Large cell neuroendocrine - Adenocarcinona mixed tumour of colon: Collision tumour with peculiar behaviour. What do we know about these tumours?

INTRODUCTION: Mixed glandular-endocrine carcinomas are rare tumours of gastrointestinal tract (MANEC). They are more frequent in stomach and hardly one hundred cases have been described in colon. According to Lewis, they are classified into collision (side by side pattern), composite (intermingled) or amphicrine (neuroendocrine and glandular features inside a same cell). Collision tumours are related to biclonal theory: two simultaneous cancerogenic events. Conversely, multidirectional differentiation from a stem cell is accepted as origin of composite tumours. The aim of this paper is to analyse the behaviour of these tumours, with an especial concern about how these tumours metastasise, and the different theories about carcinogenesis. PRESENTATION OF CASE: We report a rare case of collision adenocarcinoma-large cell neuroendocrine tumour of colon that after a three-year period of follow-up has presented a retroperitoneal recurrence that features adenocarcinoma and large cell neuroendocrine components. DISCUSSION: After an exhaustive review of the English literature, we found that only two cases of collision tumour of colon with metastases showing glandular and endocrine components have been described up to date, so we report the third case, and the first happening in transverse colon. CONCLUSION: We conclude that not all collision tumours follow the biclonal theory and more studies are needed to clarify the origin of these neoplasms, and consequently, to reach an adequate treatment.

Influencia de la presión atmosférica sobre la incidencia de neumotórax espontáneo / Influence of atmospheric pressure on the incidence of spontaneous pneumothorax

INTRODUCCIÓN: Se analiza la relación entre incidencia de neumotórax espontáneo idiopático (NEI) y presión atmosférica (PA). MÉTODOS: Se incluyen 288 casos de NEI, 229 hombres y 59 mujeres. Se recogió PA el día del diagnóstico, PA en los 3 días previos y PA media mensual. Se analizó la asociación entre incidencia de NEI y PA mediante cálculo de razón de incidencia estandarizada (RIE) y regresión de Poisson. RESULTADOS: La PA el día del ingreso (media ± desviación típica) (1.017,9 ± 7 hectopascales [hPa]), fue más elevada que la PA media mensual (1.016,9 ± 4,1 hPa; p = 0,005). Hubo un patrón de distribución mensual del NEI, con mayor incidencia los meses de enero, febrero y septiembre y menor en abril. Cuando la PA fue inferior a 1.014 hPa se registraron menos casos de los que estadísticamente hubiera sido esperable encontrar (58/72 casos); sin embargo, cuando la PA fue superior a 1.019 hPa se registraron más casos de los esperados (109/82 casos) (RIE = 1,25; IC95%: 1,04-1,51). El riesgo de NEI aumentó 1,15 veces (IC 95%: 1,05-1,25; p = 0,001) por cada hPa de PA, independientemente del género, la edad y la PA media mensual. Se observó relación dosis-respuesta, con aumentos progresivos del riesgo (IRR = 1,06 cuando la PA fue 1.014-1.016 hPa; 1,17 cuando la PA fue 1.016-1.019 hPa y 1,69 cuando la PA fue superior a 1.019 hPa) (p de tendencia = 0,089). CONCLUSIONES: La PA es factor de riesgo para la aparición de neumotórax espontáneo idiopático

BACKGROUND: This study analyses the relationship between the incidence of idiopathic spontaneous pneumothorax (ISP) and atmospheric pressure (AP). METHODS: A total of 288 cases of ISP were included, 229 men and 59 women. The AP of the day of diagnosis, of the 3 prior days and the monthly average was registered. The association between the incidence of ISP and AP was analyzed by calculating standardized incidence ratio (SIR) and Poisson regression. RESULTS: The AP on the day of admission (mean ± standard deviation) (1,017.9 ± 7 hectopascals [hPa]) was higher than the monthly average AP (1,016.9 ± 4.1 hPa) (P=.005). There was a monthly distribution pattern of ISP with the highest incidence in the months of January, February and September and the lowest in April. When AP was less than 1,014 hPa, there were fewer cases registered than what would statistically have been expected (58/72 cases). In contrast, when the pressure was higher than 1,019 hPa, the registered cases were more than expected (109/82 cases) (SIR = 1.25; 95% CI: 1.04 to 1.51). The risk of ISP increased 1.15 times (95% CI: 1.05 to 1.25, P = .001) for each hPa of AP, regardless of sex, age and monthly average AP. A dose-response relationship was observed, with progressive increases in risk (IRR = 1.06 when the AP was 1,014-1016 hPa; 1.17 hPa when the AP was 1,016-1,019 hPa and 1.69 when AP was superior to 1,019 hPa) (P for trend = .089). CONCLUSION: The AP is a risk factor for the onset of idiopathic spontaneous pneumothorax

Influence of atmospheric pressure on the incidence of spontaneous pneumothorax.

BACKGROUND: This study analyses the relationship between the incidence of idiopathic spontaneous pneumothorax (ISP) and atmospheric pressure (AP). METHODS: A total of 288 cases of ISP were included, 229 men and 59 women. The AP of the day of diagnosis, of the 3 prior days and the monthly average was registered. The association between the incidence of ISP and AP was analyzed by calculating standardized incidence ratio (SIR) and Poisson regression. RESULTS: The AP on the day of admission (mean±standard deviation) (1,017.9±7 hectopascals [hPa]) was higher than the monthly average AP (1,016.9±4.1 hPa) (P=.005). There was a monthly distribution pattern of ISP with the highest incidence in the months of January, February and September and the lowest in April. When AP was less than 1,014 hPa, there were fewer cases registered than what would statistically have been expected (58/72 cases). In contrast, when the pressure was higher than 1,019 hPa, the registered cases were more than expected (109/82 cases) (SIR=1.25; 95% CI: 1.04 to 1.51). The risk of ISP increased 1.15 times (95% CI: 1.05 to 1.25, P=.001) for each hPa of AP, regardless of sex, age and monthly average AP. A dose-response relationship was observed, with progressive increases in risk (IRR=1.06 when the AP was 1,014-1016 hPa; 1.17 hPa when the AP was 1,016-1,019 hPa and 1.69 when AP was superior to 1,019 hPa) (P for trend=.089). CONCLUSION: The AP is a risk factor for the onset of idiopathic spontaneous pneumothorax.

Es segura la hernioplastia sin sutura como opción para tratar las hernias de pared abdominal ? Estudio prospectivo con un adhesivo tisular sintético (n-hexil-alfa-cianoacrilato) / Effect of vitamin D deficiency on hypocalcaemia after total thyroidectomy due to benign goitre

Introducción El uso de adhesivos tisulares puede ser una alternativa a la sutura en la fijación de la malla, pero su experiencia clínica es muy limitada. Material y métodos Estudio prospectivo y descriptivo en un grupo de 35 pacientes con hernias inguinales operados mediante hernioplastia sin sutura (20 vía abierta y 15 vía endoscópica); la prótesis se fijó con adhesivo sintético (n-hexil-α-cianoacrilato). Este grupo se ha comparado con uno control operado mediante hernioplastia utilizando suturas. Todos los pacientes seguían protocolo de cirugía mayor ambulatoria. Se han registrado variables peri- y postoperatorias. El seguimiento se realizó a la semana, al mes, a los 6 meses y al año. Resultados No ha existido morbilidad asociada con el uso del adhesivo tisular. Durante una mediana de 15 meses no se han detectado complicaciones ni recurrencias. En la hernioplastia abierta el uso del adhesivo disminuye de forma significativa el tiempo quirúrgico (30min versus 62min, p=0,001), el dolor postoperatorio (de 2,4 a 4,5 a la semana, p < 0,001) y el consumo de analgésico (de 7 a 14 días, p < 0,001). En el abordaje laparoscópico se demuestran diferencias significativas a favor del adhesivo en el dolor (p=0,001 a las 24h) y consumo de analgésicos (p <0,001). El análisis económico demuestra un ahorro anual de 117.461,2 euros (sobre 460 hernias).Conclusión El uso de un adhesivo tisular sintético (n-hexil-α-cianocrilato) es seguro como medio de fijación en las hernioplastias no complejas en pacientes sin comorbilidad, con buenos resultados postoperatorios (AU)

Introduction: The purpose of this study was to analyse the relationship between preoperative serum levels of vitamin D and postoperative hypocalcaemia after total thyroidectomy. Material and methods: A prospective observational study was conducted on 113 patients treated by total thyroidectomy due to benign disease. Preoperative vitamin D serum levels and postoperative albumin-corrected calcium and parathormone (PTH) levels were determined. Sensitivity, specificity, positive predictive value and negative predictive value ofvitamin D and PTH levels, respectively, in the diagnosis of postoperative hypocalcaemia were calculated. Results: Hypocalcaemia was diagnosed in 44 (38.9%) patients. Vitamin D levels were signifi-cantly higher in the group of patients with normal postoperative calcium (median: 25.4 pg/mL; range: 4-60), compared to those who developed hypocalcaemia (median: 16.4 pg/mL; range: 6.3-46.9) (P = .001). Postoperative hypocalcaemia was more frequent in patients with vitamin D < 30 ng/mL (39/78) (50%), than among those with normal levels (5/35) (14.2%)(P = .001). Sensitivity, specificity, positive predictive value and negative predictive value were 88% and 68%, 43% and 82%, 50% and 71%, and 85% and 80% for vitamin D and PTH, respectively. Vitamin D and PTH showed independent prognostic values on the risk of hypocalcaemia. The OR associated with vitamin D < 30 ng/mL was 4.25 (95% CI: 1.31-13.78)(P = .016), and the OR of PTH < 13 pg/mL was 15.4 (95% CI: 4.83-49.1) (P < .001).Conclusion: Vitamin D deficiency is a risk factor of hypocalcaemia after total thyroidectomy for benign goitre. The vitamin D level provides independent prognostic information, which his complementary to that given by PTH (AU)

[Effect of vitamin D deficiency on hypocalcaemia after total thyroidectomy due to benign goitre]. / Efecto de la deficiencia de vitamina D sobre la hipocalcemia tras tiroidectomía total por bocio benigno.

INTRODUCTION: The purpose of this study was to analyse the relationship between preoperative serum levels of vitamin D and postoperative hypocalcaemia after total thyroidectomy. MATERIAL AND METHODS: A prospective observational study was conducted on 113 patients treated by total thyroidectomy due to benign disease. Preoperative vitamin D serum levels and postoperative albumin-corrected calcium and parathormone (PTH) levels were determined. Sensitivity, specificity, positive predictive value and negative predictive value of vitamin D and PTH levels, respectively, in the diagnosis of postoperative hypocalcaemia were calculated. RESULTS: Hypocalcaemia was diagnosed in 44 (38.9%) patients. Vitamin D levels were significantly higher in the group of patients with normal postoperative calcium (median: 25.4pg/mL; range: 4-60), compared to those who developed hypocalcaemia (median: 16.4pg/mL; range: 6.3-46.9) (P=.001). Postoperative hypocalcaemia was more frequent in patients with vitamin D < 30ng/mL (39/78) (50%), than among those with normal levels (5/35) (14.2%) (P=.001). Sensitivity, specificity, positive predictive value and negative predictive value were 88% and 68%, 43% and 82%, 50% and 71%, and 85% and 80% for vitamin D and PTH, respectively. Vitamin D and PTH showed independent prognostic values on the risk of hypocalcaemia. The OR associated with vitamin D < 30ng/mL was 4.25 (95% CI: 1.31-13.78) (P=.016), and the OR of PTH<13pg/mL was 15.4 (95% CI: 4.83-49.1) (P<.001). CONCLUSION: Vitamin D deficiency is a risk factor of hypocalcaemia after total thyroidectomy for benign goitre. The vitamin D level provides independent prognostic information, which is complementary to that given by PTH.

Caracterización de las variaciones de metales traza en suero y en orina en la práctica de motocross / Characterization of the trace metals variations in serum and in urine in the practice of motocross

Introducción: Existe poca literatura que estudie los cambios fisiológicos que se producen en la práctica del motocross, sobre todo en lo relativo a las variaciones de los elementos traza. La importancia de las funciones de dichos elementos en el ejercicio se ha descrito en numerosos estudios, participando en áreas como el metabolismo energético, la cadena de transmisión de electrones, los mecanismos de amortiguamiento de la acidosis o en la neutralización de los radicales libres, después del ejercicio físico. El objetivo de este estudio es describir y valorarlas posibles variaciones de estos elementos en la práctica de motocross, considerando que se trata de un esfuerzo tipificado como de fuerza-resistencia. Material y métodos: Se diseñó un estudio prospectivo y observacional con 12 competidores (de entre 21 y 38 años). Se recogieron parámetros analíticos antes y después de realizar dos carreras de competición de veinte minutos de duración. La intensidad de esfuerzo durante la prueba se controló mediante monitores de frecuencia cardíaca. Resultados: Las concentraciones séricas de hierro y zinc descendieron significativamente (p=0,01 y p<0,005), por el contrario, el cobre experimenta un aumento estadísticamente significativo (p<0,005). Las enzimas analizadas incrementan sus concentraciones en suero (p<0,005) así como los neutrófilos dentro de la fórmula leucocitaria (p=0,001). En orina, la presencia de zinc y cobre después de la actividad física es significativa (p<0,005), existiendo una correlación entre la proteinuria y el zinc (r=0,63; p<0,005). Los descensos de magnesio y selenio no son estadísticamente significativos. Conclusiones: La práctica del motocross supone un esfuerzo físico que provoca un descenso de las concentraciones séricas de zinc y hierro, al tiempo que se produce un incremento del cobre. La depleción en orina de cobre, zinc y proteínas se incrementa tras la realización de esfuerzos de esta modalidad deportiva, estando correlacionadas las concentraciones de zinc en orina con la proteinuria generada post-ejercicio (AU)

Introduction: There is little literature to study the physiological changes that occur in practice of motocross, especially respect to changes in trace elements. The importance of the functions of these elements has been described in numerous studies, Involved in areas such as energetic metabolism, electron transport chain, buffering mechanism of acidosis, and even neutralizing free radical generated after physical exercise. The aim of this study is to describe and assess the possible variations of these elements in the practice of motocross, considering that can be typified like a strength-endurance effort. Material and methods: We designed a prospective observational study with 12 competitors (ages from 21 to 38 years). Analytical parameters were collected before and after run two races of 20 minutes. The intensity of effort during the test was monitored using heart rate monitors. Results: Serum iron and zinc decreased significantly (p=0.01and p<0.005), however, copper experienced a statistically significant increase (p<0.005). The enzymes analyzed increased their serum concentrations (p<0.005) as well as neutrophils in the leukocyte count (p=0.001). In urine, the presence of zinc and copper after physical activity is significative (p<0.005), being a correlation between proteinuria and zinc (r=0.63, p<0.005). Decreases in magnesium and selenium were not statistically significant. Conclusions: Motocross practice involves physical effort, which causes a decrease in serum zinc and iron, while an increase of copper. Urine depletion of copper, zinc and protein is increased after perform the efforts of this sport, being a correlation between zinc concentrations in urine and proteinuria generated after exercise (AU)

Relación entre concentración intraoperatoria de parathormona y evolución postoperatoria del hiperparatiroidismo primario / Relationship between parathormone concentration during surgery and the post-operative outcome of primary hyperparathyroidism

Introducción Se analiza la relación entre la concentración intraoperatoria de parathormona (IOPTH) y la evolución a largo plazo de pacientes intervenidos por hiperparatiroidismo primario (HPTP). Pacientes y métodos Estudio prospectivo observacional que incluye 120 pacientes. Se realizaron tres determinaciones de PTH en sangre: basal, en el momento de localizar la glándula patológica y a los 10 minutos tras su extirpación. Se determinaron las concentraciones de calcio, PTH y vitamina D (25-OH-D3) durante el seguimiento. Resultados En 96 (80%) pacientes se observó disminución de IOPTH > 50% y el valor postextirpación volvió al rango normal (Grupo I), en 18 (15%) disminución > 50% pero el valor final se mantuvo superior al nivel normal (Grupo II) y en 6 (5%) la disminución fue<50% (Grupo III). Durante el seguimiento se detectó HPTP persistente en 6 pacientes (5%): uno en el Grupo I (1%), 3 (16,7%) en el II y 2 (33,3%) en el III (p<0,001). El riesgo de HPTP persistente fue superior en el Grupo II (odds ratio: 19; IC95%: 1,85-194) y en el III (odds ratio: 47; IC95%: 3,53-639). No se observaron casos de HPTP recidivado. Se detectó calcemia normal con PTH elevada en 20 pacientes del el Grupo I (20,8%), 11 (61,1%) en el II y 3 (50%) en el III (p<0,001). Estos pacientes presentaron menor concentración de vitamina D postoperatoria (17 ng/ml, rango: 24; frente a 28 ng/ml, rango: 21) (p=0,008) y mayor frecuencia de hipovitaminosis D (70,6% frente a 26,2%) (p>0,001).Conclusion El riesgo de persistencia del HPTP es superior cuando la IOPTH disminuye más del 50% pero se mantiene en niveles elevados (AU)

Introduction: The relationship between the intra-operative concentration of parathyroid hormone (IOPTH) and the long-term outcome of patients intervened due to primary hyperparathyroidism (PHPT).Patients and methods: A prospective observational study was performed with 120 patients. Three determinations were made of PTH in blood: baseline, when the diseases gland was located, and 10 minutes after its extirpation. The calcium, PTH and vitamin D (25-OH-D3)levels were measured during follow up. Results: A decrease in IOPTH > 50% was observed in 96 (80%) patients, and the postextirpation value returned to the normal range (Group I), in 18 (15%) a decrease of > 50%but the final value remained higher than normal (Group II) and in 6 (5%) the decrease was < 50% (Group III). Persistent PHPT was detected during follow up in 6 patients (5%): one in Group I (1%), 3 (16.7%) in II and 2 (33.3%) in group III (P < .001). The risk of persistent PHPT was higher in Group II (odds ratio: 19; 95% CI: 1.85-194) and in Group III (odds ratio: 47; 95% CI:3.53-639). There were no cases of recurrent PHPT. A normal calcium with an increased PTH was detected in 20 patients of Group I (20.8%), 11 (61.1%) in II and 3 (50%) in III (P < .001).These patients had a lower concentration of post-operative vitamin D (17 ng/ml, range: 24;compared to 28 ng/ml, range: 21) (P = .008) and higher frequency of hypovitaminosis D(70.6% compared to 26.2%) (P>.001). Conclusion: The risk of persistent PHPT is higher when the IOPTH decreases more than 50%but still remains high (AU)

[Relationship between parathormone concentration during surgery and the post-operative outcome of primary hyperparathyroidism]. / Relación entre concentración intraoperatoria de parathormona y evolución postoperatoria del hiperparatiroidismo primario.

INTRODUCTION: The relationship between the intra-operative concentration of parathyroid hormone (IOPTH) and the long-term outcome of patients intervened due to primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: A prospective observational study was performed with 120 patients. Three determinations were made of PTH in blood: baseline, when the diseases gland was located, and 10 minutes after its extirpation. The calcium, PTH and vitamin D (25-OH-D3) levels were measured during follow up. RESULTS: A decrease in IOPTH > 50% was observed in 96 (80%) patients, and the post-extirpation value returned to the normal range (Group I), in 18 (15%) a decrease of > 50% but the final value remained higher than normal (Group II) and in 6 (5%) the decrease was<50% (Group III). Persistent PHPT was detected during follow up in 6 patients (5%): one in Group I (1%), 3 (16.7%) in II and 2 (33.3%) in group III (P<.001). The risk of persistent PHPT was higher in Group II (odds ratio: 19; 95% CI: 1.85-194) and in Group III (odds ratio: 47; 95% CI: 3.53-639). There were no cases of recurrent PHPT. A normal calcium with an increased PTH was detected in 20 patients of Group I (20.8%), 11 (61.1%) in II and 3 (50%) in III (P<.001). These patients had a lower concentration of post-operative vitamin D (17 ng/ml, range: 24; compared to 28 ng/ml, range: 21) (P=.008) and higher frequency of hypovitaminosis D (70.6% compared to 26.2%) (P>.001). CONCLUSION: The risk of persistent PHPT is higher when the IOPTH decreases more than 50% but still remains high.

El estudio de instrumentos de viento se asocia con un patrón obstructivo en la espirometría de adolescentes con buena capacidad de resistencia aeróbica / Playing of wind instruments is associated with an obstructive pattern in the spirometry of adolescents with a good aerobic resistance capacity

ObjetivoExiste controversia en la literatura médica respecto al efecto beneficioso o perjudicial de la práctica con instrumentos musicales de viento sobre el sistema respiratorio. El objetivo de este estudio es analizar esta relación en sujetos jóvenes en periodo de aprendizaje, ponderando su nivel de condición física.DiseñoEstudio observacional transversal.EmplazamientoCentro Integrado de Enseñanzas Artísticas y Musicales (estudios musicales reglados de Grado Medio) y de Educación Primaria y Secundaria, de titularidad pública.ParticipantesJóvenes estudiantes de entre 13–17 años.Mediciones principalesSe recogieron parámetros epidemiológicos básicos (sexo, edad, peso, talla, estado de salud) y a cada sujeto se le realizó un test de condición física (prueba de aptitud cardiorespiratoria de «course navette»), y una espirometría forzada.ResultadosSe incluyeron 90 alumnos, 53 mujeres y 37 varones, de los cuales 32 eran instrumentistas de viento y 58 de otros instrumentos. Los 2 grupos fueron homogéneos respecto a sexo, edad e índice de masa corporal. El consumo máximo de oxígeno no mostró diferencias significativas (p=0,255), manifestando además un adecuado nivel de condición física respecto a la población general. La CVF fue normal y comparable en ambos grupos (p=0,197). El VEMS porcentual y el cociente VEMS/CVF fueron significativamente menores (p<0,0005) en el grupo de viento. La práctica con instrumentos de viento se comportó como variable predictora de VEMS/CVF patológico (<70%) en el análisis multivariante (p<0,0005).ConclusionesEl estudio de instrumentos de viento se asoció con un patrón espirométrico obstructivo en músicos jóvenes con un nivel normal de condición física(AU)

ObjectiveThere is controversy in the medical literature regarding the beneficial or detrimental effects of playing wind musical instruments on the respiratory system. The aim of this study is to analyse this relationship, taking the physical condition of the subjects into consideration.DesignCross-sectional observational study.SettingPublic institution with coordinated medium grade musical instruction and primary and secondary education.ParticipantsYoung performers (between 13 and 17 years).DataWe collected basic epidemiological parameters (gender, age, weight, size, heath status), and each subject underwent a fitness test (“course navette” cardiorespiratory fitness test) and a forced spirometry.ResultsWe included 90 students, 53 females and 37 males. Thirty two were wind instrument players and 58 studied other instruments. The two groups were homogeneous with respect to gender, age and body mass index. The maximum oxygen uptake showed no significant difference (P=0.255), further demonstrating an adequate level of fitness compared to the general population. FVC was normal and similar in both groups (P=0.197). The FEV1 percentage and the FEV1/FVC ratio were significantly lower (P<0.0005) in the “wind” group. Practice with wind instruments behaved as a predictor of pathological FEV1/FVC (<70%) in the multivariate analysis (P<0.0005).ConclusionThe study of wind instruments was associated with an obstructive spirometric pattern in young musicians with a normal level of physical fitness(AU)

[Playing of wind instruments is associated with an obstructive pattern in the spirometry of adolescents with a good aerobic resistance capacity]. / El estudio de instrumentos de viento se asocia con un patrón obstructivo en la espirometría de adolescentes con buena capacidad de resistencia aeróbica.

OBJECTIVE: There is controversy in the medical literature regarding the beneficial or detrimental effects of playing wind musical instruments on the respiratory system. The aim of this study is to analyse this relationship, taking the physical condition of the subjects into consideration. DESIGN: Cross-sectional observational study. SETTING: Public institution with coordinated medium grade musical instruction and primary and secondary education. PARTICIPANTS: Young performers (between 13 and 17 years). DATA: We collected basic epidemiological parameters (gender, age, weight, size, heath status), and each subject underwent a fitness test ("course navette" cardiorespiratory fitness test) and a forced spirometry. RESULTS: We included 90 students, 53 females and 37 males. Thirty two were wind instrument players and 58 studied other instruments. The two groups were homogeneous with respect to gender, age and body mass index. The maximum oxygen uptake showed no significant difference (P=0.255), further demonstrating an adequate level of fitness compared to the general population. FVC was normal and similar in both groups (P=0.197). The FEV(1) percentage and the FEV(1)/FVC ratio were significantly lower (P<0.0005) in the "wind" group. Practice with wind instruments behaved as a predictor of pathological FEV1/FVC (<70%) in the multivariate analysis (P<0.0005). CONCLUSION: The study of wind instruments was associated with an obstructive spirometric pattern in young musicians with a normal level of physical fitness.

Herpesvirus saimiri transformation may help disclose inherent functional defects of mucosal T lymphocytes in patients with gastric adenocarcinoma.

To dissect the phenotypic and functional features of mucosal T lymphocytes in patients with gastric adenocarcinoma, we have used the Herpesvirus saimiri transformation procedure to achieve T-cell lines from gastric origin. Once achieved, cell function was assessed by in vitro stimulation with mitogens. CD2-specific monoclonal antibodies (alpha-CD2), alone or in combination with interleukin (IL)-2, rendered fewer counts in patients (34 408+/-3965 and 52 157+/-6473 c.p.m., respectively) than in controls (67 471+/-11 755 c.p.m., P<0.01 and 77 864+/-12 545 c.p.m., P<0.05, respectively). Likewise, CD3-based responses were defective in cancer cell lines: alpha-CD3 (54 794+/-9269 vs 86 104+/-10 341 c.p.m., P<0.01), alpha-CD3+IL-2 (57 789+/-8590 vs 88855+/-8516 c.p.m., P<0.01) and alpha-CD3+alpha-CD2 (52 130+/-7559 vs 120 852+/-16 552 c.p.m., P<0.01). Finally, IL-2 failed to adequately stimulate patient cell lines (39 310+/-4023 vs 60 945+/-9463 c.p.m., P<0.05). These results suggest that mucosal T lymphocytes in cancer patients are inherently impaired in their proliferative ability. This may be crucial in the control of tumour growth.

Expression of CD45 and proliferative response to CD3 as suitable classification markers of patients with gastric adenocarcinoma.

25 patients with resectable gastric adenocarcinoma, subdivided according to the absence or presence of residual neoplasic disease (RND- or RND+, respectively), were studied. Cytofluorometric analysis and proliferative responses to mitogens was performed in peripheral blood mononuclear cells of patients. When compared to healthy subjects, the percentage of CD3-expressing cells was significantly reduced in both groups of patients studied (p < 0.0001 in all instances). However, when CD45 is considered instead of (CD3, its expression is found to be significantly reduced only in the RND+ patients (72% +/- 11), when compared with the control group (96 +/- 1%, p < 0.0001). Likewise, cells from these patients significantly less proliferated when stimulated with monoclonal antibodies to CD3 than control cells (18,920 +/- 6,019 cpm vs. 42,697 +/- 1,798 cpm, p = 0.0036); a difference not found if RND- patients (33,619 +/- 11,733 cpm) were considered. We propose that the low expression of CD45 and the poor response to CD3 are markers that are able to identify the subgroup of patients in whom the disease will tend to progress more rapidly. We also suggest the use of such markers as additional criteria for the classification of patients with gastric adenocarcinoma or to identify patients who require more aggressive therapeutic strategies.

Variación del valor pronóstico de la proteína p53 en relación con el estadio tumoral en pacientes con adenocarcinoma colorrectal / Variation in the prognostic value of p53 protein in relation to tumoral stage in patients with colorectal adenocarcinoma

Objetivo. Analizar el valor pronóstico que posee la proteína p53 en cada estadio tumoral, como indicador de riesgo de recidiva. Pacientes y método. Estudio prospectivo de una cohorte de 288 pacientes intervenidos por adenocarcinoma colorrectal. Cuarenta y dos pacientes (14,6%) se encontraban en estadio I de la clasificación TNM (tu-mor-nodo-metástasis); 144 (50%), en estadio II, y 102 (35,4%), en estadio III. Se analizaron, en muestras tu-morales fijadas en formol y parafinadas, variables histopatológicas y se determinaron mediante inmunohistoquímica las proteínas p53 (anticuerpo DO7) y PCNA (proliferative cell nuclear antigen) (anticuerpo PC10). Se analizaron los resultados de p53 en cada una de las categorías de las variables clínicas e histopatológicas. Se calculó la supervivencia sin recidiva mediante el método de Kaplan-Meier. Se analizó el valor de cada variable como indicador predictivo de aparición de recidiva tumoral mediante análisis de regresión de Cox. Se calcularon las hazard ratio y los intervalos de confianza (IC) del 95%, como indicadores del riesgo relativo. El análisis se aplicó en toda la cohorte de pacientes y, posteriormente, fue repetido en cada estadio tumoral TNM por separado. Resultados. Los tumores con sobreexpresión de proteína p53 desarrollaron con mayor frecuencia recidiva tumoral y presentaron menor supervivencia sin recurrencia a los 5 años de seguimiento. Sin embargo, únicamente en los tumores en estadio III la asociación entre expresión de p53 y evolución postoperatoria alcanzó significación estadística. En este subgrupo de pacientes, la supervivencia sin recidiva a los 60 meses de seguimiento fue del 60% en los tumores con p53 negativo y del 26% en aquellos con p53 positivo (p = 0,010). En el análisis multivariante, p53 se mostró como un factor pronóstico independiente asociado a un riesgo elevado de recidiva en tumores en estadio III (hazard ratio = 2,76; IC del 95%, 1,29-5,9; p = 0,009). La sobreexpresión de p53 aportó valor pronóstico como indicador de riesgo elevado de recidiva en forma de metástasis (hazard ratio = 2,23; IC del 95%, 1,04-4,75) y no como factor pronóstico de recidiva locorregional. No se observó relación entre el estado de la proteína p53 y el efecto de la quimioterapia adyuvante postoperatoria. Conclusión. La proteína p53 no posee el mismo valor como factor pronóstico en todos los estadios tu-morales. Esta proteína únicamente posee valor predictivo indicativo de riesgo elevado de recidiva en el subgrupo de pacientes con tumores en estadio III (AU)

Objective. To analyze the prognostic value of p53 protein as a marker of recurrence risk in each tumoral stage. Patients and method. A prospective study of a cohort of 288 patients who underwent surgery for colo-rectal adenocarcinoma was performed. Stage 1 of the tumor-node-metastasis (TNM) classification was found in 42 patients (14.6%), stage II in 144 (50%) and stage III in 102 (35.4%). Histopathological variables were examined in tumor samples fixed in formol and embedded in paraffin and p53 (DO7 antibody) and proliferative cell nuclear antigen (PC-10 antibody) proteins were determined using immunohistochemistry. The results of p53 were analyzed in each of the categories of clinical and histopathological variables. Recurrence-free survival was calculated using the Kaplan-Meier method. The value of each variable as a predictive marker for tumoral recurrence was analyzed using Cox regression analysis. Hazard ratios and 95% confidence intervals were calculated as indicators of relative risk. The analysis was applied to the whole cohort and was subsequently repeated in each TNM tumoral stage separately. Results. Tumors with p53 protein overexpression more frequently recurred and showed lower recurren-ce-free survival at 5 years. However, the association between p53 expression and postoperative outcome was statistically significant in stage III tumors only. In this subgroup of patients, recurrence-free survival at 60 months was 60% in p53-negative tumors and was 26% in p53-positive tumors (p = 0.010). In the multivariate analysis, p53 was an independent prognostic factor associated with a high risk of recurrence in stage III tumors (hazard ratio = 2.76; 95% CI, 1.29-5.9; p = 0.009). Overexpression of p53 showed prognostic value as a marker of high risk of recurrence in the form of metastases (hazard ratio = 2.23; 95% CI, 1.04-4.75), but not as a prognostic marker of locoregional recurrence. No relationship was found between the state of p53 protein and the effect of postoperative adjuvant therapy. Conclusion. The p53 protein does not have the same prognostic value in all tumoral stages. This protein is only predictive of high recurrence risk in the subgroup of patients with stage III tumors (AU)

[Variation in the prognostic value of p53 protein in relation to tumoral stage in patients with colorectal adenocarcinoma]. / Variación del valor pronóstico de la proteína p53 en relación con el estadio tumoral en pacientes con adenocarcinoma colorrectal.

OBJECTIVE: To analyze the prognostic value of p53 protein as a marker of recurrence risk in each tumoral stage. PATIENTS AND METHOD: A prospective study of a cohort of 288 patients who underwent surgery for colorectal adenocarcinoma was performed. Stage 1 of the tumor-node-metastasis (TNM) classification was found in 42 patients (14.6%), stage II in 144 (50%) and stage III in 102 (35.4%). Histopathological variables were examined in tumor samples fixed in formol and embedded in paraffin and p53 (DO7 antibody) and proliferative cell nuclear antigen (PC-10 antibody) proteins were determined using immunohistochemistry. The results of p53 were analyzed in each of the categories of clinical and histopathological variables. Recurrence-free survival was calculated using the Kaplan-Meier method. The value of each variable as a predictive marker for tumoral recurrence was analyzed using Cox regression analysis. Hazard ratios and 95% confidence intervals were calculated as indicators of relative risk. The analysis was applied to the whole cohort and was subsequently repeated in each TNM tumoral stage separately. RESULTS: Tumors with p53 protein overexpression more frequently recurred and showed lower recurrence-free survival at 5 years. However, the association between p53 expression and postoperative outcome was statistically significant in stage III tumors only. In this subgroup of patients, recurrence-free survival at 60 months was 60% in p53-negative tumors and was 26% in p53-positive tumors (p=0.010). In the multivariate analysis, p53 was an independent prognostic factor associated with a high risk of recurrence in stage III tumors (hazard ratio=2.76; 95% CI, 1.29-5.9; p=0.009). Overexpression of p53 showed prognostic value as a marker of high risk of recurrence in the form of metastases (hazard ratio=2.23; 95% CI, 1.04-4.75), but not as a prognostic marker of locoregional recurrence. No relationship was found between the state of p53 protein and the effect of postoperative adjuvant therapy. CONCLUSION: The p53 protein does not have the same prognostic value in all tumoral stages. This protein is only predictive of high recurrence risk in the subgroup of patients with stage III tumors.