7 and 30 days after treatment. Response was assessed by computed tomographic scan according to the modified response evaluation criteria in solid tumors criteria, and a second DEBDOX/M1 TACE was scheduled within 6 weeks in case of a noncomplete response. RESULTS: All patients had well-compensated cirrhosis (97.7 % Child A, 44.4 % hepatitis C virus, median age 61 years). Twenty patients (44.4 %) had Barcelona Clinic for Liver Cancer class B disease; the median number of nodules and their sum of diameters were 2 (range 1-6) and 43 mm (range 10-190), respectively. The mean number of TACE procedures per patient was 1.4. Objective response rate (complete + partial response) was 77.7 % with a median time to best response of 3 months (95 % confidence interval 2-4). In 13 patients, DEBDOX/M1 TACE served as a bridge/downstaging to LT/surgery. Pathology showed that more than 90 % necrosis was achieved in 10 of 28 nodules. DEBDOX/M1 TACE was well tolerated, and the grade 3/4 adverse event rate was low (1 of 65 procedures). CONCLUSION: DEBDOX/M1 TACE is an effective procedure with a favorable safety profile and promising results in terms of objective response rate, tumor downstaging, and necrosis.
    CardioVascular and Interventional Radiology 05/2014; · 2.09 Impact Factor
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    ABSTRACT: Background and Aims: Hepatocellular carcinoma (HCC) is a worldwide public health problem, accounting for increasing mortality and high costs. Aim of our study was to identify and test outcome indicators (OIs) in HCC, in light of their potential use in policy decision models. Methods: A panel of experts identified a list of OIs using a modified Delphi method; three of these OIs with the highest RAND/UCLA scores were tested in a prospective multicenter observational study (Value Based Medicine in Hepatology, VBMH). During 18 months, 711 HCC patients were enrolled and prospectively followed. Median follow-up time was 14 months. Results: The first OI was survival after 1–3–5 years stratified for BCLC stage or treatment (OI#1). One-year survival for BCLC stage 0/A, B, C, D was 93%, 86%, 50%, 26% respectively. One-year survival of 288 patients who had the first treatment during the study time was 88% for liver transplantation, 97% surgical resection, 100% ablation and 89% for TACE. The remaining two OIs meant to evaluate the appropriateness of treatments. Worsening of BCLC and/or CPT score after loco-regional therapy or surgical resection recorded at three months (OI#2), occurred in 16% of cases (76% after TACE). Very early HCC recurrence (within 6 months) after curative treatments (OI#3) happened in 15% of patients treated (20% after ablation). Conclusions: This set of outcome indicators proved their feasibility in a large cohort of patients and could serve as a benchmark for healthcare providers to move towards a value-based approach in the management of HCC.
    Journal of Hepatology 04/2014; 60(Suppl 1):S399 -. · 9.86 Impact Factor
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    ABSTRACT: Background and Aims: Liver disease (LD) is a major cause of morbidity and mortality worldwide. Development of outcome indicators (OIs) provides health care policy makers with objective criteria that can be used to generate a virtuous competition to improve value of care. Aim of our study was to generate and test a set of health care OIs for the major LDs. Methods: Using a modified Delphi method, 7 expert panels identified a set of OIs according to experience and scientific evidence (as of 2010). Each OI was rated in a two-step process using the RAND 9-point agreement scale. Median scores were computed for each OI. After the second rating, a disagreement index (DI) was calculated to identify and accept (if DI≤1) OIs with median rating ≥7. The final set of selected OIs was tested through an ongoing prospective multicenter observational study involving three tertiary centers in Lombardy, Italy. Results: A total of 51 OIs were identified by the focus groups. We recruited 3213 consecutive liver patients, of whom 91% had at least one follow-up visit after a median follow-up time of 15 months. Among these patients, 1752 were cirrhotic and 711 were affected by HCC. During observation time, 156 patients were transplanted and 210 patients died. All the identified OIs were successfully tested in the clinical setting showing excellent performance and correlation with natural history information. Conclusions: This study provides a set of validated outcomes indicators that can be used to monitor the performance of referral centers and improve the value and sustainability of care.
    Journal of Hepatology 04/2014; 60(Suppl 1):S517 -. · 9.86 Impact Factor
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    ABSTRACT: To determine the benefits and risks of hepatic resection versus non-resectional liver-directed treatments in patients with potentially resectable neuroendocrine liver metastases. A systematic review identified 1594 reports which alluded to a possible liver resection for neuroendocrine tumour metastases, of which 38 reports (all retrospective), comprising 3425 patients, were relevant. Thirty studies reported resection alone, and 16 studies reported overall survival (OS). Only two studies addressed quality-of-life (QoL) issues. Five-year overall survival was reported at 41-100%, whereas 5-year progression-free survival (PFS) was 5-54%. We identified no robust evidence that a liver resection was superior to any other liver-directed therapies in improving OS or PFS. There was no evidence to support the use of a R2 resection (debulking), with or without tumour ablation, to improve either OS or QoL. There was little evidence to guide sequencing of surgery for patients presenting in Stage IV with resectable disease, and none to support a resection of asymptomatic primary tumours in the presence of non-resectable liver metastases. Low-level recommendations are offered to assist in the management of patients with neuroendocrine liver metastases, along with recommendations for future studies.
    HPB 03/2014; · 1.94 Impact Factor
  • Jordi Bruix, Gregory J Gores, Vincenzo Mazzaferro
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    ABSTRACT: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death and is currently the main event leading to death in patients with cirrhosis. Evolving information suggests that the metabolic syndrome with non-alcoholic liver disease may be an important cause of HCC in addition to viral hepatitis and alcohol-induced liver disease. The molecular pathogenesis is extremely complex and heterogeneous. To date the molecular information has not impacted on treatment decisions. Periodic surveillance imaging of patients with cirrhosis is widely practiced, especially because diagnostic, radiographic criteria for early-stage HCC have been defined (including nodules between 1 and 2 cm) and effective treatment is available for tumours detected at an early stage. Worldwide the approach to resection versus transplantation varies depending upon local resources, expertise and donor availability. The criteria for transplantation are discussed, and the controversial areas highlighted with evidence-based recommendations provided. Several approaches are available for intermediate stage disease, including radiofrequency ablation, transarterial chemoembolisation and radioembolisation; the rationale for these therapies is buttressed by appropriate outcome-based studies. For advanced disease, systemic therapy with sorafenib remains the option best supported by current data. Thus, while several trials have failed to improve the benefits of established therapies, studies assessing the sequential or combined application of those already known to be beneficial are needed. Also, new concepts are provided in regards to selecting and stratifying patients for second-line studies, which may help explain the failure of prior studies.
    Gut 02/2014; · 10.73 Impact Factor
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    Digestive and Liver Disease 02/2014; 46(Suppl 1):e63. · 3.16 Impact Factor
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    ABSTRACT: Purpose Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter (90Y) and a medium-energy beta/gamma emitter (177Lu) in patients with metastatic NET refractory to conventional therapy. Methods A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [177Lu]DOTA-TATE (5.55 GBq) and [90Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [177Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. Results Administration of tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment Conclusion The results of our study indicates that combined [90Y]DOTA-TATE and [177Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach.
    European journal of nuclear medicine and molecular imaging 02/2014; 41(2). · 5.11 Impact Factor
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    European Journal of Nuclear Medicine 01/2014; · 4.53 Impact Factor
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    ABSTRACT: Study Objective To present our preliminary experience using a thoracic paravertebral block (TPVB) as the sole anesthetic in percutaneous hepatic radiofrequency ablation (RFA). Design Retrospective case series of 12 ASA physical status 1, 2, and 3 patients of average risk scheduled for RFA. Setting University medical center. Measurements The first 12 procedures performed using TPVB were analyzed to evaluate the efficacy and safety of this anesthetic technique. Data collected included patients’ characteristics, procedure, pain referred during paravertebral punctures, and RFA (verbal numerical scale; VNS). Anesthesia and medical records also were reviewed for any major complications that occurred during or after the RFA. Main Results Ten of the 12 patients presented for hepatocellular carcinoma; the other two patients had melanoma metastasis. Nine patients were ASA physical status 1 or 2; the other three patients were ASA physical status 3. Nine had liver cirrhosis. All patients had normal coagulation profiles. The TPVBs were performed in a median time of 6.5 (4–15) minutes. Onset of sensory loss to pinprick test occurred approximately 15 to 20 minutes after the injections. No evidence of bilateral blockade was seen in any patient. In most cases, the extent of anesthesia ranged from T6 to T11 or T12. In one patient (no. 2), the stimulating needle elicited no sensory or motor response at the T7 level; the local anesthetic was then injected one cm beyond the transverse process. All patients were very pleased with their anesthetic care; all were discharged from the hospital with no procedure-related complications. Conclusion The use of thoracic paravertebral block as the sole anesthetic for RFA of liver produced satisfactory unilateral anesthesia and minor adverse events.
    Journal of Clinical Anesthesia. 01/2014;
  • Vincenzo Mazzaferro, Sasan Roayaie, Ronnie Poon, Pietro E Majno
    Annals of surgery 12/2013; · 7.90 Impact Factor
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    ABSTRACT: AimsEwing sarcoma primary to the ileum (IES) has rarely been documented. Little is known about the pathogenesis and clinical implications of IES, which may be critical to identify novel molecular markers. EWSR1-FEV translocation is exceedingly rare in ES, as FEV expression is restricted to prostate, brain, and serotonin neuroendocrine cells (NE) and related tumors. Methods and resultsParaffin sections or snap-frozen material was used in this investigation. Tumors were investigated by means of immunohistochemistry, RT-PCR (EWSR1-FLI1, EWSR1-ERG and EWSR1-FEV transcripts), FISH analysis (EWSR1 break-apart and specific EWSR1-FEV translocation) and spectral karyotyping (SKY). Ten ileum neuroendocrine tumors (INET) made up the control group for EWSR1-FEV translocation.Among 445 ES cases spanning a period of 20 years, seven (1.6%) were IES. All tumors were immunoreactive for synaptophysin, CD99, FLI 1 and vimentin. FISH identified EWSR1 rearrangement in all cases, with EWSR1-FLI1 transcripts being detected in all but one tumor showing the uncommon EWSR1-FEV rearrangement upon SKY, RT-PCR and FISH confirmation. The mean survival of EWSR1-FLI1 patients was 14 months, whereas the EWSR1-FEV patient was alive after 15 years despite several recurrences controlled by surgery alone. No INET showed EWSR1 translocation. Conclusions Most IES share the common EWSR1-FLI1 translocation, but EWSR1-FEV could be specific of tumors arising in the ileum and showing better prognosis.This article is protected by copyright. All rights reserved.
    Histopathology 12/2013; · 2.86 Impact Factor
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    Carlo Sposito, Vincenzo Mazzaferro
    Journal of Hepatology 11/2013; · 9.86 Impact Factor
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    ABSTRACT: The operative approach to large retrohepatic tumors can be challenging because of the difficulty in exposing the inferior vena cava (IVC) and controlling bleeding. The anterior approach to the IVC associated with the hanging maneuver for liver transection, originally described in large hepatic tumors, may also facilitate removal of large masses set behind the liver. A prospective cohort of 10 patients with large retrohepatic tumors involving the IVC was selected according to restrictive criteria (ie, single low-grade tumor, sufficient liver remnant, normal hepatic function, absence of cholestasis, and symptoms secondary to lower vena cava obstruction). In all cases, the anterior approach and the hanging maneuver were applied intentionally to expose the IVC without any liver mobilization. Depending on tumor invasiveness, either IVC-preserving (n = 7) or IVC-removing (n = 3) strategies were applied. Our aim was to assess the safety of the technique and the possible benefits for patient outcome. The cohort represented less than 1% of a series of 1,168 major hepatectomies performed in our unit between 2005 and 2011. The median age of the patients was 58; adrenal tumors and retroperitoneal sarcomas accounted for 70% of the series. Total vascular liver exclusion was necessary in 3 patients. Median operative time was 420 min. R0 resection was obtained in all cases, with no mortality and 40% overall morbidity. Overall survival was 83% at 5 years. The transhepatic, anterior approach to the IVC is a safe procedure that improves vascular control, facilitates vein repair or reconstruction, and allows potentially curative resection of large retrohepatic tumors. This approach should be the preferred choice to be adopted in properly selected patients.
    Surgery 11/2013; 154(5):1061-8. · 3.37 Impact Factor

Publication Stats

10k Citations
1,263.16 Total Impact Points

Institutions

  • 1992–2014
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
  • 1988–2014
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      • • s.c. Medicina Nucleare
      • • s.c. Pediatria Oncologica
      Milano, Lombardy, Italy
  • 2013
    • Mount Sinai Hospital
      New York City, New York, United States
    • Università degli Studi di Milano-Bicocca
      • Department of Health Science
      Milano, Lombardy, Italy
  • 1993–2013
    • CRO Centro di Riferimento Oncologico di Aviano
      • • Division of Experimental Oncology 1
      • • Department of Surgery
      Aviano, Friuli Venezia Giulia, Italy
  • 2012
    • Istituto di Cura e Cura a Carattere Scientifico Basilicata
      Rionero in Vulture, Basilicate, Italy
    • Institut Paoli Calmettes
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • University of California, San Diego
      San Diego, California, United States
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
  • 2008–2012
    • Icahn School of Medicine at Mount Sinai
      • • Department of Pathology
      • • Department of Medicine
      Manhattan, New York, United States
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
  • 2011
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 1988–2009
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      Meldola, Emilia-Romagna, Italy
  • 1988–2008
    • University of Pittsburgh
      • Department of Surgery
      Pittsburgh, PA, United States
  • 1997–2007
    • University of Milan
      • • International Center for the Assessment of Nutritional Status ICANS
      • • Department of Internal Medicine
      Milano, Lombardy, Italy
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
  • 2005
    • University of Barcelona
      Barcino, Catalonia, Spain
  • 2002–2003
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      Milano, Lombardy, Italy
  • 1996
    • IEO - Istituto Europeo di Oncologia
      • Psycho-Oncology Unit
      Milano, Lombardy, Italy
  • 1989–1995
    • Azienda Ospedaliera Niguarda Ca' Granda
      • Department of Surgery
      Milano, Lombardy, Italy
    • University of Padova
      Padua, Veneto, Italy
  • 1989–1991
    • Università degli Studi di Bari Aldo Moro
      • Dipartimento di Scienze Biomediche ed Oncologia Umana (DIMO)
      Bari, Apulia, Italy