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Berretta M.,Italian National Cancer Institute | Di Benedetto F.,Liver and Multivisceral Transplant Center | Dal Maso L.,Epidemiology and Biostatistics Unit | Cacopardo B.,University of Catania | And 9 more authors.
Anti-Cancer Drugs | Year: 2013

Few data are available on the safety and efficacy of sorafenib in HIV-infected patients with unresectable hepatocellular carcinoma (HIV-u-HCC) and concomitant highly active antiretroviral therapy (HAART). Between July 2007 and October 2010, 27 consecutive HIV-u-HCC patients were treated with sorafenib and concomitant HAART within the Gruppo Italiano Cooperativo AIDS e Tumori (GICAT). Three patients achieved a partial response, 12 achieved a stable disease, and 12 showed progression. The median time to progression and overall survival was 5.1 (range 0.5-13.3) and 12.8 (range 1.1-23.5) months, respectively. Grades 3-4 toxicities included diarrhea (four patients, 14.8%), hypertension (three patients, 11%), and hand-and-foot skin reaction (four patients, 14.9%). Most drug-related side effects were low grade and manageable. This retrospective study shows favorable survival data among HIV-u-HCC patients treated with sorafenib together with a reasonable safety profile. © 2013 Wolters Kluwer Health Lippincott Williams & Wilkins.

Montalti R.,Liver and Multivisceral Transplant Center | Mimmo A.,Liver and Multivisceral Transplant Center | Rompianesi G.,Liver and Multivisceral Transplant Center | Di Gregorio C.,Section of Pathologic Anatomy | And 11 more authors.
Transplantation | Year: 2014

BACKGROUND: Prognostic factors for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) are still a matter of debate. The absence of viable tumor in the native liver, due to effectiveness of pre-LT locoregional treatment or liver resection, is an intriguing prognostic factor that had never been evaluated. METHODS: Between November 2000 and December 2011, 210 LTs were performed in patients with evidence of HCC and cirrhosis. RESULTS: Fifty-three (25.2%) patients did not show any evidence of active residual HCC in the native liver (Group NVH), whereas 157 (74.8%) patients showed viable HCC (Group VH). All patients in Group NVH were treated before LT with a multimodal approach combining transarterial chemoembolization, liver resection, radiofrequency ablation, percutaneous ethanol injection, or sorafenib, whereas, in Group VH, 110 of the 157 (70.1%) patients received bridging therapy (P<0.001). HCC recurrence occurred in none of the patients in Group NVH (0%) and in 25 (15.9%) patients in Group VH (P=0.003). Liver resection was the most effective treatment in obtaining absence of HCC on liver explantation. The results of multivariate analysis showed that existence of pathologic HCC findings outside of the University of California-San Francisco criteria (P=0.001; odds ratio, 4; confidence interval, 1.7-9.2) and the presence of viable HCC (P=0.003; odds ratio, 5.9; confidence interval, 1.5-17.6) were independently associated with HCC recurrence. CONCLUSIONS: The histologic absence of viable HCC in the native liver after LT and morphologic criteria, due to the high effectiveness of pre-LT bridging treatments, is a highly positive prognostic factor against HCC recurrence after LT.

Di Benedetto F.,Liver and Multivisceral Transplant Center | Berretta M.,Italian National Cancer Institute | D'Amico G.,Liver and Multivisceral Transplant Center | Montalti R.,Liver and Multivisceral Transplant Center | And 9 more authors.
Journal of the American Geriatrics Society | Year: 2011

Objectives To assess the safety and long-term results of hepatic resection of colorectal liver metastases (CLM) in older adults. Design Case-control. Setting Single liver and multivisceral transplant center. Participants Individuals with CLM: 32 aged 70 and older (older group) and 32 younger than 70 (younger group) matched in a 1:1 ratio according to sex, primary tumor site, liver metastases at diagnosis, number of metastases, maximum tumor size, infiltration of cut margin, type of hepatic resection, and hepatic resection timing. Measurements Postoperative complications and survival rates. Results There was no significant difference in preoperative clinical findings between the two study groups. The incidence of cumulative postoperative complications was similar in the older (28.1%) and younger (34.4%) groups (P =.10). One-, 3-, and 5-year disease-free survival rates were 57.6%, 32.9%, and 16.4%, respectively, in the younger group and 67.9%, 29.2%, and 19.5%, respectively, in the older group (P =.72). One-, 3-, and 5-year participant survival rates were 84.1%, 51.9%, and 33.3%, respectively, in the older group and 93.6%, 63%, and 28%, respectively, in the younger group (P =.50). Conclusions Resection of colorectal liver metastases in older adults can be performed with low mortality and morbidity and offers a long-time survival advantage to many of these individuals. Based on the results of this case-control study, older adults should be considered for surgical treatment whenever possible. © 2011, Copyright the Authors.

Montalti R.,Liver and Multivisceral Transplant Center | Di Benedetto F.,Liver and Multivisceral Transplant Center | Aiello S.,Azienda Ospedaliero Universitaria di Modena Policlinico | Rompianesi G.,Liver and Multivisceral Transplant Center | Gerunda G.E.,Liver and Multivisceral Transplant Center
European Journal of Anaesthesiology | Year: 2010

Background and objective Despite clinical and laboratory evidence of perioperative hypercoagulability, alterations in haemostasis after potentially haemorrhagic oncologic surgery are difficult to predict. This study aims to evaluate the entity, the extent and the duration of perioperative coagulative alterations following pancreas and liver oncologic surgery, by the use of both routine tests and thromboelastogram (TEG). Methods Fifty-six patients undergoing liver (n=38) and pancreatic (n=18) surgery were studied. The coagulation profile was evaluated by platelet count, prothrombin timeinternational normalized ratio, activated partial thromboplastin time, antithrombin III and TEG at the beginning, at the end of the operation and on postoperative days 1, 3, 5 and 10. Results All preoperative coagulative screening and TEG traces were normal before incision. In the postoperative period of the liver and pancreas groups, despite an increase in prothrombin time-international normalized ratio, a reduction in antithrombin III and platelet count and normal activated partial thromboplastin time and fibrinogen, TEG evidenced a normocoagulability in the liver group, with a major tendency towards hypocoagulability in the pancreas group, as evidenced by a transient increase in R-time and K-time between postoperative days 1 and 3. During the study period, four cases of pulmonaryembolism, resolved with heparin infusion, were recorded, in the absence of laboratory and thromboelastographic evidence of hypercoagulability. Conclusion Despite laboratory tests evidencing hypocoagulability in both groups, TEG traces showed a normocoagulability in liver resections, whereas a transient thromboelastographic hypocoagulability was evident in patients undergoing pancreas surgery. The discrepancy between laboratory values and thromboelastographic variables was even more evident in patients undergoing major liver resections compared with minor ones. Our study supports the role of thromboelastography, despite its limitations, as a valuable tool for the evaluation of the perioperative whole coagulation process and hypercoagulability changes and to increase patient safety through better management of antithrombotic therapy. © 2010 Copyright European Society of Anaesthesiology.

Roat E.,University of Modena and Reggio Emilia | De Biasi S.,University of Modena and Reggio Emilia | Bertoncelli L.,University of Modena and Reggio Emilia | Rompianesi G.,Liver and Multivisceral Transplant Center | And 8 more authors.
Cytometry Part A | Year: 2012

Several immunosuppressive drugs with different mechanisms of action are available to inhibit organ rejection after transplant. We analyzed different phenotypic and functional immunological parameters in liver-transplanted patients who received cyclosporin A (CsA) or Everolimus (Evr). In peripheral blood mononuclear cells (PBMC) from 29 subjects receiving a liver transplant and treated with two different immunosuppressive regimens, we analyzed T cell activation and differentiation, regulatory T cells (Tregs) and Tregs expressing homing receptors such as the chemokine receptor CXCR3. T cell polyfunctionality was studied by stimulating cells with the superantigen staphylococcal enterotoxin B (SEB), and measuring the simultaneous production of interleukin (IL)-2 and interferon (IFN)-γ, along with the expression of a marker of cytotoxicity such as CD107a. The analyses were performed by polychromatic flow cytometry before transplantation, and at different time points, up to 220 days after transplant. Patients taking Evr had a higher percentage of total CD4+ and naïve CD4+ T cells than those treated with CsA; the percentage of CD8+ T cells was lower, but the frequency of naïve CD8+ T cells higher. Patients taking Evr showed a significantly higher percentage of Tregs, and Tregs expressing CXCR3. After stimulation with SEB, CD8+ T cells from Evr-treated patients displayed a lower total response, and less IFN-γ producing cells. The effects on the immune system, such as the preservation of the naïve T cell pool and the expansion of Tregs (that are extremely useful in inhibiting organ rejection), along with the higher tolerability of Evr, suggest that this drug can be safely used after liver transplantation, and likely offers immunological advantages. © 2012 International Society for Advancement of Cytometry.

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