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1.
Artif Organs ; 46(9): 1771-1782, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35548925

RESUMO

BACKGROUND: Few studies explored the role of hypothermic machine perfusion (HMP) in the sub-group of non-standard renal grafts with a biopsy-proven advanced histological impairment. This study aimed to investigate the role of HMP in grafts with a Karpinski Score >3 in terms of the need for dialysis, creatinine reduction ratio at day-7 (CRR7), and 3-year graft survival. METHODS: Twenty-three perfused grafts with Karpinski Score >3 evaluated between November 2017 and December 2018 were retrospectively analyzed and compared with a control group of 32 non-perfused grafts transplanted between January 2014 and October 2017. RESULTS: After transplantation, perfused grafts had fewer cases requiring dialysis (8.7% vs. 34.4%; p = 0.051), a better reduction in serum creatinine (median at 7 days: 2.2 vs. 4.3 mg/dl; p = 0.045), and shorter length of hospital stay (median 11 vs. 15 days; p = 0.01). Three-year death-censored graft survival was better in the perfused cases (91.3% vs. 77.0%; p = 0.16). In perfused grafts, initial renal resistance (RR) had the best predictive value for renal function recovery after the first week, as defined by CRR7 ≤ 70% (AUC = 0.83; p = 0.02). A cut-off value of 0.5 mm Hg/ml/min showed a sensitivity of 82.4%, a specificity of 83.3%, and diagnostic odds ratio = 23.4. After dividing the entire population into a Low-RR (n = 8) and a High-RR Group (n = 15), more cases with CRR7 ≤ 70% were reported in the latter group (86.7 vs. 13.3%; p = 0.03). CONCLUSION: HMP yielded promising results in kidneys with Karpinski Score >3. Initial RR should be of interest in selecting non-standard organs for single kidney transplantation even in impaired histology.


Assuntos
Transplante de Rim , Função Retardada do Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Rim/cirurgia , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Estudos Retrospectivos , Doadores de Tecidos
2.
Clin Nephrol ; 93(2): 92-98, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31793872

RESUMO

Acute kidney injury (AKI) in liver transplant (LT) setting is a recognized complication and is related to increased morbidity and mortality. Pre-LT renal function is difficult to estimate, in particular for the female gender. The aim of the study was to evaluate the incidence of post-LT AKI, its relationship with survival, and related risk factors. In a single-center retrospective study of consecutive LT patients (2008 - 2015), we assessed patient characteristics and intra-LT events, and post-operative data were collected. The occurrence of AKI post-LT was also evaluated (KDIGO guidelines). Data of 145 LT patients were analyzed. 45 (31.0%) patients showed an overestimation of glomerular filtration rate (over-GFR), defined as GFR > 120 mL/min/1.73m2; 83 patients (57.2%) developed post-LT AKI. The patients (n = 145) were divided into two groups: 123 (84.8%) patients with no-AKI & AKI stage 1 and 22 (15.2%) patients with AKI stages 2 and 3. Patients with AKI stages 2 and 3 were characterized by a significantly decreased 5-year survival (p < 0.001). On the multivariable analysis, female gender and over-GFR were significantly predictive for development of AKI stages 2 and 3. Female gender has already been reported as a discriminant factor for LT candidates. Altered estimation of renal function also needs to be considered in this setting, as this could mask the presence of an unknown compromised renal function.


Assuntos
Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Taxa de Filtração Glomerular , Transplante de Fígado/efeitos adversos , Injúria Renal Aguda/fisiopatologia , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Taxa de Sobrevida
3.
Am J Pathol ; 188(3): 627-639, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29248458

RESUMO

Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are human primary cholangiopathies characterized by the damage of mature cholangiocytes and by the appearance of ductular reaction (DR) as the results of hepatic progenitor cell activation. This study evaluated the differences in progenitor cell niche activation between these two cholangiopathies. Liver tissue was obtained from healthy liver donors (n = 5) and from patients with PSC (n = 20) or PBC (n = 20). DR, progenitor cell phenotype, and signaling pathways were investigated by IHC analysis and immunofluorescence. Our results indicated that DR was more extended, appeared earlier, and had a higher proliferation index in PBC compared with PSC. In PBC, DR was strongly correlated with clinical prognostic scores. A higher percentage of sex determining region Y-box (SOX)9+ and cytokeratin 19+ cells but fewer features of hepatocyte fate characterized progenitor cell activation in PBC versus PSC. Lower levels of laminin and neurogenic locus notch homolog protein 1 but higher expression of wingless-related integration site (WNT) family pathway components characterize progenitor cell niche in PSC compared with PBC. In conclusion, progenitor cell activation differs between PSC and PBC and is characterized by a divergent fate commitment and different signaling pathway predominance. In PBC, DR represents a relevant histologic prognostic marker.


Assuntos
Colangite Esclerosante/patologia , Cirrose Hepática Biliar/patologia , Fígado/patologia , Células-Tronco/patologia , Adulto , Proliferação de Células , Colangite Esclerosante/metabolismo , Feminino , Humanos , Laminina/metabolismo , Fígado/metabolismo , Cirrose Hepática Biliar/metabolismo , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/fisiologia , Nicho de Células-Tronco/fisiologia , Células-Tronco/metabolismo
4.
Pancreatology ; 18(5): 592-600, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29776725

RESUMO

BACKGROUND/OBJECTIVES: Celiac axis stenosis (CAS) represents an uncommon and typically innocuous condition. However, when a pancreatic resection is required, a high risk for upper abdominal organs ischemia is observed. In presence of collaterals, such a risk is minimized if their preservation is realized. The aim of the present study is to systematically review the literature with the intent to address the routine management of collateral arteries in the case of CAS patients requiring pancreatoduodenectomy. METHODS: A systematic search was done in accordance with the PRISMA guidelines, using "celiac axis stenosis" AND "pancreatoduodenectomy" as MeSH terms. Seventy-four articles were initially screened: eventually, 30 articles were identified (n = 87). RESULTS: The main cause of CAS was median arcuate ligament (MAL) (n = 31; 35.6%), followed by atherosclerosis (n = 20; 23.0%). CAS was occasionally discovered during the Whipple procedure in 15 (17.2%) cases. Typically, MAL was divided during surgery (n = 24/31; 77.4%). In the great majority of cases (n = 83; 95.4%), vascular abnormalities involved the pancreatoduodenal arteries (i.e., dilatation, arcade, channels, aneurysms). Collateral arteries were typically preserved, being divided or reconstructed in only 14 (16.1%) cases, respectively. Severe ischemic complications were reported in six (6.9%) patients, 20.0% of whom were reported in patients with preoperatively unknown CAS (p-value 0.06). CONCLUSIONS: A correct pre-operative evaluation of anatomical conditions as well as a correct surgical planning represent the paramount targets in CAS patients with arterial collaterals. Vascular flow must be always safeguarded preserving/reconstructing the collaterals or resolving the CAS, with the final intent to avoid dreadful intra- and post-operative complications.

5.
Stem Cells ; 34(5): 1332-42, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26850087

RESUMO

Peribiliary glands (PBGs) are niches in the biliary tree and containing heterogeneous endodermal stem/progenitors cells that can differentiate, in vitro and in vivo, toward pancreatic islets. The aim of this study was to evaluate, in experimental and human diabetes, proliferation of cells in PBGs and differentiation of the biliary tree stem/progenitor cells (BTSCs) toward insulin-producing cells. Diabetes was generated in mice by intraperitoneal injection of a single dose of 200 mg/kg (N = 12) or 120 mg/kg (N = 12) of streptozotocin. Liver, pancreas, and extrahepatic biliary trees were en bloc dissected and examined. Cells in PBGs proliferated in experimental diabetes, and their proliferation was greatest in the PBGs of the hepatopancreatic ampulla, and inversely correlated with the pancreatic islet area. In rodents, the cell proliferation in PBGs was characterized by the expansion of Sox9-positive stem/progenitor cells that gave rise to insulin-producing cells. Insulin-producing cells were located mostly in PBGs in the portion of the biliary tree closest to the duodenum, and their appearance was associated with upregulation of MafA and Gli1 gene expression. In patients with type 2 diabetes, PBGs at the level of the hepatopancreatic ampulla contained cells showing signs of proliferation and pancreatic fate commitment. In vitro, high glucose concentrations induced the differentiation of human BTSCs cultures toward pancreatic beta cell fates. The cells in PBGs respond to diabetes with proliferation and differentiation towards insulin-producing cells indicating that PBG niches may rescue pancreatic islet impairment in diabetes. These findings offer important implications for the pathophysiology and complications of this disease. Stem Cells 2016;34:1332-1342.


Assuntos
Sistema Biliar/citologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/patologia , Células Secretoras de Insulina/citologia , Nicho de Células-Tronco , Células-Tronco/citologia , Animais , Compartimento Celular , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glucose/farmacologia , Humanos , Insulina/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Estreptozocina
6.
J Hepatol ; 61(5): 1097-105, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24953023

RESUMO

BACKGROUND & AIMS: Human biliary tree stem/progenitor cells (hBTSCs) are multipotent epithelial stem cells, easily obtained from the biliary tree, with the potential for regenerative medicine in liver, biliary tree, and pancreas diseases. Recent reports indicate that human mesenchymal stem cells are able to modulate the T cell immune response. However, no information exists on the capabilities of hBTSCs to control the allogeneic response. The aims of this study were to evaluate FasL expression in hBTSCs, to study the in vitro interaction between hBTSCs and human lymphocytes, and the role of Fas/FasL modulation in inducing T cell apoptosis in hBTSCs/T cell co-cultures. METHODS: Fas and FasL expression were evaluated in situ and in vitro by immunofluorescence and western blotting. Co-cultures of hBTSCs with human leukocytes were used to analyze the influence of hBTSCs on lymphocytes activation and apoptosis. RESULTS: hBTSCs expressed HLA antigens and FasL in situ and in vitro. Western blot data demonstrated that hBTSCs constitutively expressed high levels of FasL that increased after co-culture with T cells. Confocal microscopy demonstrated that FasL expression was restricted to EpCAM(+)/LGR5(+) cells. FACS analysis of T cells co-cultured with hBTSCs indicated that hBTSCs were able to induce apoptosis in activated CD4(+) and CD8(+) T cell populations. Moreover, the Fas receptor appears to be more expressed in T cells co-cultured with hBTSCs than in resting T cells. CONCLUSIONS: Our data suggest that hBTSCs could modulate the T cell response through the production of FasL, which influences the lymphocyte Fas/FasL pathway by inducing "premature" apoptosis in CD4(+) and CD8(+) T cells.


Assuntos
Sistema Biliar/citologia , Sistema Biliar/imunologia , Proteína Ligante Fas/metabolismo , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/imunologia , Receptor fas/metabolismo , Células-Tronco Adultas/citologia , Células-Tronco Adultas/imunologia , Células-Tronco Adultas/metabolismo , Apoptose/imunologia , Sistema Biliar/metabolismo , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Técnicas de Cocultura , Células-Tronco Fetais/citologia , Células-Tronco Fetais/imunologia , Células-Tronco Fetais/metabolismo , Humanos , Imunomodulação , Ativação Linfocitária , Células-Tronco Multipotentes/metabolismo , Transdução de Sinais
7.
Arch Gynecol Obstet ; 290(2): 349-53, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24615568

RESUMO

PURPOSE: To compare the fertility outcome among women subjected to unilateral ovariectomy and other abdominal or non-gynaecologic pelvic surgery. METHODS: In this retrospective cohort study, 113 fertile women, surgically treated between 1990 and 2001 at Sapienza University of Rome with unilateral ovariectomy (UO), appendectomy (AP) or cholecystectomy (CO) for benign disease, were analysed for fertility outcome. Patients with assessed pre-surgical fertility defects, previous abdominal or pelvic surgeries and post-surgical contraception were not included. RESULTS: Thirty-five women underwent UO, 39 were subjected to AP and 39 were treated with CO. After a minimum 10-year post-surgical interval, the overall number of successful pregnancies was 75. The rate of women who experienced at least one post-operative successful pregnancy was: 48.5 % in UO, 41 % in AP and 53.8 % in CO (UO vs. AP, P = 0.55; UO vs. CO, P = 0.99; AP vs. CO, P = 0.53). One patient (2.8 %) in UO, one patient (2.6 %) in AP and two patients (5.1 %) in CO underwent Assisted Reproductive Technology to become pregnant. The rate of women who reported at least one miscarriage was: 10/35 (28.5 %) in UO, 11/39 (28.2 %) in AP, 12/39 (30.8 %) in CO (UO vs. AP, P = 0.93; UO vs. CO, P = 0.89; AP vs. CO, P = 0.81). One ectopic pregnancy was reported in CO group and one stillbirth occurred in one AP patient. CONCLUSIONS: No statistical difference in terms of post-operative fertility outcome between patients subjected to UO, AP or CO was found, thus allowing to suppose that the removal of one ovary does not significantly worsen the female fertility outcome respect to other abdominal or pelvic procedures.


Assuntos
Fertilidade , Ovariectomia/métodos , Aborto Espontâneo/epidemiologia , Adulto , Apendicectomia/estatística & dados numéricos , Coeficiente de Natalidade , Colecistectomia/estatística & dados numéricos , Feminino , Humanos , Itália/epidemiologia , Ovariectomia/estatística & dados numéricos , Seleção de Pacientes , Gravidez , Gravidez Ectópica/epidemiologia , Técnicas de Reprodução Assistida , Estudos Retrospectivos , Natimorto/epidemiologia , Resultado do Tratamento
8.
J Hepatol ; 57(5): 974-9, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22771712

RESUMO

BACKGROUND & AIMS: Greater tumor aggressiveness and different management modalities of hepatocellular cancer (HCC) before liver transplantation (LT) may explain the higher recurrence rates reported in Asia. This study investigates the prognostic factors for HCC recurrence in a Western and an Eastern HCC patient cohort in order to analyze the respective roles of tumor- and management-related factors on the incidence of post-LT HCC recurrence. METHODS: Data of 273 HCC patients, transplanted during the period January 1999-March 2009, were obtained from the Rome Inter-University Liver Transplant Consortium (n=157) and Hong Kong University (n=116) databases. Median follow-up was 4.3 years (range: 0.2-12). Recurrence rate and multivariate logistic regression analysis was performed on the entire population and on Milan criteria-in (MC-in) patients. RESULTS: Multivariate analysis on the entire population identified four independent risk factors for post-LT HCC recurrence: microvascular invasion (odds ratio, OR=4.88; p=0.001), poor tumor grading (OR=6.86; p=0.002), diameter of the largest tumor (OR=4.72; p=0.05), and previous liver resection (LR) (OR=3.34; p=0.04). After removal of LR, only tumor-related variables were independent risk factors for recurrence. When only MC-in patients were analyzed, no difference was observed between the two cohorts in terms of recurrence rate after LR patient removal. CONCLUSIONS: LR followed by salvage "for HCC recurrence" LT represents the main reason for a higher HCC recurrence rate in the Hong Kong patients, but not LR followed by salvage "for liver failure" LT in the Roman group. This approach towards HCC before LT may not be universally applicable. The precise patient background must be taken into account in order to identify the best pre-LT strategy.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Terapia de Salvação , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Gerenciamento Clínico , Feminino , Hong Kong , Humanos , Incidência , Neoplasias Hepáticas/diagnóstico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Cidade de Roma , Resultado do Tratamento
9.
Clin Transplant ; 26(2): E125-31, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22192083

RESUMO

BACKGROUND: In the last several years, there has been no agreement on how to possibly expand the Milan criteria (MC) in the selection of patients with hepatocellular carcinoma (HCC) for listing for liver transplant (LT). The aim of the study is to evaluate morphological and biological tumor parameters to identify new expanded criteria for the selection of patients with HCC as candidates for LT. METHODS: We retrospectively analyzed 158 consecutive patients with HCC who underwent LT. RESULTS: Twelve (7.6%) recurrences were observed. At multivariate analysis, alpha-fetoprotein (AFP) >400 ng/mL (odds ratio [OR] 8.4, p<0.01) and total tumor diameter (TTD) >8 cm (OR 7.4, p=0.01) were the strongest predictors for recurrence. AFP-TTD criteria resulted in a low five-yr recurrence rate (4.9%) and an increased number of LT compared with the MC (22.2% increase). The five-yr disease-free survival rate was 74.4% in AFP-TTD criteria in patients, with a higher effectiveness in stratifying the cohort with respect to the MC. CONCLUSIONS: Both AFP and TTD are good independent predictors of HCC recurrence. Their combination appears to obtain a better selection of candidates for LT without worsening patient survival and recurrence rates. This approach allows for an increase in the number of potentially transplantable patients.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Seleção de Pacientes , Listas de Espera , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , alfa-Fetoproteínas/análise
10.
G Ital Nefrol ; 29 Suppl 54: S109-13, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-22388840

RESUMO

Hepatitis C virus (HCV) infection occurs much more frequently in the hemodialysis population than in the general population. Patients with chronic kidney disease with persistent HCV infection may develop serious and progressive chronic liver disease, with associated long-term morbidity and mortality related to cirrhosis and hepatocellular carcinoma. Monocytes and macrophages are known to produce extrahepatic breeding sites and spread the disease. Our aim was to lower the levels of macrophages, granulocytes, monocytes, proinflammatory cells and viremia using an extracorporeal device: the Adacolumn ® leukocyte apheresis system (Otsuka). The Adacolumn is a direct hemoperfusion-type leukapheresis device. The column is a single-use (disposable) polycarbonate column with a capacity of about 335 mL, filled with 220-g cellulose acetate beads of 2 mm in diameter bathed in physiological saline. The carriers adsorb ''activated'' granulocytes and monocytes/macrophages that bear Fc and complement receptors. The patients underwent five 1-hour sessions for five consecutive days. The column was placed in an extracorporeal setting with a perfusion rate of 30 mL/min and a duration of 60 minutes. A reduction of viremia was observed in all patients in association with a decrease in cytokine levels and a proportional decrease in immune cells. Although this study investigated responses in a small number of patients, it was shown that the Adacolumn changed the cellular immunity and promoted early viral response.


Assuntos
Remoção de Componentes Sanguíneos/instrumentação , Hepacivirus , Hepatite C/terapia , Transplante de Rim , Feminino , Hepacivirus/isolamento & purificação , Humanos , Falência Renal Crônica/terapia , Leucaférese/instrumentação , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento
11.
G Ital Nefrol ; 29 Suppl 54: S31-5, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-22388827

RESUMO

The fundamental role of antibodies in the development of acute graft rejection has been established recently. Antibody-mediated acute rejection may develop at any time during the post-transplant period. Several therapeutic approaches have been proposed in the last decades. However, there is no standardized therapy. The aim of this study is to report the Sapienza University experience of combined plasma treatment and high-dose intravenous immunoglobulin ± extracorporeal photopheresis. From January 2006 to September 2009, 6 patients were treated at Sapienza University. In 5 cases (83%) complete regression of the acute rejection was observed, followed by stable renal function (median creatinine value at 1-year follow-up: 1.5 mg/dL). No adverse events were reported. Our approach seems to give good results in terms of graft survival and procedure safety. Further studies on a larger number of patients will be needed to confirm the validity of these findings. Moreover, comparison between our protocol and other treatments is necessary.


Assuntos
Rejeição de Enxerto/terapia , Sobrevivência de Enxerto , Imunoglobulinas Intravenosas/uso terapêutico , Transplante de Rim , Fotoferese , Plasmaferese , Doença Aguda , Adulto , Terapia Combinada/métodos , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Plasmaferese/métodos , Estudos Retrospectivos , Resultado do Tratamento
12.
Sci Rep ; 11(1): 2557, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510179

RESUMO

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with marked resistance to chemotherapeutics without therapies. The tumour microenvironment of iCCA is enriched of Cancer-Stem-Cells expressing Epithelial-to-Mesenchymal Transition (EMT) traits, being these features associated with aggressiveness and drug resistance. Treatment with the anti-diabetic drug Metformin, has been recently associated with reduced incidence of iCCA. We aimed to evaluate the anti-cancerogenic effects of Metformin in vitro and in vivo on primary cultures of human iCCA. Our results showed that Metformin inhibited cell proliferation and induced dose- and time-dependent apoptosis of iCCA. The migration and invasion of iCCA cells in an extracellular bio-matrix was also significantly reduced upon treatments. Metformin increased the AMPK and FOXO3 and induced phosphorylation of activating FOXO3 in iCCA cells. After 12 days of treatment, a marked decrease of mesenchymal and EMT genes and an increase of epithelial genes were observed. After 2 months of treatment, in order to simulate chronic administration, Cytokeratin-19 positive cells constituted the majority of cell cultures paralleled by decreased Vimentin protein expression. Subcutaneous injection of iCCA cells previously treated with Metformin, in Balb/c-nude mice failed to induce tumour development. In conclusion, Metformin reverts the mesenchymal and EMT traits in iCCA by activating AMPK-FOXO3 related pathways suggesting it might have therapeutic implications.


Assuntos
Colangiocarcinoma/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Metformina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Proteína Forkhead Box O3/metabolismo , Humanos , Camundongos , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos
14.
Pathol Res Pract ; 215(10): 152602, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31472995

RESUMO

BACKGROUND AND AIMS: Carcinoma cuniculatum (CC) is a rare variant of an extremely well-differentiated squamous cell carcinoma. The most commonly involved site is the skin, with a preference for the sole. Only 15 cases of esophageal CC have been reported so far. Based on published data, the clinical behavior of CC has not been clearly defined. We describe the clinical-pathologic features of two cases of esophageal CC, and provide a review of the available literature, to shed more light on this unusual tumor. METHODS: A detailed gross and histologic analysis was performed on two cases of surgically treated esophageal CC. The patients were followed-up after surgery. A systematic search was also done concerning studies focused on esophageal CC. A search of the electronic databases MEDLINE-PubMed was conducted using the following research terms: (esophagus) AND (cuniculatum carcinoma). RESULTS: Both patients were alive at last follow-up at six and nine months from surgery without any recurrence. Concerning the fifteen cases reported from the systematic review, median follow-up after surgery was very long as compared to common esophageal cancers (4.0 years), with only one recurrence observed. CONCLUSION: CC shows an indolent clinical behavior, with a low recurrence rate after radical surgery. The diagnosis of this rare tumor is typically made after surgery. An aggressive approach is required with curative intents.


Assuntos
Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Recidiva Local de Neoplasia/patologia , Idoso , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia , Esôfago/patologia , Esôfago/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Transplant Direct ; 4(1): e222, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29399624

RESUMO

BACKGROUND: Renal dysfunction in end-stage liver disease (ESLD) results from systemic conditions that affect both liver and kidney with activation of vasoconstrictor systems. In this setting, estimated glomerular filtration rate (eGFR) may undergo variations often outside Kidney Disease Improving Global Outcomes criteria for acute kidney injury (AKI) diagnosis, whose meaning is not clear. The aim of this study was to evaluate eGFR variations in ESLD outpatients listed for liver transplant (liver Tx) and the association with post-Tx outcome. METHODS: Fifty-one patients with ESLD were retrospectively evaluated from listing to transplant (L-Tx time), intraoperatively (Tx time), and up to 5 years post-Tx time. Variations between the highest and the lowest eGFR occurring in more than 48 hours, not satisfying Kidney Disease Improving Global Outcomes guideline, were considered as fluctuations (eGFR-F). Fluctuations of eGFR greater than 50% were defined as eGFR drops (DeGFR). Early graft dysfunction, AKI within 7 days, chronic kidney disease, and short- and long-term patient survivals were considered as outcomes. RESULTS: All patients presented eGFR-F, whereas DeGFR were observed in 18 (35.3%) of 51 (DeGFR+ group). These patients presented higher levels of Model for End-stage Liver Disease score, pre-Tx bilirubin and significantly greater incidence of post-Tx AKI stages 2 to 3 compared with patients without drops (DeGFR-). DeGFR was the only independent predictive factor of the occurrence of post-Tx AKI. The occurrence of AKI post-Tx was associated with the development of chronic kidney disease at 3 months and 5 years post-Tx. CONCLUSIONS: Drops of eGFR are more frequently observed in patients with a worse degree of ESLD and are associated with a worse post-Tx kidney outcome.

16.
PLoS One ; 12(9): e0183932, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28873435

RESUMO

Cholangiocarcinoma (CCA) and its subtypes (mucin- and mixed-CCA) arise from the neoplastic transformation of cholangiocytes, the epithelial cells lining the biliary tree. CCA has a high mortality rate owing to its aggressiveness, late diagnosis and high resistance to radiotherapy and chemotherapeutics. We have demonstrated that CCA is enriched for cancer stem cells which express epithelial to mesenchymal transition (EMT) traits, with these features being associated with aggressiveness and drug resistance. TGF-ß signaling is upregulated in CCA and involved in EMT. We have recently established primary cell cultures from human mucin- and mixed-intrahepatic CCA. In human CCA primary cultures with different levels of EMT trait expression, we evaluated the anticancer effects of: (i) CX-4945, a casein kinase-2 (CK2) inhibitor that blocks TGF-ß1-induced EMT; and (ii) LY2157299, a TGF-ß receptor I kinase inhibitor. We tested primary cell lines expressing EMT trait markers (vimentin, N-cadherin and nuclear catenin) but negative for epithelial markers, and cell lines expressing epithelial markers (CK19-positive) in association with EMT traits. Cell viability was evaluated by MTS assays, apoptosis by Annexin V FITC and cell migration by wound-healing assay. RESULTS: at a dose of 10 µM, CX4945 significantly decreased cell viability of primary human cell cultures from both mucin and mixed CCA, whereas in CK19-positive cell cultures, the effect of CX4945 on cell viability required higher concentrations (>30µM). At the same concentrations, CX4945 also induced apoptosis (3- fold increase vs controls) which correlated with the expression level of CK2 in the different CCA cell lines (mucin- and mixed-CCA). Indeed, no apoptotic effects were observed in CK19-positive cells expressing lower CK2 levels. The effects of CX4945 on viability and apoptosis were associated with an increased number of γ-H2ax (biomarker for DNA double-strand breaks) foci, suggesting the active role of CK2 as a repair mechanism in CCAs. LY2157299 failed to influence cell proliferation or apoptosis but significantly inhibited cell migration. At a 50 µM concentration, in fact, LY2157299 significantly impaired (at 24, 48 and 120 hrs) the wound-healing of primary cell cultures from both mucin-and mixed-CCA. In conclusion, we demonstrated that CX4945 and LY2157299 exert relevant but distinct anticancer effects against human CCA cells, with CX4945 acting on cell viability and apoptosis, and LY2157299 impairing cell migration. These results suggest that targeting the TGF-ß signaling with a combination of CX-4945 and LY2157299 could have potential benefits in the treatment of human CCA.


Assuntos
Apoptose , Colangiocarcinoma/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Colangiocarcinoma/patologia , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Humanos , Naftiridinas/química , Células-Tronco Neoplásicas/citologia , Fenazinas , Cultura Primária de Células , Pirazóis/química , Quinolinas/química , Transdução de Sinais , Cicatrização
18.
Ann Transplant ; 9(2): 46-7, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15478918

RESUMO

Our study population consisted of 402 Living Related Donors (LRD)--of which 344 pairs shared 1 haplotype (Group A) and of 209 Living Unrelated Donors (LURD) (Group B): 175 between spouse pairs (Group C)--132 from wife to husband (Group C1) and 43 from husband to wife (Group C2) as well as 32 between relatives in law or emotionally related patients and 2 between members of clergy (Group D). 199 pairs showed 3-6 HLA A B Dr mismatches (MM) with the donor and in 10 cases 0-2 MM. Donor and recipient mean age was 49 +/- 13.4 and 29 +/- 10.3 in Group A and respectively 46 +/- 11.2 and 48 +/- 9.6 in Group B. The post-transplant immunosuppression therapy was based on Cyclosporin A (CsA). Chi2 test was used to assess statistical significance. Donor mortality was 0%; perioperative morbidity was 15.2%. Graft function immediately started after surgery. The actuarial 1 yr, 5 yrs, 10 yrs and 15 yrs graft survival was in Group A: 94%, 86%, 84%, 75% vs. Group B: 89%, 78%, 71%, 70% (NS), Group C1: 90%, 75%, 67%, 69% vs. Group C2: 81%, 74%, 72%, 62% (NS) and Group C: 88%, 78%, 66%, 60% vs. Group D: 91%, 80%, 71%, 61% (NS). There was no statistically significant difference between LURD and LRD as far as graft survival. In conclusion, we certainly agree with the guidelines issued by the International Congress on Ethics in Organ Transplantation (Munich, December 10-13,2002): kidney transplantation from living donors is a safe and effective procedure and should not be discouraged.


Assuntos
Ética Clínica , Ética Médica , Transplante de Rim/ética , Doadores Vivos/ética , Análise Atuarial , Coerção , Comércio , Haplótipos , Humanos , Rim/fisiopatologia , Transplante de Rim/mortalidade , Análise de Sobrevida
19.
Exp Clin Transplant ; 12(3): 238-40, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24907725

RESUMO

OBJECTIVES: Portal vein thrombosis may complicate liver transplant. The purpose of this study was to analyze our cohort of transplanted recipients to evaluate the relation between preoperative portal vein thrombosis and patient and graft survival after liver transplant. MATERIALS AND METHODS: We retrospectively analyzed 209 patients who had liver transplant; 2 patients who had the diagnosis of portal vein thrombosis made during surgery were excluded. Patients were stratified in 2 groups according to whether they had (15 patients) or did not have portal vein thrombosis (192 patients) before liver transplant and were compared for early and late survival. RESULTS: In all 15 patients who had portal vein thrombosis, the Yerdel grade was I or II. Patients who had preoperative portal vein thrombosis had lower median survival (portal vein thrombosis, 47 mo; no portal vein thrombosis, 61 mo), frequency of total number of deaths (portal vein thrombosis, 4 [27%]; no portal vein thrombosis, 68 [35%]), and frequency of death within 3 months after transplant (portal vein thrombosis, 1 [7%]; no portal vein thrombosis, 23 [12%]). However, there was no significant difference between the 2 groups in patient or graft survival. CONCLUSIONS: Low-grade portal vein thrombosis detected before liver transplant is not an absolute contraindication for liver transplant. Radiographic screening before liver transplant is recommended to minimize surgical difficulty.


Assuntos
Sobrevivência de Enxerto , Hepatopatias/cirurgia , Transplante de Fígado , Veia Porta/cirurgia , Trombose Venosa/cirurgia , Contraindicações , Feminino , Humanos , Estimativa de Kaplan-Meier , Hepatopatias/complicações , Hepatopatias/diagnóstico , Hepatopatias/mortalidade , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia , Trombose Venosa/mortalidade
20.
Exp Clin Transplant ; 11(4): 364-6, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23432594

RESUMO

Organ shortages present a problem for liver transplant. Use of traumatized livers could be a way of expanding the donor pool. We report the case of a liver transplant we did in which we used a deeply lacerated liver obtained from a donor, previously treated with a super-selective embolization of segment VI-VII arterial branches to control bleeding. At the back table, the lacerations were repaired using fibrin sealant and stitches. Organ reperfusion was homogeneous, without signs of bleeding. The recipient's postoperative course was uneventful. Injured livers, if well selected, may not be considered an absolute contraindication for liver transplant. However, in these cases, arterial embolization must not routinely be used for a graft for a liver transplant.


Assuntos
Seleção do Doador , Embolização Terapêutica , Cirrose Hepática/cirurgia , Transplante de Fígado/métodos , Fígado/lesões , Fígado/cirurgia , Doadores de Tecidos/provisão & distribuição , Adolescente , Morte Encefálica , Feminino , Hepatectomia , Hepatite C/complicações , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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