RESUMEN

BACKGROUND: The 23-h surgery model consists of elective operative care with an overnight hospital stay for patients unsuitable for day case surgery. The aim of this study was to assess the success of the 23-h surgery model. METHODS: This was a prospective follow-up study of patients undergoing surgery with the planned 23-h model in a tertiary-care university hospital during a 12-month period 2 years after the model was implemented. Patients were interviewed 2 weeks after surgery, and the hospital operative database and patient records were searched. The primary outcome was the success of the process, defined as discharge before 10.00 hours on the first morning after surgery. Secondary outcomes were 30-day readmission and reoperation rates, adverse events, and patient satisfaction with the process. RESULTS: Between May 2017 and May 2018, 993 adult patients underwent surgery with the 23-h model, of whom 937 adhered to the model as planned (success rate 94·4 per cent). Gynaecological, gastrointestinal and orthopaedic surgery were the three most common surgical specialties. The surgical process was changed to an in-hospital model for 45 patients (4·5 per cent), and 11 (1·1 per cent) were discharged on the day of surgery. The readmission rate was 1·9 per cent (19 of 993), and five patients (0·5 per cent) had a reoperation within 30 days of surgery. Fifty-nine adverse events were noted in 53 patients (5·3 per cent), most commonly infection. Patient satisfaction was a median of 6-7 (maximum 7) points for various aspects of the model. CONCLUSION: The success rate and patient satisfaction for the 23-h surgery model was high.

---

ANTECEDENTES: El modelo de cirugía de 23 horas consiste en un procedimiento quirúrgico electivo con estancia en el hospital durante una noche en aquellos pacientes que no son adecuados para cirugía ambulatoria. MÉTODOS: Se puso en marcha un estudio prospectivo de seguimiento de pacientes sometidos a cirugía con un modelo planificado de 23 horas en un hospital universitario de tercer nivel durante un periodo de 12 meses a los dos años de la implementación del modelo. Los pacientes fueron entrevistados a las dos semanas tras la cirugía, y se realizaron búsquedas en las bases de datos operativas y en los informes de los pacientes. El resultado primario fue el éxito del proceso definido como el alta antes de las 10 horas en la primera mañana postoperatoria. Los resultados secundarios fueron el reingreso a los 30 días y la tasa de reoperaciones, eventos adversos, y satisfacción del paciente con el proceso. RESULTADOS: Entre mayo de 2017 y mayo de 2018, 993 pacientes adultos fueron sometidos a cirugía con un modelo planificado de 23 horas, de los cuales 937 pacientes siguieron el modelo tal como se planificó (tasa de éxito 94,4%). Las tres especialidades quirúrgicas más frecuentes fueron ginecología, aparato digestivo y ortopedia. El proceso quirúrgico se cambió a un modelo de hospitalización en 45 (4,5%) pacientes, y 11 (1,1%) pacientes fueron dados de alta en el día de la cirugía. La tasa de reingreso fue del 1,9% (n = 19) y 5 pacientes (0,5%) precisaron de una reoperación en los primeros 30 días tras la cirugía. Se observaron eventos adversos en 53 pacientes (5,3%), siendo una infección el más frecuente. La satisfacción del paciente tuvo una mediana de 6-7 (de un total de 7) puntos para varios aspectos del modelo. CONCLUSIÓN: La tasa de éxito y la satisfacción del paciente del modelo de cirugía de 23 horas son elevadas.

Asunto(s)

Procedimientos Quirúrgicos Ambulatorios/estadística & datos numéricos , Procedimientos Quirúrgicos Electivos/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Modelos Anatómicos , Satisfacción del Paciente , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Finlandia , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Estudios Prospectivos , Reoperación/estadística & datos numéricos , Centros de Atención Terciaria , Adulto Joven

RESUMEN

This report describes the case of a patient with prostate cancerat the age of 59 years, who was treated by interstitial prostate brachytherapy with iodine-125 seeds. Ten years later, he developed a probable secondary squamous cell cancer in his prostate.

Asunto(s)

Braquiterapia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/radioterapia , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

The members of the Wnt glycoprotein family are important in embryogenesis and adult tissue homeostasis, and deletion of WNT-4 gene in mice leads to improper development of many organs including the adrenals. The objective of this study was to investigate the expression of WNT-4 gene in human adrenals and adrenocortical tumors. The WNT-4 mRNA expression (analyzed by quantitative real-time RT-PCR) was significantly higher in Conn's adenomas (p<0.01) and lower in Cushing's adenomas, virilizing carcinomas and fetal adrenals (p<0.05) compared with normal adult adrenals. WNT-4 mRNA expression was clearly upregulated by ACTH and 8-bromo-cAMP (8-BrcAMP) in primary cultures of normal adult adrenocortical cells, but downregulated by 8-BrcAMP and 12- O-tetradecanoylphorbol-13-acetate (TPA) in human NCI-H295R adrenocortical carcinoma cells. Angiotensin II tended to increase WNT-4 mRNA expression at 24 hours and decreased it at 48 hours time point in both cell culture types. The abundant WNT-4 mRNA expression in Conn's adenomas and its hormonal regulation in adrenocortical cells suggest a role for WNT-4 in human adrenocortical function.

Asunto(s)

Neoplasias de la Corteza Suprarrenal/genética , Glándulas Suprarrenales/citología , Glándulas Suprarrenales/metabolismo , Regulación de la Expresión Génica , Proteínas Wnt/genética , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , Hormona Adrenocorticotrópica/farmacología , Adulto , Angiotensina II/farmacología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Feto/citología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Factores de Tiempo , Proteínas Wnt/metabolismo , Proteína Wnt4 , beta Catenina/genética , beta Catenina/metabolismo

RESUMEN

We describe a patient with a very unusual penile abscess. Antibiotic treatment for Clostridium sordellii and Candida albicans infection and drainage of pus was curative. We propose that the penile abscess may have been an unusual manifestation of a rectal fistula.

Asunto(s)

Absceso/patología , Candida/patogenicidad , Candidiasis/patología , Pene/microbiología , Pene/patología , Sepsis/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Radiografía Abdominal , Tomografía Computarizada por Rayos X

RESUMEN

OBJECTIVE: The study was designed to analyse the prognostic value of proliferation markers Ki-67 and cyclin D1 and apoptosis in prostate cancer (PC) patients treated by radical prostatectomy. PATIENTS AND METHODS: Two hundred and eleven patients treated by radical prostatectomy for localised prostate cancer were clinically followed up for a mean of 7.3 years. The primary histopathological specimens were re-analysed to ensure uniform histoplthological grading and pT classification. A tissue microarray construction (TMA) was used in immunohistochemisty to assess the expression of Ki-67, cyclin D1 and the apoptosis marker Tag. The results were analysed with light microscopy and the findings were compared to standard histology, pT and clinical follow-up data. RESULTS: The co-expression of Ki-67 and cyclin Dl (p=0.05) was common. High fraction of Ki-67 positive cells and a high fraction of apoptotic cells were often present in same tumours (p=0.05). High apoptotic rate was related to positive surgical margin status (p=0.047). Low expression of Ki-67 was related to a low Gleason score (p<0.001), an absence of either capsule penetration (p = 0.029) or perineural invasion (p=0.004). High expression of cyclin Dl was related to perineural growth (p=0.039). Prostate specific antigen (PSA) recurrence-free survival (RFS) was predicted by Gleason grade (p<0.001) and capsule invasion (p=0.006). High expression of Ki-67 (p=0.03), as well as high apoptotic rate (p=0.04) were related to a high risk of cancer death. In multivariate analysis the seminal vesicle invasion was the only independent predictor of cancer death (p = 0.01). CONCLUSION: The expression of Ki-67, cyclin D1 and a high apoptotic rate are related to a malignant phenotype in prostate cancer, but their prognostic value is inferior to standard histological prognostic factors.

Asunto(s)

Apoptosis/fisiología , Ciclina D1/biosíntesis , Antígeno Ki-67/biosíntesis , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Estudios de Cohortes , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Prostatectomía , Neoplasias de la Próstata/metabolismo , Resultado del Tratamiento

RESUMEN

UNLABELLED: The aim of this study was to determine the prognostic value of alpha- and beta-catenin expressions in local prostate cancer (PC). MATERIALS AND METHODS: One hundred and eighty-one PC patients treated with radical prostatectomy were followed-up for a mean of 7.3 years. The alpha- and beta-catenin expression were analysed by immunohistochemistry TMT (tissue microarray technique) and light microscopy. RESULTS: Strong a-catenin expression was related to low Gleason grade (p < 0.001), cancer-free seminal vesicles (p = 0.04) and low preoperative PSA (p = 0.02). Strong beta-catenin expression was related to low Gleason grade (p < 0.001) and cancer-free seminal vesicle status (p = 0.03). Absence of nuclear beta-catenin expression was related to local disease (pT1-T2) (p = 0.05). alpha-catenin (p = 0.06), beta-catenin (p = 0.05), Gleason grade (p = 0.03) and capsular invasion (p = 0.01) were related to PSA recurrence in patients who reached PSA zero postoperatively. PSA recurrence-free survival (RFS) was significantly related to Gleason grade (p < 0.001), capsule invasion (p = 0.01), perineural growth (p = 0.05) and preoperative PSA (p = 0.05). In Cox's analysis, independent predictors of PSA RFS were Gleason grade (p < 0.001) and capsular invasion (p = 0.006). Low expressions of alpha- (p = 0.06) and beta-catenin (p = 0.05) were related to shortened PSA RFS. Survival was related to low alpha- (p = 0.011) and beta-catenin (p = 0.016) expressions. Independent predictors of shortened survival were seminal vesicle invasion (p = 0.016) and low alpha-catenin expression (p = 0.049). CONCLUSION: Reduced alpha- or beta-catenin expressions are related to malignant phenotype in local prostate cancer and predict PSA failure as well as shortened survival.

Asunto(s)

Neoplasias de la Próstata/metabolismo , alfa Catenina/biosíntesis , beta Catenina/biosíntesis , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Prostatectomía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Tasa de Supervivencia

RESUMEN

OBJECTIVE: To establish a multi-centre database of a large number of patients treated with brachytherapy across Europe. METHODS: A total of 1175 patient files were registered in the database and the completeness of the data on these patients resulted in the majority being included in the analysis. RESULTS: The database of patients treated with brachytherapy across Europe indicates that optimal patient selection for this procedure has been made, both in terms of outcome and side-effects, which will be subject of future analyses. This should enable refinement of the treatment choice and administration as well as provide useful guidance to other centres that want to establish this procedure for their patients. It will also set the ground for prospective studies. CONCLUSIONS: The established database indicates that brachytherapy as a treatment option for prostate cancer is well established in many centres.

Asunto(s)

Braquiterapia/métodos , Neoplasias de la Próstata/radioterapia , Anciano , Bases de Datos Factuales , Europa (Continente) , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Selección de Paciente , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patología , Estudios Retrospectivos

RESUMEN

OBJECTIVE: HA (hyaluronan) is involved in cell migration, differentiation and cell proliferation, which all are essential to tumour growth. In addition, the cell surface receptor of HA, CD44, is important in cancer cell adhesion, cell migration and tumour neovascularisation. We studied the expression of HA and CD44 and their relationship with other prognostic factors and prostate-specific antigen (PSA) recurrence in local prostate cancer (PC). MATERIALS AND METHODS: 77 PC patients treated with radical prostatectomy were followed-up for a mean of 4 years. HA was detected by using a HA specific probe and CD44 expression was analysed by conventional immunohistochemistry. RESULTS: All specimens expressed HA in tumour stroma and 78% (60/77) of the tumours showed strong stromal expression of HA. The fraction of positively stained specimens for CD44 was 66% (51/77). The strong stromal HA expression was related to perineural infiltration (p = 0.001) and capsule invasion (p = 0.05). No correlation was demonstrated between the stromal HA expression and CD44 expression, preoperative PSA, clinical or pathological T classification, pN status, Gleason grade, seminal vesicle invasion or surgical margin invasion. Reduced CD44 expression was related only to preoperative PSA level (p = 0.008). The PSA recurrence was predicted by strong stromal HA expression, pT classification, seminal vesicle invasion, capsule invasion and surgical margin invasion (p

Asunto(s)

Ácido Hialurónico/biosíntesis , Recurrencia Local de Neoplasia/metabolismo , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/cirugía , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

OBJECTIVE: We evaluated the effects of transurethral needle ablation (TUNA) in chronic pelvic pain syndrome (CPPS). MATERIAL AND METHODS: CPPS patients were subjected to TUNA (n = 21) or sham therapy (urethrocystoscopy) (n = 6). Digital rectal examination and transrectal ultrasound were performed. Prostate-specific antigen and urine were analysed before and 1 month after treatment. Symptoms, the DAN-PSS-1 questionnaire, urine flow, residual urine volume, medication and a subjective estimation of the effect of treatment were evaluated during a follow-up period of 12 months. RESULTS: In both groups the maximal urine flow increased and the DAN-PSS-1 score decreased, but the decrease in the DAN-PSS-1 score was significant (p = 0.002) only in the TUNA group. The total symptom score decreased from 14 to 8.3 points in the TUNA group, and from 12.6 to 8.0 points in sham patients. TUNA relieved pain significantly. In the TUNA group symptoms were ameliorated in patients with small (< or = 20 ml; p = 0.002) and large prostates (> 20 ml; p = 0.04). Similarly, patients with both mild (p = 0.004) and severe (p = 0.02) symptoms at baseline benefitted from TUNA. Of the TUNA patients, 72% felt better at 1-year follow-up, although 57% still had symptoms and 38% needed medication. The figures in the sham group were 50%, 66% and 50%, respectively. CONCLUSIONS: TUNA relieved symptoms in CPPS patients for at least 12 months. The need for medication and the presence of symptoms were reduced, and the fraction of patients satisfied with treatment was higher in the TUNA group than in the sham group. However, these differences between the groups were not statistically significant. To assess the clinical value of TUNA in CPPS a prospective double-blind study with a large number of patients is needed to confirm the results of this pilot study.

Asunto(s)

Ablación por Catéter , Dolor Pélvico/cirugía , Anciano , Ablación por Catéter/instrumentación , Ablación por Catéter/métodos , Enfermedad Crónica , Cistoscopía , Estudios de Seguimiento , Humanos , Masculino , Agujas , Dolor Pélvico/etiología , Estudios Prospectivos , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/cirugía , Síndrome , Uretra , Obstrucción Uretral/complicaciones , Obstrucción Uretral/cirugía

RESUMEN

Several epithelial tumours accumulate hyaluronan (HA) which promotes cancer cell invasion and metastasis. We analysed the expression of HA and its receptor CD44 and their prognostic value in 166 prostate cancer patients followed up for a mean of 13 years; standard deviation (S.D.) 2.7; range 8.7-21.4 years. HA was detected with a specific biotinylated probe prepared from cartilage aggrecan and link protein, and CD44 with an antibody recognising all forms of CD44. The peri- and intratumoral stroma from half of the patients strongly expressed immunohistochemically detectable HA in < or = 15% of the stromal area; the tumours in the remaining half expressed HA in > 15% of the area. The staining of cancer cells for HA was scored positive or negative, and for CD44 the median value of 80% of positive tumour cells was used as a cut-off point. The expression of HA in cancer cells was weakly associated with perineural infiltration of the tumour (P = 0.03) and high Gleason score (P = 0.002). There was also a significant inverse relationship between the expression of HA and CD44 in cancer cells (P < 0.001). The high level of HA in the peri-and intratumoral stroma was related to metastasis, high T-category, high Gleason score, perineural infiltration and high mitotic activity of the tumour (for all P < 0.001). There was a significant inverse relationship between the expression of CD44 in cancer cells and high level of strong expression of HA in the tumour stroma (P < 0.001). A low fraction of CD44-positive cells was related to a high TM-category, high Gleason score and rapid cell proliferation (for all P < 0.0001; M/V P value = 0.0013). In the univariate survival analysis, the high level of strong expression of HA in tumour stroma predicted an unfavourable outcome in the entire series (P = 0.003) and also in the M0 tumours (P = 0.07), while in T1-2 M0 tumours the prognostic value did not reach the level of statistical significance (P = 0.1). A low fraction of CD44-positive cells predicted a poor outcome in the entire series (P < 0.001) and also in M0 tumours (P = 0.003). Cancer cell-associated HA expression had no prognostic value in any tumour categories. In the multivariate analysis of prognostic factors, HA expression in the cancer cells or in the tumour stroma had no additional value to the standard prognostic factors TM-classification, Gleason score and CD44 expression. Our results show that stromal HA accumulation is related to several malignant features and adverse clinical outcome in prostate cancer. However, further studies based on uniformly treated patient cohorts are needed to establish the clinical significance of these findings in current clinical practice.

Asunto(s)

Transformación Celular Neoplásica/patología , Ácido Hialurónico/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Adulto , Anciano , Anciano de 80 o más Años , Transformación Celular Neoplásica/metabolismo , Estudios de Seguimiento , Humanos , Receptores de Hialuranos/metabolismo , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Pronóstico , Análisis de Supervivencia

RESUMEN

BACKGROUND: The adhesion molecule CD44 standard (CD44s), and its variant isoforms v3 and v6 are associated with cell-to-cell adhesion. The down-regulation of CD44 standard and its variant isoform CD44v6 is linked with early cancer cell dissemination, but the relationship between CD44v3 and malignant features of prostate cancer (PC) has not been established previously. METHODS: The expression of CD44s and its CD44v3 and CD44v6 isoforms was analysed by immunohistochemistry in 209 archival PC biopsy specimens to establish their prognostic value. RESULTS: Down-regulation of CD44s and CD44v6 was related to high T classification, metastasis, high Gleason score, DNA aneuploidy, high S-phase fraction, high mitotic index, perineural growth and dense amount of tumour infiltrating lymphocytes (p < 0.03 for all). Down-regulation of CD44s and CD44v6 was related to poor survival in the entire cohort (p < 0.0001), in M0 tumours (p < 0.001) and in T1-2M0 tumours (p < 0.05). In needle biopsies and TURP specimens, the prognostic impact of the investigated parameters was similar. In the multivariate analysis, T classification (p = 0.0009), presence of metastases (p < 0.0001), Gleason score (p = 0.0060) and CD44v6 (p = 0.0220) expression were independent prognostic factors. In M0 tumours, T classification (p < 0.0001) and CD44v6 (p = 0.003) independently predicted survival. CONCLUSION: Down-regulation of CD44s and its CD44v6 isoform is related to tumour malignancy and unfavourable prognosis in PC.

Asunto(s)

Regulación Neoplásica de la Expresión Génica , Receptores de Hialuranos/genética , Neoplasias de la Próstata/genética , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Isoformas de Proteínas

RESUMEN

OBJECTIVE: The clinical and histological data of prostate cancer patients were compared with the expression of CD44 standard (CD44s), variant isoforms CD44v3, CD44v6 and alpha-catenin. The prognostic value of these adhesion molecules was also analysed. PATIENTS AND METHODS: We analysed the clinical and histological data of 87 prostate cancer patients treated by radical prostatectomy in two Finnish hospitals. The mean (SD) age of the patients at diagnosis was 64 years (6) and the mean follow-up was 3 years (8). Immunohistochemistry was used to detect the expression of CD44s and its v3 (CD44v3) and v6 (CD44v6) isoforms and alpha-catenin. RESULTS: The mean (SD) fractions of positively stained cancer cells were 38 (38), 10 (22), 56 (41) and 93% (17) for CD44s, CD44v3, CD44v6 and alpha-catenin, respectively. Low fractions of CD44s- and CD44v6-positive cancer cells were related to high preoperative prostate-specific antigen (PSA) levels (p<0.05 for both). Low fraction of CD44s positive cancer cells was linked with presence of seminal vesicle invasion (p = 0.07), surgical margin positivity (p = 0.09), high Gleason score (p = 0.04) and high mitotic index (p = 0. 02). Low fraction of CD44v3-positive cancer cells was related to positive surgical margins (p = 0.05), high Gleason score (p = 0.04), presence of perineural infiltration (p = 0.02) and absence of tumour-infiltrating lymphocytes (p = 0.02). Low fraction of CD44v6-positive cancer cells was related to high pT classification (p = 0.07), capsule invasion (p = 0.03), positive surgical margins (p = 0.05), high Gleason score (p = 0.008), perineural infiltration (p = 0.0001) and high mitotic index (p = 0.001). alpha-Catenin expression was not related to any of the clinicopathological variables included in this study. Gleason score (p = 0.001), pT classification (p = 0.007), perineural infiltration (p = 0.01) and the fraction of CD44v3-positive cancer cells (p = 0.04) were predictors of PSA failure in univariate analysis. pT category (p = 0. 012), Gleason score (p = 0.02) and expression of CD44v3 (p = 0.0003) were independent predictors of PSA failure. CONCLUSIONS: The expression of CD44s, CD44v3 and CD44v6 is related to tumour differentiation. The expression of CD44v3 independently predicts PSA failure in addition to Gleason score and pT category during a short-term follow-up.

Asunto(s)

Cadherinas/genética , Proteínas del Citoesqueleto/genética , Regulación Neoplásica de la Expresión Génica , Receptores de Hialuranos/genética , Prostatectomía , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/cirugía , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Próstata/patología , Isoformas de Proteínas/genética , alfa Catenina

RESUMEN

OBJECTIVE: To compare the clinical and histological data from patients with prostate cancer with the results of the immunohistochemical analysis of inducible nitric oxide synthase (iNOS), and thus determine the prognostic value of iNOS. PATIENTS AND METHODS: The study included 82 patients (mean age 64.6 years, SD 6.1) with local prostate cancer treated by radical prostatectomy in two Finnish hospitals. Their mean (SD) follow-up was 3.3 (2.2) years. An immunohistochemical method was used to detect the expression of iNOS in these specimens, and the expression graded according to staining intensity as none, weak or strong. RESULTS: There was weak or strong expression of iNOS in 25 (31%) and 56 (68%) of the patients, respectively, and one specimen was negative for iNOS. Strong expression of iNOS was related to high a preoperative prostate specific antigen (PSA) level (P = 0.006) and high pT classification (P < 0.001), but not to nodal status, grade, seminal vesicle or capsular invasion, surgical margin status, perineural infiltration, tumour infiltrating lymphocytes or proliferation rate of cancer cells. A PSA failure was detected in 29 patients but was not predicted by iNOS expression. A Cox multivariate analysis showed that surgical margin positivity, seminal vesicle involvement and number of tumour infiltrating lymphocytes predicted the PSA failure. CONCLUSION: A high expression of iNOS was related to a high pT classification and the preoperative PSA level but not to other established prognostic factors; iNOS expression was not a predictor of PSA failure in patients with local prostate cancer.

Asunto(s)

Proteínas de Neoplasias/análisis , Óxido Nítrico Sintasa/análisis , Neoplasias de la Próstata/enzimología , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo II , Pronóstico , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/patología

RESUMEN

OBJECTIVES: Activator protein 2 (AP-2) is a DNA-binding transcription factor that can activate the expression of p21 (waf1/cip1), which in turn causes growth arrest of cells through inhibition of cyclin-dependent kinases required in G1-S progression. The aims of the present study were to analyze the expression of AP-2 in prostate cancer and to relate the results of AP-2 immunohistochemistry to other known prognostic factors and patient survival. METHODS: AP-2alpha was demonstrated by an immunohistochemical method in 215 prostate cancer cases, and the results of immunohistochemistry were related to other known prognostic factors and patient survival. RESULTS: The expression of AP-2alpha in carcinomas was usually weak and cytoplasmic, similar to normal prostatic epithelium adjacent to tumors. In 6% of the tumors, the expression was strong, and in 15% no staining signal was detected. Nuclear expression was detected in 22% of cases. Low fraction of AP-2-expressing cells was related to high mitotic index, Ki67 labeling and high expression of p21 (waf1/cip1). Nuclear expression of AP-2 was related to high Gleason score, advanced T category, DNA aneuploidy and high S-phase fraction. Nuclear expression was an indicator of unfavorable disease outcome, but in multivariate analysis, expression of AP-2 had no prognostic value. CONCLUSIONS: Cytoplasmic expression of AP-2alpha is reduced in poorly differentiated prostate carcinomas. The rare nuclear expression occurs in a small proportion of tumors which are aneuploid, have a high T category and high Gleason score. The expression of AP-2 seems to have no prognostic value in prostate cancer.

Asunto(s)

Ciclinas/biosíntesis , Proteínas de Unión al ADN/biosíntesis , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Adulto , Anciano , Anciano de 80 o más Años , División Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico

RESUMEN

We have studied 118 renal cell carcinomas to analyse the expressions of cyclins A and D1 and p21(waf1/cip1), and their relationship to clinical and histopathological parameters as well as to clinical outcome. Cyclins A and D1 and cyclin-dependent kinase inhibitor p21 (waf1/cip1) were not expressed in normal renal tissue. Staining signals of cyclin D1 and p21(waf1/cip1) were always nuclear but cyclin A was also expressed in the cytoplasm of the tumour cells. The mean (range) fractions of cyclin A, cyclin D1 and p21(waf1/cip1)-positive tumour cells were 2.2% (range 0-20%), 23.3% (range 0-90%) and 6.8% (range 0-70%) respectively. The expression of cyclin A was related to venous invasion, high nuclear grade, high mitotic rate, high Ki-67 and high PCNA expressions (P < or = 0.006 for all). The expression of cyclin D1 was linked with age over 65 years, low nuclear grade and high p53 expression (P < or = 0.05 for all). An inverse correlation was present between p21(waf1/cip1) and cyclin D1 (P = 0.011). Cyclin A predicted survival in the entire study group (P = 0.0014), in T1-4/N0-2/M0 (P = 0.0007) and in T1-2/N0/M0 tumours (P = 0.0007). Cyclin A was also a powerful predictor of disease-free survival in T1-4/N0/M0 (P = 0.0027) tumours (P = 0.0007). Cyclin D1 and p21(waf1/cip1) were not significantly related to survival or disease-free survival in any of the groups. In the entire material the independent prognostic factors were the presence of distant metastases (relative risk (RR) 5.16, P < 0.001), T category (RR 2.68, P < 0.001), Ki-67 expression (RR 1.02, P = 0.026) and cyclin A expression (RR 1.12, P = 0.001). The independent predictors in T1-4/N0/M0 tumours were T-category (RR 2.67, P = 0.001) and cyclin A (RR 1.21, P < 0.001), and in T1-2/N0/M0 tumours the only significant predictor was cyclin A (RR 1.19, P = 0.0002). In renal cell carcinoma, cyclin A is a powerful and independent prognostic factor in all clinical stages of the disease, whereas cyclin D1 and p21(waf1/cip1) have no prognostic value.

Asunto(s)

Carcinoma de Células Renales/patología , Ciclina A/análisis , Ciclinas/análisis , Neoplasias Renales/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biopsia , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Ciclina D , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Inhibidores Enzimáticos/análisis , Estudios de Seguimiento , Humanos , Antígeno Ki-67/análisis , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Persona de Mediana Edad , Índice Mitótico , Invasividad Neoplásica , Metástasis de la Neoplasia , Antígeno Nuclear de Célula en Proliferación/análisis , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Proteína p53 Supresora de Tumor/análisis

RESUMEN

Normally functioning cell-cell adhesion plays an important role in the maintenance of tissue architecture and cell cohesion. E-cadherin is an important adhesion molecule of epithelial cells. In many types of cancer the expression of E-cadherin is reduced leading to increased risk of disease progression. alpha-Catenin is one of the intracellular elements of the E-cadherin-catenin complex. The abnormalities in the expression of alpha-catenin seem to associate with malignant cellular features and disease progression in prostate cancer. To further analyse the significance of alpha-catenin expression, we studied 215 cases of prostate cancer by immunohistochemistry and the results were related to other known prognostic factors and patient survival during a mean follow-up period of 13 years. alpha-Catenin expression was down-regulated in 19% of the cases and 3% of the tumours were totally alpha-catenin-negative. The abnormal alpha-catenin expression and cytoplasmic signal were significantly linked with high T-category, metastatic disease, high Gleason score, perineural growth, high mitotic rate, high S phase fraction and DNA aneuploidy (P < 0.05 for all). In the survival analysis, reduced alpha-catenin expression (P = 0.06) and cytoplasmic signal (P = 0.04) were related to unfavourable patient outcome. In the multivariate analysis, including TM-classification and Gleason score, alpha-catenin expression had independent prognostic value in T1-2 M0 tumors. In the M0 tumours, abnormal alpha-catenin signal was independently associated with recurrence-free survival as well. The results indicate that down-regulation of alpha-catenin is related to several malignant cellular features, and it seems to have prognostic significance in the early phases of cancer progression. We suggest that alpha-catenin expression can provide prognostic information in early prostate cancer.

Asunto(s)

Proteínas del Citoesqueleto/biosíntesis , Neoplasias de la Próstata/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/ultraestructura , alfa Catenina

RESUMEN

BACKGROUND: p21(waf1/cip1) protein is a cyclin-dependent kinase inhibitor able to arrest the cell cycle at the G1 phase by inhibiting DNA replication. The expression of p21(waf1/cip1) and its prognostic value in prostate cancer are largely unexplored. METHODS: We used immunohistochemistry to analyze the expression of p21(waf1/cip1) in 213 prostate cancer cases, and the results were related to other known prognostic factors and patient survival during a long-term follow-up. RESULTS: The expression of p21 (waf1/cip1) protein was significantly associated with high Gleason score (P = 0.001), DNA aneuploidy (P = 0.013), high S-phase fraction (P = 0.019), and expression of Ki-67 (P = 0.021) and bcl-2 (P = 0.001) as well as cyclin A (P = 0.035) and D proteins (P<0.001). In univariate survival analysis the signal of p21(waf1/cip1) was significantly related to unfavorable prognosis (P = 0.010) both in the entire cohort and in local tumors (P = 0.034). In multivariate analysis, M-category, clinical T-category, Gleason score, and patient age were independent prognostic factors. In local tumors the expression of p21(waf1/cip1) together with clinical T-category and S-phase fraction were significant independent predictors of cancer related survival. CONCLUSIONS: The results suggest that the expression of p21(waf1/cip1) protein is associated both with cell proliferation and patient survival in prostate cancer.

Asunto(s)

Ciclinas/biosíntesis , Inhibidores Enzimáticos/metabolismo , Neoplasias de la Próstata/metabolismo , Anciano , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Tasa de Supervivencia , Factores de Tiempo

RESUMEN

BACKGROUND: Cell proliferation and its regulation are important determinants of the prognosis of prostate cancer patients. Cyclins are important regulators of cell proliferation in human cancer, but their prognostic value has not been previously analyzed in prostate cancer. METHODS: The immunohistochemical expression and prognostic value of cyclins A and D were studied in prostate cancer in a cohort of 213 patients followed-up for a mean of 12 years. RESULTS: The expression of cyclin A was both cytoplasmic and nuclear, whereas the expression of cyclin D was nuclear. The mean (SD) fraction of cyclin A- and cyclin D-positive cells was 2.1 (7.9)% and 16.3 (23.4)%, respectively. The expression of cyclin A was related to TM-category, histological differentiation, perineural invasion, S-phase fraction, and expression of Ki67 and bcl-2 (for all, P<0.05). The expression of cyclin D was related to TM-classification, histological differentiation, perineural invasion, DNA ploidy, S-phase fraction, expression of Ki67, and mitotic index (for all, P< or =0.01). In survival analysis, expression of cyclin A predicted cancer-related survival in the entire cohort (P<0.001). Expression of cyclin D predicted cancer-related survival in the entire cohort (P<0.0001), in MO (P = 0.0007), and in T1-2NxM0 tumors (P = 0.0003). In Cox multivariate analysis, T-category, M-category, patient age, and the fraction of cyclin A-positive cells were independent predictors of survival in the entire series. In local tumors, T-category, Gleason score, DNA ploidy, or S-phase fraction were independent prognostic factors, and cyclins had no independent prognostic value. CONCLUSIONS: The results show that the expression of cyclins A and D is related to several malignant cellular features in prostate cancer, but they have no independent prognostic value.

Asunto(s)

Ciclina A/biosíntesis , Ciclinas/biosíntesis , Proteínas de Neoplasias/biosíntesis , Neoplasias de la Próstata/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Ciclina D , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Tasa de Supervivencia

RESUMEN

BACKGROUND AND AIMS: In a prospective study, Bard BTA (bladder tumour antigen) test was compared to voided urine cytology (VUC) in detecting primary and recurrent bladder cancer (BC). MATERIALS AND METHODS: 407 control cystoscopies, BTA test and VUC were performed on 150 patients, of which 96 (23.6%) recurrent tumours were found, and 43 patients with a new BC were noticed. RESULTS: BTA test was superior to VUC in detecting superficial Ta (23% vs. 3%, p < 0.001) and grade 1 (16% vs. 0%, p < 0.001) as well as grade 2 (35% vs. 11%, p < 0.01) tumours. In Tis and T2-T4 tumours as well as in grade 3 tumours both tests performed similarly. The sensitivity of BTA test compared to VUC in detecting recurrent tumours was higher (24 % vs. 9%, p < 0.01), but VUC had more specificity than BTA test (99% vs. 80%, p < 0.001). CONCLUSIONS: BTA test was superior to VUC in detecting BC and its recurrence. The simultaneous use of the BTA test and VUC did not add any information in detecting tumour growth in the bladder as compared to the BTA test alone.

Asunto(s)

Pruebas de Fijación de Látex , Neoplasias de la Vejiga Urinaria/diagnóstico , Orina/citología , Anciano , Citodiagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Estudios Prospectivos , Sensibilidad y Especificidad

RESUMEN

OBJECTIVES: p21(waf1/cip1) protein is a cyclin-dependent kinase inhibitor able to arrest the cell at the G1 phase by inhibiting DNA replication through interaction with proliferating cell nuclear antigen (PCNA). Experimental analyses of human bladder cancer cell lines show that p21 might be considered a tumour suppressor gene since it is able to induce apoptosis like p53. The prognostic value and expression of p21(waf1/cip1) is incompletely studied in bladder cancer at present. METHODS: The expression of p21 protein was immunohistochemically analysed in paraffin-embedded specimens of 186 patients with primary transitional cell bladder tumours. The results of immunohistochemical analysis were related to known prognostic factors and complete long clinical follow-up data (over 11 years). RESULTS: The expression of p21(waf1/cip1) protein was significantly related to DNA ploidy, S phase fraction, mitotic index, apoptotic index, morphometric nuclear factors, and the expression of p53 and PCNA proteins, whereas it was unrelated to grade or TNM classification. In univariate survival analysis, the expression of p21(waf1/cip1) protein was not significantly related to prognosis. Independent prognostic factors were T category, papillary status and mitotic index. CONCLUSION: The results indicate that although the expression of p21(waf1/cip1) protein is related to indicators of cell proliferation, apoptosis and p53 expression, it has no better prognostic value than already established prognostic factors in bladder cancer.

Asunto(s)

Biomarcadores de Tumor/análisis , Carcinoma de Células Transicionales/química , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Ciclinas/análisis , Inhibidores Enzimáticos/análisis , Neoplasias de la Vejiga Urinaria/química , Adulto , Anciano , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , División Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/análisis , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología