Abel Gómez-Caro

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.

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.

False-negative rate after positron emission tomography/computer tomography scan for mediastinal staging in cI stage non-small-cell lung cancer

OBJECTIVES To assess the false-negative (FN) rate of positron emission tomography (PET)-chest computed tomography (CT) scan in clinical non-central cIA and cIB non-small-cell lung cancer (NSCLC) for mediastinal staging. METHODS Between January 2007 and December 2010, 402 patients with potentially operable NSCLC were assessed by thoracic CT scan and 18-fluoro-2-deoxy-d-glucose PET-CT for mediastinal staging and to detect extrathoracic metastases, of which 153 surgically treated patients (79 cIA and 74 cIB cases) were prospectively included in the study. Central tumours were excluded on the basis of CT scan criteria, defined as contact with the intrapulmonary main bronchi, pulmonary artery, pulmonary veins or the origin of the first segmental branches. CT scan was considered negative if lymph nodes were <1 cm at the smaller diameter. 18FDG PET-CT was considered negative when the high maximum standard uptake value (SUVmax) was <2.5. Non-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. RESULTS Composite non-invasive staging (CT scan, PET-CT) showed a negative predictive value (NPV) of 92% (CI 83.6-96.8) in the cIA group and 85% (CI 74-92) in the cIB group. There were 6 of 79 (7.6%) false-negatives (FNs) in cIA and 11 of 74 (14.8%) in cIB. Multilevel pN2 were detected in four cases, all of them in the cIB group. The most frequently involved N2 was subcarinal (two cases) in cIA and right lower paratracheal (R4) and seven (five cases) in cIB. Occult (pN2) lymph nodes were more frequent in tumour sizes≥5 cm (pT2b, nine cases, four FNs, P=0.03), pN1, adenocarcinoma [excluding minimally invasive adenocarcinoma (MIA) and lepidic predominant growth (LPA)] (P=0.029) and female patients, but no other risk factors for mediastinal metastases were identified (age, clinical stage, tumour location, central or peripheral, P>0.05). Multilevel pN2 was significantly more frequent in the cIB group (P<0.03). In pT≤1 cm (T1a), NPV was significantly better (NPV=100%, P<0.05) than the other subgroups studied (IA>1 cm and IB). CONCLUSIONS Composite results for non-invasive mediastinal staging (CT scan, PET-CT) showed 11% of FNs in cI stage (7.6% in non-central cIA and 14.8% in cIB). In tumours≤1 cm, NPV makes surgical staging unnecessary. In women with adenocarcinoma and non-central cIB, however, the high FN rate makes invasive staging necessary, particularly in pT2b to decrease the incidence of unexpected pN2 in thoracotomy.

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.

Platelet rich plasma improves the healing process after airway anastomosis

This study investigated whether platelet-rich plasma (PRP) promotes healing and reduces anastomotic complications following airway surgery in a pig model. PRP was obtained by spinning down the animals own blood (60 ml) and collecting the buffy coat containing platelets and white blood cells. Fifteen adult pigs were randomized into three groups: (1) sham treatment (cervicotomy), (2) non-PRP group (50% tracheal resection and end-to-end anastomosis), and (3) PRP group (50% tracheal resection, end-to-end anastomosis and PRP application). Blood samples were taken at baseline and at one, six and 24. Animals were monitored for anastomotic complications, infection and local reactivity. Laser Doppler flowmetry was performed intraoperatively and at 30 days to assess differences in pre- and post-anastomotic blood flow. The tensile strength of the anastomosis was also tested. The platelet level was higher in PRP fluid than in the baseline blood sample (P<0.002). Vascular endothelial growth factor, transforming growth factor β-1 and epidermal growth factor immunoassay readings peaked at one and six hours in the animals that had received PRP (P<0.03); these also showed significantly increased transanastomotic flow and stress-strain resistance (P<0.04) at 30 days than the animals that had not received PRP. PRP therefore, accelerates the onset of healing in airway surgery by promoting an earlier release of platelet-derived growth factors that stimulate transanastomotic angiogenesis.

Matrix Stiffening and β1 Integrin Drive Subtype-Specific Fibroblast Accumulation in Lung Cancer

The crucial role of tumor-associated fibroblasts (TAF) in cancer progression is now clear in non–small cell lung cancer (NSCLC). However, therapies against TAFs are limited due to a lack of understanding in the subtype-specific mechanisms underlying their accumulation. Here, the mechanical (i.e., matrix rigidity) and soluble mitogenic cues that drive the accumulation of TAFs from major NSCLC subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC) were dissected. Fibroblasts were cultured on substrata engineered to exhibit normal- or tumor-like stiffnesses at different serum concentrations, and critical regulatory processes were elucidated. In control fibroblasts from nonmalignant tissue, matrix stiffening alone increased fibroblast accumulation, and this mechanical effect was dominant or comparable with that of soluble growth factors up to 0.5% serum. The stimulatory cues of matrix rigidity were driven by β1 integrin mechano-sensing through FAK (pY397), and were associated with a posttranscriptionally driven rise in β1 integrin expression. The latter mechano-regulatory circuit was also observed in TAFs but in a subtype-specific fashion, because SCC–TAFs exhibited higher FAK (pY397), β1 expression, and ERK1/2 (pT202/Y204) than ADC–TAFs. Moreover, matrix stiffening induced a larger TAF accumulation in SCC–TAFs (>50%) compared with ADC–TAFs (10%–20%). In contrast, SCC–TAFs were largely serum desensitized, whereas ADC–TAFs responded to high serum concentration only. These findings provide the first evidence of subtype-specific regulation of NSCLC–TAF accumulation. Furthermore, these data support that therapies aiming to restore normal lung elasticity and/or β1 integrin-dependent mechano regulation may be effective against SCC–TAFs, whereas inhibiting stromal growth factor signaling may be effective against ADC–TAFs. Implications: This study reveals distinct mechanisms underlying the abnormal accumulation of tumor-supporting fibroblasts in two major subtypes of lung cancer, which will assist the development of personalized therapies against these cells. Mol Cancer Res; 13(1); 161–73. ©2014 AACR.

Surgical management of benign tracheal stenosis.

This chapter provides a step-by-step explanation of the indications, basic technique and pitfalls of tracheal surgery for cases of benign tracheal stenosis. Approach, trachea dissection and end-to-end anastomosis in tracheal surgery is described in detail. An algorithm for laryngotracheal technique selection according to different criteria (stenosis location, vocal cords status and tracheal mucosa and/or cartilaginous larynx involvement) is also depicted. Finally, a review of the most important reported series in tracheal surgery is presented.

Asistencia respiratoria extracorpórea en la insuficiencia respiratoria grave y el SDRA. Situación actual y aplicaciones clínicas

Despite improvements in ventilation support techniques, lung protection strategies, and the application of new support treatment, acute respiratory distress syndrome continues to have a high mortality rate. Many strategies and treatments for this syndrome have been investigated over the last few year. However, the only therapeutic measure that has systematically shown to be able to improve survival is that of low volume lung protective ventilation. Thus, using a low tidal volume prevents added lung damage by the same mechanical ventilation that is essential for life support. In this context, the use of extracorporeal lung assist systems is considered an exceptional use rescue treatment in extreme cases. On the other hand, it could be a potentially useful complementary method for an ultra-protective ventilation strategy, that is, by using even lower tidal volumes. The currently available extracorporeal lung assist systems are described in this article, including high flow systems such as traditional extracorporeal membrane oxygenation, CO₂ removal systems (interventional lung assist or iLA, with or without associated centrifugal pumps), and the new low flow and less invasive systems under development. The aim of this review is to update the latest available clinical and experimental data, the indications for these devices in adult respiratory distress syndrome (ARDS), and their potential indications in other clinical situations, such as the bridge to lung transplantation, multiple organ dysfunction syndrome, or COPD.

Cirugía broncoangioplástica en el tratamiento del cáncer de pulmón

El cáncer de pulmón es la neoplasia más prevalente en el mundo, con 1.400.000 nuevos casos anuales. En España se diagnostica anualmente a 20.000 nuevos pacientes, con una tasa bruta de incidencia de 78,3/10 en varones y 11,8/10 en mujeres, y la supervivencia total estimada es del 13–15% a los 5 años. Aproximadamente, sólo un 25% de los cánceres de pulmón diagnosticados recibe tratamiento quirúrgico, siendo éstos los que presentan una supervivencia mayor: el 40% de los pacientes sobrevive a los 5 años. La intervención quirúrgica es, por lo tanto, el mejor tratamiento disponible en casos seleccionados desde el punto de vista oncológico y funcional. Es precisamente en este último apartado, en candidatos con función lı́mite, en el que la cirugı́a de preservación (sparing) pulmonar mediante técnicas broncoangioplásticas permite un tratamiento quirúrgico oncológicamente adecuado, con una aceptable morbimortalidad postoperatoria y una mejor calidad de vida posterior. Asimismo, este conjunto de técnicas son extremadamente útiles en pacientes de edad avanzada con tumoraciones centrales, en quienes una neumonectomı́a podrı́a ocasionar una mortalidad superior al 20%, y en especial en pacientes con tratamiento quimiorradioterápico de inducción. Thomas, en el Brompton Hospital, publicó la primera operación de broncoplastia en manguito (sleeve) en un tumor carcinoide, y Paulson y Shaw demostraron posteriormente que se alcanzaban supervivencias largas con estos procedimientos. La localización inicial y más frecuente es el implante del intermediario sobre el bronquio principal derecho, localización donde se realiza cerca del 60% de este tipo de intervenciones, tratando de evitar ası́ la neumonectomı́a derecha. Las técnicas broncoangioplásticas se describieron inicialmente para limitar el número de neumonectomı́as en pacientes con función pulmonar comprometida. Sin embargo, en la actualidad se consideran el tratamiento de elección incluso en pacientes con función pulmonar normal. Esta tendencia se fundamenta en 2 vertientes: en la disminución de la morbimortalidad postoperatoria, sustancialmente menor casi siempre que se evitan las complicaciones propias de la neumonectomı́a, y en una mejor calidad de vida a largo plazo, recogida en estudios mediante cuestionarios especı́ficos, relacionada con la extensión de la resección de parénquima pulmonar. Las técnicas de lobectomı́a en manguito, a las que se refiere este editorial, son de especial utilidad en tumores localmente avanzados a los que se ha aplicado con anterioridad quimiorradioterapia por afectación ganglionar. En estos pacientes es fundamental evitar la neumonectomı́a, y mantener un remanente pulmonar es ciertamente muy aconsejable para disminuir el número de complicaciones relacionadas con la dehiscencia de sutura bronquial. El ı́ndice de complicaciones bronquiales desaconsejan la realización de neumonectomı́as, sobre todo derechas tras tratamiento neoadyuvante, y es recomendable cualquier técnica que permita disminuir esa incidencia de complicaciones sin alterar la capacidad curativa. Sin embargo, las técnicas broncoangioplásticas son técnicamente más exigentes y no están exentas de complicaciones propias. Las resecciones con reconstrucción bronquial presentan un ı́ndice de fı́stulas bronquiales de un 6–12%, y cuando la reconstrucción es combinada con arteria pulmonar, la trombosis arterial y el daño de isquemia-reperfusión en el lóbulo reimplantado ocurren en un 2–4%. Las complicaciones vasculares relacionadas con la reconstrucción, aun siendo muy limitadas, pueden disminuirse si se procede a la heparinización sistémica y local durante el tiempo de interrupción de flujo. Posiblemente el ı́ndice de complicaciones bronquiales o broncovasculares se amplı́a con radioterapia previa, aunque en la literatura médica no se describe un aumento significativo de complicaciones. Sin embargo, son esperables una cicatrización deficiente en los pacientes con este tipo de tratamiento previo y un mayor ı́ndice de complicaciones de cicatrización bronquial. También es propia de este tipo de cirugı́a una mayor frecuencia de retención de esputo por disrupción del aclaramiento ciliar secundaria a la sutura circular bronquial, por lo que una fisioterapia respiratoria enérgica es fundamental. Por otra parte, la neumonectomı́a presenta un ı́ndice de complicaciones bronquiales más elevado en conjunto, sin contar con el sı́ndrome de distrés respiratorio del adulto, de infausto pronóstico, y la disminución de la reserva cardiopulmonar, lo cual incide en una peor calidad de vida a largo plazo. Un punto de difı́cil decisión reside en la detección de ganglios interlobares afectados; hoy dı́a existe la tendencia a aplicar este tipo de técnicas incluso en enfermedad N1, acompañada de una linfadeARTICLE IN PRESS

Chest-wall reconstruction in case of infection of the operative site: is there any interest in titanium rib osteosynthesis?

OBJECTIVES To describe the management of thoracic reconstructions in the presence of primary chest-wall infection (PCWI) or secondary deep chest-wall infection (SCWI), focussing on local tolerance of a titanium rib osteosynthesis system. METHODS PCWI included infected chest wall tumours (CWT), infected T3 non-small-cell lung carcinoma (NSCLC) and open flail chest. SCWI was defined by deep infection of previous thoracic-wall reconstructions. Infection was identified by preoperative bacterial analysis of the tumour or surgical site. In PCWI, a one-step procedure combined extensive resection of infected tissues and rigid reconstruction of the defect; skeletal rigidity was achieved using titanium implants. In SCWI, we removed all synthetic material except titanium implants. In both groups, the surgical field was thoroughly cleaned and implants were wrapped or covered by flaps. RESULTS From January 2005 to December 2011, 11 patients (54 ± 10.2 years) with either PCWI (3 CWT, 3 T3 NSCLC, 1 open flail chest) or SCWI (3 CWT, 1 funnel chest) were treated. Infection was polymicrobial in all but 1 case. Bacteria observed in PCWI patients were multidrug resistant. In PCWI, we resected 4.2 ± 0.6 ribs en bloc with the lung (n = 5), the skin and the pectoralis major and then used mesh and 2.1 ± 1.2 titanium implants for reconstruction (n = 6). The mean defect was 1154.4 ± 318 cm(3). Surgical SCWI management removed polytetrafluoroethylene-mesh and preserved the titanium implants. A Vicryl mesh (n = 3) and greater omentum flap (n = 3) were added. One of the 2 postoperative deaths in the PCWI group was related to infection recurrence. No other patient had infection at the 6-month follow-up with leucocyte-labelled scintigraphy. CONCLUSION Titanium rib osteosynthesis is reliable in two complex and life-threatening situations: PCWIs and SCWIs. In combination with a flap, this allows rapid, reliable, rigid reconstruction of infected full-thickness chest-wall defects in a single-step procedure.