RESUMO
PURPOSE: Preoperative evaluation of Image Defined Risk Factors (IDRFs) in neuroblastoma (NB) is crucial for determining suitability for upfront resection or tumor biopsy. IDRFs do not all carry the same weighting in predicting tumor complexity and surgical risk. In this study we aimed to assess and categorize a surgical complexity (Surgical Complexity Index, SCI) in NB resection. METHODS: A panel of 15 surgeons was involved in an electronic Delphi consensus survey to identify and score a set of shared items predictive and/or indicative of surgical complexity, including the number of preoperative IDRFs. A shared agreement included the achievement of at least 75% consensus focused on a single or two close risk categories. RESULTS: After 3 Delphi rounds, agreement was established on 25/27 items (92.6%). A severity score was established for each item ranging from 0 to 3 with an overall SCI range varying from a minimum score of zero to a maximum score of 29 points for any given patient. CONCLUSIONS: A consensus on a SCI to stratify the risks related to neuroblastoma tumor resection was established by the panel experts. This index will now be deployed to critically assign a better severity score to IDRFs involved in NB surgery.
Assuntos
Neuroblastoma , Humanos , Neuroblastoma/cirurgia , Neuroblastoma/patologia , Fatores de Risco , Cuidados Pré-Operatórios , BiópsiaRESUMO
INTRODUCTION: Surgery plays a key role in the management of Neuroblastic tumours (NB), where the standard approach is open surgery, while minimally invasive surgery (MIS) may be considered an option in selected cases. The indication(s) and morbidity of MIS remain undetermined due to small number of reported studies. The aim of this study was to critically address the contemporary indications, morbidity and overall survival (OS) and propose guidelines exploring the utility of MIS for NB. MATERIALS & METHODS: A SIOPEN study where data of patients with NB who underwent MIS between 2005 and 2018, including demographics, tumour features, imaging, complications, follow up and survival, were extracted and then analysed. RESULTS: A total of 222 patients from 16 centres were identified. The majority were adrenal gland origin (54%) compared to abdominal non-adrenal and pelvic (16%) and thoracic (30%). Complete and near complete macroscopic resection (>95%) was achieved in 95%, with 10% of cases having conversion to open surgery. Complications were reported in 10% within 30 days of surgery. The presence of IDRF (30%) and/or tumour volume >75 ml were risk factors for conversion and complications in multivariate analysis. Overall mortality was 8.5%. CONCLUSIONS: MIS for NB showed that it is a secure approach allowing more than 95% resection. The presence of IDRFs was not an absolute contraindication for MIS. Conversion to open surgery and overall complication rates were low, however they become significant if tumour volume >75 mL. Based on these data, we propose new MIS guidelines for neuroblastic tumours.
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Neoplasias Abdominais/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgia , Ganglioneuroblastoma/cirurgia , Ganglioneuroma/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neuroblastoma/cirurgia , Neoplasias Pélvicas/cirurgia , Neoplasias Torácicas/cirurgia , Neoplasias Abdominais/patologia , Neoplasias das Glândulas Suprarrenais/patologia , Criança , Pré-Escolar , Conversão para Cirurgia Aberta , Feminino , Ganglioneuroblastoma/patologia , Ganglioneuroma/patologia , Humanos , Lactente , Masculino , Neuroblastoma/patologia , Neoplasias Pélvicas/patologia , Guias de Prática Clínica como Assunto , Neoplasias Torácicas/patologia , Carga TumoralRESUMO
BACKGROUND: Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes. METHODS: An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken. RESULTS: Of a total of 116 patients, five (4·3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0·3-33) years, bowel continuity was established in 75 (73·5 per cent) at a median age of 11 (0·5-156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with a J pouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged over 4 years, long-term functional bowel symptoms after reconstruction included difficulties in holding back defaecation in 22 (39 per cent), more than one faecal accident per week in nine (16 per cent), increased frequency of defaecation in 51 (89 per cent), and social restrictions due to bowel symptoms in 35 (61 per cent). Enterocolitis occurred in 35 (47 per cent) of 72 patients. Supplementary enteral and/or parenteral nutrition was required by 51 (55 per cent) of 93 patients at any time during follow-up. Of 56 responders aged 2-20 years, true low BMI for age was found in 20 (36 per cent) and 13 (23 per cent) were short for age. CONCLUSION: Reconstruction for TCA was associated with persistent bowel symptoms, and enterocolitis remained common. Multidisciplinary follow-up, including continuity of care in adulthood, might improve care standards in patients with TCA.
ANTECEDENTES: La cirugía de la aganglionosis colónica total (total colonic aganglionosis, TCA) está diseñada para preservar la continencia y lograr una calidad de vida satisfactoria. Este estudio evaluó un gran número de resultados clínicos y sociales. MÉTODOS: Se realizó un estudio internacional multicéntrico en ocho hospitales nórdicos en el que se incluyeron las historias clínicas de todos los pacientes nacidos con TCA entre 1987 y 2006. Se invitó a los pacientes y a sus cuidadores a responder una encuesta sobre la función intestinal, el crecimiento y las necesidades nutricionales, así como la repercusión social de la enfermedad a largo plazo. RESULTADOS: De un total de 116 pacientes, 5 (4,3%) habían fallecido y 102 respondieron la encuesta. Con una mediana de seguimiento de 12 años (rango 0,5-33), se había restablecido la continuidad intestinal en 75/102 (74%) a una mediana de edad de 11 meses (0,5-156). La mucosectomía con un manguito muscular corto y anastomosis ileoanal directa (short muscular cuff and straight ileo-anal anastomosis, SIAA) n = 29 o con reservorio en J (JIAA) n = 26 (55/72, 76%) fueron las reconstrucciones más habituales. Las complicaciones postoperatorias precoces que precisaron una intervención quirúrgica fueron muy poco frecuentes, pero se presentaron en 4/72 (5%) pacientes. Los síntomas a largo plazo relacionados con la función intestinal tras la reconstrucción, valorados en 57 niños mayores de cuatro años, fueron la dificultad para retener la defecación en 14 (25%), la encopresis en 21 (37%), las pérdidas fecales > 1/semana en 9 (16%) y el aumento de la frecuencia de defecación en 51 (89%). A largo plazo, se desarrolló una enterocolitis en 35/72 (47%) pacientes. Se precisó de nutrición enteral y/o parenteral suplementaria en algún momento del período de seguimiento en 51/93 (55%) pacientes. En los pacientes que respondieron a la encuesta entre 2 y 20 años (n = 56) de edad, se detectó un índice de masa corporal menor en 20 (35%) y una altura baja en 13 (23%) para su edad. En 35/57 (61%) pacientes mayores de 4 años con restauración del tránsito intestinal había restricciones sociales debido a los síntomas intestinales, de los que en 10 (17%) casos fueron moderadas o graves. CONCLUSIÓN: La reconstrucción de una TCA se asocia con síntomas intestinales persistentes y la enterocolitis sigue siendo frecuente. Un seguimiento multidisciplinario, incluso en la edad adulta, podría mejorar los resultados en la cirugía de la TCA.
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Procedimentos Cirúrgicos do Sistema Digestório/métodos , Doença de Hirschsprung/cirurgia , Íleo/cirurgia , Medidas de Resultados Relatados pelo Paciente , Complicações Pós-Operatórias/epidemiologia , Adolescente , Anastomose Cirúrgica , Criança , Pré-Escolar , Comorbidade , Feminino , Seguimentos , Doença de Hirschsprung/mortalidade , Humanos , Masculino , Qualidade de Vida , Países Escandinavos e Nórdicos/epidemiologia , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
AIM OF THE STUDY: Preoperative gastric emptying (GE) rate in patients with gastrointestinal reflux disease (GERD) was evaluated as a predictor of outcome after antireflux surgery. METHODS AND PATIENTS: GE was assessed using radionuclide scintigraphy and a standardized meal with cow's milk. GE half time (T1/2), patient demographics and GERD symptoms including vomiting (>4days/week), retching (>4days/week), prolonged feeding time (>3h/day), and discomfort after meals were recorded pre- and postoperatively. A standardized follow-up included a 24-h pH-monitoring and an upper gastrointestinal contrast study. Of 74 patients undergoing Nissen fundoplication between 2003 and 2009, 35 underwent a preoperative GE study. The remaining 39 patients were not examined owing to volume intolerance, cow's milk intolerance or allergy, inability to lie still, or parents refusing participation. MAIN RESULTS: Median age at fundoplication was 4.9 [range 1.1-15.4] years, and follow-up time was median 4.3 [1.9-8.9] years. GERD recurred in 7 (20%) patients. Preoperative T1/2 in the seven patients with recurrent GERD was median 45 [21-87] min compared to 44 [16-121] min in the 28 patients without recurrent GERD (p=0.92). There was no significant difference between the one third of patients with the slowest GE [T1/2 54-121min] and the remaining patients [T1/2 16-49min] regarding GERD recurrence or postoperative vomiting, retching, prolonged feeding time, or discomfort after meals. CONCLUSION: Preoperative GE rate did not predict outcome after antireflux surgery, as slow GE was not associated with recurrent GERD or postoperative troublesome symptoms such as vomiting, retching, or meal discomfort.
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Fundoplicatura , Esvaziamento Gástrico/fisiologia , Refluxo Gastroesofágico/fisiopatologia , Refluxo Gastroesofágico/cirurgia , Adolescente , Animais , Criança , Pré-Escolar , Feminino , Fundoplicatura/métodos , Humanos , Lactente , Masculino , Leite , Complicações Pós-Operatórias , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Cintilografia , Recidiva , Resultado do TratamentoRESUMO
The biological function of the metastasis-associated gene S100A4 is not fully understood, although there is evidence indicating interactions between the gene product and the cytoskeleton. We have examined whether an association could exist between S100A4 and the regulation of matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs). For these studies, three clones of a highly metastatic human osteosarcoma cell line (OHS) transfected with a hammerhead ribozyme directed against the S100A4 gene transcript were used. The clones demonstrated different expression levels of S100A4 and also different metastatic capacity. In the clone with the most prominent down-regulation of S100A4, the mRNA levels of MMP2, membrane type (MT) 1-MMP, and TIMP-1 were significantly reduced in exponentially growing cultures. Western blots, gelatin zymography, and ELISA showed similar expression patterns of MMPs and TIMPs at the protein level. In the clones with an intermediate expression of S100A4, reduced expression of MT1-MMP and TIMP-1 was detected, whereas the expression of MMP-2 was at the same level as in the control cells. In contrast to the other factors, TIMP-2 was up-regulated in all of the clones independent of the extent of ribozyme-induced down-regulation of S100A4. The transwell chamber assay demonstrated that the capacity of the ribozyme-transfected cells to cross uncoated filters was reduced, relative to control cells, according to the reduction in the S100A4 expression level. The clone with the lowest reduction in S100A4 did not demonstrate different motility compared with control cells, whereas transfectants with only 5% S100A4 mRNA showed a 50% reduction in motility. Interestingly, this trend was even more striking when the capacity to cross Matrigel-coated filters was analyzed, as all the clones demonstrated between 40 and 75% reduced invasion. It is concluded that S100A4 may exert its effect on metastasis formation not only by stimulating the motility of tumor cells but also by affecting their invasive properties through influencing the expression of MMPs and their endogenous inhibitors.
Assuntos
Neoplasias Ósseas/patologia , Colagenases/genética , Gelatinases/genética , Regulação Neoplásica da Expressão Gênica , Metaloendopeptidases/genética , Osteossarcoma/patologia , RNA Catalítico/genética , RNA Catalítico/metabolismo , Proteínas S100/fisiologia , Inibidor Tecidual de Metaloproteinase-1/genética , Neoplasias Ósseas/metabolismo , Humanos , Metaloproteinase 1 da Matriz , Metaloproteinase 2 da Matriz , Invasividade Neoplásica , Metástase Neoplásica , Osteossarcoma/metabolismo , RNA Mensageiro/genética , Proteína A4 de Ligação a Cálcio da Família S100 , Proteínas S100/genética , Transcrição Gênica , Transfecção , Células Tumorais CultivadasRESUMO
A number of studies have emphasized the role of PAI-1 as an important regulator of tumor cell invasion and metastasis. The hallmark of primary tumors of the central nervous system and glioblastomas in particular is the diffuse invasion into the normal brain tissue. Since PAI-1 is expressed in such tumors, we studied the effect of adenoviral-mediated transfer of the PAI-1 gene in regulating the in vitro invasiveness of D54Mg glioma cells into Matrigel, and into fetal rat brain aggregates. Treatment of D54Mg cells with 50 MOI (multiplicity of infection) of the replication defective vector AdCMVPAI-1 increased PAI-1 expression 23-fold compared to control vectors, and the invasion through Matrigel was reduced by 67%. The motility of the cells was reduced by 58% compared to controls (indicating that inhibition of motility was the principal effect of PAI-1 in these cells). The ability of D54Mg tumor spheroids to invade fetal rat brain aggregates was not reduced by the PAI-1 gene transfer. The results show that overexpression of PAI-1 can inhibit glioma cell motility and invasion through extracellular matrix (ECM) components, like laminin and collagen, but does not inhibit tumor cell invasion in a three-dimensional invasion assay, simulating normal brain tissue having a different ECM and interstitial composition. The different results obtained in the two invasion assays reflect the complex biological effects of the uPA/PAI-1 system, and questions a simplistic view of PAI- I as an inhibitor of brain tumor invasion.
Assuntos
Adenoviridae/genética , Neoplasias Encefálicas/genética , Técnicas de Transferência de Genes , Glioma/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidores de Serina Proteinase/genética , Animais , Northern Blotting , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Adesão Celular/efeitos dos fármacos , Movimento Celular , Colágeno/metabolismo , Combinação de Medicamentos , Ensaio de Imunoadsorção Enzimática , Feto/metabolismo , Feto/patologia , Vetores Genéticos/genética , Glioma/metabolismo , Glioma/patologia , Humanos , Técnicas Imunoenzimáticas , Laminina/metabolismo , Invasividade Neoplásica , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Proteoglicanas/metabolismo , Ratos , Ratos Nus , Inibidores de Serina Proteinase/metabolismo , Esferoides Celulares/patologia , Células Tumorais CultivadasRESUMO
Hormone-independent growth and invasiveness represent phenotypic properties acquired during early progression of breast cancer. We compared human mammary adenocarcinoma cells, MCF-7, which are estrogen-dependent and poorly metastatic, with the estrogen-independent and highly metastatic subline, MCF7/LCC1, with regard to expression of tissue-degrading factors of the matrix metalloproteinase (MMP)-and urokinase (uPA)-dependent degradative pathways, as well as for their in vitro invasive properties. Both cell lines showed low constitutive mRNA expression of the MMP inhibitor TIMP-1. Baseline expression of TIMP-2 mRNA was also very low in MCF-7 cells, whereas the MCF7/LCC1 level was much higher (approximately 10-fold). Furthermore, both cell lines revealed low constitutive capacity to migrate in an in vitro invasion assay. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nM) induced the mRNAs for TIMP-1 as well as for MMP-1, MMP-9, the uPA receptor, and the uPA inhibitor PAI-1, amongst which only the responses of MMP-9 and PAI-1 were cell-specific. The mRNA levels of MMP-9 and PAI-1 were approximately 10-fold and approximately 15-fold higher in MCF7/LCC1 cells compared to MCF-7 cells. The secretion of immunoreactive PAI-1 was considerably elevated (> 20-fold) in TPA-treated MCF7/LCC1 cells, whereas the TPA-dependent level of 92-kDa MMP-9 was only approximately 2-fold higher in MCF7/LCC1 cells than in MCF-7 cells. In both cell lines treatment with TPA was associated with an increase (approximately 10-fold) in in vitro migration, which in the MCF7/LCC1 cells was significantly attenuated by a reconstituted basement membrane extract (Matrigel). These data suggest that TPA-responsive in vitro invasive properties that are probably associated with PAI-1 expression may co-vary with progression from hormone-dependent to -independent breast cancer.
Assuntos
Neoplasias da Mama/patologia , Invasividade Neoplásica , Neoplasias da Mama/enzimologia , Movimento Celular , Matriz Extracelular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metaloendopeptidases/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Proteína Quinase C/fisiologia , RNA Mensageiro/genética , RNA Neoplásico/genética , Acetato de Tetradecanoilforbol/farmacologia , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-2/genética , Células Tumorais Cultivadas , Ativador de Plasminogênio Tipo Uroquinase/genéticaRESUMO
proteinases are required for invasion through the extracellular matrix (ECM) during tumor invasion and metastasis. Polymorphonuclear (PMN) elastase can degrade ECM components and modulate other proteinases. In the present study PMN elastase activity was found in tissue extracts from 8 of 15 human colorectal carcinomas. Immunoreactive PMN elastase was demonstrated in all carcinoma biopsies with particular enrichment at the tumor-host interface. Immunofluorescence staining localized immunoreactive PMN elastase mainly to neutrophile granulocytes. The human colon carcinoma cell lines Caco-2 and HT-29 did not express PMN elastase. An interaction between tumor cells and elastase producing leukocytes is suggested.
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Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Elastase de Leucócito/análise , Idoso , Neoplasias do Colo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neutrófilos/enzimologia , Neutrófilos/patologia , Células Tumorais CultivadasRESUMO
When mouse fibroblast L-929 cells were pre-infected with vesicular stomatitis virus, an enhancement of invasiveness by Salmonella typhimurium was observed. The effect was more pronounced when higher virus doses were used. Short-time (5 h) pre-incubation with virus caused a moderate enhancement of invasiveness. When virus pre-incubation time was increased to 8 h or 13 h, a further enhancement was observed. Results obtained after pre-incubation with UV inactivated virus were similar to that achieved by the short-time pre-incubation with the corresponding viable virus preparation. This indicates (i) an early phase of virus infection, when virus causes enhancement of invasiveness that is not dependent on viral nucleic acid induced metabolism, and (ii) a later phase, when virus-induced metabolism is necessary for the enhancement. When virus and bacteria were given concomitantly to infant mice, lethality was increased compared to groups that only received virus or bacteria. The data indicate that vesicular stomatitis virus aggravates infection with a facultatively intracellular bacterium, partly by enhancing the invasiveness of the bacteria.
Assuntos
Salmonelose Animal/complicações , Salmonella typhimurium/patogenicidade , Estomatite/complicações , Viroses/complicações , Animais , Linhagem Celular , Modelos Animais de Doenças , Camundongos , Salmonelose Animal/microbiologia , Raios Ultravioleta , Vírus da Estomatite Vesicular Indiana/efeitos da radiaçãoRESUMO
Hirschsprung's disease (HD) is considered a focal disease usually confined to the distal colon and rectum. However, autonomic dysfunction and dysmotility in the upper gastrointestinal tract have been reported, suggesting that this disease is not only confined to the distal gastrointestinal tract. This study examines the fasting and postprandial levels of glucose and insulin in adult patients with HD to elucidate whether there might also be an endocrine involvement in this disease. Sixteen patients with surgically treated HD during early childhood and 17 healthy subjects were studied. All subjects ingested a caloric liquid meal containing glucose, lactose, maize oil, and water (2,020 kJ) after an overnight fast. Blood samples were collected at regular intervals for insulin and glucose analyses. Fasting levels of both glucose (P <.05) and insulin (P <.02) were significantly higher in patients compared with healthy controls. Peak concentration of insulin following meal intake was significantly higher in the patient group (P <.05), and peak concentration of glucose tended to be higher in patients compared with controls (P =.06). There was no correlation between body mass index and serum levels of glucose or insulin. The present study shows that adult patients treated for HD during childhood have an impaired glucose and insulin homeostasis, indicating a mild degree of insulin resistance. This may imply susceptibility towards development of non-insulin-dependent diabetes mellitus.
Assuntos
Diabetes Mellitus Tipo 2/etiologia , Doença de Hirschsprung/complicações , Adolescente , Adulto , Glicemia/análise , Índice de Massa Corporal , Jejum , Feminino , Alimentos , Humanos , Insulina/sangue , Resistência à Insulina , Cinética , MasculinoRESUMO
Whether the phenotypes of drug resistance and metastatic activity in cancer are dependent on each other or not is controversial. We compared in vitro invasive properties of human hepatoma cells resistant to epirubicin and rich in P-glycoprotein (Pgp) (HB8065/R) with the parental epirubicin-sensitive, Pgp-poor cells (HB8065/S). The HB8065/R cells displayed elevated capacity to migrate in a transwell chamber assay (three- to fourfold compared to the HB8065/S cells), both in the absence and presence of a reconstituted basement membrane extract (Matrigel). In the presence of the P-gp inhibitor PSC 833 (1.5 micrograms/ml) the capacity of the HB8065/R cells to cross Matrigel-coated filters was attenuated by approximately 25%. Compared to the HB8065/S cells, the resistant cell line expressed higher level of plasminogen activator inhibitor (PAI)-1 mRNA (approximately threefold), which was reflected by a approximately fivefold increase in secreted PAI-1 immunoactivity (approximately 50 ng/10(6) HB8065/R cells). Furthermore, treatment with PSC 833 was associated with upregulation of PAI-1 mRNA (approximately 3.5-fold) and immunoactivity (approximately twofold) in the HB8065/R cells. Level of tissue inhibitor of metalloproteinases (TIMP)-1 was also significantly increased in the HB8065/R cells compared to the HB8065/S cells, whereas both cell lines showed low constitutive expression of TIMP-2. Levels of TIMPs were not altered by PSC 833. These data suggest that overexpression of Pgp in these hepatoma cells may covariate with the phenotypes of both enhanced in vitro invasiveness and high PAI-1 expression, whether randomly acquired or not.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/fisiologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Carcinoma Hepatocelular/química , Humanos , Neoplasias Hepáticas/química , Invasividade Neoplásica , Inibidor 1 de Ativador de Plasminogênio/genética , RNA Mensageiro/análise , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-2/genética , Células Tumorais CultivadasRESUMO
Proteolytic enzymes are believed to be necessary for tumor cell invasion. We have studied the effects of the cysteine proteinase inhibitor E-64 and the serine and cysteine proteinase inhibitor leupeptin, on the ability of human malignant melanoma cells (LOX) to pass through an artificial basement membrane. Transwell chambers containing filters coated with the reconstituted basement membrane, Matrigel, were used. Nontoxic concentrations of the proteinase inhibitors reduced the invasion of LOX cells through Matrigel. E-64 (250 mumol/l) by 27% and leupepetin (250 micrograms/ml) by 46%. The proteinase inhibitors did not alter the growth rate of the tumor cells, their motility through uncoated filters, or their attachment to the Matrigel coated wells. Our results indicate that cysteine proteinases are involved in the degradation of basement membranes and thus contribute to the invasion of malignant melanoma cells.
Assuntos
Inibidores de Cisteína Proteinase/farmacologia , Leucina/análogos & derivados , Leupeptinas/farmacologia , Melanoma/patologia , Invasividade Neoplásica , Animais , Adesão Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Humanos , Leucina/farmacologia , Melanoma/fisiopatologia , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
Plasminogen activators (PAs) and their inhibitors (PAIs) can be produced by tumor cells and surrounding inflammatory cells and fibroblasts. The present study evaluate both the expression and release of PAs (uPA and tPA) and PAIs (PAI-1 and PAI-2) from cultured cells, and also the expression of uPA receptor (uPAR). Immunocytochemistry showed that PAs, PAIs and uPAR were present to different extents on the surface of colon carcinoma cells (Caco-2, HT-29), malignant melanoma cells (LOX) and normal fibroblasts. uPA immunoreactivity was intermediate in Caco-2, HT-29 and LOX and weak in the fibroblasts. tPA immunoreactivity was intermediate in Caco-2 and LOX and weak in HT-29 and fibroblasts. PAI-1 and PAI-2 immunoreactivities were absent in HT-29, weak in Caco-2 and strong in fibroblasts. In LOX the immunoreactivity was intermediate for PAI-1 and strong for PAI-2. uPAR immunoreactivity was weak in Caco-2, HT-29 and LOX and negative in fibroblasts. ELISAs on conditioned medium detected that the colon carcinoma cells Caco-2 and HT-29 did not release any PAs or PAIs. LOX released tPA (median 9 ng/million cells at 72 hours), PAI-1 (1050 ng/million cells) and PAI-2 (245 ng/million cells), and fibroblasts released uPA (1 ng/million cells) and PAI-1 (910 ng/million cells). These results show that both tumor cells and fibroblasts express tissue destructive enzymes, PAs and PAIs, whereas only the tumor cells express the uPAR required for focalization and regulation of PA activity at the cell surface. The melanoma cells LOX and fibroblasts also released PAs and PAIs, in contrast to the colon carcinoma cells Caco-2 and HT-29.
Assuntos
Expressão Gênica , Inibidor 1 de Ativador de Plasminogênio/biossíntese , Inibidor 2 de Ativador de Plasminogênio/biossíntese , Receptores de Superfície Celular/biossíntese , Ativador de Plasminogênio Tecidual/biossíntese , Ativador de Plasminogênio Tipo Uroquinase/biossíntese , Linhagem Celular , Neoplasias do Colo , Meios de Cultivo Condicionados , Fibroblastos/metabolismo , Humanos , Imuno-Histoquímica , Cinética , Melanoma , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Pele , Fatores de Tempo , Células Tumorais CultivadasRESUMO
PURPOSE: The aim of this study was to review all available studies reported in the English-language literature from 1975 through 1998, and by meta-analysis assess the importance of prenatal diagnosis, associated malformations, side of hernia, timing of surgery, and study population on mortality rates in patients with congenital diaphragmatic hernia (CDH). METHODS: One-hundred-two studies were identified, and 51 studies (2,980 patients) fulfilled the prespecified inclusion criteria. Studies were grouped according to study population into: (I) fetuses diagnosed prenatally; (II) neonates admitted to a treatment center; and (III) population-based studies. RESULTS: Pooled total mortality rate was significantly higher in category I than in category III (75.6% v 58.2%, P < .001). Pooled hidden postnatal mortality rate (deaths before admittance to a treatment center) in population-based studies was 34.9%. Prenatally diagnosed patients in both category II and III had significantly higher mortality rates than those diagnosed postnatally. Mortality rates were significantly higher among CDH infants with associated major malformations compared with isolated CDH in all 3 categories. An increased mortality rate in right-sided CDH was found in category II and III. CONCLUSIONS: Prenatal diagnosis of CDH, presence of associated major malformations, and the study population have a major influence on mortality rate. The very high mortality rate in studies of fetuses with a prenatal diagnosis of CDH should be taken into account in prenatal counselling.
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Hérnia Diafragmática/mortalidade , Hérnias Diafragmáticas Congênitas , Anormalidades Múltiplas/mortalidade , Estudos de Casos e Controles , Feminino , Hérnia Diafragmática/diagnóstico por imagem , Humanos , Recém-Nascido , Gravidez , Prevalência , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: Matrix metalloproteinases (MMPs) and their endogenous inhibitors (tissue inhibitors of MMPs; TIMPs) have been shown to correlate with in vitro invasiveness and clinical outcome in several adult malignancies. The importance of MMP and TIMP expression in neuroblastoma (NB) and primitive neuroectodermal tumors (PNET) is incompletely understood. The aim of the current study was to relate in vitro invasion of NB and PNET cell lines with MMP and TIMP expression and evaluate the effect of a synthetic MMP inhibitor. Furthermore, S100A4 levels were determined because recent reports have suggested a possible association between MMPs, TIMPs, and the metastasis-associated gene S100A4. METHODS: Expression of MMPs, TIMPs, and S100A4 was evaluated at both mRNA and protein levels in 2 human NB and 2 PNET cell lines. In vitro invasion and effects of the synthetic MMP inhibitor Marimastat were assessed in the Transwell chamber assay. RESULTS: The most invasive cells expressed the highest levels of MMPs and S100A4. Marimastat reduced invasion by 30%. CONCLUSIONS: In vitro invasion correlated with MMP and S100A4 expression. The fact that Marimastat reduced in vitro invasion is encouraging for further studies on a possible therapeutic application for proteinase inhibitors.
Assuntos
Metaloproteinases da Matriz/análise , Invasividade Neoplásica/genética , Neuroblastoma/química , Neuroblastoma/genética , Tumores Neuroectodérmicos Primitivos/química , Tumores Neuroectodérmicos Primitivos/genética , Proteínas S100/genética , Northern Blotting , Ensaio de Imunoadsorção Enzimática , Humanos , Metaloproteinases da Matriz/genética , Neuroblastoma/patologia , Tumores Neuroectodérmicos Primitivos/patologia , RNA Mensageiro/análise , Proteína A4 de Ligação a Cálcio da Família S100 , Inibidores Teciduais de Metaloproteinases/análise , Células Tumorais Cultivadas/química , Células Tumorais Cultivadas/patologiaRESUMO
BACKGROUND: Dysmotility of the upper gastrointestinal (GI) tract has been reported in children with Hirschsprung's disease (HD). In the present study, motility of the oesophagus and the small bowel was studied in adults treated for HD during early childhood to elucidate whether there are alterations in motility of the upper GI tract in this patient group. [Correction added after online publication 15 Sep: The preceding sentence has been rephrased for better clarity.] METHODS: Ambulatory small bowel manometry with recording sites in duodenum/jejunum was performed in 16 adult patients with surgically treated HD and 17 healthy controls. In addition, oesophageal manometry was performed with station pull-through technique. KEY RESULTS: The essential patterns of small bowel motility were recognized in all patients and controls. During fasting, phase III of the migrating motor complex (MMC) was more prominent in patients with HD than in controls when accounting for duration and propagation velocity (P = 0.006). Phase I of the MMC was of shorter duration (P = 0.008), and phase II tended to be of longer duration (P = 0.05) in the patients. During daytime fasting, propagated clustered contractions (PCCs) were more frequent in the patients (P = 0.01). Postprandially, the patients demonstrated a higher contractile frequency (P = 0.02), a shorter duration of contractions (P = 0.008) and more frequent PCCs (P < 0.001). The patients had normal oesophageal motility. CONCLUSIONS & INFERENCES: This study demonstrates that adult patients with HD have preserved essential patterns of oesophageal and small bowel motility. However, abnormalities mainly characterized by increased contractile activity of the small bowel during fasting and postprandially are evident. These findings indicate alterations in neuronal control of motility and persistent involvement of the upper GI tract in this disease.
Assuntos
Esôfago/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Doença de Hirschsprung/fisiopatologia , Intestino Delgado/fisiopatologia , Adolescente , Adulto , Distribuição de Qui-Quadrado , Criança , Doença de Hirschsprung/cirurgia , Humanos , Técnicas In Vitro , Masculino , Manometria , Complexo Mioelétrico Migratório/fisiologia , Estatísticas não ParamétricasRESUMO
BACKGROUND: Complications and unsatisfactory long-term results after antireflux surgery in children have received increased attention. The aim of this study was to report parental assessment of outcome after Nissen fundoplication. METHODS: Ninety-three patients operated with primary Nissen fundoplication between 1990 and 2001 were included. Medical records were reviewed, and parents were interviewed for evaluation of postoperative results. RESULTS: Of the 93 children, 51 were neurologically impaired and 14 children had repaired esophageal atresia. Median follow-up time was 6.0 years. Total mortality for the patient population was 13%. Five children died as a complication of the surgery, whereas eight deaths were unrelated to the Nissen fundoplication. Ninety-two percent of the parents reported better well-being of the child after the Nissen fundoplication, and 83% were completely satisfied with the postoperative results. Pulmonary symptoms were reduced in 59%, and quality of sleep improved in 68% of the children. Nine children (10%) had been operated with a redo NF. CONCLUSION: The majority of parents were satisfied with the long term results of the Nissen fundoplication.
Assuntos
Fundoplicatura , Refluxo Gastroesofágico/cirurgia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Pais , Satisfação do Paciente , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To test whether postnatal psychological distress in parents of babies with congenital malformations is reduced by prenatal diagnosis. METHODS: A prospective observational longitudinal cohort study was conducted at two Norwegian hospitals. We included 293 parents of babies with congenital malformations (prenatal detection rate: 36.5%) referred for neonatal surgery and 249 parents of healthy babies (comparison group). Parental psychological responses were assessed on three postnatal occasions by psychometric instruments (GHQ-28, STAI-X1, and IES). RESULTS: Significantly increased psychological distress (GHQ-28) was reported by parents who received prenatal diagnosis as compared to postnatal diagnosis; acutely 28.9 versus 24.4, P = 0.006 (comparison group: 19.6); at 6 weeks 26.8 versus 21.5, P < 0.001 (comparison group: 17.7); and at 6 months 22.6 versus 18.7, P = 0.015 (comparison group: 16.6). Mothers consistently reported higher levels of distress than fathers. Multiple linear regression analysis showed that prenatal diagnosis and being a mother significantly predicted severity of acute psychological distress. At 6 weeks and 6 months, mortality and associated anomalies were significant independent predictors of psychological distress. CONCLUSION: Controlling for other covariates, we found that prenatal diagnosis of congenital malformations was a significant independent predictor of acute parental psychological distress after birth.
Assuntos
Anormalidades Congênitas/diagnóstico , Pais/psicologia , Diagnóstico Pré-Natal/psicologia , Estresse Psicológico/epidemiologia , Adulto , Anormalidades Congênitas/psicologia , Feminino , Humanos , Modelos Lineares , Masculino , Mães/psicologia , Gravidez , Estudos Prospectivos , Testes PsicológicosRESUMO
Self-examination of the breasts is common among women from 24 to 70 years of age. This information was obtained from a study conducted on 600 women. They were asked 12 questions concerning self-examination of breasts. 37.3% examined their breasts once a month or more frequently, while 32.3% performed self-examination only irregularly. 191 found self-examination difficult, and 165 said that they forgot to examine themselves regularly. 60% of the women interviewed wanted more instruction in self-examination of breasts.
Assuntos
Neoplasias da Mama/prevenção & controle , Educação de Pacientes como Assunto , Autocuidado , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , NoruegaRESUMO
Between 1976 and 1988, 16 patients underwent a Whipple resection or total pancreatectomy for carcinoma of the head of the pancreas, the ampulla of Vater or the distal common bile duct. Nine patients had carcinoma of the pancreas. Two of these patients are long-term survivors. The tumors in these patients were highly differentiated and localized close to the common bile duct. Four had ampullary lesions, and are all alive today. Three patients had carcinoma of the common bile duct. One of these patients is alive.