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1.
PLoS Med ; 16(7): e1002847, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31265453

RESUMEN

BACKGROUND: The identification of patients with high-risk prostate cancer (PC) is a major challenge for clinicians, and the improvement of current prognostic parameters is an unmet clinical need. We and others have identified an association between the nuclear localization of NF-κB p65 and biochemical recurrence (BCR) in PC in small and/or single-centre cohorts of patients. METHODS AND FINDINGS: In this study, we accessed 2 different multi-centre tissue microarrays (TMAs) representing cohorts of patients (Test-TMA and Validation-TMA series) of the Canadian Prostate Cancer Biomarker Network (CPCBN) to validate the association between p65 nuclear frequency and PC outcomes. Immunohistochemical staining of p65 was performed on the Test-TMA and Validation-TMA series, which include PC tissues from patients treated by first-line radical prostatectomy (n = 250 and n = 1,262, respectively). Two independent observers evaluated the p65 nuclear frequency in digital images of cancer tissue and benign adjacent gland tissue. Kaplan-Meier curves coupled with a log-rank test and univariate and multivariate Cox regression models were used for statistical analyses of continuous values and dichotomized data (cutoff of 3%). Multivariate analysis of the Validation-TMA cohort showed that p65 nuclear frequency in cancer cells was an independent predictor of BCR using continuous (hazard ratio [HR] 1.02 [95% CI 1.00-1.03], p = 0.004) and dichotomized data (HR 1.33 [95% CI 1.09-1.62], p = 0.005). Using a cutoff of 3%, we found that this biomarker was also associated with the development of bone metastases (HR 1.82 [95% CI 1.05-3.16], p = 0.033) and PC-specific mortality (HR 2.63 [95% CI 1.30-5.31], p = 0.004), independent of clinical parameters. BCR-free survival, bone-metastasis-free survival, and PC-specific survival were shorter for patients with higher p65 nuclear frequency (p < 0.005). As the small cores on TMAs are a limitation of the study, a backward validation of whole PC tissue section will be necessary for the implementation of p65 nuclear frequency as a PC biomarker in the clinical workflow. CONCLUSIONS: We report the first study using the pan-Canadian multi-centre cohorts of CPCBN and validate the association between increased frequency of nuclear p65 frequency and a risk of disease progression.


Asunto(s)
Biomarcadores de Tumor/análisis , Núcleo Celular/química , Inmunohistoquímica , Neoplasias de la Próstata/química , Factor de Transcripción ReIA/análisis , Anciano , Neoplasias Óseas/secundario , Canadá , Núcleo Celular/patología , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Supervivencia sin Progresión , Prostatectomía , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Análisis de Matrices Tisulares
2.
Am J Pathol ; 189(7): 1451-1461, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31202437

RESUMEN

Prostate cancer (PC) commonly metastasizes to the bone, resulting in pathologic fractures and poor prognosis. CCN3/nephroblastoma overexpressed is a secreted protein with a known role in promoting breast cancer metastasis to bone. However, in PC, CCN3 has been ascribed conflicting roles; some studies suggest that CCN3 promotes PC metastasis, whereas others argue a tumor suppressor role for CCN3 in this disease. Indeed, in the latter context, CCN3 has been shown to sequester the androgen receptor (AR) and suppress AR signaling. In the present study, we demonstrate that CCN3 functions as a bone-metastatic mediator, which is dependent on its C-terminal domain for this function. Analysis of tissue microarrays comprising >1500 primary PC patient radical prostatectomy specimens reveals that CCN3 expression correlates with aggressive disease and is negatively correlated with the expression of prostate-specific antigen, a marker of AR signaling. Together, these findings point to CCN3 as a biomarker to predict PC aggressiveness while providing clarity on its role as a functional mediator of PC bone metastasis.

3.
J Immunother Cancer ; 7(1): 86, 2019 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-30922393

RESUMEN

BACKGROUND: Permanence of front-line management of lung cancer by immunotherapies requires predictive companion diagnostics identifying immune-checkpoints at baseline, challenged by the size and heterogeneity of biopsy specimens. METHODS: An innovative, tumor heterogeneity reducing, immune-enriched tissue microarray was constructed from baseline biopsies, and multiplex immunofluorescence was used to profile 25 immune-checkpoints and immune-antigens. RESULTS: Multiple immune-checkpoints were ranked, correlated with antigen presenting and cytotoxic effector lymphocyte activity, and were reduced with advancing disease. Immune-checkpoint combinations on TILs were associated with a marked survival advantage. Conserved combinations validated on more than 11,000 lung, breast, gastric and ovarian cancer patients demonstrate the feasibility of pan-cancer companion diagnostics. CONCLUSIONS: In this hypothesis-generating study, deepening our understanding of immune-checkpoint biology, comprehensive protein-protein interaction and pathway mapping revealed that redundant immune-checkpoint interactors associate with positive outcomes, providing new avenues for the deciphering of molecular mechanisms behind effects of immunotherapeutic agents targeting immune-checkpoints analyzed.

4.
Sci Rep ; 6: 27485, 2016 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-27270835

RESUMEN

Mutations in the CdGAP/ARHGAP31 gene, which encodes a GTPase-activating protein for Rac1 and Cdc42, have been reported causative in the Adams-Oliver developmental syndrome often associated with vascular defects. However, despite its abundant expression in endothelial cells, CdGAP function in the vasculature remains unknown. Here, we show that vascular development is impaired in CdGAP-deficient mouse embryos at E15.5. This is associated with superficial vessel defects and subcutaneous edema, resulting in 44% embryonic/perinatal lethality. VEGF-driven angiogenesis is defective in CdGAP(-/-) mice, showing reduced capillary sprouting from aortic ring explants. Similarly, VEGF-dependent endothelial cell migration and capillary formation are inhibited upon CdGAP knockdown. Mechanistically, CdGAP associates with VEGF receptor-2 and controls VEGF-dependent signaling. Consequently, CdGAP depletion results in impaired VEGF-mediated Rac1 activation and reduced phosphorylation of critical intracellular mediators including Gab1, Akt, PLCγ and SHP2. These findings are the first to demonstrate the importance of CdGAP in embryonic vascular development and VEGF-induced signaling, and highlight CdGAP as a potential therapeutic target to treat pathological angiogenesis and vascular dysfunction.


Asunto(s)
Vasos Sanguíneos/embriología , Proteínas Activadoras de GTPasa/fisiología , Neovascularización Fisiológica/fisiología , Factor A de Crecimiento Endotelial Vascular/fisiología , Proteína de Unión al GTP cdc42/fisiología , Animales , Ratones , Ratones Noqueados
5.
Cell Signal ; 26(6): 1283-93, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24583284

RESUMEN

The protein tyrosine phosphatase DEP-1/PTPRJ positively regulates Src family kinases and critical biological functions in endothelial and hematopoietic cells. Phosphorylation of DEP-1 on Y1311/Y1320 mediates the association and activation of Src, and promotes Src-dependent angiogenic responses including endothelial cell permeability. We have identified T1318 as a phosphorylated residue proximal to Y1320. The aim of this study was to determine if T1318 phosphorylation exerts a regulatory role over the function of DEP-1. We show that phosphorylation of DEP-1 on Y1320 was reduced when T1318 was mutated. This led to the decreased association of DEP-1 T1318A with Src, and defective Src activation in both HEK 293T and VEGF-stimulated endothelial cells. Consistent with these findings, VEGF-induced tyrosine phosphorylation of VE-cadherin, its association to ß-arrestin1/2, and cell permeability were impaired in cells expressing DEP-1 T1318A. Conversely, expression of the phosphomimetic mutant DEP-1 T1318E constitutively enhanced the phosphorylation of Y1320 and VE-cadherin over that induced by WT DEP-1, and resulted in increased VEGF-dependent permeability. DEP-1 T1318 is part of a CK2 consensus phosphorylation site and was identified as a CK2 substrate. Modulation of CK2 expression or activity in endothelial cells regulated T1318 phosphorylation, and correlated with the status of Y1320 phosphorylation, Src activation, and cell permeability. CK2-dependent phosphorylation of DEP-1 T1318 promotes Y1320 phosphorylation and Src activation upon VEGF stimulation. Phosphorylation of T1318 is thus part of a regulatory mechanism that channels the activity of DEP-1 towards Src to allow its optimal activation and the promotion of endothelial cell permeability.


Asunto(s)
Células Endoteliales de la Vena Umbilical Humana/metabolismo , Procesamiento Proteico-Postraduccional , Factor A de Crecimiento Endotelial Vascular/fisiología , Secuencia de Aminoácidos , Animales , Quinasa de la Caseína II/metabolismo , Bovinos , Permeabilidad de la Membrana Celular , Activación Enzimática , Células HEK293 , Humanos , Fosforilación , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/metabolismo , Treonina/metabolismo , Familia-src Quinasas/metabolismo
6.
Blood ; 120(13): 2745-56, 2012 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-22898603

RESUMEN

DEP-1/CD148 is a receptor-like protein tyrosine phosphatase with antiproliferative and tumor-suppressive functions. Interestingly, it also positively regulates Src family kinases in hematopoietic and endothelial cells, where we showed it promotes VE-cadherin-associated Src activation and endothelial cell survival upon VEGF stimulation. However, the molecular mechanism involved and its biologic functions in endothelial cells remain ill-defined. We demonstrate here that DEP-1 is phosphorylated in a Src- and Fyn-dependent manner on Y1311 and Y1320, which bind the Src SH2 domain. This allows DEP-1-catalyzed dephosphorylation of Src inhibitory Y529 and favors the VEGF-induced phosphorylation of Src substrates VE-cadherin and Cortactin. Accordingly, RNA interference (RNAi)-mediated knockdown of DEP-1 or expression of DEP-1 Y1311F/Y1320F impairs Src-dependent biologic responses mediated by VEGF including permeability, invasion, and branching capillary formation. In addition, our work further reveals that above a threshold expression level, DEP-1 can also dephosphorylate Src Y418 and attenuate downstream signaling and biologic responses, consistent with the quiescent behavior of confluent endothelial cells that express the highest levels of endogenous DEP-1. Collectively, our findings identify the VEGF-dependent phosphorylation of DEP-1 as a novel mechanism controlling Src activation, and show this is essential for the proper regulation of permeability and the promotion of the angiogenic response.


Asunto(s)
Capilares/metabolismo , Permeabilidad de la Membrana Celular , Endotelio Vascular/citología , Neovascularización Patológica , Tirosina/metabolismo , Familia-src Quinasas/metabolismo , Antígenos CD/metabolismo , Western Blotting , Cadherinas/metabolismo , Adhesión Celular , Movimiento Celular , Proliferación Celular , Células Cultivadas , Cortactina/metabolismo , Endotelio Vascular/metabolismo , Técnica del Anticuerpo Fluorescente , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inmunoprecipitación , Mutación/genética , Invasividad Neoplásica , Fosforilación , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/genética , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/metabolismo , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismo
7.
Cell Signal ; 21(6): 943-53, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19233262

RESUMEN

Gab1 was previously described as a positive modulator of Akt, Src, ERK1/2, endothelial cell migration, and capillary formation in response to vascular endothelial growth factor (VEGF). However, its involvement in endothelial cell survival, as well as the potential contribution of the other family member Gab2 to signalling and biological responses remained unknown. Here, we show that Gab2 is tyrosine phosphorylated in a Grb2-dependent manner downstream of activated VEGF receptor-2 (VEGFR2), and that it associates with signalling proteins including PI3K and SHP2, but apparently not with the receptor. Similarly to Gab1, over-expression of Gab2 induces endothelial cell migration in response to VEGF, whereas its depletion using siRNAs results in its reduction. Importantly, depletion of both Gab1 and Gab2 leads to an even greater inhibition of VEGF-induced cell migration. However, contrary to what has been reported for Gab1, the silencing of Gab2 results in increased Src, Akt and ERK1/2 activation, slightly reduced p38 phosphorylation, and up-regulation of Gab1 protein levels. Accordingly, re-expression of Gab2 in Gab2-/- fibroblasts leads to opposite results, suggesting that the modulation of both Gab2 and Gab1 expression in these conditions might contribute to the impaired signalling observed. Consistent with their opposite roles on Akt, the depletion of Gab1, but not of Gab2, results in reduced FOXO1 phosphorylation and VEGF-mediated endothelial cell survival. Mutation of VEGFR2 Y801 and Y1214, which abrogates the phosphorylation of Gab1, also correlates with inhibition of Akt. Altogether, these results underscore the non-redundant and essential roles of Gab1 and Gab2 in endothelial cells, and suggest major contributions of these proteins during in vivo angiogenesis.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Movimiento Celular/efectos de los fármacos , Células Endoteliales/citología , Fosfoproteínas/metabolismo , Factor A de Crecimiento Endotelial Vascular/farmacología , Animales , Bovinos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Activación Enzimática/efectos de los fármacos , Humanos , Ratones , Proteínas Mutantes/metabolismo , Fosfoproteínas/deficiencia , Fosforilación/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo
8.
Dig Dis Sci ; 52(10): 2601-9, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17429735

RESUMEN

The noninvasive evaluation of liver fibrosis is a major clinical goal in liver diseases. Our aim was to identify MRI parameters to quantify liver fibrosis in vivo in an animal model of liver fibrosis with slight inflammation. We evaluated serum hyaluronate, liver hydroxyproline, area of liver fibrosis (image analysis), and 1.5-T MRI in 10 sham rats and 24 bile duct ligated rats with different stages of liver fibrosis. Liver signal intensity (SI)/muscle SI ratio and liver relaxation times (rT) were measured on T1 and T2 weighted sequences at different echo (TE) or recovery (RT) times of MRI. Among the 66 MRI parameters tested, the highest correlation with the area of fibrosis was observed for rT2 (r=0.78, P < 0.01). The area of liver fibrosis was independently predicted by five MRI variables (adjusted R (2)=0.78, with R (2)=0.64 for rT2 and rT1). Diagnostic accuracy for liver fibrosis was 100% using two variables: liver/muscle SI ratio on T2 at 30-ms TE and liver/muscle SI ratio on T1 at 50-ms RT. We conclude that in this animal model, fibrosis could be diagnosed with an accuracy of 100% using two MRI parameters. The quantification of liver fibrosis was very accurate either with only one MRI parameter (r=0.78 for rT2) or with five parameters (r=0.90) in this cholestatic model.


Asunto(s)
Conductos Biliares Extrahepáticos/cirugía , Cirrosis Hepática Experimental/patología , Imagen por Resonancia Magnética/métodos , Animales , Ligadura/efectos adversos , Cirrosis Hepática Experimental/etiología , Valor Predictivo de las Pruebas , Ratas , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad
9.
Eur Radiol ; 16(7): 1501-8, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16485132

RESUMEN

The distinction between intracellular (ICE) and extracellular edema (ECE) has a crucial prognostic and therapeutic importance in patients with severe traumatic brain injury (STBI). Indeed, ICE usually leads to cellular death, and maintenance of a cerebral perfusion pressure (CPP) above 70 mmHg is still under debate since this practice may increase ECE. The purpose of this study was to describe the ECE and ICE kinetics associated with STBI using quantitative diffusion MRI. Twelve patients were prospectively studied. The initial ADC in ICE measured on day 1.3+/-0.7 is significantly reduced compared to normal-appearing parenchyma (0.51+/-0.12 * 10(-3) mm2/s vs. 0.76+/-0.03 * 10(-3) mm2/s, n=12, P<0.0001) and reaches normality on MRI 3 performed on day 14.2+/-3.3. In patients presenting an extension of ICE on MRI 2 performed on day 6.7+/-1.4 (ADC(MRI2)=0.40+/-0.11 * 10(-3) mm2/s), ADC values in the extension area at the first MRI were slightly, but not significantly reduced compared to normal parenchyma (0.69+/-0.05 * 10(-3) mm2/s, P=0.29). Normalization occurred equally by day 14. ADC in ECE (1.34+/-0.22 * 10(-3) mm2/s) was elevated and stable with time under CPP therapy. Therefore, ECE is not worsened by CCP therapy, and ICE appears more relevant than ECE in STBI.


Asunto(s)
Agua Corporal/metabolismo , Edema Encefálico/diagnóstico , Edema Encefálico/metabolismo , Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/metabolismo , Encéfalo/metabolismo , Imagen de Difusión por Resonancia Magnética/métodos , Adolescente , Adulto , Encéfalo/patología , Edema Encefálico/etiología , Lesiones Encefálicas/complicaciones , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Cinética , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Estudios Prospectivos
10.
J Pediatr Orthop ; 26(1): 119-24, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16439915

RESUMEN

The purpose of this study was to determine whether there is a significant association between function and well-being in children with cerebral palsy. To determine this, the authors used validated measures of function (Gillette Functional Assessment Questionnaire, Gross Motor Function Classification System, Gross Motor Function Measure, and walking speed) and correlated them to health-related quality of life (HRQOL) measures (Pediatric Outcomes Data Collection Instrument, Pediatric Quality of Life instrument). In a cross-sectional study of ambulatory children with mild to moderate cerebral palsy aged 10.2 +/- 3.2 years, mild to moderate decreases in function were found when compared with normative data. As the assessment of HRQOL comprises both functional well-being and psychosocial well-being, the authors decided to specify the aspect of well-being to which they were referring. It was found that the child's function was not correlated to psychosocial well-being. The children with mild cerebral palsy had greater effects on their psychosocial well-being than would be predicted by their functional disability. Functional measures were good at predicting the functional well-being but were weak at predicting the psychosocial arm of well-being.


Asunto(s)
Actividades Cotidianas , Parálisis Cerebral/diagnóstico , Parálisis Cerebral/psicología , Bienestar del Niño , Calidad de Vida , Adaptación Fisiológica , Adaptación Psicológica , Adolescente , California , Parálisis Cerebral/terapia , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Índice de Severidad de la Enfermedad , Perfil de Impacto de Enfermedad , Caminata/fisiología
11.
AJR Am J Roentgenol ; 184(1): 55-62, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15615951

RESUMEN

OBJECTIVE: Our purpose was to compare the accuracy of MR cholangiopancreatography and endoscopic sonography for the diagnosis of common bile duct stones in patients with a mild to moderate clinical suspicion of common bile duct stones. SUBJECTS AND METHODS: Forty-seven patients were prospectively enrolled. Inclusion criteria included acute pancreatitis, subclinical jaundice, and clinical features of common bile duct stone migration. Radial endoscopic sonography and MR cholangiopancreatography with the single-shot fast spin-echo technique were performed a maximum of 48 hr apart. The gold-standard diagnosis was obtained with ERCP (n = 20) or intraoperative cholangiography (n = 14) if the results of endoscopic sonography or MR cholangiopancreatography were abnormal or if a cholecystectomy was performed, or by clinical and biochemical follow-up (n = 11) if the results of endoscopic sonography and MR cholangiopancreatography were normal. RESULTS: The final diagnosis was common bile duct stones in 16 patients, malignant obstructions in four, and another biliary disease in two (lithiasis migration aspect with papillary edema); 23 patients had no biliary disease. The sensitivity and specificity of MR cholangiopancreatography were, respectively, 90.5% and 87.5% for etiologic diagnosis and 87.5% and 96.6% for the detection of common bile duct stones. The corresponding values for endoscopic sonography were 86.4% and 91.3% for etiologic diagnosis and 93.8% and 96.6% for visualization of choledocholithiasis. Accuracy did not significantly differ between the techniques. CONCLUSION: In cases of mild to moderate suspicion of choledocholithiasis, the accuracies of endoscopic sonography and MR cholangiopancreatography are similar. Because MR cholangiopancreatography is noninvasive, it may be preferred for this indication.


Asunto(s)
Coledocolitiasis/diagnóstico , Endosonografía , Imagen por Resonancia Magnética , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Coledocolitiasis/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad
12.
Eur J Gastroenterol Hepatol ; 16(8): 743-51, 2004 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15256975

RESUMEN

OBJECTIVES: To determine whether ultrasound and, particularly, new Doppler signs increased the diagnostic accuracy of the most accurate, currently available markers for the diagnosis of cirrhosis or severe fibrosis. METHODS: Thirty-two clinical (n = 4), biochemical (n = 11) and Doppler ultrasound (n = 17) variables were recorded in 106 patients with compensated chronic liver disease. Diagnostic accuracy was evaluated by discriminant analysis; first, globally, using all variables then by stepwise analysis. RESULTS: (A) Diagnosis of cirrhosis. Using Doppler ultrasound, diagnostic accuracy was 92% (95% confidence interval 81-98) globally, and 89% (76-95) with three variables (spleen length, hepatic vein spectrum and maximum portal vein velocity). Based upon clinical signs, diagnostic accuracy was 86% (77-92) globally, and 85% (76-91) with one variable (firm liver). Based upon biochemical parameters, diagnostic accuracy was 80% (70-88) globally, and 81% (72-88) with two variables (hyaluronate and platelet count). Based upon all parameters, diagnostic accuracy was 91% (79-96.5) globally, and 91% (79-96.5) with four variables (firm liver, hyaluronate, platelet and hepatic vein spectrum). On an intention to diagnose basis, Doppler ultrasound provided a lower independent contribution due to missing data. (B) In the diagnosis of severe fibrosis, diagnostic accuracy was 83% (69-92) globally, and 77% (62-87) with one variable. CONCLUSIONS: Cirrhosis can be correctly diagnosed in approximately 90% of patients with compensated chronic liver disease using a few Doppler ultrasound signs including a new sign, the hepatic vein spectrum. Doppler ultrasound could be used for the first line diagnosis and biochemical markers, such as hyaluronate, in patients with missing Doppler ultrasound data.


Asunto(s)
Cirrosis Hepática/diagnóstico por imagen , Hígado/diagnóstico por imagen , Ultrasonografía Doppler , Adulto , Femenino , Fibrosis , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Sensibilidad y Especificidad
13.
J Am Coll Surg ; 194(4): 454-62, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11949751

RESUMEN

BACKGROUND: The aim of this study was to evaluate pancreatogastrostomy (PG) permeability after duodenopancreatectomy (PD) and to determine a correlation with pancreatic endocrine and exocrine functions. STUDY DESIGN: This prospective study included 19 patients who underwent PD with PG between 1992 and 1999. There were 12 men and 7 women, with a mean age of 58 years (range 35 to 76 years). The mean interval between operation and evaluation was 40.3 months (range 3 to 104 months). Indications for pancreatectomy were benign lesions (n = 13) or adenocarcinoma (n = 6). Histology of the pancreatic resection margin was normal in all patients with malignancy, and the pancreatic remnant was macroscopically normal without evidence of obstructive pancreatitis. Pancreatic exocrine and endocrine functions were respectively evaluated by fecal-1 elastase and fasting blood glucose concentrations. PG permeability was determined by secretin magnetic resonance cholangiopancreatography (Secretin-MRCP). RESULTS: Anastomotic permeability was considered good in seven patients (group 1, 36.8%), moderately stenosed in six patients (group 2, 31.6%), significantly stenosed in four patients (group 3, 21.1%), and obstructed in two patients (group 4, 10.5%). Fecal-1 elastase concentration was decreased in 18 patients, with a mean concentration of 80 microg/g in group 1, 98 microg/g in group 2, 67 microg/g in group 3, and 0 microg/g in group 4. There was a statistically significant correlation between Secretin-MRCP group and fecal-1 elastase concentration. Results of fasting glucose estimation were normal for 14 of 19 patients. There was no correlation between pancreatic endocrine function and Secretin-MRCP group. CONCLUSIONS: Exocrine pancreatic insufficiency was presented in 95% of the patients despite a PG permeability in 68.4%. These results may be explained in part by neutralization of pancreatic enzymatic secretions by gastric acid.


Asunto(s)
Imagen por Resonancia Magnética , Páncreas/fisiopatología , Pancreaticoduodenectomía , Secretina , Estómago/cirugía , Insuficiencia Pancreática Exocrina/fisiopatología , Femenino , Estudios de Seguimiento , Gastrostomía , Humanos , Islotes Pancreáticos/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedades Pancreáticas/cirugía , Conductos Pancreáticos/cirugía , Neoplasias Pancreáticas/cirugía , Factores de Tiempo
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