Josep Maria Gimferrer

Experimental reconstruction of the canine trachea with a free revascularized small bowel graft

Extensive tracheal stenotic lesions caused by tracheomalacia or neoplasms represent a surgical challenge. Segmental tracheal substitution is sometimes required to obtain radical cure. We present an experimental study of 27 dogs undergoing replacement of the cervical trachea using a vascularized small bowel segment as a tubular graft. A silicone stent was placed in the lumen of the intestinal fragment and was removed the second week after operation. Endoscopic and histological examinations were performed between the first week and second month after operation, and rigidity of the graft was assessed in all cases. No evidence of anastomotic stricture or mucous formation was found. Microscopic examination showed the substitution of bowel mucosa by squamous epithelium as well as the development of connective tissue favoring the fixation of the skeletal muscular structures of the neck to the serous layer of the graft, thus avoiding collapse of the new airway.

Incidence of occult mediastinal node involvement in cN0 non-small-cell lung cancer patients after negative uptake of positron emission tomography/computer tomography scan.

OBJECTIVE This study sought to assess the real incidence of pN2 among patients with non-small-cell lung cancer (NSCLC) (cN0) with negative mediastinal uptake of 2-deoxy-2-(18F)-fluoro-o-glucose (FDG). METHODS During 30 consecutive months (January 2007-May 2009), all patients with NSCLC scheduled for surgery in our unit had a preoperative FDG-positron emission tomography (PET)/computed tomography (CT) in our institution, after a dedicated chest CT (n=259). Only patients with both FDG-PET/CT and negative dedicated chest CT scan (N1 and N2 nodes <1cm) were prospectively included (n=125). Patients with cN1/cN2/cN3 and patients who had undergone preoperative chemo-radiotherapy were excluded. No invasive surgical staging was carried out in this group and curative resection plus systematic mediastinal dissection was performed except in the event of unexpected oncological contraindication. All variables were collected prospectively and, when pathological information was obtained, all the cases were carefully reviewed. RESULTS Mediastinal assessment by FDG-PET/CT, negative predictive value (NPV) was 85.6%, confidence interval (CI): [77-91]; false negatives (FNs) for mediastinal lymph nodes involvement was 14.4% (18 cases). The pN2 stations most frequently involved were: 4R (six cases), seven (six cases) and five (five cases). Multiple-level pN2 occurred in six (4.8%) cases. Occult (pN2) lymph nodes were more frequent in women (p<0.01), adenocarcinoma (p<0.05) and pN1 (p<0.05). Pathological N2 prevalence for pN1 was 34 (27.7%). Considering pathological staging as the gold standard, the agreement was 70% and 47.5% for stage IA and IB (Kappas index: 0.72 and 0.76) and, in all patients, 47% (Kappas index: 0.27). In general, down-staging is more frequent than up-staging. CONCLUSIONS Mediastinal staging of NSCLC by FDG-PET/CT showed a considerable incidence of FNs. NPV is lower than previously reported and the preoperative mediastinal staging by 18FDG-PET/CT may jeopardise the accurate treatment for early stage NSCLC patients.

A Dual Role for KRT81: A miR-SNP Associated with Recurrence in Non-Small-Cell Lung Cancer and a Novel Marker of Squamous Cell Lung Carcinoma

MicroRNAs (miRNAs) play an important role in carcinogenesis through the regulation of their target genes. miRNA-related single nucleotide polymorphisms (miR-SNPs) can affect miRNA biogenesis and target sites and can alter microRNA expression and functions. We examined 11 miR-SNPs, including 5 in microRNA genes, 3 in microRNA binding sites and 3 in microRNA-processing machinery components, and evaluated time to recurrence (TTR) according to miR-SNP genotypes in 175 surgically resected non-small-cell lung cancer (NSCLC) patients. Significant differences in TTR were found according to KRT81 rs3660 (median TTR: 20.3 months for the CC genotype versus 86.8 months for the CG or GG genotype; P = 0.003) and XPO5 rs11077 (median TTR: 24.7 months for the AA genotype versus 73.1 months for the AC or CC genotypes; P = 0.029). Moreover, when patients were divided according to stage, these differences were maintained for stage I patients (P = 0.002 for KRT81 rs3660; P<0.001 for XPO5 rs11077). When patients were divided into sub-groups according to histology, the effect of the KRT81 rs3660 genotype on TTR was significant in patients with squamous cell carcinoma (P = 0.004) but not in those with adenocarcinoma. In the multivariate analyses, the KRT81 rs3660 CC genotype (OR = 1.8; P = 0.023) and the XPO5 rs11077 AA genotype (OR = 1.77; P = 0.026) emerged as independent variables influencing TTR. Immunohistochemical analyses in 80 lung specimens showed that 95% of squamous cell carcinomas were positive for KRT81, compared to only 19% of adenocarcinomas (P<0.0001). In conclusion, miR-SNPs are a novel class of SNPs that can add useful prognostic information on the clinical outcome of resected NSCLC patients and may be a potential key tool for selecting high-risk stage I patients. Moreover, KRT81 has emerged as a promising immunohistochemical marker for the identification of squamous cell lung carcinoma.

Determining the appropriate sleeve lobectomy versus pneumonectomy ratio in central non-small cell lung cancer patients: an audit of an aggressive policy of pneumonectomy avoidance

OBJECTIVE To study the outcomes of broncho ± angioplastic sleeve lobectomy (SL) versus pneumonectomy (PN), and the PN:SL ratio after an aggressive policy of parenchyma-sparing surgery to improve postoperative complications rate and long-term quality of life (QoL). METHODS A prospective study was conducted in 490 patients with non-small cell lung cancer between 2005 and 2009. All patients not suitable for standard lobectomy were scheduled for SL, if possible, or for PN; eight patients with functional impairment were directly scheduled for SL. RESULTS Of 76 procedures, 21 (4%) were PN and 55 (11%) SL (29 bronchoplastic, seven bronchovascular, seven angioplastic; 11 extended to more than one lobe). There were no surgical, oncological or physiological preoperative differences between the groups. The 5-year PN:SL ratio was 1:2.6 (2005: 1:2.1; 2006: 1:2.6; 2007: 1:3.6; 2008: 1:3; 2009: 1:3.5). SL and PN mortality were 2 (3.6%) and 1 (5%), respectively. Postoperative complications occurred in 18 (32%) SL and 7 (33%) PN patients. pN1 (p = 0.04), vascular reconstruction and upper-left SL were risk factors for postoperative complications of SL (p = 0.03) but were not detected as a mortality risk. Overall 5-year survival was 61% for SL and 31% for PN. Survival at 5 years was significantly higher for SL (p = 0.03, Kaplan-Meier). Age <70 years and SL were positive factors for long-term survival. In multivariate modelling, both remained positive factors. Surviving PN patients experienced significantly greater loss of respiratory function and lower QoL than those who avoided this surgery (preoperative score, PN vs SL: 52 vs 51; 3 months, 41 vs 43; and 6 months, 42 vs 51, p = 0.04). The adjuvant treatment complement was higher in SL at 34 (62%) than at PN 10 (47%). The side effects of this treatment were more frequent in patients with more extirpated parenchyma (p = 0.04). CONCLUSIONS Parenchyma-sparing procedures can reduce the PN rate to less than 10%. A PN:SL index lower than 1:1.5 as a quality standard in a specialised thoracic unit should encourage the use of broncho-angioplastic procedures and improve patient outcomes. Long-term survival, QoL, postoperative lung function test and tolerance of adjuvant therapies are significantly better after SL than PN intervention.

Low miR-145 and high miR-367 are associated with unfavourable prognosis in resected nonsmall cell lung cancer

The transcription factors SRY-related HMG box (SOX)2 and octamer-binding transcription factor (OCT)4 regulate the expression of the miR-302–367 cluster. miR-145 regulates SOX2 and OCT4 translation and p53 regulates miR-145 expression. We analysed the expression of the miR-302–367 cluster and miR-145 and the mutational status of p53 in resected nonsmall cell lung cancer (NSCLC) patients and correlated results with time to relapse (TTR). Tumour and paired normal tissue samples were obtained from 70 NSCLC patients. MicroRNA expression was assessed with TaqMan MicroRNA Assays. p53 exons 5 to 8 were sequenced. miR-145 was downregulated (p<0.0001) and miR-367 was upregulated (p<0.0001) in tumour compared with normal tissue. Mean TTR was 18.4 months for patients with low miR-145 levels and 28.2 months for those with high levels (p=0.015). Mean TTR was 29.1 months for patients with low miR-367 levels and 23.4 months for those with high levels (p=0.048). TTR was shorter for patients with both unfavourable variables (p=0.009). Low miR-145 expression (p=0.049), the combination of unfavourable microRNA levels (p=0.02) and the combination of low miR-145 with p53 mutations (p=0.011) were independent markers of shorter TTR. In conclusion, miR-145 and miR-367 expression could be novel markers for relapse in surgically treated NSCLC. p53 may play a role in modulating miR-145 expression in NSCLC.

Simpatectomía torácica por videotoracoscopia para el tratamiento del rubor facial: bisturí ultrasónico frente a diatermia

Objetivo Valorar las ventajas de la utilizacion del bisturi ultrasonico frente a la electrocoagulacion, en los pacientes operados de rubor facial incontrolable mediante simpaticolisis o simpaticotomia toracica por videotoracoscopia. Metodo Se han realizado 200 interrupciones del simpatico toracico bilaterales por videotoracoscopia en 100 pacientes afectados de rubor facial invalidante. Dos de ellas se realizaron mediante cirugia videoasistida por presentar sinfisis pleural. La edad media de los pacientes fue de 34 anos (rango: 15–67). La cadena simpatica fue interrumpida desde la porcion inferior de T1 hasta T3 inclusives. Resultados Todos los pacientes fueron dados de alta en 24 h, a excepcion del paciente en el que se realizo toracotomia de asistencia. En el grupo en que se utilizo el bisturi armonico no hubo complicaciones. En el grupo de diatermia hubo un caso de sindrome de Horner transitorio (4 meses) y tres casos de dolor toracico persistente (superior a dos semanas). En total, hubo 9 neumotorax parcelarios y asintomati-cos que no requirieron tratamiento ni prolongaron la estan-cia hospitalaria. Conclusiones El bisturi ultrasonico permite una seccion del simpatico mas firme y con mejor visualizacion. Evita lesiones perifericas en el parenquima pulmonar y tejidos adyacentes (vasos y nervios intercostales), asi como el sindrome de Horner que se puede producir por efecto calorifico. Produciria tambien una menor incidencia de neuralgias posquirurgicas.

Cryopreserved Arterial Allograft Reconstruction After Excision of Thoracic Malignancies

BACKGROUND The purpose of this study was to evaluate the long-term clinical and immunologic outcome of cryopreserved arterial allograft (CAA) revascularization of intrathoracic vessels invaded by malignancies. METHODS Since January 2002, consecutive patients whose intrathoracic vessels were invaded by malignancies were operated on and revascularizion made using human lymphocyte antigen (HLA)- and ABO-mismatched CAAs. Immunologic studies were performed preoperatively, and 1, 3, 6, 12, and 24 months postoperatively. Postoperative oral anticoagulation therapy was not given. RESULTS Twenty-six patients aged 53.1 +/- 15 years with a nonsmall-cell lung cancer (n = 10), invasive mediastinal tumors (n = 7), pulmonary artery sarcoma (n = 3), laryngeal (n = 2), or other rare lung neoplasms (n = 4) underwent operation. Cardiopulmonary bypass was used in 10 cases (38%), and all resections were pathologically complete. Revascularization was either for venous (n = 12) or arterial (n = 14) vessels, and a total of 30 allografts revascularized the superior vena cava (n = 6), pulmonary artery (n = 7), innominate vein (n = 3) or artery (n = 2), ascendent (n = 4) or descending (n = 1) aorta, and subclavian vein (n = 3) or artery (n = 4). Hospital morbidity and mortality were 50% (n = 13) and 3.8% (n = 1), respectively, all CAA unrelated. With a median follow-up of 18 months (range, 3 to 60+), 5-year survival and allograft patency were 84% and 95%, respectively. Preoperative anti-HLA antibodies were detected in 2 patients (7.7%) and a postoperative anti-HLA antibody response, clinically irrelevant, in 1 of 24 patients (4%). CONCLUSIONS Revascularization of intrathoracic venous and arterial vessels in patients with malignancies using HLA- and ABO-mismatched CAA is technically feasible and clinically attractive because of no infection risk and postoperative anticoagulation, and excellent long-term survival, patency, and nonimmunogeneicity.

Improvement in performance status after erythropoietin treatment in lung cancer patients undergoing concurrent chemoradiotherapy.

PURPOSE A prospective Phase II trial was carried out to evaluate the effectiveness of erythropoietin in improving or maintaining performance status as determined by the Karnofsky performance status (KPS) score and hemoglobin (Hb) levels in lung cancer patients treated with concurrent chemoradiation (CH-RT). METHODS AND MATERIALS A total of 51 patients with lung cancer (11 with small-cell, limited stage and 40 with non-small-cell disease, 17 with Stage IIIA and 23 with Stage IIIB), who underwent three different concurrent CH-RT protocols were enrolled. Baseline Hb and KPS values were recorded, as were the nadir Hb and KPS values before concurrent CH-RT. The final Hb and KPS values were recorded the last week of concurrent CH-RT. An Hb level of <or=11 g/dL before concurrent CH-RT was required before receiving erythropoietin. Prognostic factors for KPS improvement and survival were assessed by univariate and multivariate studies. RESULTS Of the 51 patients, 47 (92.3%) were men (mean age 63.6 years, range 40-75). The median baseline KPS score was 80, and the mean baseline Hb was 12.2 +/- 1.76 g/dL (range 9-16.9). The mean nadir and final Hb value was 9.98 +/- 0.67 g/dL (range 8.6-11) and 11.33 +/- 1.59 g/dL (range 6.9-14.4), respectively. A significant increase was seen in the Hb and KPS score (p <0.05) in the final measurements. Differences were found between the final and nadir Hb in the predictive value for differences in performance status (p = 0.001). On univariate study, pathologic findings (p = 0.0234), weight loss (p = 0.0049), baseline Hb (p = 0.0057), and final Hb improvement (p = 0.0237) were prognostic factors for survival. Nadir Hb (p = 0.027), final Hb improvement (p = 0.0069), pathologic findings (p = 0.0006), and weight loss (p = 0.0001) had significant prognostic value for survival in multivariate analysis. CONCLUSION In this study, erythropoietin appears to have a significant, beneficial impact on the KPS and Hb of patients undergoing concurrent CH-RT.

Tumor carcinoide bronquial. Análisis retrospectivo de 62 casos tratados quirúrgicamente

Objetivo Evaluar los resultados del tratamiento quirurgico del tumor carcinoide pulmonar Pacientes y Metodo Se han revisado las historias clinicas de 62 pacientes intervenidos quirurgicamente por un tumor carcinoide pulmonar entre mayo de 1985 y octubre de 2000 Resultados Cincuenta y dos pacientes tenian un carcinoide tipico y 10 un carcinoide atipico. Nueve pacientes presentaban metastasis ganglionares hiliares o mediastinicas y 5 presentaban metastasis a distancia. Estas ultimas fueron mas frecuentes en el subtipo histologico carcinoide atipico con diferencias estadisticamente significativas. Cinco pacientes tenian clinica de sindrome carcinoide. La supervivencia global a los 15 anos fue del 70% y la supervivencia media de 138 ± 11 meses. No encontramos asociacion estadistica entre el habito tabaquico y el desarrollo de tumor carcinoide Conclusiones Aunque el tumor carcinoide se comporta como un tumor de bajo grado de malignidad, su tratamiento debe realizarse de modo similar al del resto de los tumores malignos pulmonares; la reseccion quirurgica con intencion curativa es la tecnica de eleccion siempre que sea posible

Video-assisted Thoracoscopic Sympathectomy for the Treatment of Facial Blushing: Ultrasonic Scalpel Versus Diathermy

OBJECTIVE To evaluate the advantages of the ultrasonic scalpel compared to electrocoagulation in patients undergoing video-assisted thoracoscopic sympatholysis or sympathectomy for uncontrolled facial blushing. METHODS Two hundred bilateral video-assisted thoracoscopic procedures to interrupt transmission in the thoracic sympathetic nerve were performed in 100 patients with incapacitating facial blushing. In 2 cases, the video-assisted approach was chosen because of pleural symphysis. The mean age of patients was 34 years (range: 15 to 67). The sympathetic chain was interrupted from the lower portion of the first thoracic ganglion through the third. RESULTS All patients were discharged within 24 hours with the exception of one on whom an emergency thoracotomy had been performed. No complications were reported in the group in which a harmonic scalpel was used. One case of temporary Horner syndrome (4 months) and 3 cases of persistent chest pain (more than 2 weeks) were reported in the diathermy group. There were 9 cases of partial and asymptomatic pneumothorax that resolved without treatment or prolonged hospital stays. CONCLUSION Dissection of the sympathetic nerve is accomplished more reliably and with better visualization with the ultrasonic scalpel. Peripheral lesions in lung parenchyma and adjacent tissues (intercostal vessels and nerves) are avoided, as is Horner syndrome, which can be caused by dispersion of heat. Use of the ultrasonic scalpel would also lead to a lower incidence of postoperative neuralgia.