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OBJECTIVE: Cytokine release syndrome is suggested to be the most important mechanism triggering acute respiratory distress syndrome and end organ damage in COVID-19. The severity of disease may be measured by different biomarkers. METHODS: We studied markers of inflammation and coagulation as recorded in 29 patients on admission to the hospital in order to identify markers of severe COVID-19 and need of ICU. RESULTS: Patients who were eventually admitted to ICU displayed significantly higher serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. No statistical differences were found between the groups in median levels of lymphocytes, D-dimer or ferritin. CONCLUSIONS: IL-6 and CRP were the strongest predictors of severity in hospitalized patients with COVID-19.
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COVID-19/sangre , COVID-19/diagnóstico , Interleucina-6/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
There is an increasing need for novel biomarkers that enable better diagnostic and prognostic stratification of patients with suspected infection. A proprotein convertase enzyme FURIN is upregulated upon immune cell activation, and it promotes infectivity by cleaving and activating pathogens. In this study, we determined FURIN levels in plasma using ELISA from 537 patients that were admitted to emergency room with suspected infection. Patients were sorted to high- and low-level FURIN groups with a cut-off level of 370 pg/ml. The study cohort included five diagnostic groups: Group 1, no systemic inflammatory response syndrome (SIRS, n = 59 patients); Group 2, bacterial infection without SIRS (n = 67); Group 3, SIRS, but no bacterial infection (n = 308); Group 4, sepsis without organ failure (n = 308); and Group 5, severe sepsis (n = 49). Statistically significant associations were not found between the plasma level of FURIN and the prevalence of sepsis (P = 0.957), diagnostic group of a patient (P = 0.737) or the bacteria in blood culture (P = 0.499). Additionally, the concentration of FURIN did not predict the severity or case fatality of the infectious disease. However, statistically significant associations were found between high plasma level of FURIN and diagnosed rheumatic disease (P < 0.001) as well as with the prevalence of non-smokers (P = 0.034). Thus, albeit the plasma level of FURIN does not predict the severity of infectious disease, it may be of use in the diagnostics of autoimmune diseases.
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Enfermedades Autoinmunes/diagnóstico , Infecciones Bacterianas/diagnóstico , Furina/sangre , Sepsis/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/sangre , Infecciones Bacterianas/sangre , Infecciones Bacterianas/complicaciones , Biomarcadores/sangre , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedades Reumáticas/sangre , Sepsis/sangre , Sepsis/complicaciones , Adulto JovenRESUMEN
OBJECTIVES: The soluble form of urokinase-type plasminogen activator (suPAR) was evaluated as an early prognostic marker of sepsis in patients with suspected infection. DESIGN: A single-centre prospective cohort study. METHODS: The cohort comprised 539 patients in the emergency department with suspected infection: 59 without systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 68 with bacterial infection and without SIRS (group 2), 54 with SIRS and without bacterial infection (group 3), 309 with sepsis (SIRS and bacterial infection) and without organ failure (group 4) and 49 with severe sepsis (SIRS, bacterial infection and organ failure) (group 5). suPAR was measured on admission using a commercial solid-phase enzyme-linked immunosorbent assay. RESULTS: The median soluble form of the receptor (suPAR) concentrations in groups 1-5 were 4.7, 5.0, 4.4, 4.8 and 7.9 ng mL(-1) , respectively (P < 0.001). The levels were significantly higher in nonsurvivors compared with survivors (8.3 vs. 4.9 ng mL(-1) , P < 0.001) and in patients with severe sepsis (group 5) compared with those in the other groups (7.9 vs. 4.8 ng mL(-1) , P < 0.001). Area under the receiver operating characteristics curve (AUC(ROC) ) for the prediction of case fatality was 0.79 (95% confidence interval [CI]: 0.72-0.86, P < 0.0001) and 0.75 for severe sepsis (95% CI: 0.68-0.81, P < 0.0001). At a cut-off level of 6.4 ng mL(-1) , suPAR had 76% sensitivity and 69% specificity for fatal disease; at a cut-off level of 6.6 ng mL(-1) , the sensitivity and specificity for severe sepsis were 67% and 72%, respectively. In multivariate models, high suPAR remained an independent predictor of case fatality and severe sepsis after adjusting for potential confounders. CONCLUSIONS: A high suPAR level predicts case fatality and severe sepsis in patients with suspected infection.
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Infecciones Bacterianas/diagnóstico , Sepsis/diagnóstico , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Activador de Plasminógeno de Tipo Uroquinasa/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Infecciones Bacterianas/sangre , Infecciones Bacterianas/mortalidad , Biomarcadores/sangre , Calcitonina/sangre , Servicio de Urgencia en Hospital , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Estudios Prospectivos , Precursores de Proteínas/sangre , Curva ROC , Sensibilidad y Especificidad , Sepsis/sangre , Sepsis/mortalidad , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/mortalidad , Adulto JovenRESUMEN
OBJECTIVES: To study whether levofloxacin, added to standard treatment, could reduce the high mortality and complication rates in Staphylococcus aureus bacteraemia. DESIGN: A prospective randomized multicentre trial from January 2000 to August 2002. SETTING: Thirteen tertiary care or university hospitals in Finland. SUBJECTS: Three hundred and eighty-one adult patients with S. aureus bacteraemia. Patients with meningitis, and those with fluoroquinolone- or methicillin-resistant S. aureus were excluded. INTERVENTIONS: Standard treatment (mostly semisynthetic penicillin) (n = 190) or that combined with levofloxacin (n = 191). Supplementary rifampicin was recommended if deep infection was suspected. MAIN OUTCOME MEASURES: Primary end-points were mortality at 28 days and at 3 months. Clinical and laboratory parameters were analysed as secondary end-points. RESULTS: Adding levofloxacin to the standard treatment offered no survival benefit. Case fatality rates were 14% in both groups at 28 days, and 21% in the standard treatment and 18% in the levofloxacin group at 3 months. Levofloxacin combination did not differ from the standard treatment in the number of complications, time to defervescence, decrease in serum C-reactive protein concentration or length of antibiotic treatment. Deep infection was found in 84% of patients within 1 week following randomization with no difference between the treatment groups. At 3 months, the case fatality rate for patients with deep infection was 17% amongst those who received rifampicin versus 38% for those without rifampicin (P < 0.001, odds ratio = 3.06, 95% confidence intervals = 1.69-5.54). CONCLUSIONS: Levofloxacin combined with standard treatment in S. aureus bacteraemia did not decrease mortality or the incidence of deep infections, nor did it speed up recovery. Interestingly, deep infections in S. aureus bacteraemia appeared to be more common than previously reported.
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Antibacterianos/uso terapéutico , Levofloxacino , Ofloxacino/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/mortalidad , Staphylococcus aureus , Adulto , Anciano , Bacteriemia/tratamiento farmacológico , Bacteriemia/mortalidad , Distribución de Chi-Cuadrado , Quimioterapia Combinada , Femenino , Finlandia , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Penicilinas/uso terapéutico , Estudios Prospectivos , Rifampin/uso terapéutico , Sepsis/tratamiento farmacológico , Sepsis/mortalidad , Insuficiencia del TratamientoRESUMEN
Tumor-associated trypsin inhibitor (TATI) is a marker of mucinous ovarian carcinoma, but it is also widely expressed in other malignant tumors and normal human tissues. Elevated serum concentrations of TATI are of prognostic value in ovarian, kidney, and bladder cancer. Tumor-associated trypsin is co-expressed with TATI in many malignancies and is thought to be involved in tumor invasion. TATI mRNA has been shown to be overexpressed in bladder cancer. We therefore studied whether trypsinogen expression also can be detected in bladder cancer and how this and TATI expression are associated with the clinicopathological characteristics of the tumors. We used RT-PCR, in situ hybridization and immunohistochemistry to detect trypsinogen- and TATI mRNA and protein in tissue samples from 28 bladder cancer patients and ten benign urothelia. TATI expression was detected in all benign tissues and non-invasive tumors. However, the expression was lower in the muscle-invasive tumors (pT2; n=5), whereas trypsinogen expression was seen in all but one non-invasive tumor. We conclude that trypsinogen is expressed in both malignant and benign bladder epithelium, whereas TATI expression decreases with increasing stage and grade of the tumor. This may suggest that a balanced expression of TATI and trypsinogen is required in normal tissue and that this balance is disrupted during tumor progression.
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Inhibidor de Tripsina Pancreática de Kazal/biosíntesis , Tripsinógeno/biosíntesis , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Transformación Celular Neoplásica , Progresión de la Enfermedad , Epitelio , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE AND DESIGN: The effect of the granulocyte colony-stimulating factor filgrastim on systemic inflammation was investigated in a prospective, randomized, placebo-controlled, double-blind study in critically ill patients. SUBJECTS: 59 critically ill patients were recruited within 48 h of intubation due to ventilatory insufficiency. TREATMENT: Subcutaneous dosage of placebo or 300 microg filgrastim once daily. METHODS: Serum samples were collected at study entry, and 1 and 3 days after the start (Day1 and Day3, respectively). Levels of soluble E-selectin (sE-selectin) and interleukin (IL)-10 were determined by ELISA, and those of IL-6, and soluble IL-2 receptor (sIL-2R) by Immulite chemiluminescence immunoassay. RESULTS: The median sE-selectin level decreased by day 3 significantly in the control group but not in the filgrastim group. The difference in the change between the study groups was significant (p = 0.049). IL-10 levels decreased significantly in the filgrastim group, tended to decrease in controls (p = 0.052), and the difference in the change tended to be significant (p = 0.058). IL-6 levels decreased in both groups comparably. sIL-2R levels were elevated and stable. CONCLUSIONS: Filgrastim prolongs endothelial activation and possibly inhibits development of immune suppression mediated by IL-10.
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Enfermedad Crítica/terapia , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Inflamación/inmunología , Adulto , Anciano , Biomarcadores , Recuento de Células Sanguíneas , Femenino , Humanos , Inflamación/sangre , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: On behalf of the European Association of Urology (EAU) guidelines for diagnosis, therapy and follow-up of upper urinary tract transitional cell carcinoma (UUTT) patients were established. Criteria for recommendations are based of level 2 only, as large randomised clinical trials have not been performed in this type of disease. METHOD: A systematic literature research using Medline Services was conducted. References were weighted by a panel of experts. RESULTS: TNM classification 2002 is recommended. Recommendations are developed for diagnosis, radical and conservative treatment and for local chemo-immunotherapy. Prognostic factors are defined. Recommendations for follow-up after different types of treatment are given.
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Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/terapia , Neoplasias Renales/diagnóstico , Neoplasias Renales/terapia , Neoplasias Ureterales/diagnóstico , Neoplasias Ureterales/terapia , Carcinoma de Células Transicionales/clasificación , Carcinoma de Células Transicionales/secundario , Estudios de Seguimiento , Humanos , Neoplasias Renales/clasificación , Pronóstico , Factores de Riesgo , Neoplasias Ureterales/clasificaciónRESUMEN
The purpose of the study was to determine, in addition to well-known prognostic factors, histological grade, stage, tumour size and multiplicity, the correlation of BTA stat Test on disease free interval (DFI) on primary superficial bladder cancer. A total of 116 patients with newly diagnosed bladder cancer were evaluated in a prospective multicentre study. A voided urine sample was obtained prior to TURB and split for culture, cytology and BTA stat testing. Follow-up data for the patients were collected until the first recurrence or the last visit and the DFI was analysed by Kaplan-Meier method and Cox analysis. Ninety-seven of the 116 (83.6%) patients were eligible for analysis. The BTA stat Test was positive in 73 (75.3%) patients, whereas cytology detected 20 (20.6%) cases. The DFI was found to be shorter among patients with a positive BTA stat Test, and also among those with intermediate or high-grade tumours. The BTA stat Test result divided patients with grade 2 tumours into two prognostic groups, in that those testing positive had 68.6% risk of recurrence during the first year compared to 42.9% risk of those with a negative test result (P = 0.041). Although the effect of tumour size on DFI was notable, the difference did not reach statistical significance (P = 0.064). Number of tumours was not related to DFI, nor was the difference between different stage of tumour of significance. BTA stat Test is not only sensitive in detection of primary bladder cancer, but also might have some independent prognostic significance.
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Biomarcadores de Tumor/análisis , Carcinoma de Células Transicionales/patología , Factor H de Complemento/análisis , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/análisis , Carcinoma de Células Transicionales/genética , Cromatografía , Factor H de Complemento/genética , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunoensayo , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
OBJECTIVE: This study aimed to evaluate the results of vasovasostomies performed in the authors' clinic over 15 years. MATERIAL AND METHODS: Between 1983 and 1998 39 vasovasostomies were performed using a macroscopic technique. The medical charts were reviewed and a postal survey was sent to 36 of these patients. The patients were invited to visit the outpatient department and to give semen for analysis and a blood sample for determination of serum antisperm antibodies and serum follicle-stimulating hormone. Twenty-five patients filled in the questionnaire and 10 patients were obtained for further semen and serum analyses. RESULTS: The overall pregnancy rate was 56% (14/25 respondents). Three of these 14 men used an assisted reproduction method with their own ejaculated sperm. The postoperative patency was recorded in the medical charts only sporadically. The age and the interval between the vasectomy and vasectomy reversal averaged 42 years and 8.6 years, respectively. Those men who could father a child had a somewhat shorter mean obstructive interval than those who failed (8.0 vs 9.3 years), although the difference was not statistically significant in this small patient sample. The serum follicle-stimulating hormone concentrations were normal, with no association with the pregnancy rate. CONCLUSION: Macroscopic vasovasostomy is an effective means of re-establishing fertility in vasectomized men.
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Vasovasostomía , Adulto , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
The Nordic Urological Association Urothelial Group has been organizing phase 3 trials in urinary bladder cancer therapy since 1986. In total, around 1,000 patients from three countries have entered these studies. The results of the different trials are reviewed, and the problems with cooperative trials are discussed. The importance of these kind of trials in setting up management guidelines is underscored.
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Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias de la Vejiga Urinaria/terapia , Finlandia , Humanos , Cooperación Internacional , SueciaRESUMEN
Group II phospholipase A2 (PLA2-II), procalcitonin (PCT) and C-reactive protein (CRP) are useful indicators of the severity of inflammation in various infections. To compare their discriminatory abilities at an early phase of bacteremia, PLA2-II, PCT and CRP were measured upon admission and 24-48 h thereafter in 29 patients with bacteremia, non-bacteremic bacterial or viral infections. The levels of PLA2-II and PCT were higher in bacteremia than in non-bacteremic bacterial or viral infections. PCT was highest upon admission, PLA2-II peaked at 12-24h, whereas CRP peaked one day later. At < or =24h, the AUC(ROC)s of PLA2-II and PCT were superior to those of CRP. Thereafter, the AUC(ROC)s of PLA2-II and PCT decreased and those of CRP increased. PLA2-II at cut-off level of 150 microg/L and PCT at 2-6 microg/L showed high sensitivity and specificity for bacteremia within the first 24h. In conclusion, PLA2-II and PCT are useful markers for early diagnosis of bacteremia. Devising analytical methods suitable for point-of-care testing would further enhance the clinical utility of the measurement of serum PLA2-II and PCT.
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Bacteriemia/diagnóstico , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Calcitonina/sangre , Inflamación/diagnóstico , Fosfolipasas A/sangre , Precursores de Proteínas/sangre , Adulto , Bacteriemia/sangre , Péptido Relacionado con Gen de Calcitonina , Femenino , Humanos , Inflamación/sangre , Masculino , Persona de Mediana Edad , Fosfolipasas A2 , Sensibilidad y EspecificidadAsunto(s)
Cuidados Críticos/estadística & datos numéricos , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Enfermedad Aguda , Recolección de Datos , Femenino , Finlandia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/terapia , Resultado del TratamientoRESUMEN
OBJECTIVE: To compare the prognostic significance of bactericidal/permeability-increasing protein (BPI), group II phospholipase A2 (PLA2-II), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF), interleukin-8 (IL-8) and interferon-gamma (IFN) in terms of predicting severity of sepsis and outcome. DESIGN: A prospective study. SETTING: Medical intensive care unit (ICU) of a university hospital. PATIENTS: Thirty-four patients with severe sepsis requiring ICU treatment. MEASUREMENTS AND RESULTS: The levels of BPI, PLA2-II, CRP, TNF, IL-8 and IFN were measured in these 34 patients. High levels of BPI were associated particularly with Gram-negative sepsis. BPI and BPI/neutrophil ratios correlated positively with PLA2-II, CRP, TNF and IL-8 and negatively with blood pressure. At 24 h, BPI/neutrophil ratios, IL-8 and Simplified Acute Physiology Scores II (SAPS II) scores were higher in non-survivors than in survivors. No such associations were noted in the levels of CRP, PLA2-II, TNF or IFN. The areas under the curve (AUC(ROC)s) of SAPS II scores and IL-8 were higher than AUC(ROC) of BPI/neutrophil ratio. CONCLUSION: The BPI and BPI/neutrophil ratios may serve as adjunctive tools to illustrate the severity of sepsis. However, their predictive power for sepsis-related death was not comparable to that of SAPS II scores and IL-8.
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Proteínas Sanguíneas/metabolismo , Proteínas de la Membrana , Sepsis/sangre , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Péptidos Catiónicos Antimicrobianos , Área Bajo la Curva , Proteína C-Reactiva/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Unidades de Cuidados Intensivos , Interferón gamma/metabolismo , Interleucina-8/metabolismo , Masculino , Persona de Mediana Edad , Fosfolipasas A/metabolismo , Fosfolipasas A2 , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Curva ROC , Sensibilidad y Especificidad , Sepsis/microbiología , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To assess the effect of protein C (PC) substitution on imminent peripheral necroses and overall outcome in patients with sepsis-associated purpura fulminans. DESIGN: Case series. SETTING: Intensive care units of two university hospitals. PATIENTS: A total of 12 patients with purpura fulminans, disseminated intravascular coagulation and imminent peripheral necroses in association with sepsis caused by Neisseria meningitidis (n = 5), Streptococcus pneumoniae (n = 2), Capnocytophaga canimorsus (n = 2), and Staphylococcus aureus (n = 1). In two patients, no pathogens were identified. INTERVENTIONS: Intravenous administration of PC concentrate (100 IU/kg every 6 hrs). In addition, antithrombin III substitution, antimicrobial therapy, hemodynamic support, and mechanical ventilation in all patients and hemodiafiltration in 10 patients. MAIN RESULTS: After the onset of PC, progressive peripheral ischemia was reversed irrespective of the etiology of infection. Laboratory variables reflecting disseminated intravascular coagulation improved rapidly, although the recovery of the platelet count was retarded in the patients who subsequently died. No drug-related adverse events were noted. Amputations were necessary in two patients, and necrotic tips of fingers and toes were macerated in a third. The hospital mortality was 42%. Of the five lethal cases, two were caused by S. pneumoniae, one by N. meningitidis, one by C. canimorsus, and one by an unknown pathogen. CONCLUSIONS: This article provides encouraging results on the use of PC substitution in meningococcal purpura and presents new data on the administration of this drug to patients with septic purpura caused by other bacterial species. By clinical judgment, PC limited the extent of tissue necrosis. The small number of patients does not allow for any conclusions on the potential effect of PC on mortality. A controlled and randomized study with a larger number of patients is needed before any recommendations can be given on the use of PC in sepsis-related purpura fulminans and shock.
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Anticoagulantes/uso terapéutico , Capnocytophaga , Dacarbazina/sangre , Vasculitis por IgA/complicaciones , Neisseria meningitidis , Proteína C/uso terapéutico , Sepsis/complicaciones , Sepsis/microbiología , Streptococcus pneumoniae , APACHE , Adolescente , Adulto , Anciano , Antitrombina III/uso terapéutico , Proteína C-Reactiva/metabolismo , Femenino , Gangrena/cirugía , Hemodiafiltración , Mortalidad Hospitalaria , Humanos , Vasculitis por IgA/tratamiento farmacológico , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Respiración Artificial , Inhibidores de Serina Proteinasa/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the effect of steroid treatment in the late phase of primary acute lung injury (ALI) with special emphasis on pneumococcal pneumonia. DESIGN: Retrospective study. SETTING: Multidisciplinary intensive care unit (ICU) in a university hospital. PATIENTS: Of 31 patients with primary ALI requiring mechanical ventilation for more than 10 days, 16 were treated with methylprednisolone and 15 served as controls. MEASUREMENTS AND RESULTS: Steroid and control groups were comparable regarding demographic data, APACHE II score, Multiple Organ Dysfunction Score (MODS), and PaO2/FiO2-ratio on admission to ICU. The mean start of steroid therapy was 9.7 days after establishment of respiratory failure, and values for control patients were registered on day 10. The PaO2/FiO2 ratio improved significantly within 3 days after the start of steroid therapy, and MODS and C-reactive protein decreased concurrently. No differences in mortality, in length of ICU stay, or in length of mechanical ventilation were detectable. In a subgroup analysis, for patients with Streptococcus pneumoniae pneumonia, beneficial change in physiological variables was evident. CONCLUSIONS: In patients with primary ALI, steroid therapy, started 10 days after the start of mechanical ventilation, improves gas exchange and is associated with a decrease in multiorgan dysfunction.
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Glucocorticoides/uso terapéutico , Metilprednisolona/uso terapéutico , Insuficiencia Multiorgánica/tratamiento farmacológico , Infecciones Neumocócicas/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , APACHE , Enfermedad Aguda , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/mortalidad , Insuficiencia Multiorgánica/terapia , Infecciones Neumocócicas/clasificación , Infecciones Neumocócicas/terapia , Respiración Artificial , Síndrome de Dificultad Respiratoria/clasificación , Síndrome de Dificultad Respiratoria/terapia , Estudios RetrospectivosRESUMEN
PURPOSE: We evaluated alternatives to bacillus Calmette-Guerin (BCG) monotherapy using a new combination of chemotherapy and immunotherapy for recurrent superficial bladder carcinoma. MATERIALS AND METHODS: A total of 236 patients with frequently recurrent stage Ta or T1 bladder tumors were enrolled in our prospective, randomized, multicenter Finnbladder IV study. The initial mitomycin C instillation was instilled in all patients perioperatively after transurethral resection, followed by 4 weekly instillations of mitomycin C. Thereafter patients were randomized to receive monthly for up to 1 year BCG only or interferon-alpha2b and BCG alternating monthly. Primary end points were time to initial recurrence, recurrence rate (number of recurrences per patient-year) and recurrence index (number of recurrent tumors per patient-year). RESULTS: Of the 236 randomized patients 205 were eligible for study with a median overall followup of 30.7 months. Monthly BCG was superior to alternating monthly interferon-alpha and/or BCG with respect to time to initial recurrence (log rank test p <0.00001) as well as recurrence rate (0.4 versus 0.9, p <0.00001) and index (0.9 versus 3.0, p <0.00001). Side effects were limited. CONCLUSIONS: Monthly BCG given for up to 1 year preceded by perioperative and an additional 4 weekly mitomycin C instillations is a well tolerated mode of instillation therapy, providing excellent tumor control comparable to that of the best reported instillation regimens. No benefit was obtained by alternating interferon-alpha2b with BCG.
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Adyuvantes Inmunológicos/administración & dosificación , Antibióticos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Vacuna BCG/administración & dosificación , Carcinoma Papilar/prevención & control , Interferón-alfa/administración & dosificación , Mitomicina/administración & dosificación , Recurrencia Local de Neoplasia/prevención & control , Neoplasias de la Vejiga Urinaria/prevención & control , Administración Intravesical , Anciano , Terapia Combinada , Esquema de Medicación , Femenino , Humanos , Interferón alfa-2 , Masculino , Estudios Prospectivos , Proteínas RecombinantesRESUMEN
PURPOSE: We compared the sensitivity of the BTA statdagger test, a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine, to that of voided urine cytology in patients with primary bladder cancer. We also assessed the effect of tumor size, number, histological grade and stage on test sensitivity. MATERIALS AND METHODS: We evaluated 151 patients with newly diagnosed bladder cancer in a prospective multicenter study. A voided urine sample obtained before transurethral bladder tumor resection was divided for culture, cytology and BTA stat testing. RESULTS: Overall sensitivity of the BTA stat test and urine cytology for detecting primary bladder cancer was 81.5% and 30.3%, respectively (p <0.0001). The sensitivity of each test increased as tumor size, number, histological grade and stage increased. CONCLUSIONS: Sensitivity of the BTA stat test was superior to that of voided urine cytology in all tumor categories. This noninvasive, easy to perform, point of care test may have the potential to replace cytology for diagnosing bladder cancer.
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Carcinoma de Células Transicionales/diagnóstico , Factor H de Complemento/química , Neoplasias de la Vejiga Urinaria/diagnóstico , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/orina , Femenino , Humanos , Masculino , Estudios Prospectivos , Juego de Reactivos para Diagnóstico , Sensibilidad y Especificidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/orina , Orina/citologíaRESUMEN
PURPOSE: The combination of interferon alfa-2a (IFNalpha2a) plus vinblastine (VLB) induces objective tumor responses in patients with advanced renal cell cancer. However, no prospective randomized trial has shown that this treatment prolongs overall survival. We compared overall survival after treatment with IFNalpha2a plus VLB versus VLB alone in patients with advanced renal cell cancer. PATIENTS AND METHODS: We prospectively randomized 160 patients with locally advanced or metastatic renal cell cancer to receive either VLB alone or IFNalpha2a plus VLB for 12 months or until progression of disease. In both groups, VLB was administered intravenously at 0.1 mg/kg every 3 weeks, and in the combination group IFNalpha2a was administered subcutaneously at 3 million units three times a week for 1 week, and 18 million units three times a week thereafter for the second and subsequent weeks. For patients unable totolerate IFNalpha2a at 18 million units per injection, the dose was reduced to 9 million units. RESULTS: Median survival was 67.6 weeks for the 79 patients receiving IFNalpha2a plus VLB and 37.8 weeks for the 81 patients treated with VLB (P =.0049). Overall response rates were 16. 5% for patients treated with IFNalpha2a plus VLB and 2.5% for patients treated with VLB alone (P =.0025). Treatment with the combination was associated with constitutional symptoms and abnormalities in laboratory parameters, but no toxic deaths were reported. CONCLUSION: The combination of IFNalpha2a plus VLB is superior to VLB alone in the treatment of patients with locally advanced or metastatic renal cell carcinoma. This is the first study to demonstrate that survival can be prolonged by using IFNalpha2a for these patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Adulto , Anciano , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/secundario , Supervivencia sin Enfermedad , Femenino , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Proteínas Recombinantes , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Vinblastina/administración & dosificaciónRESUMEN
OBJECTIVE: A prospective randomized study was undertaken to determine whether cell proliferation indices (M/V index, MIB1), papillary status, the expression of p53 and epidermal growth factor receptor (EGFr) have prognostic value in superficial (pTa-pT1) bladder cancer (SBC). METHODS: 207 patients with primary SBC were followed up over a period of 4.9 (range 3.7-6.0) years. M/V index and papillary status were assessed by light microscopy, and expression of MIB1, p53 and EGFr was assessed by immunohistochemistry. The results of histopathological analyses were related to the survival data of the patients. RESULTS: Using univariate analysis, stage (p < 0.001), grade (p < 0.001), papillary status (p < 0.001), MIB1 (p < 0.001), M/V index (p < 0.001), EGFr (p < 0.001) and p53 (p = 0.002) were significant predictors of progression. Using multivariate analysis, MIB-1 score and papillary status were independent predictors of progressive disease and cancer-specific survival. Tumor grade was the only independent predictor of recurrence. CONCLUSION: Evaluation of tumor cell proliferation rate by M/V index or by MIB1 immunohistochemistry and assessment of papillary status by light microscopy are useful prognostic tools in tailoring treatment and follow-up schedule of patients with SBC.
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Biomarcadores de Tumor/análisis , Carcinoma de Células Transicionales/patología , Receptores ErbB/análisis , Genes p53 , Índice Mitótico , Proteínas Nucleares/análisis , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Análisis de Supervivencia , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
We studied whether detection of messenger-RNA (mRNA) for the beta-subunit of chorionic gonadotropin (CGbeta) in urinary cells from bladder cancer patients could be used as a marker of disease activity. Sixty-eight urine samples from patients under follow-up for bladder cancer and 23 samples from patients with other malignancies and non-malignant surgical conditions, as well as 14 samples from healthy controls were analyzed. RNA was isolated from urinary cells collected by centrifugation. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect CGbeta mRNA. The results were compared to those obtained by cystoscopy and urinary cytology. For comparison, we determined CG and CGbeta in serum and urine and the core fragment of CGbeta (CGbeta cf) in urine by immunofluorometric assays. CGbeta mRNA was detected in 29 of 68 urine samples from patients with a history of bladder cancer, whereas all 14 samples from healthy controls tested negative. Elevated levels of CGbeta were observed in serum in 18 of 45 bladder cancer patients, but the association with CGbeta mRNA was weak. However, CGbeta mRNA expression in the absence of detectable cancer also occurred in some conditions associated with cellular atypia such as urinary tract infection, instrumentation and certain therapies. There was a highly significant association between histologically verified transitional cell carcinoma of the bladder and CGbeta mRNA in urine (p = 0.0014), implying CGbeta mRNA expression in tumor tissue. We conclude that CGbeta mRNA is a potential new marker for monitoring of bladder cancer. Further studies are needed to evaluate whether it provides independent clinical information.