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BACKGROUND: Comparison of operative morbidity rates after pancreatoduodenectomy between units may be misleading because it does not take into account the physiological variable of the condition of the patients. The aim of the present study was to evaluate the Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) for pancreatoduodenectomy patients and to look for risk factors associated with morbidity in a high-volume center. METHODS: Between January 1993 and April 2006, 652 patients underwent a pancreatoduodenectomy, 502 of them for malignant disease. POSSUM performance was evaluated by assessing the "goodness-of-fit" with the linear analysis method. RESULTS: Overall, 332 of the 652 patients (50.9%) had one or more complication after pancreatoduodenectomy, and 9 patients (1.4%) died. POSSUM had a significant lack of fit using goodness-of-fit analysis. In multivariate analysis, one statistically significant factor associated with morbidity and not incorporated in POSSUM (P < 0.05) was identified: ampulla of Vater adenocarcinoma (OR = 1.73, 95% CI: 1.07-2.80). CONCLUSIONS: Overall, there is a lack of calibration of POSSUM among patients who undergo pancreatoduodenectomy.
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Invasividad Neoplásica/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/mortalidad , Complicaciones Posoperatorias/mortalidad , Anciano , Análisis de Varianza , Estudios de Cohortes , Intervalos de Confianza , Supervivencia sin Enfermedad , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Países Bajos , Oportunidad Relativa , Neoplasias Pancreáticas/patología , Pancreaticoduodenectomía/métodos , Cuidados Posoperatorios/métodos , Valor Predictivo de las Pruebas , Cuidados Preoperatorios/métodos , Probabilidad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Análisis de SupervivenciaRESUMEN
INTRODUCTION: Even after potentially curative esophagectomy, the majority of patients with adenocarcinoma of the esophagus or gastroesophageal junction die due to cancer recurrence. To predict individual disease-specific survival, a nomogram has been developed in a high-volume center in the Netherlands. The validity of this nomogram was externally tested in patients treated in another country at a different high-volume institution. METHODS: Clinicopathological data from patients who underwent a macroscopically radical resection in a high-volume center in Leuven, Belgium, were used to validate the original nomogram based on a Cox regression model. Moreover, it was examined whether adjusting the value of the original coefficients of the predictors or adding new predictors would improve the fit of the nomogram in the validation cohort. Calibration was evaluated by comparing the observed survival with the expected survival as predicted by the original nomogram across patients with different risk profiles. The discriminatory ability of the nomogram was determined in the validation cohort, using the concordance index and compared with the original estimate. RESULTS: A total of 382 patients were used in the validation study. The median esophageal cancer-specific survival was 38 months. None of the coefficients re-estimated in the validation cohort differed significantly from the values of the original nomogram. Observed and expected survival curves showed good calibration. Discrimination of the original nomogram was preserved in the validation cohort: the concordance index hardly decreased from 0.77 in the original cohort to 0.76 in the validation cohort. CONCLUSIONS: The nomogram model that was originally developed in a Dutch institute had good individual discriminatory properties and good overall calibration when applied to an independent series of patients. The nomogram was updated using the data from both cohorts to provide even more robust estimates of survival for individual patients. This tool is clinically helpful to supply more reliable prognostic information, to offer tailored follow-up schedules and/or novel therapeutic strategies in subgroups of patients with higher risk of recurrence.
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Adenocarcinoma/mortalidad , Neoplasias Esofágicas/mortalidad , Esofagectomía/mortalidad , Unión Esofagogástrica , Nomogramas , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Unión Esofagogástrica/patología , Femenino , Humanos , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Análisis de SupervivenciaRESUMEN
BACKGROUND/AIMS: To provide a qualitative ranking of clinical variables by surgeons that influence their decision for reoperation and to evaluate whether these variables are related to positive findings at relaparotomy. METHODS: Importance in decision making for relaparotomy was evaluated for 21 factors using a 10-point visual analogue scale (VAS). Variables with median VAS scores >5.0 were labeled 'important'. Predictive value for positive findings was evaluated by multivariate analysis. RESULTS: The response rate was 64%. For each variable, a wide range of VAS scores was given. Of variables labeled 'important', a diffuse extent of abdominal contamination (odds ratio, OR 1.9; 95% CI 0.99-3.8; p = 0.052), localization of the infectious focus (upper gastrointestinal tract including small bowel: OR 2.6, 95% CI 0.98-7.0, p = 0.055; colon: OR 2.4, 95% CI 0.93-6.0, p = 0.071), and both low (<3 x 10(9)/l: OR 4.6, 95% CI 1.3-17, p = 0.021) and high (>20 x 10(9)/l: OR 2.2, 95% CI 1.0-4.9, p = 0.042) leukocyte counts independently predicted positive relaparotomy. As a set, these variables had only moderate predictive accuracy (c-statistic 0.69). CONCLUSIONS: There was no consensus among surgeons which variables were important in decision making for relaparotomy. Only three out of ten variables labeled as 'important' were indeed independently predictive, but even as a set had only moderate predictive accuracy.
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Toma de Decisiones , Laparotomía , Peritonitis/diagnóstico , Peritonitis/cirugía , Adulto , Anciano , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Reoperación , Medición de Riesgo , Factores de RiesgoRESUMEN
SUMMARY: Lymphatic dissemination is the most important prognostic factor in patients with esophageal carcinoma. However, the clinical significance of lymph node micrometastases is still debated due to contradictory results. The aim of the present study was to identify the incidence of potentially relevant micrometastatic disease in patients with histologically node-negative esophageal adenocarcinoma and to analyze the sensitivity and specificity of three different immunohistochemical assays. From a consecutive series of 79 patients who underwent a transthoracic resection with extended 2-field lymphadenectomy, all 20 patients with pN0 esophageal adenocarcinoma were included in this study. A total of 578 lymph nodes were examined for the presence of micrometastases by immunohistochemical analysis with the antibodies Ber-EP4, AE1/AE3 and CAM 5.2. Lymph node micrometastases were detected in five of the 20 patients (25%). They were identified in 16 of the 578 lymph nodes examined (2.8%) and most frequently detected with the Ber-EP4 and AE1/AE3 antibody (sensitivity 95% and 79% respectively). In 114 of the 559 negative lymph nodes (20.4%), positive single cells were found that did not demonstrate malignant characteristics. These false-positive cells were more frequently found with the AE1/AE3 staining (specificity of the Ber-Ep4 and AE1/AE3 antibody 94% and 84% respectively). The presence of nodal micrometastases was associated with the development of locoregional recurrences (P=0.01), distant metastases (P=0.01), and a reduced overall survival (log rank test, P=0.009). For the detection of clinically relevant micrometastatic disease in patients operated upon for adenocarcinoma of the distal esophagus or gastric cardia, Ber-EP4 is the antibody of first choice because of its high sensitivity and specificity. Immunohistochemically detected micrometastases in histologically negative lymph nodes have potential prognostic significance and are associated with a high incidence of both locoregional and systemic recurrence. Therefore, this technique has the potential to refine the staging system for esophageal cancer and to help identify patients who will not be cured by surgery alone.
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Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Unión Esofagogástrica/patología , Ganglios Linfáticos/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Biopsia con Aguja , Distribución de Chi-Cuadrado , Neoplasias Esofágicas/mortalidad , Esofagectomía/métodos , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Probabilidad , Medición de Riesgo , Sensibilidad y Especificidad , Estadísticas no Paramétricas , Análisis de Supervivencia , Toracotomía , Resultado del TratamientoRESUMEN
Authority-based surgery is slowly being replaced by evidence-based surgery. New and existing interventions are increasingly being studied in randomised controlled trials (RCTs). RCTs allow not only for comparison of different types of surgical interventions but also for comparison with non-surgical interventions and adjuvant therapies. Surgical RCTs have many methodological limitations, such as inherent difficulties with randomisation and blinding, and ethical limitations in using placebo controls. Choosing appropriate intervention groups, providing adequate training for participating surgeons and ensuring a high volume per surgeon reduces the risk of complications due to inexperience. Unplanned cross-over is a potential source of bias in explanatory RCTs comparing surgical interventions. Conducting a surgical RCT requires good collaboration between large and small hospitals due to organisational complexity, ethical limitations, funding and long term follow-up. Acceptance and implementation of the results from surgical RCTs through evidence-based guidelines depends heavily on local opinion leaders and the training of surgical residents.
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Medicina Basada en la Evidencia , Cirugía General/normas , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Países BajosRESUMEN
BACKGROUND: The aims of the present study were to validate the Physiological and Operative Severity Score for the enUmeration of Mortality adjusted for oesophagogastric surgery (O-POSSUM). METHODS: Data on patients who underwent potentially curative oesophagectomy in a tertiary referral centre for adenocarcinoma or squamous cell carcinoma of the oesophagus were analysed. The in-hospital mortality predicted by O-POSSUM was compared with the actual value by linear analysis. RESULTS: Twenty-four (3.6 per cent) of 663 patients died in hospital. The observed : predicted ratio for in-hospital mortality was 0.29. The model had a poor fit (P < 0.001). The area under the receiver-operator characteristic curve was 0.60 (95 per cent confidence interval 0.47 to 0.72); P = 0.113). O-POSSUM score was not related to the severity of complications. CONCLUSION: O-POSSUM overpredicted in-hospital mortality threefold and could not identify patients at higher risk of death. O-POSSUM needs substantial modification before it can be used for comparison of treatment outcomes between centres.
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Adenocarcinoma/mortalidad , Carcinoma de Células Escamosas/mortalidad , Neoplasias Esofágicas/mortalidad , Esofagectomía/mortalidad , Mortalidad Hospitalaria , Índice de Severidad de la Enfermedad , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
AIMS: This study aimed to analyse the current outcome after palliative surgical drainage of malignant biliary obstruction. METHOD: From 1992 to 2003, perioperative parameters and the incidence and indications of readmissions were analysed in 269 patients who underwent a palliative biliary bypass for periampullary carcinoma. RESULTS: Hospital mortality occurred in seven patients and median postoperative stay was 10 days. Anastomotic leakage occurred in three patients and intraabdominal haemorrhage in eight patients. Overall 75 patients experienced a complication. Nine patients underwent a relaparotomy during initial hospital admission. Overall, 142 patients were readmitted, 13 for indications related to the biliary bypass, 11 for surgery-related indications. Twenty-five patients were readmitted for radiochemotherapy, 112 for progressive disease and 23 for indications not related to the disease. Median survival was 7.5 months and the 3-year survival 3%. Survival was significantly lower in patients with metastases and in those who underwent elective bypass for gastric outlet obstruction. CONCLUSION: Current hospital mortality after palliative biliary bypass as well as readmission rates for complications related to the biliary bypass or surgical procedure are low. Surgical biliary bypass is a safe and effective palliative treatment for patients with malignant biliary obstruction.
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Ampolla Hepatopancreática/cirugía , Carcinoma/complicaciones , Colestasis Extrahepática/cirugía , Enfermedades del Conducto Colédoco/cirugía , Neoplasias del Conducto Colédoco/complicaciones , Drenaje , Cuidados Paliativos , Anastomosis Quirúrgica/efectos adversos , Quimioterapia Adyuvante , Colestasis Extrahepática/etiología , Enfermedades del Conducto Colédoco/etiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Laparotomía , Tiempo de Internación , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Hemorragia Posoperatoria/etiología , Radioterapia Adyuvante , Reoperación , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To analyse the volume-outcome effect of pancreatic surgery by means of a systematic review, and to determine the effect of the ongoing plea for centralisation of pylorus-preserving pancreaticoduodenectomy in the Netherlands. DESIGN: Systematic review and retrospective evaluation. METHOD: A systematic search for studies comparing hospital mortality rates after pancreatic resection in high- and low-volume hospitals was conducted. The studies were independently assessed regarding design, inclusion criteria, threshold value for high and low volume and primary hospital mortality outcome. Data were obtained from the Dutch nation-wide registry on the mortality outcome of pancreaticoduodenectomy in 1994-2003. Hospitals were divided into 4 categories based on the number of pancreaticoduodenectomies performed. The effect of the ongoing plea for centralisation was analysed. RESULTS: Twelve observational studies comprising a total of 19,688 patients were included. Because the studies were too heterogeneous to allow a meta-analysis, a qualitative analysis was performed. The relative risk of dying in a high-volume hospital compared with a low-volume hospital was between 0.07 and 0.76 and was inversely proportional to the arbitrarily defined volume cut-off values. Various analyses conducted over a to-year period in the Netherlands reported mortality rates of 14-17% in hospitals that performed fewer than 5 pancreaticoduodenectomies per year, compared with rates of 0.0-3.50 degrees h in hospitals that performed more than 24 pancreaticoduodenectomies per year. The percentage of patients undergoing surgery in hospitals with a volume less than ro pancreaticoduodenectomies per year was 57% in 2000-2003 (454/792), compared with 65% (280/428) in 1994-1995. CONCLUSION: This systematic review provided evidence of an inverse relationship between hospital volume and mortality after pancreaticoduodenectomy and confirmed the value of centralisation of this procedure in high-volume hospitals. The 10-year-long plea of the Dutch surgical community for quality assessment and, if necessary, centralisation has not resulted in a reduction in mortality rates after pancreatic resection or a change in referral patterns in The Netherlands.
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PURPOSE: To assess 3 years of quality of life in patients with esophageal cancer in a randomized trial comparing limited transhiatal resection with extended transthoracic resection. PATIENTS AND METHODS: Quality-of-life questionnaires were sent at baseline and at 5 weeks; 3, 6, 9, and 12 months; and 1.5, 2, 2.5, and 3 years after surgery. Physical and psychological symptoms, activity level, and global quality of life were assessed with the disease-specific Rotterdam Symptom Checklist. Generic quality of life was measured with the Medical Outcomes Study Short Form-20. RESULTS: A total of 199 patients participated. Physical symptoms and activity level declined after the operation and gradually returned toward baseline within the first year (P < .01). Psychological well-being consistently improved after baseline (P < .01), whereas global quality of life showed a small initial decline followed by continuous gradual improvement (P < .01). Quality of life stabilized in the second and third year. Three months after the operation, patients in the transhiatal esophagectomy group (n = 96) reported fewer physical symptoms (P = .01) and better activity levels (P < .01) than patients in the transthoracic group (n = 103), but no differences were found at any other measurement point. For psychological symptoms and global quality of life, no differences were found at any follow-up measurement. A similar pattern was found for generic quality of life. CONCLUSION: No lasting differences in quality of life of patients who underwent either transhiatal or transthoracic resection were found. Compared with baseline, quality of life declined after the operation but was restored within a year in both groups.
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Adenocarcinoma/fisiopatología , Adenocarcinoma/psicología , Neoplasias Esofágicas/fisiopatología , Neoplasias Esofágicas/psicología , Esofagectomía/métodos , Calidad de Vida , Adulto , Anciano , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
PURPOSE: The extent of lymph node dissection appropriate for gastric cancer is still under debate. We have conducted a randomized trial to compare the results of a limited (D1) and extended (D2) lymph node dissection in terms of morbidity, mortality, long-term survival and cumulative risk of relapse. We have reviewed the results of our trial after follow-up of more than 10 years. PATIENTS AND METHODS: Between August 1989 and June 1993, 1,078 patients with gastric adenocarcinoma were randomly assigned to undergo a D1 or D2 lymph node dissection. Data were collected prospectively, and patients were followed for more than 10 years. RESULTS: A total of 711 patients (380 in the D1 group and 331 in the D2 group) were treated with curative intent. Morbidity (25% v 43%; P <.001) and mortality (4% v 10%; P =.004) were significantly higher in the D2 dissection group. After 11 years there is no overall difference in survival (30% v 35%; P =.53). Of all subgroups analyzed, only patients with N2 disease may benefit of a D2 dissection. The relative risk ratio for morbidity and mortality is significantly higher than one for D2 dissections, splenectomy, pancreatectomy, and age older than 70 years. CONCLUSION: Overall, extended lymph node dissection as defined in this study generated no long-term survival benefit. The associated higher postoperative mortality offsets its long-term effect in survival. For patients with N2 disease an extended lymph node dissection may offer cure, but it remains difficult to identify patients who have N2 disease. Morbidity and mortality are greatly influenced by the extent of lymph node dissection, pancreatectomy, splenectomy and age. Extended lymph node dissections may be of benefit if morbidity and mortality can be avoided.
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Adenocarcinoma/cirugía , Escisión del Ganglio Linfático , Neoplasias Gástricas/cirugía , Adenocarcinoma/mortalidad , Factores de Edad , Anciano , Análisis de Varianza , Femenino , Gastrectomía , Humanos , Masculino , Países Bajos/epidemiología , Pancreatectomía , Complicaciones Posoperatorias/epidemiología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Riesgo , Esplenectomía , Neoplasias Gástricas/mortalidad , Tasa de SupervivenciaRESUMEN
Survival data of patients with pancreatic carcinoma are often overestimated because of incomplete follow-up. Therefore, the aim of this study was to approach complete follow-up and to analyse survival and prognostic factors of patients who underwent surgical treatment for pancreatic adenocarcinoma. Between 1992 and 2002, 343 patients underwent surgical treatment for pancreatic adenocarcinoma. One hundred and sixty patients underwent a resection with a curative intention and 183 patients underwent bypass surgery for palliation. Follow-up was complete for 93% of patients. Median survival after resection and bypass was 17.0 and 7.5 months, and 5-year survival was 8% and 0, respectively. In multivariate analysis, tumour-positive lymph nodes, non-radical surgery, poor tumour differentiation, and tumour size were independent prognostic factors for survival after resection. For patients treated with bypass surgery, metastatic disease and tumour size independently predicted survival. In conclusion, actual survival of patients with pancreatic adenocarcinoma is disappointing compared with the actuarial survival rates reported in the literature. The independent prognostic factors for survival of patients who underwent surgical treatment for pancreatic adenocarcinoma are tumour-related.
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Adenocarcinoma/cirugía , Neoplasias Pancreáticas/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Pancreaticoduodenectomía/mortalidad , Pronóstico , Radioterapia Adyuvante , Análisis de Regresión , Análisis de SupervivenciaRESUMEN
Significant prolongation of survival of nonrelated DLA-mismatched renal allografts has been obtained in beagle recipients receiving three blood transfusions from nonrelated donors prior to kidney transplantation and immunosuppression after transplantation. Nontransfused DLA-identical or DLA 1 haplotype-different littermates of the transfused dogs were used as controls. Lymphocytotoxic antibodies were formed after the blood transfusions. A quantitative immune reactivity score correlated with graft survival. Low scores prior to transplantation were found in five transfused dogs that did not reject their allografts. High scores prior to transplantation were found in four animals rejecting their graft and in one dog that survived after an abortive rejection episode. The great similarities between the results obtained in this animal model and the observations made in human transplant patients indicate that this model can be utilized for a further analysis of the possibilities of blood transfusions in protecting subsequent renal allografts from immunological rejection.
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Transfusión Sanguínea , Supervivencia de Injerto , Antígenos de Histocompatibilidad , Prueba de Histocompatibilidad , Trasplante de Riñón , Animales , Formación de Anticuerpos , Perros , Femenino , Rechazo de Injerto , Inmunosupresores/farmacología , Riñón/patología , Masculino , Mortalidad , Factores de Tiempo , Trasplante HomólogoRESUMEN
The influence of subregions of the canine major histocompatibility complex (MHC) on renal allograft survival is assessed in recipients without immunosuppressive therapy. Results in six beagle littermate donor-recipient pairs in which the donor or recipient had a recombination in the MHC are compatible with the concept of a predominant role for the subregion containing the major mixed lymphocyte reaction (MLR) locus in determining allograft survival. Results in unrelated mongrel dogs indicate that compatibility for MLR induces a longer kidney allograft survival than compatibility for the serologically defined (SD) antigens. However, the effect of combined matching for MLR and SD antigens in unrelated donor-recipient pairs is slight in comparison to the effect of MLR and/or SD matching in littermate-related dogs. This indicates that other important histocompatibility systems probably exist in this species.
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Perros/genética , Supervivencia de Injerto , Inmunoterapia , Trasplante de Riñón , Complejo Mayor de Histocompatibilidad , Animales , Prueba de Histocompatibilidad , Prueba de Cultivo Mixto de Linfocitos , Recombinación Genética , Trasplante HomólogoRESUMEN
Renal allografting was performed between DLA-identical beagle littermates without immunosuppressive treatment. One transfusion of 200 ml of parental blood donor to induce the formation of antibodies against non-DLA antigens that might enhance renal graft survival. Kidney graft survival times of transfused dogs were compared with the survival times of transfused dogs were compared with the survival times of transfused dogs were compared with the survival times of DLA-identical nontransfused littermates. Blood transfusions did not have a significant influence on the median graft survival time. Antibodies against the kidney donor lymphocytes were not demonstrated after blood transfusion. However, antibodies were induced in three of the six animals tested as shown by the reactivity of the sera of these animals against a lymphocyte panel. Antibodies occurred in animals with long-term as well as short-term surviving grafts.
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Transfusión Sanguínea , Supervivencia de Injerto , Antígenos de Histocompatibilidad/inmunología , Trasplante de Riñón , Animales , Pruebas Inmunológicas de Citotoxicidad , Perros , Factores de TiempoRESUMEN
The relevance of matching for the serologically defined (SD) and lymphocyte-defined (LD) antigens of the major histocompatibility complex (MHC) for renal allograft survival was evaluated in a dog model. Kidney recipients were treated with a standard regimen of immunosuppressive drugs (azathioprine, 2 mg/kg body wt, and prednisolone, 1 mg/kg body wt, daily i.v.) after transplantation. In seven of the eight SD- and LD-identical beagle littermate donor-recipient pairs (DRPs), and in all seven SD- and LD-identical beagle nonlittermate DRPs, kidney function remained normal for the period of 150 days during which immunosuppressants were given. Of the 8 beagle littermate DRPs differing in one haplotype and all 25 unrelated mismatched mongrel DRPs, kidney function deteriorated during immunosuppressive therapy, and most of the recipients died eventually from graft rejection. Thus, it seems that, in moderately immunosuppressive dogs, non-DLA incompatibilities rarely, if ever, cause rejection, whereas DLA incompatibilities almost always do so. The data differ from those obtained in a previous study in nonimmunosuppressed dogs, in which non-DLA incompatibilities seemed to be as strong as DLA incompatibilities in this respect. Differences in minor histocompatibility antigens can apparently be overcome more easily by immunosuppressive drug therapy than differences in major histocompatibility antigens. After the gradual complete withdrawal of immunosuppression, 11 of the 15 matched littermate and nonlittermate DRPs survived for another 150 days or more, implying that some kind of unresponsiveness was induced in those dogs.
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Supervivencia de Injerto/inmunología , Prueba de Histocompatibilidad/métodos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Animales , Perros , Supervivencia de Injerto/efectos de los fármacos , Terapia de Inmunosupresión/métodos , Trasplante de Riñón/mortalidad , Prueba de Cultivo Mixto de Linfocitos , Factores de Tiempo , Trasplante Homólogo/inmunologíaRESUMEN
A single transfusion of 200 ml of donor blood 14 days before renal transplantation in prospectively DL-A tissue typed beagle littermates appeared to have an effect on graft survival. Seventeen per cent of the recipients did respond to the transfusion with formation of lymphocytotoxic and haemagglutinating antibodies. These "responder dogs" rejected kidney grafts in an accelerated way, compared with the "nonresponders" and with the nontreated control dogs. Responsiveness appeared to occur in pairs of littermates, which suggests that responding potency is genetically determined. There was histological evidence of acute arteritis in the renal grafts of responders, whereas cell-mediated rejection was noted in nonresponders.
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Transfusión Sanguínea , Rechazo de Injerto , Histocompatibilidad , Trasplante de Riñón , Trasplante Homólogo , Animales , Creatinina/sangre , Pruebas Inmunológicas de Citotoxicidad , Perros , Pruebas de Hemaglutinación , Prueba de HistocompatibilidadRESUMEN
Previous studies from our laboratory have already shown that pretransplant blood transfusions from third-party donors significantly prolong kidney allograft survival in mismatched unrelated immunosuppressed dogs. In the present study, a similar effect was found in related donor-recipient pairs mismatched for two haplotypes (P less than 0.05); no significant effect was observed in one-haplotype-mismatched combinations (P = 0.34). Pretransplant blood transfusions did not have a beneficial influence on kidney allograft survival in immunosuppressed DLA-identical, related donor recipient pairs. After withdrawal of immunosuppressive therapy, transfused dogs in this group rejected their kidneys even more frequently than did nontransfused dogs (P = 0.16). A comparable undesired effect of blood transfusions was found for recipients of unrelated kidneys which were identical with respect to DLA-A, B, and D: transfused recipients of those kidneys rejected the graft significantly more often than the untransfused controls (P less than 0.01). The most likely explanation for this adverse effect is that blood transfusions given to the recipient may cause crossimmunization for undefined, probably minor, antigens of the donor kidney. Apparently, differences arising from these minor histocompatibility antigens become manifest only after withdrawal of the immunosuppressive therapy. Furthermore, it appeared that the effect of histocompatibility matching on kidney allograft survival is less for transfused than for untransfused dogs. The most important conclusion is, however, that the beneficial effect of blood transfusions appears to be dependent on the degree of matching: while blood transfusions are on the whole beneficial for unmatched kidneys, they are likely to have no effect, or even to be harmful, for matched kidneys.
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Transfusión Sanguínea , Supervivencia de Injerto , Trasplante de Riñón , Animales , Azatioprina/uso terapéutico , Perros , Prueba de Histocompatibilidad , Inmunosupresores/uso terapéutico , Prueba de Cultivo Mixto de Linfocitos , Complejo Mayor de Histocompatibilidad , FenotipoRESUMEN
The relationships between immune reactivity after blood transfusions, subsequent kidney allograft survival, and donor selection were studied in dogs. Animals with a high as well as low serological immune reactivity toward antigens contained in blood transfusion were observed. Genetic control of this reactivity or a linkage of this property to DLA, sex, or red blood cell markers inheritance was not apparent in the four beagle families studied. The two recipients with the lowest immune reactivity scores were also found to be the longest survivors after a DLA-mismatched kidney graft. Seven other recipients with higher scores rejected their DLA-mismatched kidneys as rapidly as did untransfused animals. Kidney graft survival was decreased in some recipients of DLA-identical kidneys (n = 5), presumably through sensitization for minor histocompatibility antigens. A normal or an increased survival time of DLA-identical kidneys was found in the remaining animals (n = 6). The majority of these recipients appeared to have a higher than average reactivity in two-stage microcytotoxicity testing. This might have been attributable to the presence of enhancing antibodies. Further studies in preclinical animal models are needed to define the optimal transfusion policy for human patients awaiting a kidney graft.
Asunto(s)
Transfusión Sanguínea , Supervivencia de Injerto , Trasplante de Riñón , Animales , Formación de Anticuerpos , Perros , Eritrocitos/inmunología , Femenino , Antígenos de Histocompatibilidad/genética , Isoantígenos/genética , Masculino , Factores de Tiempo , Trasplante HomólogoRESUMEN
Activated Kupffer cells (KC) have been implicated in the damage sustained by preserved liver grafts during ischemia and reperfusion. The aim of this study was to compare ischemia/reperfusion injury in preserved, KC-depleted rat livers and preserved control livers, with special regard to sinusoidal endothelial cell (SEC) injury. Wistar rats were injected with liposome-encapsulated dichloromethylene diphosphonate, 48 hr before hepatectomy, to eliminate KC, or were withheld this pretreatment (controls). Livers were flushed with cold University of Wisconsin solution and after 0, 8, 16, or 24 hr of storage at 4 degrees C, were reperfused in a recirculation system with 200 ml of oxygenated Krebs-Henseleit solution at 37 degrees C for 90 min. Damage to SEC was measured by the uptake of hyaluronic acid (HA) from the perfusate and release of purine nucleoside phosphorylase (PNP). Perfusate samples were, furthermore, analyzed for aspartate aminotransferase (AST) and tumor necrosis factor-alpha. Carbon particles were infused in the perfusate to determine the phagocytotic capacity of KC. Biopsies were taken for histological examination and sections were stained with ED2 monoclonal antibodies to confirm the absence of KC. After 90 min of reperfusion, immediately after cold flush (t0), the uptake of HA was 72.2+/-2.3% and 69.3+/-1.3% in KC-depleted livers and in control livers, respectively (n.s.). After 8 hr of storage, HA uptake was 21.6+/-4.5% and 34.6+/-8.0%, respectively (n.s.). After 16 and 24 hr of storage and reperfusion, no uptake of HA was found in either KC-depleted or control livers, indicating abolished SEC function. PNP activities in the perfusate were higher in control livers (after 8 and 24 hr of storage), presumably due to release from damaged KC. No difference was found in AST and no tumor necrosis factor-alpha was measured in the perfusates of normal and KC-depleted livers. Electron microscopic studies showed that after 8 and 24 hr of storage and reperfusion, KC were activated and were able to phagocytose colloidal carbon. Our conclusion was that the elimination of Kupffer cells did not result in reduction of ischemic and reperfusion damage in livers preserved up to 24 hr, as assessed in vitro by SEC uptake of HA, PNP release, and AST release.
Asunto(s)
Frío , Macrófagos del Hígado , Trasplante de Hígado/efectos adversos , Preservación de Órganos , Daño por Reperfusión/etiología , Animales , Aspartato Aminotransferasas/metabolismo , Separación Celular , Femenino , Ácido Hialurónico/metabolismo , Inmunohistoquímica , Hígado/metabolismo , Hígado/fisiopatología , Hígado/ultraestructura , Trasplante de Hígado/patología , Microscopía Inmunoelectrónica , Preservación de Órganos/métodos , Purina-Nucleósido Fosforilasa/metabolismo , Ratas , Ratas Wistar , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Of the 172 patients with carcinoma of the esophagus or the gastro-esophageal junction seen between January 1978 and January 1981, 69 patients had combined treatment, radiotherapy and resection, and 38 had curative radiotherapy. The remaining 65 were treated palliatively. The 4-year actuarial survival of the first two treatment groups was respectively 40% and 4%. The resectability rate of the operated patients was 84% with a post-operative mortality of 20%. The tumor size and sex were two important prognostic factors. Patients with combined treatment and a tumor size of less than two corresponding underlying vertebrae, had a 4-year actuarial survival of 60%.