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1.
Eur J Clin Pharmacol ; 74(6): 737-744, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29430582

RESUMO

PURPOSE: The dihydrouracil (DHU):uracil (U) plasma ratio is a promising marker for identification of dihydropyrimidine dehydrogenase (DPD)-deficient patients. The objective of this study was to determine the effect of liver resection on the DHU:U plasma ratio in patients with colorectal liver metastases (CRLM). METHODS: An observational study was performed in which DHU:U plasma ratios in patients with CRLM were analyzed prior to and 1 day after liver resection. In addition, the DHU:U plasma ratio was quantified in six additional patients 4-8 weeks after liver resection to explore long-term effects on the DHU:U plasma ratio. Quantification of U and DHU plasma levels was performed using a validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay. RESULTS: The median (range) DHU:U plasma ratio in 15 patients prior to liver resection was 10.7 (2.6-14.4) and was significantly reduced to 5.5 (< quantification limit (LLOQ-10.5) 1 day after resection (p = 0.0026). This reduction was caused by a decrease in DHU plasma levels from 112.0 (79.8-153) ng/mL to 41.2 (< LLOQ-160) ng/mL 1 day after resection (p = 0.0004). Recovery of the DHU:U plasma ratio occurred 4-8 weeks after liver resection, which was shown by a median (range) DHU:U plasma ratio in six patients of 9.1 (6.9-14.5). CONCLUSION: Liver resection leads to very low DHU:U plasma ratios 1 day after liver resection, which is possibly caused by a reduction in DPD activity. Quantification of the DHU:U plasma ratios directly after liver resection could lead to false-positive identification of DPD deficiency and is therefore not advised.


Assuntos
Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Uracila/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Capecitabina/efeitos adversos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Uracila/sangue
2.
Neoplasia ; 19(2): 93-99, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28088688

RESUMO

Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF). Recurrence after resection of colorectal liver metastases (CRLMs), presumably caused by VEGF-mediated outgrowth of micrometastases, might decrease when VEGF is inhibited. This study examines the efficacy and safety of adding bevacizumab to an adjuvant regimen of CAPOX in patients undergoing radical resection for their CRLMs. Patients with resected CRLMs were randomized after surgery to receive CAPOX and bevacizumab (arm A) or CAPOX alone (arm B) as adjuvant treatment. CAPOX was given in both arms for a total of eight cycles. Bevacizumab was administered for 16 cycles. The primary end point was disease-free survival (DFS). Secondary outcomes were overall survival (OS), toxicity, and quality of life (QoL). In total, 79 patients were randomized. At the time of analysis, 23 events were encountered in arm A and 20 in arm B. One-year DFS rate was 79% [95% confidence interval (CI): 68%-93%] and 68% (95% CI: 55%-85%) for arm A and B, respectively (P=.89). Toxicity was evaluated for 75 patients. No significant differences in toxicity between the two arms were found. QoL scores were higher in arm A, of which emotional functioning and global QoL scores were significant. Adding bevacizumab to a CAPOX regimen in patients undergoing a resection for their CLM is safe and showed higher QoL scores compared with CAPOX alone. Because of premature closure of the study, conclusions about the effect on DFS of additional VEGF inhibition in this setting could not yet be made.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Quimioterapia Adjuvante , Neoplasias Colorretais/mortalidade , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Cuidados Pós-Operatórios , Qualidade de Vida , Resultado do Tratamento
3.
Clin Cancer Res ; 22(10): 2575-82, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-26733613

RESUMO

PURPOSE: Risk stratification after surgery for colorectal cancer liver metastases (CRLM) is achieved using clinicopathologic variables, however, is of limited accuracy. We sought to derive and externally validate a multigene expression assay prognostic of overall survival (OS) that is superior to clinicopathologic variables in patients with surgically resected CRLM. EXPERIMENTAL DESIGN: We measured mRNA expression in prospectively collected frozen tumor from 96 patients with surgically resected CRLM at Memorial Sloan Kettering Cancer Center (MSKCC, New York, NY). We retrospectively generated a 20-gene molecular risk score (MRS) and compared its prognostic utility for OS and recurrence-free survival (RFS) with three common clinical risk scores (CRS). We then tested the prognostic ability of the MRS in an external validation cohort (European) of 119 patients with surgically resected CRLM at the University Medical Center Utrecht (Utrecht, the Netherlands) and Paul Brousse Hospital (Villejuif, France). RESULTS: For OS in the MSKCC cohort, MRS was the strongest independent prognosticator (HR, 3.7-4.9; P < 0.001) followed by adjuvant chemotherapy (HR, 0.3; P ≤ 0.001). For OS in the European cohort, MRS was the only independent prognosticator (HR, 3.5; P = 0.007). For RFS, MRS was also independently prognostic in the MSKCC cohort (HR, 2.4-2.6; P ≤ 0.001) and the European cohort (HR, 1.6-2.5; P ≤ 0.05). CONCLUSIONS: Compared with CRSs, the MRS is more accurate, broadly applicable, and an independent prognostic biomarker of OS in resected CRLM. This MRS is the first externally validated prognostic multigene expression assay after metastasectomy for CRLM and warrants prospective validation. Clin Cancer Res; 22(10); 2575-82. ©2016 AACR.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Família Multigênica/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , RNA Mensageiro/genética , Estudos Retrospectivos
4.
Clin Cancer Res ; 21(12): 2870-9, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25779952

RESUMO

PURPOSE: Chemotherapy treatment of metastatic colon cancer ultimately fails due to development of drug resistance. Identification of chemotherapy-induced changes in tumor biology may provide insight into drug resistance mechanisms. EXPERIMENTAL DESIGN: We studied gene expression differences between groups of liver metastases that were exposed to preoperative chemotherapy or not. Multiple patient-derived colonosphere cultures were used to assess how chemotherapy alters energy metabolism by measuring mitochondrial biomass, oxygen consumption, and lactate production. Genetically manipulated colonosphere-initiated tumors were used to assess how altered energy metabolism affects chemotherapy efficacy. RESULTS: Gene ontology and pathway enrichment analysis revealed significant upregulation of genes involved in oxidative phosphorylation (OXPHOS) and mitochondrial biogenesis in metastases that were exposed to chemotherapy. This suggested chemotherapy induces a shift in tumor metabolism from glycolysis towards OXPHOS. Indeed, chemotreatment of patient-derived colonosphere cultures resulted in an increase of mitochondrial biomass, increased expression of respiratory chain enzymes, and higher rates of oxygen consumption. This was mediated by the histone deacetylase sirtuin-1 (SIRT1) and its substrate, the transcriptional coactivator PGC1α. Knockdown of SIRT1 or PGC1α prevented chemotherapy-induced OXPHOS and significantly sensitized patient-derived colonospheres as well as tumor xenografts to chemotherapy. CONCLUSIONS: Chemotherapy of colorectal tumors induces a SIRT1/PGC1α-dependent increase in OXPHOS that promotes tumor survival during treatment. This phenomenon is also observed in chemotherapy-exposed resected liver metastases, strongly suggesting that chemotherapy induces long-lasting changes in tumor metabolism that potentially interfere with drug efficacy. In conclusion, we propose a novel mechanism of chemotherapy resistance that may be clinically relevant and therapeutically exploitable.


Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fosforilação Oxidativa , Sirtuína 1/genética , Fatores de Transcrição/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Metabolismo Energético/efeitos dos fármacos , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/secundário , Mitocôndrias/genética , Mitocôndrias/metabolismo , Oxirredução , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Sirtuína 1/metabolismo , Fatores de Transcrição/metabolismo
5.
Surgeon ; 13(2): 77-82, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24486032

RESUMO

BACKGROUND: Resection of colorectal liver metastases (CRLM) is often hindered by their location close to the major hepatic vessels. So far, radiofrequency ablation for perivascular tumours was thought to be ineffective and unsafe due to either the heat sink effect or vascular thrombosis. The aim of this study was to examine whether RFA using multipolar probes could be a safe and effective option for CRLM adjacent to major hepatic vessels. METHODS: Patients were treated with multipolar RFA during an open procedure using 3 simultaneously placed electrodes. In 52 consecutive patients with CRLM, 144 tumours were ablated with RFA. In 16 out of 52 (31%) patients, metastases were abutting major hepatic vessels. We examined whether perivascular location was a risk factor for local tumour progression. The relation between perivascular location and time to local tumour progression and recurrence free survival was assessed using cox-regression analysis. RESULTS: All patients were followed for at least 3 years after RFA unless they deceased before this time. Local tumour progression following RFA occurred in 17 out of 144 tumours (12%), of which 4 out of 21 were perivascular tumours. Tumour size was the only risk factor for local tumour progression in this study. Proximity to large vessels was neither a risk factor for local local tumour progression, nor for time to local tumour progression or recurrence free survival. DISCUSSION: This study indicates that patients with CRLM abutting any of the large hepatic vessels can be safe and effectively treated with RFA when using a multipolar system.


Assuntos
Ablação por Cateter , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/cirurgia , Fígado/irrigação sanguínea , Fígado/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ablação por Cateter/instrumentação , Feminino , Artéria Hepática/cirurgia , Veias Hepáticas/cirurgia , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Veia Porta/cirurgia , Estudos Retrospectivos
6.
Neoplasia ; 15(2): 204-17, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23441134

RESUMO

In epithelial tumors, the platelet-derived growth factor receptor B (PDGFRB) is mainly expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGFRB expression following epithelial-to-mesenchymal transition (EMT), which occurs during metastasis formation. Little is known about PDGFRB signaling in colorectal tumor cells. We studied the relationship between PDGFRB expression, EMT, and metastasis in human colorectal cancer (CRC) cohorts by analysis of gene expression profiles. PDGFRB expression in primary CRC was correlated with short disease-free and overall survival. PDGFRB was co-expressed with genes involved in platelet activation, transforming growth factor beta (TGFB) signaling, and EMT in three CRC cohorts. PDGFRB was expressed in mesenchymal-like tumor cell lines in vitro and stimulated invasion and liver metastasis formation in mice. Platelets, a major source of PDGF, preferentially bound to tumor cells in a non-activated state. Platelet activation caused robust PDGFRB tyrosine phosphorylation on tumor cells in vitro and in liver sinusoids in vivo. Platelets also release TGFB, which is a potent inducer of EMT. Inhibition of TGFB signaling in tumor cells caused partial reversion of the mesenchymal phenotype and strongly reduced PDGFRB expression and PDGF-stimulated tumor cell invasion. These results suggest that PDGFRB may contribute to the aggressive phenotype of colorectal tumors with mesenchymal properties, most likely downstream of platelet activation and TGFB signaling.


Assuntos
Neoplasias Colorretais/genética , Transição Epitelial-Mesenquimal/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Transformador beta/genética , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/secundário , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Camundongos , Ativação Plaquetária/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais , Transcriptoma/genética , Fator de Crescimento Transformador beta/metabolismo
7.
PLoS One ; 7(11): e49442, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23185333

RESUMO

BACKGROUND AND OBJECTIVES: This study was designed to identify and validate gene signatures that can predict disease free survival (DFS) in patients undergoing a radical resection for their colorectal liver metastases (CRLM). METHODS: Tumor gene expression profiles were collected from 119 patients undergoing surgery for their CRLM in the Paul Brousse Hospital (France) and the University Medical Center Utrecht (The Netherlands). Patients were divided into high and low risk groups. A randomly selected training set was used to find predictive gene signatures. The ability of these gene signatures to predict DFS was tested in an independent validation set comprising the remaining patients. Furthermore, 5 known clinical risk scores were tested in our complete patient cohort. RESULT: No gene signature was found that significantly predicted DFS in the validation set. In contrast, three out of five clinical risk scores were able to predict DFS in our patient cohort. CONCLUSIONS: No gene signature was found that could predict DFS in patients undergoing CRLM resection. Three out of five clinical risk scores were able to predict DFS in our patient cohort. These results emphasize the need for validating risk scores in independent patient groups and suggest improved designs for future studies.


Assuntos
Neoplasias Colorretais/patologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/secundário , Idoso , Área Sob a Curva , Estudos de Coortes , Neoplasias Colorretais/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico , Análise de Sequência com Séries de Oligonucleotídeos , Modelos de Riscos Proporcionais , Recidiva , Risco , Resultado do Tratamento
8.
Anticancer Res ; 31(12): 4507-12, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22199323

RESUMO

AIM: To assess whether circulating soluble CD95 ligand (sCD95L) levels are associated with recurrence-free survival (RFS) in patients with synchronous colorectal liver metastases. PATIENTS AND METHODS: Blood samples were obtained from 62 patients with synchronous colorectal liver metastases before and after liver surgery. Serum sCD95L levels were determined using enzyme-linked immunosorbent assay (ELISA). Cox regression analysis was performed to determine the correlation between sCD95L levels and RFS and overall survival (OS). RESULTS: Median follow-up was 33 months. High pre-operative sCD95L levels were associated with poor RFS and OS in univariable (p=0.019 and p=0.020) and multivariable analyses (p=0.020 and p=0.003). CONCLUSION: Preoperatives CD95L is a potential prognostic factor for RFS and OS of patients undergoing surgery for synchronous colorectal liver metastases. Low preoperatives CD95L levels may help identify a subgroup of patients with synchronous liver metastases that are likely to benefit from liver surgery.


Assuntos
Neoplasias Colorretais/patologia , Proteína Ligante Fas/sangue , Neoplasias Hepáticas/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/sangue , Intervalo Livre de Doença , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva
9.
Ann Surg Oncol ; 18(13): 3702-10, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21590455

RESUMO

BACKGROUND: Local tumor progression (LTP) is a serious complication after local ablation of malignant liver tumors, negatively influencing patient survival. LTP may be the result of incomplete ablation of the treated tumor. In this study, we determined whether viable tumor cells attached to the needle applicator after ablation was associated with LTP and disease-free survival. METHODS: In this prospective study, tissue was collected of 96 consecutive patients who underwent local liver ablations for 130 liver malignancies. Cells and tissue attached to the needle applicators were analyzed for viability using glucose-6-phosphate-dehydrogenase staining and autofluorescence intensity levels of H&E stained sections. Patients were followed-up until disease progression. RESULTS: Viable tumor cells were found on the needle applicators after local ablation in 26.7% of patients. The type of needle applicator used, an open approach, and the omission of track ablation were significantly correlated with viable tumor tissue adherent to the needle applicator. The presence of viable cells was an independent predictor of LTP. The attachment of viable cells to the needle applicators was associated with a shorter time to LTP. CONCLUSIONS: Viable tumor cells adherent to the needle applicators were found after ablation of 26.7% of patients. An independent risk factor for viable cells adherent to the needle applicators is the omission of track ablation. We recommend using only RFA devices that have track ablation functionality. Adherence of viable tumor cells to the needle applicator after local ablation was an independent risk factor for LTP.


Assuntos
Carcinoma Hepatocelular/secundário , Ablação por Cateter , Neoplasias Hepáticas/patologia , Agulhas/efeitos adversos , Recidiva Local de Neoplasia/etiologia , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Progressão da Doença , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
11.
BMC Cancer ; 10: 545, 2010 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-20937118

RESUMO

BACKGROUND: About 50% of patients with colorectal cancer are destined to develop hepatic metastases. Radical resection is the most effective treatment for patients with colorectal liver metastases offering five year survival rates between 36-60%. Unfortunately only 20% of patients are resectable at time of presentation. Radiofrequency ablation is an alternative treatment option for irresectable colorectal liver metastases with reported 5 year survival rates of 18-30%. Most patients will develop local or distant recurrences after surgery, possibly due to the outgrowth of micrometastases present at the time of liver surgery. This study aims to achieve an improved disease free survival for patients after resection or resection combined with RFA of colorectal liver metastases by adding the angiogenesis inhibitor bevacizumab to an adjuvant regimen of CAPOX. METHODS/DESIGN: The Hepatica study is a two-arm, multicenter, randomized, comparative efficacy and safety study. Patients are assessed no more than 8 weeks before surgery with CEA measurement and CT scanning of the chest and abdomen. Patients will be randomized after resection or resection combined with RFA to receive CAPOX and Bevacizumab or CAPOX alone. Adjuvant treatment will be initiated between 4 and 8 weeks after metastasectomy or resection in combination with RFA. In both arms patients will be assessed for recurrence/new occurrence of colorectal cancer by chest CT, abdominal CT and CEA measurement. Patients will be assessed after surgery but before randomization, thereafter every three months after surgery in the first two years and every 6 months until 5 years after surgery. In case of a confirmed recurrence/appearance of new colorectal cancer, patients can be treated with surgery or any subsequent line of chemotherapy and will be followed for survival until the end of study follow up period as well. The primary endpoint is disease free survival. Secondary endpoints are overall survival, safety and quality of life. CONCLUSION: The HEPATICA study is designed to demonstrate a disease free survival benefit by adding bevacizumab to an adjuvant regime of CAPOX in patients with colorectal liver metastases undergoing a radical resection or resection in combination with RFA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00394992.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Compostos Organoplatínicos/administração & dosagem , Inibidores da Angiogênese/farmacologia , Anticorpos Monoclonais Humanizados , Antineoplásicos/farmacologia , Bevacizumab , Capecitabina , Quimioterapia Adjuvante/métodos , Desoxicitidina/administração & dosagem , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Metástase Neoplásica , Oxaliplatina , Qualidade de Vida , Recidiva , Resultado do Tratamento
12.
Cancer Biol Ther ; 9(9): 743-8, 2010 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-20215863

RESUMO

BACKGROUND: In preclinical models recruitment of bone-marrow derived (endothelial) progenitor cells (BD(E)PCs) contributes to tumor growth and metastasis formation. Here we investigated whether these (E)PCs and mobilizing cytokines are released after partial hepatectomy or radiofrequency ablation (RFA) for liver tumors. In addition, we tested whether G-CSF could play a role in EPC mobilization in mice and in human volunteers. RESULTS: Patients undergoing partial hepatectomy or RFA showed an instantaneous release of EPCs following laparotomy and mobilization of the liver. Elevated EPC levels were maintained during the entire procedure, but dropped to near-baseline levels 4 h after completion of the procedure. Plasma G-CSF levels showed a 5-10-fold increase after the procedure and low-dose G-CSF administration to mice or healthy volunteers was sufficient to induce an immediate release of EPCs. Surgery also caused an increase in the plasma levels of VEGF, but not SDF-1alpha. METHODS: Before, during and after liver surgery plasma and mononuclear cells were collected from 12 patients undergoing partial hepatectomy or RFA. To explore the role of G-CSF C57Bl/6 mice and 20 human volunteers received G-CSF (0.3, 3 or 300microg). In all individuals, (E)PC numbers were determined by flow cytometry at predefined timepoints shortly after therapy. Plasma levels of G-CSF, VEGF and SDF-1alpha were measured by ELISA. CONCLUSION: Compliant with previous published data concerning VDA and chemotherapy treatment, liver surgery induces an instantaneous release of EPCs, conceivably in response to elevated G-CSF levels. This suggests the value of exploring therapeutic avenues to prevent this process.


Assuntos
Endotélio Vascular/patologia , Fator Estimulador de Colônias de Granulócitos/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Células-Tronco/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Ablação por Cateter , Citocinas/sangue , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Hepatectomia , Humanos , Neoplasias Hepáticas/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Prognóstico , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
13.
Dig Surg ; 26(1): 56-62, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19169031

RESUMO

AIM: Local recurrence and needle track seeding are serious complications after local ablation for liver malignancies and potentially affect long-term survival. The aim of this study was to assess the incidence of viable tissue adherent to the needle applicators after ablation to gain insight into the possible mechanisms of local recurrence and needle track seeding. METHODS: A total of 40 consecutive patients underwent 59 local liver ablations. Cells and tissue attached to the needle applicators were analysed for morphology (HE, PAP and Giemsa staining) and viability (G6PD staining). RESULTS: Macroscopic tissue adherence was visible following 31 of the ablative procedures, all with radiofrequency ablation. Four applications were performed percutaneously and 27 during an open procedure. Morphologically intact tumour cells could be identified in 8 patients (20%), and viable tumour cells in 5 patients (12.5%). Morphologically intact tumour cells or viable tumour cells could only be demonstrated when track ablation was not performed. CONCLUSION: Viable tumour cells adherent to the needle applicators were found in an alarming 12.5% of patients after local ablation. We recommend track ablation not only after the procedure but also during any shifting and (re-)positioning to prevent shedding of viable tumour cells during or after ablation.


Assuntos
Ablação por Cateter/efeitos adversos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia/patologia , Inoculação de Neoplasia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Agulhas/efeitos adversos , Recidiva Local de Neoplasia/etiologia
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