Pectus excavatum. Surgical treatment: Structural or aesthetic?

INTRODUCTION: Pectus excavatum is a wall deformity that often warrants medical evaluation. In most cases, it's a purely visual aesthetic alteration, while in others, it comes with symptoms. Several surgical techniques have been described, but their outcomes are difficult to assess due to the heterogeneity of presentations and the lack of long-term follow-up. We present our experience as thoracic surgeons, assessing correction as either structural (remodeling of the thoracic cage through open surgery) or aesthetic (design and implantation of a customized 3D prosthesis). MATERIAL AND METHODS: Retrospective observational study of the indication for surgical treatment of pectus excavatum carried out by a team of thoracic surgeons and the short- to mid-term results. RESULTS: Between 2021 and 2023, we treated 36 cases surgically, either through thoracic cage remodeling techniques or with 3D prostheses. There were few minor complications, and the short- to mid-term results were positive: alleviation of symptoms or compression of structures when present, or aesthetic correction of the defect in other cases. CONCLUSIONS: Surgery for pectus excavatum should be evaluated for structural correction of the wall or aesthetics. In the former, thoracic cage remodeling requiring cartilage excision and possibly osteotomies is necessary. In the latter, the defect is corrected with a customized 3D prosthesis.

Translation of a tissue epigenetic signature to circulating free DNA suggests BCAT1 as a potential noninvasive diagnostic biomarker for lung cancer.

Lung cancer patients are diagnosed at late stages when curative treatments are no longer possible; thus, molecular biomarkers for noninvasive detection are urgently needed. In this sense, we previously identified and validated an epigenetic 4-gene signature that yielded a high diagnostic performance in tissue and invasive pulmonary fluids. We analyzed DNA methylation levels using the ultrasensitive digital droplet PCR in noninvasive samples in a cohort of 83 patients. We demonstrated that BCAT1 is the candidate that achieves high diagnostic efficacy in circulating DNA derived from plasma (area under the curve: 0.85). Impact of potentially confounding variables was also explored.

A Standardised Approach to the Biomechanical Evaluation of Tracheal Grafts.

The ideal tracheal substitute must have biomechanical properties comparable to the native trachea, but currently there is no standardised approach to evaluating these properties. Here we propose a novel method for evaluating and comparing the properties of tracheal substitutes, thus systematising both measurement and data curation. This system was tested by comparing native rabbit tracheas to frozen and decellularised specimens and determining the histological characteristics of those specimens. We performed radial compression tests on the anteroposterior tracheal axis and longitudinal axial tensile tests with the specimens anastomosed to the jaw connected to a measuring system. All calculations and results were adjusted according to tracheal size, always using variables relative to the tracheal dimensions, thus permitting comparison of different sized organs. The biomechanical properties of the decellularised specimens were only slightly reduced compared to controls and significant in regard to the maximum stress withstood in the longitudinal axis (-0.246 MPa CI [-0.248, -0.145] MPa) and the energy stored per volume unit (-0.124 mJ·mm-3 CI [-0.195, -0.055] mJ·mm-3). The proposed method is suitable for the systematic characterisation of the biomechanical properties of different tracheal substitutes, regardless of the size or nature of the substitute, thus allowing for direct comparisons.

CXCR7 Reactivates ERK Signaling to Promote Resistance to EGFR Kinase Inhibitors in NSCLC.

Although EGFR mutant-selective tyrosine kinase inhibitors (TKI) are clinically effective, acquired resistance can occur by reactivating ERK. We show using in vitro models of acquired EGFR TKI resistance with a mesenchymal phenotype that CXCR7, an atypical G protein-coupled receptor, activates the MAPK-ERK pathway via ß-arrestin. Depletion of CXCR7 inhibited the MAPK pathway, significantly attenuated EGFR TKI resistance, and resulted in mesenchymal-to-epithelial transition. CXCR7 overexpression was essential in reactivation of ERK1/2 for the generation of EGFR TKI-resistant persister cells. Many patients with non-small cell lung cancer (NSCLC) harboring an EGFR kinase domain mutation, who progressed on EGFR inhibitors, demonstrated increased CXCR7 expression. These data suggest that CXCR7 inhibition could considerably delay and prevent the emergence of acquired EGFR TKI resistance in EGFR-mutant NSCLC. SIGNIFICANCE: Increased expression of the chemokine receptor CXCR7 constitutes a mechanism of resistance to EGFR TKI in patients with non-small cell lung cancer through reactivation of ERK signaling.

Video-Assisted Thoracic Surgical Repair of the Airway.

We communicate the first reported application of video-assisted thoracic surgery for early repair of a postintubation tracheal laceration. The patient was a 60-year-old man. After an initial unsuccessful approach with conservative measures, surgical repair was indicated. The patient underwent 2-port video-assisted thoracic surgery for direct tracheal repair using a 3-0 resorbable monofilament running suture and two reinforcing X-stitches. Bronchoscopic control after 2 and 4 weeks showed complete restoration of the airway, with no complication.

Clinical Significance of Molecular Micrometastasis in the Sentinel Lymph Node of Early-stage Non-Small Cell Lung Cancer Patients.

OBJECTIVES: Metastatic affectation of lymph node is the main prognostic factor in localized lung cancer. A pathologic study of the obtained samples, even after adequate lymphadenectomy, showed tumor relapses for 20% of stage I patients after oncological curative surgery. We evaluated the prognostic value of molecular micrometastasis in the sentinel lymph node of patients with early-stage lung cancer. PATIENTS AND METHODS: The sentinel node was marked immediately after performing thoracotomy by peritumorally injecting 0.25 mCi of nanocoloid of albumin (Nanocol1) labeled with Tc-99m in 0.3 mL. Guided by a Navigator1 gammagraphic sensor, we proceeded to its resection. The RNA of the tissue was extracted, and the presence of genes CEACAM5, BPIFA1, and CK7 in mRNA was studied. The significant association between the presence of micrometastasis, clinicopathologic characteristics, and patients' outcome was assessed. RESULTS: Eighty-nine stage I-II non-small cell lung cancer patients were included in the study. Of the 89 analyzed sentinel lymph nodes, 44 (49.4%) were positive for CK7, 24 (26.9%) for CEACAM5, and 17 (19.1%) for BPIFA1, whereas 10 (11.2%) were positive for the 3 analyzed genes. A survival analysis showed no significant relation between the presence of molecular micrometastasis in the sentinel node and patients' progression. CONCLUSIONS: The molecular analysis of the sentinel node in patients with early-stage lung cancer shows node affectation in cases staged as stage I/II by hematoxylin-eosin or an immunohistochemical analysis. However, this nodal affectation was not apparently related to patients' outcome.

Reflections on the Implementation of Low-Dose Computed Tomography Screening in Individuals at High Risk of Lung Cancer in Spain. / Reflexiones sobre la implementación del cribado mediante tomografía computarizada de baja dosis en personas con riesgo elevado de padecer cáncer de pulmón en España.

Lung cancer (LC) is a major public health issue. Despite recent advances in treatment, primary prevention and early diagnosis are key to reducing the incidence and mortality of this disease. A recent clinical trial demonstrated the efficacy of selective screening by low-dose computed tomography (LDCT) in reducing the risk of both lung cancer mortality and all-cause mortality in high-risk individuals. This article contains the reflections of an expert group on the use of LDCT for early diagnosis of LC in high-risk individuals, and how to evaluate its implementation in Spain. The expert group was set up by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), the Spanish Society of Thoracic Surgery (SECT), the Spanish Society of Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM).

[Sentinel lymph node in pulmonary carcinoma. Molecular study after radioisotope detection]. / El ganglio centinela en el carcinoma pulmonar. Estudio molecular tras detección con radioisótopo.

INTRODUCTION: Metastatic lymph node affectation is the main prognostic factor in localized lung cancer. Pathological study of the obtained samples even after an adequate lymphadenectomy, present tumoral relapses of 40% of stage I patients after oncological curative surgery. In this paper we have studied micrometastasis in the sentinel lymph node by molecular methods in patients with stage I lung cancer. MATERIAL AND METHODS: The sentinel node was marked by injecting peritumorally performed just after performing the thoracotomy with 2 mCi of nanocoloid of albumin (Nanocol®) marked with 99mTc in 0.3 ml. Guided with a Navigator® gammagraphic sensor, we proceeded to its resection. RNA of the tissue was extracted and the presence of genes CEACAM5, PLUNC and CK7 in mRNA was studied. RESULTS: Twenty nine 29 patients were included. Of the tested genes, CEACAM5 and PLUNC were the ones that showed a high expression in lung tissue. Of the 29 analyzed sentinel lymph nodes, 7 (24%) were positive in the molecular study. A positive sentinel lymph node was found in 4/7 adenocarcinomas and 3/12 squamous-cell tumors. Affected lymph nodes were: station 5 (1/3), station 7 (0/6), station 9 (0/1); station 10 (5/11); station 11 (1/1). CONCLUSIONS: Detection of sentinel node in patients with stage I lung cancer by marking with radioisotope is a feasible technique. The application of molecular techniques shows the tumoral affectation in cases staged as stage I.

Endotracheal metastases from colon adenocarcinoma.

Endotracheal metastases (ETM) from non-lung cancer are seldom seen. Their main clinical symptoms are cough, haemoptysis and dyspnoea, although occasionally an incidental finding is made during a bronchoscopy. Breast, colon and kidney adenocarcinoma might be associated with ETM, lung cancer being the most frequent cause. Its finding is associated with advanced disease but survival will depend on the primary origin, patient status and comorbidity. Therefore, treatment should be individual for each patient. In our centre we recommend pre-surgery bronchoscopy to exclude metastatic endotracheal lesions in patients with metastatic colon adenocarcinoma disease, as this might affect the final outcome and therefore management of the disease.

[Computed tomography-guided radiofrequency ablation of malignant lung lesions: early experience]. / Ablación mediante radiofrecuencia guiada por tomografía computarizada de las lesiones pulmonares malignas: experiencia inicial.

OBJECTIVE: To present our early experience in the treatment of primary malignant and metastatic lung lesions by radiofrequency ablation. PATIENTS AND METHODS: From August 2004 through January 2007 we treated 19 patients (in 26 procedures) with curative or palliative intent. None of the lesions was amenable to surgery and some had been treated previously. The procedure was performed in the radiology room under conscious sedation-analgesia administered by an anesthesiologist. Fourteen patients were treated for pulmonary lesions and 5 for metastatic lung disease in a context of controlled primary disease. Treatment was with curative intent in 15 cases and palliative in 4. RESULTS: The radiofrequency technique was applicable in 26 procedures and the mean follow-up was 8.68 months. The principal complications of radiofrequency treatment were pneumothorax in 4 patients, requiring drainage in only 2 cases; pneumonitis in 4; self-limiting pulmonary hemorrhage in 1; and pleural effusion in 5. There were no procedure-related deaths. Six patients died during the follow-up period. CONCLUSIONS: In our experience, radiofrequency offers a safe and minimally invasive option for the treatment of malignant lung lesions in appropriately selected, nonsurgical patients. Morbidity is low, and in combination with other treatments this technique opens up a wide range of possibilities still to be explored.

[Pneumonectomy with extracorporeal circulation to treat pulmonary metastasis]. / Neumonectomía por metástasis pulmonar con utilización de circulación extracorpórea.

Surgical resection of pulmonary metastasis is appropriate provided the general principals of oncological surgery are followed. Complete excision of the metastatic tumor is associated with long-term survival and low perioperative mortality. We present 2 cases of single pulmonary metastasis from osteosarcoma with cardiac involvement. In both cases, complete excision required left pneumonectomy by sternotomy with extracorporeal circulation. The outcomes were favorable, no perioperative complications were reported, and the patients remained free of disease at 14 and 17 months after surgery. In conclusion, we believe that the cases presented confirm that extended pneumonectomy with extracorporeal circulation if necessary is a valid approach for complete resection of pulmonary metastasis.

Protocol for the implantation of a venous access device (Port-A-Cath System). The complications and solutions found in 560 cases.

INTRODUCTION: The cannulation of suitable peripheral veins may be a very painful experience. Implantable venous access systems have to some degree relieved this problem and help to provide an improvement in terms of quality of life. MATERIAL AND METHODS: We have evaluated 560 patients during a follow up period of two years. A low overall complication percentage of 7.32% was seen when using the venous access device. RESULTS: Complications and treatments were: pneumothorax; portal rotation or infection; catheter infection; embolism and migration; extravasation; partial or total obstruction of the device; rupture of the catheter or the membrane. CONCLUSIONS: There is no other system that allows repeated venous access on such a long term basis. Placing the devices completely under the skin allows the patient to conduct a normal life style, and its maintenance does not need any special care, with the exception of the monthly heparinised serum infusion. The preferred option is to insert the catheter through the cephalic vein in the delto pectoral groove.

Cell-free DNA concentration in pleural fluid and serum: quantitative approach and potential prognostic factor in patients with cancer and pleural effusions.

PURPOSE: The presence of pleural effusions in patients with tumors is often indicative of locally advanced or metastatic disease, and detection of malignancy in effusion samples frequently leads to a disease upstaging. Our purpose was to quantify the DNA in pleural effusion and serum in patients presenting pleural effusion in order to assess the potential prognostic impact. PATIENTS AND METHODS: The DNA level was determined by amplifying hRNase P in paired samples of serum and pleural fluid in 70 consecutive patients with cancer showing pleural effusion. A group of 30 patients without cancer was included. The correlation between serum and pleural DNA was calculated. Survival curves according to serum and pleural DNA were analyzed. RESULTS: Median DNA concentrations were greater in patients with neoplasia than in patients without malignancy: 105 ng/mL versus 40 ng/mL (P = 0.001) in serum samples, respectively; 93 ng/mL versus 21 ng/mL (P = 0.001) in pleural fluids, respectively. A positive correlation between serum and pleural levels was confirmed (r = 0.3; P < 0.05). Median survival time for patients with serum DNA < or = 105 ng/mL was 11.03 months in contrast to only 3.63 months for patients with higher values (P = 0.036). Accordingly, median survival time for patients with pleural DNA < or = 93 ng/mL was 12.3 months versus only 4.63 months in case of higher levels (P = 0.027). CONCLUSION: This study shows that there is a strong correlation between higher levels of free DNA in pleural fluid or serum and malignancy. Survival is worse for patients with higher DNA levels in serum and pleural fluid.

Potential diagnostic value of methylation profile in pleural fluid and serum from cancer patients with pleural effusion.

BACKGROUND: The objective of this study was to investigate the diagnostic value of methylation profiles for discrimination between malignant and benign pleural effusions. A secondary objective was to examine the concordance of methylation in samples of serum and pleural fluid. METHODS: The authors used methylation-specific polymerase chain reaction (MSP) analysis to examine the promoter methylation status of 4 genes in patients with pleural effusion: death-associated protein kinase (DAPK), Ras association domain family 1A (RASSF1A), retinoic acid receptor beta (RARbeta), and p16/INK4a. Pleural effusions were collected from 87 patients who had their diagnoses confirmed on cytologic and/or histologic examinations and clinical evolution. Pleural effusions were classified as malignant (n = 53 patients) or benign (n = 34 patients). RESULTS: Methylation was detected in serum from 45.3% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions, and it was detected in pleural fluid samples from 58.5% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions (P = .001). The sensitivity of MSP was greater than that of cytologic examination alone (39.1%; P = .001). When MSP was used together with cytologic examination, sensitivity increased to 69.8% (P = .001). CONCLUSIONS: Cell-free methylated DNA in pleural fluid can be detected in patients with neoplastic malignancy in a single extraction by thoracocentesis. Adequate management of the extracted pleural fluid can provide a rapid and reliable diagnosis in patients with pleural effusions who have suspected malignancy. MSP, used together with cytologic examination, may obviate the need for other invasive diagnostic tests.