A Tetra-Panel of Serum Circulating miRNAs for the Diagnosis of the Four Most Prevalent Tumor Types.

The purpose of this study is to clinically validate a series of circulating miRNAs that distinguish between the 4 most prevalent tumor types (lung cancer (LC); breast cancer (BC); colorectal cancer (CRC); and prostate cancer (PCa)) and healthy donors (HDs). A total of 18 miRNAs and 3 housekeeping miRNA genes were evaluated by qRT-PCR on RNA extracted from serum of cancer patients, 44 LC, 45 BC, 27 CRC, and 40 PCa, and on 45 HDs. The cancer detection performance of the miRNA expression levels was evaluated by studying the area under the curve (AUC) of receiver operating characteristic (ROC) curves at univariate and multivariate levels. miR-21 was significantly overexpressed in all cancer types compared with HDs, with accuracy of 67.5% (p = 0.001) for all 4 tumor types and of 80.8% (p < 0.0001) when PCa cases were removed from the analysis. For each tumor type, a panel of miRNAs was defined that provided cancer-detection accuracies of 91%, 94%, 89%, and 77%, respectively. In conclusion, we have described a series of circulating miRNAs that define different tumor types with a very high diagnostic performance. These panels of miRNAs would constitute the basis of different approaches of cancer-detection systems for which clinical utility should be validated in prospective cohorts.

A different surgical approach for cardiophrenic lymph node resection in advanced ovarian cancer.

OBJECTIVE: To describe the surgical technique of a subxiphoid approach to remove cardiophrenic lymph nodes in women with advanced ovarian cancer. MATERIALS AND METHODS: The first step is to dissect and separate the anterior insertions of the diaphragm at the xiphoid appendix. Thus, the parietal peritoneum and the upper fibres of the transversus abdominis muscle are incised. Then, the anteroinferior mediastinum is identified and dissected. Diaphragmatic deinsertion may be extended 5-7 cm laterally to the xiphoid appendix following the inferior costal margin according with the localization of the enlarged lymph nodes. Thus, the dissection of the anterolateral cardiophrenic space allows the identification of both pleura. In addition, the vertical dissection of the anterior cardiophrenic space allows the removal of enlarged lymph nodes. However, it is important to bear in mind at this time that the unintentional opening of the pleura is possible. To reduce this risk, a careful dissection of the anterior cardiophrenic fat tissue is essential. Moreover, a careful dissection will avoid damage at the left phrenic nerve as well as the left pericardiophrenic artery and vein. After removing the cardiophrenic fat tissue, the diaphragm is sutured at the lower costal margin by using separated stiches of absorbable 2-0 suture. CONCLUSION: The subxiphoid approach to resect cardiophrenic lymph nodes is a feasible surgical technique. In addition, it reduces the possibility of opening the pleural cavity, while avoiding a diaphragmatic incision, in comparison with the standard trans-diaphragmatic surgical approach.

A unique set of 6 circulating microRNAs for early detection of non-small cell lung cancer.

INTRODUCTION: Circulating microRNAs are promising biomarkers for diagnosis, predication and prognostication of diseases. Lung cancer is the cancer disease accountable for most cancer deaths, largely due to being diagnosed at late stages. Therefore, diagnosing lung cancer patients at an early stage is crucial for improving the outcome. The purpose of this study was to identify circulating microRNAs for detection of early stage lung cancer, capable of discriminating lung cancer patients from those with chronic obstructive pulmonary disease (COPD) and healthy volunteers. RESULTS: We identified 7 microRNAs separating lung cancer patients from controls. By using RT-qPCR, we validated 6 microRNAs (miR-429, miR-205, miR-200b, miR-203, miR-125b and miR-34b) with a significantly higher abundance in serum from NSCLC patients. Furthermore, the 6 miRNAs were validated in a different dataset, revealing an area under the receiver operating characteristic curve of 0.89 for stage I-IV and 0.88 for stage I/II. MATERIALS AND METHODS: We profiled the expression of 754 unique microRNAs by TaqMan Low Density Arrays, and analyzed serum from 38 patients with NSCLC, 16 patients suffering from COPD and 16 healthy volunteers from Norway, to explore their potential as diagnostic biomarkers. For validation, we analyzed serum collected from high-risk individuals enrolled in the Valencia branch of the International Early Lung Cancer Action Program screening trial (n=107) in addition to 51 lung cancer patients. CONCLUSIONS: Considering the accessibility and stability of circulating miRNAs, these 6 microRNAs are promising biomarkers as a supplement in future screening studies.

Carcinoma broncogénico en pacientes con trasplante de órgano sólido. Papel de la cirugía / Bronchogenic carcinoma in patients undergoing solid organ transplant. The role of surgery

Introducción La incidencia de neoplasias es mayor en la población sometida a un trasplante de órgano sólido; sin embargo, la de carcinoma broncogénico (CB) es controvertida. Nuestro objetivo es comprobar la incidencia de CB en pacientes trasplantados y el papel de la cirugía. Material y métodos Hasta diciembre de 2006, en el Hospital Universitario La Fe, 3.596 pacientes recibieron un trasplante de órgano sólido; 24 (0,7%) pacientes desarrollaron un CB, de los que 6 fueron operados. La supervivencia se estimó mediante la prueba de Kaplan-Meier. Resultados Tres pacientes habían recibido trasplante hepático; 2, renal y 1, cardíaco. Todos eran varones y tenían historia previa de tabaquismo. La media de edad fue 58,6 años. El intervalo entre trasplante y diagnóstico de CB fue 38,1 meses. El carcinoma epidermoide fue el más frecuente. El tamaño tumoral medio fue de 3,6cm. Un tumor fue clasificado en estadio IA patológico; cuatro, en IB y uno, en IIB. Ningún paciente falleció en el perioperatorio y sólo uno presentó un hemotórax. La media de estancia fue 8,5 días. Un paciente falleció por metástasis de CB, otro por sepsis, otro por insuficiencia renal y 3 permanecían vivos. La supervivencia a los 5 años fue del 40%.ConclusionesLa incidencia de CB y la tasa de diagnósticos en estadios precoces no difieren de las observadas en pacientes no sometidos a trasplante, lo que cuestionaría el papel de la inmunosupresión en la génesis y la agresividad del CB en pacientes trasplantados. La cirugía puede ofrecer resultados aceptables en estadios precoces, con una morbimortalidad perioperatoria asumible (AU)

Background The incidence of neoplastic diseases is higher in patients undergoing solid organ transplant. However, the incidence of bronchogenic carcinoma (BC) is controversial. The objective of our study was to determine the incidence of BC in a large cohort of transplant patients and the role of surgery. Material and methods Until December 2006, 3596 patients underwent solid organ transplant at our institution; 24 (0.7%) patients subsequently developed BC, of which 6 (24%) were classified as clinical stage I and submitted to surgical treatment. Survival was estimated by the Kaplan-Meier method. Results Three patients received a liver transplant, two a kidney transplant and one a heart transplant. All were male and all had a smoking history. Mean age was 58.6 years. Two patients had cough, one accompanied by bloody expectoration, and BC was an incidental finding in the remaining cases. The interval between transplant and diagnosis of BC was 38.1 months. Epidermoid carcinoma was the most frequent histological type. Mean tumour size was 3.6cm (range, 1.3–6). One tumour was classified as pathological stage IA, four as stage IB and one as IIB due to parietal pleural invasion. No patient died during the perioperative period and only one had a haemothorax which resolved with chest tube drainage. Mean hospital stay was 8.5 days (range, 7–11). The immunosuppression regimen was maintained continuously. In subsequent follow-up, one patient died from BC metastasis, one from sepsis, one from chronic renal failure, and three remained alive. The probability of survival at 5 years was 40%, and median survival was established at 5 years Conclusions The incidence of BC in patients undergoing solid organ transplant and the proportion of patients diagnosed in early stages does not differ from non-transplant patients diagnosed with BC, which questions the role of immunosuppression in the genesis and aggressiveness of BC in transplant patients. Surgery may offer acceptable results in early stages, with acceptable rates of perioperative morbidity and mortality (AU)

[Bronchogenic carcinoma in patients undergoing solid organ transplant. The role of surgery]. / Carcinoma broncogénico en pacientes con trasplante de órgano sólido. Papel de la cirugía.

BACKGROUND: The incidence of neoplastic diseases is higher in patients undergoing solid organ transplant. However, the incidence of bronchogenic carcinoma (BC) is controversial. The objective of our study was to determine the incidence of BC in a large cohort of transplant patients and the role of surgery. MATERIAL AND METHODS: Until December 2006, 3596 patients underwent solid organ transplant at our institution; 24 (0.7%) patients subsequently developed BC, of which 6 (24%) were classified as clinical stage I and submitted to surgical treatment. Survival was estimated by the Kaplan-Meier method. RESULTS: Three patients received a liver transplant, two a kidney transplant and one a heart transplant. All were male and all had a smoking history. Mean age was 58.6 years. Two patients had cough, one accompanied by bloody expectoration, and BC was an incidental finding in the remaining cases. The interval between transplant and diagnosis of BC was 38.1 months. Epidermoid carcinoma was the most frequent histological type. Mean tumour size was 3.6cm (range, 1.3-6). One tumour was classified as pathological stage IA, four as stage IB and one as IIB due to parietal pleural invasion. No patient died during the perioperative period and only one had a haemothorax which resolved with chest tube drainage. Mean hospital stay was 8.5 days (range, 7-11). The immunosuppression regimen was maintained continuously. In subsequent follow-up, one patient died from BC metastasis, one from sepsis, one from chronic renal failure, and three remained alive. The probability of survival at 5 years was 40%, and median survival was established at 5 years. CONCLUSIONS: The incidence of BC in patients undergoing solid organ transplant and the proportion of patients diagnosed in early stages does not differ from non-transplant patients diagnosed with BC, which questions the role of immunosuppression in the genesis and aggressiveness of BC in transplant patients. Surgery may offer acceptable results in early stages, with acceptable rates of perioperative morbidity and mortality.

[Stage IB non-small cell lung cancer: impact of the number of lymph nodes examined on survival]. / Carcinoma broncogénico no microcítico en estadio IB. Impacto del número de adenopatías analizadas en la supervivencia.

INTRODUCTION AND OBJECTIVES: To determine the causes of death in patients operated on for stage IB non-small cell lung cancer (NSCLC) and to assess the impact on survival of the number of lymph nodes removed. PATIENTS AND METHOD: We studied 300 patients operated on for stage IB NSCLC. Only palpable or visible lymph nodes were excised. Kaplan-Meier survival estimates were calculated and the survival curves were compared using the log-rank test. RESULTS: The mean (SD) age of the patients was 62.9 (9.7) years; 280 were men, 20 were women. Pneumonectomy was performed in 84 patients, lobectomy in 186, double lobectomy in 23, and segmentectomy in 7. Squamous cell carcinoma was the most common histologic type. The mean number of lymph nodes excised was 5.05 (5.01). At the time of the study 201 patients (67%) had died, 63.2% from causes related to the NSCLC. Overall 5-year survival for the patient series was 51.9% (median, 5.50 years; 95% confidence interval [CI], 4.14-6.87 years), though the 5-year survival rate was 61.87% after non-NSCLC-related deaths were excluded (median, 11.05 years; 95% CI, 7.63-14.48 years). Tumor size and the number of lymph nodes examined significantly affected survival. In the multivariate analysis, these 2 variables were also significantly correlated with the risk of death from NSCLC (P<.0001), with relative risks of 1.158 (95% CI, 1.081-1.240) and 0.387 (95% CI, 0.254-0.591), respectively. CONCLUSION: Besides being affected by stage and tumor size, survival in patients operated on for stage IB NSCLC is significantly influenced by the total number of lymph nodes examined. Therefore, surgical treatment of such patients should include the examination of as many lymph nodes as possible.

Carcinoma broncogénico no microcítico en estadio IB. Impacto del número de adenopatías analizadas en la supervivencia / Stage IB Non-Small Cell Lung Cancer: Impact of the Number of Lymph Nodes Examined on Survival

Introducción y objetivos determinar las causas de mortalidad en los pacientes operados de un carcinoma broncogénico no microcítico (CBNM) en estadio IB, así como el impacto que en la supervivencia tiene el número de adenopatías analizadas. Pacientes y métodose ha estudiado a 300 pacientes operados de CBNM en estadio IB patológico. Sólo se extirparon los ganglios palpables o visibles. La supervivencia se analizó con el método de Kaplan-Meier y las curvas se compararon mediante el test de rangos logarítmicos. Resultadosla edad media (±desviación estándar) de los pacientes (280 varones) era de 62,9±9,7 años. Se realizaron 84 neumonectomías, 186 lobectomías, 23 bilobectomías y 7 segmentectomías. La histología más frecuente fue el carcinoma epidermoide. La media del número de ganglios extirpados fue 5,05±5,01. En el momento del estudio, 201 pacientes (67%) habían fallecido, el 63,2% por causas relacionadas con el CBNM. La supervivencia global de la serie a los 5 años se estableció en el 51,9% (mediana: 5,50 años; intervalo de confianza [IC] del 95%, 4,14¿6,87), mientras que la supervivencia a los 5 años relacionada con el CBNM se estableció en el 61,87% (mediana: 11,05 años; IC del 95%, 7,63-14,48). El tamaño tumoral y el número de adenopatías analizadas condicionaron significativamente la supervivencia. En el análisis multivariante mantuvieron la significación estadística (p<0,0001) en su correlación con el riesgo de muerte por CBNM, con unos riesgos relativos de 1,158 (IC del 95%, 1,081¿1,240) y 0,387 (IC del 95%, 0,254¿0,591) respectivamente. Conclusiónademás del estadio y del tamaño tumoral, el número de adenopatías analizadas en total condiciona de forma significativa la supervivencia en pacientes intervenidos de CBNM en estadio IB patológico, por lo que el tratamiento quirúrgico debe incluir el análisis del mayor número posible de adenopatías(AU)

Introduction and Objectives To determine the causes of death in patients operated on for stage IB non-small cell lung cancer (NSCLC) and to assess the impact on survival of the number of lymph nodes removed. Patients and MethodWe studied 300 patients operated on for stage IB NSCLC. Only palpable or visible lymph nodes were excised. Kaplan-Meier survival estimates were calculated and the survival curves were compared using the log-rank test. ResultsThe mean (SD) age of the patients was 62.9 (9.7) years; 280 were men, 20 were women. Pneumonectomy was performed in 84 patients, lobectomy in 186, double lobectomy in 23, and segmentectomy in 7. Squamous cell carcinoma was the most common histologic type. The mean number of lymph nodes excised was 5.05 (5.01). At the time of the study 201 patients (67%) had died, 63.2% from causes related to the NSCLC. Overall 5-year survival for the patient series was 51.9% (median, 5.50 years; 95% confidence interval [CI], 4.14¿6.87 years), though the 5-year survival rate was 61.87% after non-NSCLC¿related deaths were excluded (median, 11.05 years; 95% CI, 7.63¿14.48 years). Tumor size and the number of lymph nodes examined significantly affected survival. In the multivariate analysis, these 2 variables were also significantly correlated with the risk of death from NSCLC (P<.0001), with relative risks of 1.158 (95% CI, 1.081¿1.240) and 0.387 (95% CI, 0.254¿0.591), respectively. ConclusionBesides being affected by stage and tumor size, survival in patients operated on for stage IB NSCLC is significantly influenced by the total number of lymph nodes examined. Therefore, surgical treatment of such patients should include the examination of as many lymph nodes as possible(AU)

[Balloon dilatation of the trachea as treatment for idiopathic tracheal stenosis]. / Dilatación traqueal neumática en el tratamiento de la estenosis traqueal idiopática.

The treatment of choice for idiopathic tracheal stenosis is tracheal resection and anastomosis, although some authors prefer more conservative management. Between January 1, 1996 and January 1, 2005, 8 patients-all women-with idiopathic tracheal stenosis were treated in the chest surgery department of the Hospital Universitario La Fe in Valencia, Spain. One case was treated by means of surgery and so was excluded from this study. The remaining 7 women were treated by tracheal balloon dilatation; 4 required just 1 dilatation (and remained asymptomatic), 2 required 2 dilatations, and 1 required 4 dilatations. The median symptom-free interval was 25.5 months, and there was no associated mortality or morbidity. We conclude that balloon dilatation, which was not associated with mortality or morbidity, is a suitable treatment option for idiopathic tracheal stenosis.

Dilatación traqueal neumática en el tratamiento de la estenosis traqueal idiopática / Balloon dilatation of the trachea as treatment for idiopathic tracheal stenosis

El tratamiento de elección de la estenosis traqueal idiopática es la resección-anastomosis traqueal, aunque algunos autores defienden el tratamiento conservador. Entre el 1 de enero de 1996 y el 1 de enero de 2005, en el Servicio de Cirugía Torácica del Hospital Universitario La Fe de Valencia se trató a 8 pacientes con estenosis traqueal idiopática, en un caso mediante cirugía, por lo que se excluyó del estudio. Todos los pacientes eran mujeres y 7 de ellas fueron tratadas mediante dilataciones traqueales neumáticas periódicas. Únicamente han precisado una dilatación 4 pacientes, que hasta ahora permanecen asintomáticas. Dos han necesitado una segunda dilatación y una paciente ha requerido 4. La mediana de intervalo sin síntomas fue de 25,5 meses. No hubo mortalidad ni morbilidad asociada. En conclusión, la dilatación traqueal neumática es una opción terapéutica adecuada en el tratamiento de la estenosis traqueal idiopática, sin morbimortalidad atribuible a la técnica

The treatment of choice for idiopathic tracheal stenosis is tracheal resection and anastomosis, although some authors prefer more conservative management. Between January 1, 1996 and January 1, 2005, 8 patients­all women­with idiopathic tracheal stenosis were treated in the chest surgery department of the Hospital Universitario La Fe in Valencia, Spain. One case was treated by means of surgery and so was excluded from this study. The remaining 7 women were treated by tracheal balloon dilatation; 4 required just 1 dilatation (and remained asymptomatic), 2 required 2 dilatations, and 1 required 4 dilatations. The median symptom-free interval was 25.5 months, and there was no associated mortality or morbility. We conclude that balloon dilatation, which was not associated with mortality or morbility, is a suitable treatment option for idiopathic tracheal stenosis

Donor fat embolism and primary graft dysfunction after lung transplantation.

Primary lung graft dysfunction is one of the major causes of perioperative morbidity and mortality in lung transplantation. Primary lung graft dysfunction is a clinical syndrome occurring in the immediate postoperative period after lung transplantation and is characterized by severe hypoxemia, pulmonary edema, and pulmonary infiltrates on chest x-ray film, requiring that the patient remain intubated and thus favoring pulmonary infection, sepsis, and subsequent multiple organ failure in the transplanted patient. It has recently been shown that unexpected pulmonary embolism is relatively common in the donor and is associated with primary lung graft dysfunction. However, we believe that only one case of primary lung graft dysfunction due to pulmonary fat embolism has been documented histologically in patients undergoing lung transplantation. The objective of this study is to report our experience with a case of primary lung graft dysfunction due to fat embolism in the donor lung detected in the morphologic study.

[Pneumonectomy in octogenarian patients]. / Neumonectomía en pacientes octogenarios.

Recent decades have witnessed a progressive aging of the population and a resulting increase in the numbers of elderly patients seeking health care. Since age and pneumonectomy are independent predictors of perioperative morbidity and mortality, such surgery is not recommended for octogenarian patients. We report the experience of 6 such patients who underwent pneumonectomy for squamous cell carcinoma in 5 cases and a typical carcinoid tumor in the sixth. There was no perioperative mortality; morbidity and survival rates were acceptable.

Neumonectomía en pacientes octogenarios / Pneumonectomy in octogenarian patients

En las últimas décadas hemos asistido a un progresivo envejecimiento de la población, por lo que cada vez es mayor el número de pacientes de edad avanzada que acuden a nuestras consultas. La edad y la práctica de una neumonectomía son factores predictivos independientes de morbimortalidad perioperatoria, por lo que no se aconseja realizar este tipo de cirugía en pacientes octogenarios. Describimos la experiencia de 6 pacientes octogenarios a quienes se realizó una neumonectomía por carcinoma epidermoide en 5 casos y carcinoide típico en el restante, sin mortalidad perioperatoria, con una morbilidad asumible y una supervivencia aceptable

Recent decades have witnessed a progressive aging of the population and a resulting increase in the numbers of elderly patients seeking health care. Since age and pneumonectomy are independent predictors of perioperative morbidity and mortality, such surgery is not recommended for octogenarian patients. We report the experience of 6 such patients who underwent pneumonectomy for squamous cell carcinoma in 5 cases and a typical carcinoid tumor in the sixth. There was no perioperative mortality; morbidity and survival rates were acceptable