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1.
ESMO Open ; 9(4): 102991, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38631269

RESUMO

BACKGROUND: Advances in surgical techniques and systemic treatments have increased the likelihood of achieving radical surgery and long-term survival in metastatic colorectal cancer (mCRC) patients with initially unresectable colorectal liver metastases (CRLMs). Nonetheless, roughly half of the patients resected after an upfront systemic therapy experience disease relapse within 6 months from surgery, thus leading to the question whether surgery is actually beneficial for these patients. MATERIALS AND METHODS: A real-world dataset of mCRC patients with initially unresectable liver-limited disease treated with conversion chemotherapy followed by radical resection of CRLMs at three high-volume Italian institutions was retrospectively assessed with the aim of investigating the association of baseline and pre-surgical clinical, radiological and molecular factors with the risk of relapse within 6 or 12 months from surgery. RESULTS: Overall, 268 patients were included in the analysis and 207 (77%) experienced recurrence. Ninety-six (46%) of them had disease relapse within 6 months after CRLM resection and in spite of several variables associated with early recurrence at univariate analyses, only primary tumour resection at diagnosis [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.32-0.89, P = 0.02] remained significant in the multivariable model. Among patients with resected primary tumours, pN+ stage was associated with higher risk of disease relapse within 6 months (OR 3.02, 95% CI 1.23-7.41, P = 0.02). One hundred and forty-nine patients (72%) had disease relapse within 12 months after CRLMs resection but none of the analysed variables was independently associated with outcome. CONCLUSIONS: Clinical, radiological and molecular factors assessed before and after conversion chemotherapy do not reliably predict early recurrence after secondary resection of initially unresectable CRLMs. While novel markers are needed to optimize the cost/efficacy balance of surgical procedures, CRLM resection should be offered as soon as metastases become resectable during first-line chemotherapy to all patients eligible for surgery.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Hepatectomia/métodos
2.
PLoS One ; 18(6): e0287062, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37379311

RESUMO

Breast cancer is the most common cancer among women worldwide. Molecular and clinical evidence indicated that Fragile X Messenger Ribonucleoprotein 1 (FMRP) plays a role in different types of cancer, including breast cancer. FMRP is an RNA binding protein that regulates the metabolism of a large group of mRNAs coding for proteins involved in both neural processes and in epithelial-mesenchymal transition, a pivotal mechanism that in cancer is associated to tumor progression, aggressiveness and chemoresistance. Here, we carried out a retrospective case-control study of 127 patients, to study the expression of FMRP and its correlation with metastasis formation in breast cancer. Consistent with previous findings, we found that FMRP levels are high in tumor tissue. Two categories have been analyzed, tumor with no metastases (referred as control tumors, 84 patients) and tumor with distant metastatic repetition, (referred as cases, 43 patients), with a follow-up of 7 years (mean). We found that FMRP levels were lower in both the nuclei and the cytoplasm in the cases compared to control tumors. Next, within the category cases (tumor with metastases) we evaluated FMRP expression in the specific sites of metastasis revealing a nuclear staining of FMRP. In addition, FMRP expression in both the nuclear and cytoplasmic compartment was significantly lower in patients who developed brain and bone metastases and higher in hepatic and pulmonary sites. While further studies are required to explore the underlying molecular mechanisms of FMRP expression and direct or inverse correlation with the secondary metastatic site, our findings suggest that FMRP levels might be considered a prognostic factor for site-specific metastasis.


Assuntos
Neoplasias da Mama , Síndrome do Cromossomo X Frágil , Neoplasias Mamárias Animais , Animais , Humanos , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Estudos de Casos e Controles , Estudos Retrospectivos , Proteínas/metabolismo , Neoplasias da Mama/genética , Síndrome do Cromossomo X Frágil/genética
3.
Dig Liver Dis ; 55(4): 534-540, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36369195

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA) is a rare biliary tract tumor with poor prognosis that often is challenging to diagnose and the majority of patients present with advanced stage. Squamous cell carcinoma antigen 1 (SCCA1) overexpression has been found in different tumors associated with poor prognosis and chemoresistance. AIMS: To assess the presence and possible prognostic role of SCCA1/2 isoforms in bile and serum of patients with CCA. METHODS: Forty seven surgical patients (36 with CCA and 11 with benign diseases) were prospectively included in the study. Serum and bile specimens were collected at the time of surgery and free and IgM-complexed SCCA was quantified by ELISA (Xeptagen, srl). RESULTS: Free or IgM linked SCCA was rarely found in serum, while SCCA was detectable in bile samples of patients with CCA, especially in those with extrahepatic form (43% vs 17%, p = 0.008), but not in controls. Despite similar tumor stage, these positive patients presented a trend toward a higher percentage of portal invasion (27% vs 15%) and of tumor recurrence than negative cases (62% vs 40%), although the difference was not statistically significant. CONCLUSION: These preliminary results indicate that bile testing for SCCA is a specific marker of extrahepatic CCA, with potential prognostic value.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Bile , Biomarcadores Tumorais , Recidiva Local de Neoplasia , Neoplasias Hepáticas/diagnóstico , Colangiocarcinoma/diagnóstico , Imunoglobulina M , Neoplasias dos Ductos Biliares/diagnóstico
4.
Phys Chem Chem Phys ; 22(20): 11583-11592, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32400802

RESUMO

The human telomeric G-quadruplex structural motif of DNA has come to be known as a new and stimulating target for anticancer drug discovery. Small molecules that interact with G-quadruplex structures in a selective way have gained impressive interest in recent years as they may serve as potential therapeutic agents. Here, we show how circular dichroism, UV resonance Raman and small angle X-ray scattering spectroscopies can be effectively combined to provide insights into structural and molecular aspects of the interaction between human telomeric quadruplexes and ligands. This study focuses on the ability of berberine and palmatine to bind with human telomeric quadruplexes and provides analysis of the conformational landscape visited by the relevant complexes upon thermal unfolding. With increasing temperature, both free and bound G-quadruplexes undergo melting through a multi-state process, populating different intermediate states. Despite the structural similarity of the two ligands, valuable distinctive features characterising their interaction with the G-quadruplex emerged from our multi-technique approach.


Assuntos
Alcaloides de Berberina/metabolismo , Berberina/metabolismo , DNA/metabolismo , Quadruplex G , Berberina/química , Alcaloides de Berberina/química , Dicroísmo Circular , DNA/química , DNA/genética , Humanos , Ligantes , Espalhamento a Baixo Ângulo , Análise Espectral Raman , Difração de Raios X
5.
Eur J Surg Oncol ; 46(4 Pt A): 632-637, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31812289

RESUMO

BACKGROUND: Aim of work was to investigate the prognostic impact of liver resection (LR) on locally advanced Intrahepatic Cholangiocarcinoma (IC) in comparison to alternative palliative chemotherapy (CTx). METHOD: A retrospective cohort study performed utilizing Surveillance, Epidemiology, and End Results (SEER) database to identify Locally advanced IC patients. Based on the American Joint Committee on Cancer (AJCC) Staging System, locally advanced IC was defined as: Stage III and IVa - 7th edition (7th-ed) or stage III - 8th edition (8th-ed). Study population were sub-classified into: LR group and a propensity score (PS) matched CTx group. RESULTS: In 7th-ed module, the median survival for LR group (n = 154) was 35 months, and the 3-year survival rate was 40.8%. In PS matched CTx group (n = 154); the median survival was 14 months and the 3-year survival rate was 5.5% (P = 0.007). Survival rates were superior for LR group over PS matched CTx group in 8th-ed module as well. Worse prognosis has been reported in LR patients above 65 years old (HR 2.618, P = 001) and in multifocal lesions (HR 1.890, P = 0.025). CONCLUSION: Hepatic resection was associated with a favorable impact on prognosis over chemotherapy for IC stage III and IVa of the 7th edition and for stage IIIb of 8th edition of AJCC staging system. Worse outcome has been observed in LR patients >65 years and with multifocal lesions. Randomized control studies are recommended to confirm the role of surgical resection in the management for advanced cases of IC, and to clarify the related prognostic factors.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Hepatectomia/métodos , Neoplasias Primárias Múltiplas/cirurgia , Fatores Etários , Idoso , Antineoplásicos/uso terapêutico , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/patologia , Pontuação de Propensão , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Carga Tumoral
6.
Hernia ; 24(2): 359-368, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31407109

RESUMO

PURPOSE: In July 2013, the World Society of Emergency Surgery (WSES) held the first Consensus Conference on emergency repair of abdominal wall hernias in adult patients with the intention of producing evidence-based guidelines to assist surgeons in the management of complicated abdominal wall hernias. Guidelines were updated in 2017 in keeping with varying clinical practice: benefits resulting from the increased use of biological prosthesis in the emergency setting were highlighted, as previously published in the World Journal of Emergency Surgery. This executive summary is intended to consolidate knowledge on the emergency management of complicated hernias by providing the broad readership with a practical and concise version of the original guidelines. METHODS: This executive manuscript summarizes the WSES guidelines reporting on the emergency management of complicated abdominal wall hernias; statements are highlighted focusing the readers' attention on the main concepts presented in the original guidelines. CONCLUSIONS: Emergency repair of complicated abdominal hernias remains one of the most common and challenging surgical emergencies worldwide. WSES aims to provide an essential version of the evidence-based guidelines focusing on the timing of intervention, laparoscopic approach, surgical repair following the Centers for Disease Control and Prevention (CDC) wound classification, antimicrobial prophylaxis and anesthesia in the emergency setting.


Assuntos
Hérnia Abdominal/cirurgia , Herniorrafia/métodos , Guias de Prática Clínica como Assunto , Parede Abdominal/cirurgia , Adulto , Emergências , Feminino , Hérnia Abdominal/complicações , Humanos , Masculino , Telas Cirúrgicas , Ferida Cirúrgica/classificação
7.
Inflamm Res ; 67(7): 609-616, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29605872

RESUMO

The pathophysiology of psoriasis is very complex and involves an interplay between immune cells and keratinocytes. The keratinocyte production of calprotectin (S100A8/A9), induced by the inflammatory psoriatic milieu, may be involved in initiating immune cell invasion, as well as in propagating inflammation. However, the exact role of calprotectin in psoriasis remains unclear. Therapeutic approaches utilizing adalimumab, etanercept and ustekinumab are widely used in psoriatic treatment, but their anti-inflammatory mechanisms are not fully understood. The aim of this study was to investigate, by immunohistochemical analysis, the expression of the heterocomplex S100A8/A9 in lesional skin from psoriatic patients undergoing biological therapy with adalimumab, etanercept or ustekinumab. Our results showed that S100A8/A9, absent or present at very low level in skin biopsies from healthy subjects, is dramatically upregulated in each epidermal layer from psoriatic patients. Interestingly, calprotectin was mainly localized in keratinocyte nuclei from psoriatic patients, suggesting a role of S100A8/A9 in keratinocyte nuclear function. Furthermore, we have shown that the biological treatment induced a drastic reduction of S100A8/A9 expression in skin biopsies from treated patients, correlating with PASI reduction. Our results suggest that calprotectin may play a crucial role as a significant marker of inflammation in psoriasis, and that its reduction of expression may be considered a favourable prognostic marker in psoriasis.


Assuntos
Adalimumab , Anti-Inflamatórios não Esteroides , Calgranulina A/imunologia , Calgranulina B/imunologia , Fármacos Dermatológicos , Etanercepte , Psoríase/imunologia , Ustekinumab , Adalimumab/farmacologia , Adalimumab/uso terapêutico , Adulto , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Terapia Biológica , Fármacos Dermatológicos/farmacologia , Fármacos Dermatológicos/uso terapêutico , Regulação para Baixo , Etanercepte/farmacologia , Etanercepte/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Pele/efeitos dos fármacos , Pele/imunologia , Ustekinumab/farmacologia , Ustekinumab/uso terapêutico
8.
Transplant Proc ; 49(4): 736-739, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28457384

RESUMO

INTRODUCTION: Hepatic artery thrombosis (HAT) is a well-recognized complication of liver transplantation (LT). HAT is an important risk factor for infectious, in particular hepatic abscess, which can cause graft loss and increasing morbidity and mortality. CASE REPORT: We present a case report of complicated LT in a 52-year-old Caucasian man with primary sclerosing cholangitis. In 2007 the patient was included on the waiting list in Padua for LT. In 2012 the patient underwent percutaneous transhepatic biliary drainage for bile duct stricture, complicated with acute pancreatitis. A diagnostic laparoscopy was performed with choledochotomy and Kehr's T tube drainage. On February 14, 2012, the patient underwent LT with arterial reconstruction and choledochojejunostomy. The postoperative course was complicated with HAT, multiple liver abscesses, and sepsis associated with bacteremia due to Enterococcus faecium despite massive intravenous antibiotic therapy and percutaneous drainages. On November 28, 2012, the patient underwent retransplantation. Four years after transplantation the patient is still in good general condition. CONCLUSION: Hepatic abscess formation secondary to HAT following LT is a major complication associated with important morbidity and mortality. In selected cases retransplantation should be considered as our case demonstrates.


Assuntos
Artéria Hepática/patologia , Transplante de Fígado/efeitos adversos , Reoperação , Trombose/etiologia , Humanos , Abscesso Hepático/etiologia , Masculino , Pessoa de Meia-Idade , Reoperação/efeitos adversos , Fatores de Risco , Fatores de Tempo
9.
Transplant Proc ; 48(9): 3073-3078, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27932150

RESUMO

BACKGROUND: Many surgical procedures can produce persistent lymphorrhea, lymphoceles, and lymphedema after lymph node and lymph vessel damage. Appropriate visualization of the lymphatic system is challenging. Indocyanine green (ICG) is a well-known nontoxic dye for lymphatic flow evaluation. ICG fluorescence-guided lymphography has emerged as a promising technique for intraoperative lymphatic mapping. OBJECTIVE: Our goal was to develop a high spatial resolution, real-time intraoperative imaging technique to avoid or recognize early deep lymphatic vessel damage. METHODS: We intraoperatively performed ICG fluorescence-guided lymphography during a kidney transplant. ICG was injected in the subcutaneous tissue of the patient's groin in the Scarpa's triangle. A dedicated laparoscopic high-definition camera system was used. RESULTS: Soon after ICG injection, the lymphatic vessels were identified in the abdominal retroperitoneal compartment as fluorescent linear structures running side by side to the iliac vessels. Surgical dissection was therefore performed, avoiding iatrogenic damage to major lymphatic structures. Another ICG injection at the end of the procedure confirmed that the lymphatic vessels were intact without lymph spread. CONCLUSIONS: Intraoperative lymphatic mapping with an ICG fluorescence-sensitive camera system is a safe and feasible procedure. ICG real-time fluorescence lymphography can be used to avoid or recognize early deep lymphatic vessel damage and reduce postoperative complications related to the lymphatic system.


Assuntos
Transplante de Rim/métodos , Tratamentos com Preservação do Órgão/métodos , Idoso , Corantes , Dissecação/efeitos adversos , Feminino , Fluorescência , Humanos , Verde de Indocianina , Linfonodos/diagnóstico por imagem , Doenças Linfáticas/diagnóstico por imagem , Doenças Linfáticas/prevenção & controle , Vasos Linfáticos/diagnóstico por imagem , Vasos Linfáticos/cirurgia , Linfedema/diagnóstico por imagem , Linfedema/etiologia , Linfografia/métodos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Cirurgia Assistida por Computador/métodos
10.
Transplant Proc ; 46(7): 2287-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25242770

RESUMO

BACKGROUND: Liver transplantation (LT) for hepatocellular carcinoma (HCC) can be used for tumor recurrence after liver resection (LR) both for initially transplant-eligible patients as conventional salvage therapy (ST) and for non-transplant-eligible patients (beyond Milan criteria) with a goal of downstaging (DW). The aim of this study was to compare the intention-to-treat (ITT) survival rates of patients who are listed for LT, according to these two strategies. METHODS: We analyzed a prospective database of 399 consecutive patients who underwent hepatic resection for HCC from 2002 to 2011 to identify patients included in the waiting list for tumor recurrence. Intention-to-treat (ITT) survivals were compared with those of patients resected for HCC within and beyond Milan criteria in the same period and not included in the LT waiting list. RESULTS: The study group consisted of 42 patients, 28 in the ST group (within Milan) and 14 in the DW group (beyond Milan). The 5-year ITT survival rate was similar between the 2 groups, being 64% for ST and 60% for DW (P=.84). Twenty-five patients (15 ST and 10 DW) underwent LT, 13 (10 ST and 3 DW) were still awaiting LT, 4 (3 ST and 1 DW) dropped out of the waiting list because of tumor progression, and 7 (5 ST [33%] and 2 DW [20%]) had tumor recurrence. The 5-year ITT survival of ST patients was similar to that of 252 in-Milan HCC patients resected only (P=.3), whereas 5-year ITT survival of DW patients was significantly higher (P<.01) than that of 105 beyond-Milan HCC patients resected only. CONCLUSIONS: LR seems to be a safe and effective therapy both as alternative to transplantation and as downstaging strategy for intermediate-advanced HCC. The survival benefit of salvage LT, however, seems to be higher in the 2nd than in the 1st group.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/mortalidade , Recidiva Local de Neoplasia/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Análise de Intenção de Tratamento , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Terapia de Salvação/mortalidade , Taxa de Sobrevida , Resultado do Tratamento
11.
Phys Rev Lett ; 109(2): 025005, 2012 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-23030172

RESUMO

We present an effective approach to determine the amount of energy absorbed by solid samples exposed to ultrashort laser pulses, thus, retrieving the maximum temperature attained by the ion lattice in the picosecond time scale. The method is based on the pyrometric detection of a slow temperature fluctuation on the rear side of a sample slab associated with absorption of the laser pulse on the front side. This approach, successfully corroborated by theoretical calculations, can provide a robust and practical diagnostic tool for characterization of laser-generated warm dense matter.

12.
Transplant Proc ; 44(7): 1930-3, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22974875

RESUMO

Ex situ ex vivo liver surgery represents a method to expand the surgical indications to treat otherwise unresectable liver tumors. We report the case of a 38-year old woman with hepatic metastasis from a pancreatoblastoma that was judged to be unresectable due to the involvement of the three hepatic veins. To treat the primary tumor, she underwent a pancreaticoduodenectomy, adjuvant chemotherapy, and thermal ablation of a liver metastasis. After appropriate preoperative study and with the permission of the ethics committee, she underwent ex situ ex vivo liver resection. The hepatectomy was performed by removing the whole liver en bloc with the retrohepatic vena cava. The inferior vena cava was reconstructed by interposition of a prosthetic graft. The ex situ ex vivo hepatic resection, a left hepatic lobectomy included the lesion in segments 1-5-7-8. The two hepatic veins were reconstructed using patches of saphenous vein. The organ was preserved continuously for 6 hours using hypothermic perfusion with 4°C Celsior solution. The liver was then reimplanted performing an anastomosis between the reconstructed hepatic veins and the caval prostheses. The patient was discharged at postoperative day 22 and is currently disease-free at 8 months after surgery and 44 months after the initial diagnosis. Ex situ, ex vivo liver surgery offers an additional option for patients with both primary and secondary liver tumors considered to be unresectable using traditional surgical approaches.


Assuntos
Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Neoplasias Pancreáticas/patologia , Adulto , Terapia Combinada , Feminino , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia
13.
Transplant Proc ; 44(7): 1989-91, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22974889

RESUMO

BACKGROUND: There are scarce data on the use of sorafenib for the treatment of recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). PATIENTS AND METHODS: Ten patients were treated with sorafenib after OLT following the Italian Drug Agency guidelines: they had well-compensated liver function (Child-Pugh class A in the case of cirrhosis), intermediate-or advanced-stage HCC, good general condition (performance status 0), and not suitable for loco-regional therapies. Patients with HCC recurrence after OLT were treated with sorafenib (400 mg twice daily). Adverse events (AEs) were assessed using National Cancer Institute Common Toxicity Criteria of Adverse Events (NCI-CTCAE) v3.0 with tumor responses evaluated acording to modified Response Evaluation Criteria in Select Tumors) criteria. RESULTS: Median duration of treatment was 10 months (range, 2-18). Seven patients (70%) received an additionally targeted therapy with mTOR inhibitors as part of their immunosuppressive regimen. Most common grade 3 AEs included diarrhea (50%), hand-foot skin reaction (30%), and fatigue (20%). Sorafenib had to be discontinued in 3 patients (30%) due to AEs and 4 additional patients (40%) required a dose adjustment. No deterioration of liver graft function occurred. Three patients (30%) stopped treatment due to radiological progression of HCC, whereas 3 are still using the drug. Median time to progression was 8 months (range, 2-16). Median survival from start of therapy was 18 months (range, 4- 36). CONCLUSION: Our preliminary results suggest that sorafenib is a safe effective therapy for recurrent HCC after OLT.


Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Transplante de Fígado , Piridinas/uso terapêutico , Humanos , Niacinamida/análogos & derivados , Compostos de Fenilureia , Recidiva , Sorafenibe
14.
Transplant Proc ; 44(7): 2026-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22974898

RESUMO

We previously reported that subnormothermic machine perfusion (sMP; 20°C) is able to improve the preservation of livers obtained from non-heart-beating donors (NHBDs) in rats. We have compared sMP and standard cold storage (CS) to preserve pig livers after 60 minutes of cardiac arrest. In the sMP group livers were perfused for 6 hours with Celsior at 20°C. In the CS group they were stored in Celsior at 4°C for 6 hours as usual. To simulate liver transplantation, both sMP- and CS-preserved livers were reperfused using a mechanical continuous perfusion system with autologus blood for 2 hours at 37°C. At 120 min after reperfusion aspartate aminotransferase levels in sMP versus CS were 499 ± 198 versus 7648 ± 2806 U/L (P < .01); lactate dehydrogenase 1685 ± 418 versus 12998 ± 3039 U/L (P < .01); and lactic acid 4.78 ± 3.02 versus 10.46 ± 1.79 mmol/L (P < .01) respectively. The sMP group showed better histopathologic results with significantly less hepatic damage. This study confirmed that sMP was able to resuscitate liver grafts from large NHBD animals.


Assuntos
Temperatura Corporal , Transplante de Fígado , Modelos Animais , Perfusão/métodos , Doadores de Tecidos , Animais , Aspartato Aminotransferases/metabolismo , Dissacarídeos , Eletrólitos , Glutamatos , Glutationa , Histidina , L-Lactato Desidrogenase/metabolismo , Manitol , Contração Miocárdica , Soluções para Preservação de Órgãos , Perfusão/instrumentação , Suínos
15.
Transplant Proc ; 44(7): 2038-40, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22974902

RESUMO

BACKGROUND: Polycystic liver disease (PLD) is due to a genetic disorder and frequently coexists with polycystic kidney disease (PKD). If the cysts produce symptomatology owing to their number and size, many palliative treatments are available. When none of the liver parenchyma is spared, or kidney insufficiency is marked, the only potentially curable treatment is liver transplantation (LT). CASE REPORT: A 49-year old woman, diagnosed with PLD and PKD, was listed in January 2008 for combined LT and kidney transplantation (KT). A compatible organ became available 8 months later. Despite preserved liver function, the patient's clinical condition was poor; she experienced dyspnea, advanced anorexia, abdominal pain, and severe ascites. At LT, which took 9 hours and was performed using the classic technique, the liver was hard, massive in size (15.5 kg), and not dissociable from the vena cava. The postoperative course was complicated by many septic episodes, the last one being fatal for the patient at 4 months after transplantation. DISCUSSION: LT for PLD in many series shows a high mortality rate. The Model for End-Stage Liver Disease (MELD) score does not stage patients properly, because liver function is usually preserved. The liver can achieve a massive size causing many symptoms, especially malnutrition and ascites; in this setting LT is the only possible treatment. Patients with a low MELD score undergo LT with severe malnutrition that predisposes them to greater susceptibility to sepsis. To identify predictor factors, beyond MELD criteria that relate to the increased liver volume before development of late symptoms is essential to expeditiously treat patients with the poorest prognosis to improve their outcomes.


Assuntos
Cistos/complicações , Hepatomegalia/cirurgia , Hepatopatias/complicações , Transplante de Fígado , Feminino , Hepatomegalia/etiologia , Humanos , Pessoa de Meia-Idade , Tamanho do Órgão , Período Pós-Operatório
16.
J Phys Chem B ; 115(38): 11199-207, 2011 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-21853992

RESUMO

The capability to monitor finely the physical properties of eumelanin, an important class of biopolymers, involved in melanoma cancer pathologies, whose function and intrinsic disorder still collects the interest of many investigators, was achieved by means of electrospray deposition (ESD). By alleviating the problem of the solubility of melanin through the realization of high-quality films it was possible to spread light on the unknown biopolymer supramolecular organization. In fact, on the basis of scanning probe microscopies, electron spectroscopies, and transport properties, it was possible to delineate peculiar features of the melanin organization varying from heteropolymeric to oligomeric in character and eventually turning in a cross-linked secondary molecular structure.


Assuntos
Biopolímeros/química , Técnicas Biossensoriais , Melaninas/química , Modelos Moleculares , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Óptica e Fotônica , Espectroscopia Fotoeletrônica , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície
17.
Transplant Proc ; 43(4): 974-6, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21620029

RESUMO

BACKGROUND: The product between donor (D) age and recipient (R) Model for End-Stage Liver Disease (MELD) score at the moment of liver transplantation (LT) has been proposed as a potential D-R matching tool to reduce the risk of "futile" LT from using the MELD score as the main allocation tool. The aim of this study was to evaluate the prognostic ability of D-MELD among a cohort of Italian patients already selected for LT on the basis of a D-R matching philosophy. METHODS: We studied 303 consecutive adult patients undergoing first LT for chronic liver diseases with available D-MELD at the moment of LT from 2003 to 2009. Optimal donors were assigned to more severe cirrhotic patients (MELD ≥20); suboptimal organs were allocated to patients with hepatocellular carcinoma (HCC) not responsive to bridging therapies (specific priority score) or other exceptions with MELD <20. A suboptimal donor had age >70 years, severe steatosis by ultrasound, and/or body mass index >30 kg/m(2), partial liver, or hepatitis C (HCV) or B virus positivity. RESULTS: Characteristics of the study group were a median age of 55 years (range, 27-68 years), HCV positivity in 164 patients (54%), HCC in 134 patients (44%), partial liver use in 25 (8%), MELD 15 (range, 6-40), D-age of 56 years (range, 18-87 years), and median D-MELD score 826 (range, 126-2,988). Overall graft survival was 84%, 79%, and 77% at 1, 3, and 5 years after LT, respectively. Logistic regression did not show a significant correlation between graft failure and D-MELD score in the absence of a significant D-MELD cutoff. Cox regression with D-MELD as the continuous variable showed a hazard ratio (HR) of 0.99 (95% confidence interval [CI], 0.99-1.00; P=NS); and with D-MELD as a dichotomic variable (≥0 to <1,600) an HR of 0.98 (95% CI, 0.63-1.77; P=NS). CONCLUSION: The prognostic ability of D-MELD fails in OLT centers that use a more complex D-R matching policy.


Assuntos
Técnicas de Apoio para a Decisão , Seleção do Doador , Indicadores Básicos de Saúde , Hepatopatias/cirurgia , Transplante de Fígado , Doadores de Tecidos/provisão & distribuição , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Doença Crônica , Fígado Gorduroso/complicações , Fígado Gorduroso/diagnóstico por imagem , Feminino , Sobrevivência de Enxerto , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite C/complicações , Hepatite C/diagnóstico , Humanos , Itália , Estimativa de Kaplan-Meier , Hepatopatias/diagnóstico , Transplante de Fígado/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia , Adulto Jovem
18.
Transplant Proc ; 43(4): 997-1000, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21620035

RESUMO

BACKGROUND: Hepatic resection is the gold standard of therapy for primary and secondary liver tumors, but few patients are eligible for this procedure because of the extent of their neoplasms. Improvements in surgical experience of liver transplantation (OLT), hepatic resection and preservation with sub-normothermic machine perfusion (MP) have prompted the development of a new model of large animal autotransplantation. METHODS: Landrace pigs were used in this experiment. After intubation, hepatectomy was performed according to the classic technique. The intrahepatic caval vein was replaced with a homologous tract of porcine thoracic aorta. The liver was perfused with hypothermic Celsior solution followed by MP at 20 °C with oxygenated Krebs solution. An hepatectomy was performed during the period of preservation, which lasted 120 minutes, then the liver was reimplanted into the same animal in a 90° counterclockwise rotated position. The anastomoses were performed in the classic sequence. Samples of intravascular fluid, blood and liver biopsies were obtained at the end of the period of preservation in MP and again at 1 and 3 hours after liver reperfusion to evaluate graft function and microscopic damage. RESULTS: All animals survived the procedure. The peak of aspartate aminotransferase was recorded 60 minutes after reperfusion and the peak of alanine aminotransferase and lactate dehydrogenase after 180 minutes. Histopathologic examination under the light microscope identified no necrosis or congestion. Intraoperative echo-color Doppler documented good patency of the anastomosis and normal venous drainage. CONCLUSION: This system made it possible to perform hepatic resections and vascular reconstructions ex situ while preserving the organ with mechanical perfusion (ex vivo, ex situ surgery). Improving surgical techniques regarding autotransplantation and our understanding of ischemia-reperfusion damage may enable the development of interesting scenarios for aggressive surgical treatment or radiochemotherapy options to treat primary and secondary liver tumors unsuitable for conventional in situ surgery.


Assuntos
Hepatectomia , Soluções Isotônicas/administração & dosagem , Transplante de Fígado , Soluções para Preservação de Órgãos/administração & dosagem , Preservação de Órgãos/métodos , Perfusão , Temperatura , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Dissacarídeos/administração & dosagem , Dissacarídeos/efeitos adversos , Eletrólitos/administração & dosagem , Eletrólitos/efeitos adversos , Glutamatos/administração & dosagem , Glutamatos/efeitos adversos , Glutationa/administração & dosagem , Glutationa/efeitos adversos , Hepatectomia/efeitos adversos , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/cirurgia , Histidina/administração & dosagem , Histidina/efeitos adversos , Soluções Isotônicas/efeitos adversos , L-Lactato Desidrogenase/sangue , Transplante de Fígado/efeitos adversos , Manitol/administração & dosagem , Manitol/efeitos adversos , Modelos Animais , Preservação de Órgãos/efeitos adversos , Soluções para Preservação de Órgãos/efeitos adversos , Perfusão/efeitos adversos , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/diagnóstico por imagem , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle , Reimplante , Suínos , Fatores de Tempo , Transplante Autólogo , Ultrassonografia Doppler em Cores , Procedimentos Cirúrgicos Vasculares , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgia
19.
Transplant Proc ; 43(4): 1091-4, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21620060

RESUMO

Surgical resection for malignant hepatic tumors, especially hepatocarcinoma (HCC), has been demonstrated to increase overall survival; however, the majority of patients are not suitable for resection. Radiofrequency ablation (RFA) is the most widely used modality for radical treatment of small HCC (<3 cm). It improves 5-year survival compared with standard chemotherapy and chemical ablation, allowing down-staging of unresectable hepatic masses. Microwave ablation (MWA) has been extensively applied in Asia and was recently introduced in the United States of America and Europe with excellent results, especially with regard to large unresectable HCC. Our single-center experience between May 2009 and October 2010 included application of MWA to 154 patients of median age ± standard deviation of 63.5 ± 8.5 years, 6 males, and 1 female, of mean Model for End-Stage Liver Disease (MELD) score (10.1 ± 3.8). The HCC included, hepatitis C virus (HCV)-related (n=70; 45.5%); alcool (ETOH)-related (n=42; 27%), hepatitis B virus (HBV)-related (n=16; 10.5%); and cryptogenic cases (n=26; 17%). The cases were performed for radical treatment down-staging for multifocal pathology or bridging liver transplantation to orthotopic (OLT) in selected patients with single nodules. A computed tomography (CT) scan was performed at 1 month after the surgical procedure to evalue responses to treatment. Among 6 selected patients who underwent OLT; 5 (83.3%) showed disease-free survival at one-year follow-up. The radical treatment achieved no intraoperative evidence of tumor spread or of pathological signs of active HCC among the explanted liver specimens. In conclusion, a MWA seemed to be a safe novel approach to treat HCC and could serve as a "bridge" to OLT and down-staging for patients with HCC.


Assuntos
Técnicas de Ablação , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Micro-Ondas/uso terapêutico , Técnicas de Ablação/efeitos adversos , Técnicas de Ablação/mortalidade , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Itália , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Micro-Ondas/efeitos adversos , Pessoa de Meia-Idade , Necrose , Estadiamento de Neoplasias , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
Transplant Proc ; 43(4): 1187-9, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21620084

RESUMO

Cholangiocarcinoma has historically represented a major contraindication to liver transplantation at many centers because of its high recurrence rate and low disease-free survival rate, even after radical surgery. Novel neoadjuvant therapy protocols combined with demolitive surgery and liver transplantation seem to achieve successful results in terms of overall and disease-free survivals. Surgery frequently seems to be unsatisfactory only for patients also suffering from chronic cirrhosis or end-stage liver disease. We have reported a case of hilar cholangiocarcinoma occurring in a case of primary sclerosing cholangitis treated with neoadjuvant radiochemotherapy and endoscopic brachytherapy, followed by liver transplantation combined with pancreatoduodenectomy, who has survived free of disease for >8 years.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Colangite Esclerosante/complicações , Transplante de Fígado , Pancreaticoduodenectomia , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias dos Ductos Biliares/etiologia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Braquiterapia , Quimioterapia Adjuvante , Colangiocarcinoma/etiologia , Colangiocarcinoma/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Hepatectomia , Humanos , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Terapia Neoadjuvante , Radioterapia Adjuvante , Tacrolimo/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
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