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Ribero D.,Ospedale Mauriziano Umberto I | Amisano M.,Ospedale Mauriziano Umberto I | Bertuzzo F.,Ospedale Mauriziano Umberto I | Langella S.,Ospedale Mauriziano Umberto I | And 4 more authors.
Annals of Surgery | Year: 2013

Objectives: To determine which method of liver volumetry is more accurate in predicting a safe resection. Background: Before major or extended hepatectomy, assessment of the future liver remnant (FLR) is crucial to reduce the risk of postoperative hepatic insufficiency. The FLR volume is usually expressed as the ratio of FLR to nontumorous total liver volume (TLV), which can be measured directly by computed tomography (mTLV) or estimated (eTLV) on the basis of correlation existing with the body surface area. To date, these 2 methods have never been compared. Methods: All consecutive, noncirrhotic patients who underwent resection of 3 or more liver segments between April 2000 and April 2012 and for whom (i) preoperative computed tomographic scans and (ii) body surface area were available entered the study. The mTLV (calculated as TLV - tumor volume) was compared with the eTLV (calculated as -794.41 + 1267.28 × body surface area) using volumetric data (cm) and clinical outcome measures (specifically, hepatic insufficiency and 90-day mortality). Definition of hepatic insufficiency was peak postoperative serum total bilirubin level of more than 7 mg/dL or, in jaundiced patients, an increasing bilirubin level on day 5 or thereafter. Results: Two-hundred forty-three patients who had undergone major (n = 135) or extended (n = 108) hepatectomies met the inclusion criteria. Twenty-eight patients (11.5%) developed hepatic insufficiency, whereas 7 patients (2.9%) died postoperatively. Compared with the eTLV, the mTLV underestimated the liver volume in 60.1% of the patients (P < 0.01). Forty-seven and 73 patients had an inadequate FLR based on mTLV and eTLV, respectively. Portal vein occlusion (PVO) was used in 44 patients. In patients (n = 162) in whom both methods did not evidence the need for PVO, postoperative hepatic insufficiency and mortality were 4.9% and 0.6%, respectively. Conversely, in patients (n = 27) in whom the eTLV but not the mTLV evidenced the need for PVO, and thus PVO was not performed, hepatic insufficiency (22.2%; P = 0.001) and mortality (3.7%; P = ns) were higher. Conclusions: The use of eTLV identifies a subset of patients (∼11%) in whom liver volumetry with the mTLV underestimates the risk of hepatic insufficiency. © 2013 by Lippincott Williams & Wilkins.

Muratore A.,Istituto Per la Ricerca e la Cura del Cancro | Zimmitti G.,Ospedale Mauriziano Umberto I | Ribero D.,Ospedale Mauriziano Umberto I | Mellano A.,Istituto Per la Ricerca e la Cura del Cancro | And 2 more authors.
Annals of Surgical Oncology | Year: 2012

Background. The aim of the present study is to examine the effect of systemic chemotherapy after the 1st-stage hepatectomy (CTx2) on the progression of disease and dropout rates. A major pitfall of the 2-stage hepatectomy procedure is a high dropout rate after the 1st-stage hepatectomy due to progression of disease (PD). Routine use of CTx2 has been advocated. Methods. A total of 47 patients with multiple, bilateral unresectable liver metastases were selected for a 2-stage hepatectomy procedure (±portal vein occlusion). Results. Of the total, 37 patients (78.7%) underwent systemic chemotherapy before the 1st-stage hepatectomy (CTx1) and 25 patients (53.2%) underwent CTx2; PD was significantly more common during CTx2 than during CTx1 (P = .002). Of the 47 patients planned for the 2nd-stage hepatectomy, 36 (76.6%) completed the procedure. Of these 47 patients, 25 (53.2%) showed PD after the 1st-stage hepatectomy, 12 in the CTx2 group and 13 in the no-CTx2 group; administration of CTx2 did not significantly affect the PD rate (P = .561). The overall dropout rate was 23.4% (n = 11 patients): 16% in the CTx2 group vs. 31.8% in the no-CTx2 group (P = .303). Conclusions. The routine use of chemotherapy between the 1st- and 2nd-stage hepatectomy does not guarantee lower PD and dropout rates. © Society of Surgical Oncology 2011.

Santini D.,Biomedical University of Rome | Vincenzi B.,Biomedical University of Rome | Adamo V.,Messina University | Addeo R.,Oncology Unit | And 17 more authors.
Oncology Reports | Year: 2011

Many ErbB2-positive cancers may show intrinsic resistance, and the frequent development of acquired resistance to ErbB-targeted agents represents a substantial clinical problem. The constitutive NF-κB activation in some HER-2/neu positive breast cancer may represent a potential cause of resistance to trastuzumab therapy. Preclinical data revealed that 4-(N-Methyl-N- nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the tobacco-specific nitrosamine is able to enhance NF-κB DNA binding activity and theoretically to increase the resistance to trastuzumab. Two hundred and forty-eight women with pathologically confirmed, uni- or bidimensionally measurable, HER-2-positive metastatic breast cancer (MBC) treated with trastuzumab-based therapy as first line combination for metastatic disease were considered eligible. For all included patients data on smoking habit were detectable from medical records. We retrospectively analysed the smoking habits of 248 MBC patients and correlated these habits with activity and efficacy of trastuzumab-based therapy. No statistically significant difference in terms of response rate (RR), time to progression (TTP) and overall survival (OS) was identified between smokers (former plus active smokers) and never smokers. Moreover, no statistically significant difference in terms of RR, TTP and OS was identified either comparing active smokers and former smokers. Moreover, we did not observed any significant statistical difference in terms of TTP and OS between smokers ≥10 cigarettes/day and ≤10 cigarettes/day. This study clearly showed lack of any correlation between cigarette smoking habit and both activity and efficacy of trastuzumab-based first line therapy in metastatic HER2/neu positive breast cancer patients. Copyright © 2011 Spandidos Publications Ltd. All rights reserved.

Stacchiotti S.,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico | Longhi A.,Istituto Ortopedico Rizzoli | Ferraresi V.,Istituti Fisioterapici Ospitalieri Polo Oncologico Regina Elena | Grignani G.,Istituto Per la Ricerca e la Cura del Cancro | And 11 more authors.
Journal of Clinical Oncology | Year: 2012

Purpose: To explore the antitumor activity of imatinib in patients with advanced platelet-derived growth factor β (PDGFB)/PDGF receptor β (PDGFRB)-positive chordomas. Patients and Methods: In a collaborative Italian-Swiss, prospective, phase II clinical study conducted from November 2004 through April 2006, 56 patients with advanced PDGFB and/or PDGFRB chordoma received 800 mg/d of imatinib until progression. The primary end point was the overall tumor response rate (ORR), defined by RECIST. Secondary, exploratory end points included tissue response (ie, changes in tumor density or signal intensity/contrast enhancement, and/or [18F]-fluorodeoxyglucose positron emission tomography [PET] uptake), overall survival, progression-free survival (PFS), and pain score. Results: Among 50 patients evaluable by RECIST, the best response was one partial response (PR) obtained at 6 months (ORR, 2%). There were 35 patients with stable disease (SD, 70%) and a 64% clinical benefit rate (ie, RECIST complete response + PR + SD ≥ 6 months). A minor dimensional response (< 20%) was detected in nine patients. A maximum standard uptake value decrease ≥ 25% was observed in 10 (39%) of 26 patients evaluable for PET response at 3 months. Changes in the Brief Pain Inventory score were consistent with the response assessment. Median PFS (intention-to-treat population, 56 patients) was 9 months. No unexpected toxicities were observed. Conclusion: This is the largest phase II study in chordoma to date. It confirms anecdotal evidence that imatinib has antitumor activity in this orphan disease, and therefore, it is worth further investigation. © 2012 by American Society of Clinical Oncology.

Messina G.,Centro Unico Regionale Trapianti Alberto Neri | Giaccone L.,University of Turin | Festuccia M.,University of Turin | Irrera G.,Centro Unico Regionale Trapianti Alberto Neri | And 21 more authors.
Biology of Blood and Marrow Transplantation | Year: 2012

A non myeloablative conditioning with total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) was shown to protect against graft-versus-host disease (GVHD). To evaluate the effects of TLI-ATG in a multicenter study, 45 heavily pretreated patients, median age 51, with lymphoid (n = 38) and myeloid (n = 7) malignancies were enrolled at 9 centers. Twenty-eight patients (62%) received at least 3 lines of treatment before allografting, and 13 (29%) had refractory/relapsed disease at the time of transplantation. Peripheral blood hematopoietic cells were from HLA identical sibling (n = 30), HLA-matched (n = 9), or 1 antigen HLA-mismatched (n = 6) unrelated donors. A cumulative TLI dose of 8 Gy was administered from day -11 through -1 with ATG at the dose of 1.5 mg/kg/day (from day -11 through -7). GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. Donor engraftment was reached in 95% of patients. Grade II to IV acute GVHD (aGVHD) developed in 6 patients (13.3%), and in 2 of these patients, it developed beyond day 100. Incidence of chronic GVHD (cGVHD) was 35.8%. One-year nonrelapse mortality was 9.1%. After a median follow-up of 28 months (range, 3-57 months) from transplantation, median overall survival was not reached, whereas median event-free survival was 20 months. This multicenter experience confirms that TLI-ATG protects against GVHD and maintains graft-vs-tumor effects. © 2012 American Society for Blood and Marrow Transplantation.

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