[Outpatient Management of Primary Spontaneous Pneumothorax]. / Ambulantes Management des primären Spontanpneumothorax.

Outpatient Management of Primary Spontaneous Pneumothorax Abstract. Pneumothorax (PT) is defined as a collapse of the lung due to the collection of air in the pleural space. In primary spontaneous pneumothorax (PSP) there is no underlying pulmonary pathology. Treatment, either conservative or invasive, depends on the size of the PT, the patient's clinical situation and the patient's setting/environment. According to the actual literature, the uncomplicated PSP can at best be treated conservatively and on an outpatient basis. Management with intervention (needle aspiration or chest drainage) is historically carried out on an inpatient basis, but outpatient management (without comorbidities and without symptoms) is also possible. In these cases, the patient compliance (motivation, cognition, support, housing situation …) has to be proven. For outpatient management with intervention, a small-caliber chest tube (<14 F) with a Heimlich valve should be used.

Stage III N2 non-small cell lung cancer treatment: decision-making among surgeons and radiation oncologists.

BACKGROUND: Stage III N2 non-small cell lung cancer (NSCLC) is a very heterogeneous disease associated with a poor prognosis. A number of therapeutic options are available for patients with Stage III N2 NSCLC, including surgery [with neoadjuvant or adjuvant chemotherapy (CTx)/neoadjuvant chemoradiotherapy (CRT)] or CRT potentially followed by adjuvant immunotherapy. We have no clear evidence demonstrating a significant survival benefit for either of these approaches, the selection between treatments is not always straightforward and can come down to physician and patient preference. The very heterogeneous definition of resectability of N2 disease makes the decision-making process even more complex. METHODS: We evaluated the treatment strategies for preoperatively diagnosed stage III cN2 NSCLC among Swiss thoracic surgeons and radiation oncologists. Treatment strategies were converted into decision trees and analysed for consensus and discrepancies. We analysed factors relevant to decision-making within these recommendations. RESULTS: For resectable "non-bulky" mediastinal lymph node involvement, there was a trend towards surgery. Numerous participants recommend a surgical approach outside existing guidelines as long as the disease was resectable, even in multilevel N2. With increasing extent of mediastinal nodal disease, multimodal treatment based on radiotherapy was more common. CONCLUSIONS: Both, surgery- or radiotherapy-based treatment regimens are feasible options in the management of Stage III N2 NSCLC. The different opinions reflected in the results of this manuscript reinforce the importance of a multidisciplinary setting and the importance of shared decision-making with the patient.

Chest drains: purse string suture 4.0.

There are many discussions about the technique of removal of chest drains. In our hospital, we have used an intracutaneous suture technique with non-absorbable suture material for the purse-string suture for a few years now. Thus the cosmetic results improved considerably. Nevertheless, the thread has to be removed after 10-14 days. To further improve patient comfort we developed a purse-string suture technique using an absorbable barbed suture. We noticed better cosmetic results and less painfull drain removal. Furthermore, there is no more need for a stitch removal which reduces material costs and also pain.

A chest wall mass after breast carcinoma surgery: a simple diagnosis?

Tuberculosis affects pulmonary and extra-pulmonary sites with a multitude of differing presentations. The involvement of thoracic wall is a rare entity. We report the case of a patient who had a tumefaction on the right chest wall 6 months after a right breast mastectomy. After an initial radiological suspicion of malignancy, we detected intraoperatively an abscess in which histologic examination revealed granulomas with multinucleated giant cells.

Management of non-small cell lung cancer in the elderly.

Most developed countries accepted the chronological age of 70 years as the definition of "elderly" and there is a general consensus in clinical practice to consider this age as the threshold in risk assessment. This has a strong impact in the choice of treatment of these lung cancer patients. Indeed, more than 50% of these patients are over 70 and nearly 30% are over 75 years old. Because of the increasing number of elderly patients that are generally fitter than in the past, the treatment options should rather be based on individual fitness, taking into account risks and benefits of the diagnostic and therapeutic procedures. This means considering biological rather than chronological age to make decisions. For these reasons, we developed a simplified short comprehensive geriatric assessment (sCGA), including a standardised evaluation of activity of daily living, depression, cognitive status, comorbidities and geriatric syndromes. This allowed us the classification of these patients into 3 categories: frail, vulnerable and fit. Through the emblematic case of a fit elderly man affected by NSLCC, we present the multidisciplinary assessment and discussions to identify the best treatment options for this patient.

A rare case of mucinous cystadenoma of the lung mimicking malignancy at 18F-FDG PET/CT.

We describe a rare case of pulmonary mucinous cystadenoma (PMCA) detected F-FDG PET/CT and mimicking a malignancy. A 60-year-old female patient underwent F-FDG PET/CT for metabolic characterization of a left pulmonary nodule which showed increased F-FDG uptake (SUVmax = 3.7). Based on this PET/CT finding, the patient underwent a cuneiform resection of the left pulmonary nodule. Histology demonstrated the presence of a PMCA. In our case, F-FDG PET/CT has been useful in detecting this rare pulmonary tumor.

EGFR-targeted therapy for non-small cell lung cancer: focus on EGFR oncogenic mutation.

The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR molecular testing, as well as for testing of other oncogenes such as EML4-ALK and KRAS. Actually, the value of EGFR expressed in patients with NSCLC in predicting a benefit in terms of survival from treatment with an epidermal growth factor receptor targeted therapy is still in debate, while there is a convincing evidence on the predictive role of the EGFR mutational status with regard to the response to tyrosine kinase inhibitors (TKIs).This is a literature overview on the state-of-the-art of EGFR oncogenic mutation in NSCLC. It is designed to highlight the preclinical rationale driving the molecular footprint assessment, the progressive development of a specific pharmacological treatment and the best method to identify those NSCLC who would most likely benefit from treatment with EGFR-targeted therapy. This is supported by the belief that a rationale for the prioritization of specific regimens based on patient-tailored therapy could be closer than commonly expected.

Identification of mesenchymal stromal cells in human lung parenchyma capable of differentiating into aquaporin 5-expressing cells.

The lack of effective therapies for end-stage lung disease validates the need for stem cell-based therapeutic approaches as alternative treatment options. In contrast with exogenous stem cell sources, the use of resident progenitor cells is advantageous considering the fact that the lung milieu is an ideal and familiar environment, thereby promoting the engraftment and differentiation of transplanted cells. Recent studies have shown the presence of multipotent 'mesenchymal stem cells' in the adult lung. The majority of these reports are, however, limited to animal models, and to date, there has been no report of a similar cell population in adult human lung parenchyma. Here, we show the identification of a population of primary human lung parenchyma (pHLP) mesenchymal stromal cells (MSCs) derived from intraoperative normal lung parenchyma biopsies. Surface and intracellular immunophenotyping by flow cytometry revealed that cultures do not contain alveolar type I epithelial cells or Clara cells, and are devoid of the following hematopoietic markers: CD34, CD45 and CXCR4. Cells show an expression pattern of surface antigens characteristic of MSCs, including CD73, CD166, CD105, CD90 and STRO-1. As per bone marrow MSCs, our pHLP cells have the ability to differentiate along the adipogenic, osteogenic and chondrogenic mesodermal lineages when cultured in the appropriate conditions. In addition, when placed in small airway growth media, pHLP cell cultures depict the expression of aquaporin 5 and Clara cell secretory protein, which is identified with that of alveolar type I epithelial cells and Clara cells, respectively, thereby exhibiting the capacity to potentially differentiate into airway epithelial cells. Further investigation of these resident cells may elucidate a therapeutic cell population capable of lung repair and/or regeneration.

OCT4 expression in human non-small cell lung cancer: implications for therapeutic intervention.

Here we investigate the expression of OCT4 human lung adenocarcinoma and bronchioloalveolar carcinoma (BAC) tumor biopsies and tumor-derived primary cell cultures. OCT4 has been detected in several human tumors suggesting a potentially critical role in tumorigenesis. We assessed the presence of OCT4 in clinical tumor samples of both adenocarcinoma and BAC at the cellular and transcriptional levels, respectively. Furthermore, we evaluated tumor-derived cell cultures for potential differences in OCT4 expression. Immunohistochemical analysis depicted OCT4 in 2 of 8 adenocarcinoma tumor samples and 3 of 5 BAC tumor samples, with no apparent difference in the degree of expression among the sections examined. These results were validated by transcript analysis. Flow cytometric assessment of 11 adenocarcinoma-derived cell cultures and 3 BAC-derived cell cultures revealed significantly higher OCT4 expression in adenocarcinoma tumors compared to their normal counterparts. This, however, was not observed in the BAC cultures. Comparative studies of OCT4 in adenocarcinoma and BAC tumor cell cultures demonstrated a dramatically higher expression in the former. The expression of OCT4 may represent a specific and effective target for therapeutic intervention in adenocarcinoma and BAC. In addition, the aberrant expression and distribution of OCT4 may indicate important parameters concerning the differences between adenocarcinoma and BAC.

Reduction of airspace after lung resection through controlled paralysis of the diaphragm.

OBJECTIVES: Residual airspace following thoracic resections is a common clinical problem. Persistent air leak, prolonged drainage time, and reduced hemostasis extend hospital stay and morbidity. We report a trial of pharmacologic-induced diaphragmatic paralysis through continuous paraphrenic injection of lidocaine to reduced residual airspace. The objectives were confirmation of diaphragmatic paralysis and possible procedure related complications. METHODS: Six eligible patients undergoing resectional surgery (lobectomy or bilobectomy) were included. Inclusion criteria consisted of: postoperative predicted FEV1 greater than 1300 ml, right-sided resection, absence of parenchymal lung disease, no class III antiarrhythmic therapy, absence of hypersensitivity reactions to lidocaine, no signs of infection, and informed consent. Upon completion of resection an epidural catheter was attached in the periphrenic tissue on the proximal pericardial surface, externalized through a separate parasternal incision, and connected to a perfusing system injecting lidocaine 1% at a rate of 3 ml/h (30 mg/h). Postoperative ICU surveillance for 24h and daily measurement of vital signs, drainage output, and bedside spirometry were performed. Within 48 h fluoroscopic confirmation of diaphragmatic paralysis was obtained. The catheter removal coincided with the chest tube removal when no procedural related complications occurred. RESULTS: None of the patients reported respiratory impairment. Diaphragmatic paralysis was documented in all patients. Upon removal of catheter or discontinuation of lidocaine prompt return of diaphragmatic motility was noticed. Two patients showed postoperative hemodynamic irrelevant atrial fibrillation. CONCLUSION: Postoperative paraphrenic catheter administration of lidocaine to ensure reversible diaphragmatic paralysis is safe and reproducible. Further studies have to assess a benefit in terms of reduction in morbidity, drainage time, and hospital stay, and determine the patients who will profit.

Targeted cell replacement with bone marrow cells for airway epithelial regeneration.

It has been suggested that some adult bone marrow cells (BMC) can localize to the lung and develop tissue-specific characteristics including those of pulmonary epithelial cells. Here, we show that the combination of mild airway injury (naphthalene-induced) as a conditioning regimen to direct the site of BMC localization and transtracheal delivery of short-term cultured BMC enhances airway localization and adoption of an epithelial-like phenotype. Confocal analysis of airway and alveolar-localized BMC (fluorescently labeled) with epithelial markers shows expression of the pulmonary epithelial proteins, Clara cell secretory protein, and surfactant protein C. To confirm epithelial gene expression by BMC, we generated transgenic mice expressing green fluorescent protein (GFP) driven by the epithelial-specific cytokeratin-18 promoter and injected BMC from these mice transtracheally into wild-type recipients after naphthalene-induced airway injury. BMC retention in the lung was observed for at least 120 days following cell delivery with increasing GFP transgene expression over time. Some BMC cultured in vitro over time also expressed GFP transgene, suggesting epithelial transdifferentiation of the BMC. The results indicate that targeted delivery of BMC can promote airway regeneration.

Fluorescent microangiography (FMA): an improved tool to visualize the pulmonary microvasculature.

Visualization of the complex lung microvasculature and resolution of its three-dimensional architecture remains a difficult experimental challenge. We present a novel fluorescent microscopy technique to visualize both the normal and diseased pulmonary microvasculature. Physiologically relevant pulmonary perfusion conditions were applied using a low-viscosity perfusate infused under continuous airway ventilation. Intensely fluorescent polystyrene microspheres, confined to the vascular space, were imaged through confocal optical sectioning of 200 microm-thick lung sections. We applied this technique to rat lungs and the markedly enhanced depth of field in projected images allowed us to follow vascular branching patterns in both normal lungs and lungs from animals with experimentally induced pulmonary arterial hypertension. In addition, this method allowed complementary immunostaining and identification of cellular components surrounding the blood vessels. Fluorescent microangiography is a widely applicable and quantitative tool for the study of vascular changes in animal models of pulmonary disease.

Sildenafil extends survival and graft function in a large animal lung transplantation model.

OBJECTIVE: Restoring intracellular cGMP and inducing NO-synthesis attenuates ischemia-associated early pulmonary allograft dysfunction. Phosphodiesterase-5 (PDE), predominantly expressed in lung tissue, plays a pivotal role in modulating the cGMP/NO-synthase pathway in endothelial and epithelial cells. In this study, we evaluate the effect of employing sildenafil (Viagra), a specific inhibitor of PDE-5, to counteract ischemia/reperfusion (I/R) injury in a single lung transplantation model of extended ischemia. METHODS: Donor animals (weight matched outbred pigs, 28-35 kg) in the treatment group (I) (n=5) were injected with 0.7 mg sildenafil/kg into the pulmonary artery (PA) prior to inflow occlusion. For perfusion, Perfadex, containing 0.7 mg sildenafil/l was used, and the graft stored at 1 degrees C in the perfusion solution. After 24h ischemia, unilateral left lung transplantation was performed. Starting at reperfusion, group I received continuous sildenafil (0.7 mg sildenafil/kg), over 6h. Except for the sildenafil application, the control group (II) (n=4) was treated identically (PGE1 was injected into the PA). One hour after reperfusion, the right main bronchus (MB) and right PA were occluded. Over the next 5h, cardiopulmonary parameters (systemic atrial, PA, central venous, left atrial pressure, pCO(2), pO(2)) were measured, including extravascular lung water (EVLW). Thiobarbituric acid-reactive substance assay (TBARS) and myeloperoxidase (MPO) analysis from lung tissue were run. RESULTS: All recipients of group I survived the 6-h reperfusion period; in contrast, all control animals died within 1-2h after occlusion of the right side. In comparison to a marked rise in pulmonary vascular resistance (PVR) in group II (>1000 dynescm(-5)), PVR in group I remained stable, moderately elevated from baseline (baseline: 150-180 dynescm(-5) vs endpoint: 1000 dynescm(-5)). EVLW in group I did not increase during reperfusion (baseline: 6.75+/-1.4 mg/kg vs endpoint: 6.7+/-1.0mg/kg), in contrast to group II, where pulmonary edema at 2-h reperfusion preceded terminal graft failure (group I: 9.7+/-0.1mg/kg vs group II: 6.48+/-1.8 mg/kg). Tissue reactive free radicals at endpoint measurement in group I did not differ significantly from native tissue. Yet, when compared to specimen taken from group II at time of terminal graft failure, a significant increase in free radicals was noted (group I: 13.8+/-1.6 pmol/g vs group II: 18.5+/-3.0 pmol/g, p<0.05). CONCLUSION: Sildenafil treatment prevents terminal early graft failure, allowing lung transplantation after 24-h ischemia time. Reperfusion edema was strikingly diminished, preserving pulmonary structural and functional integrity while prolonging graft ischemia time. Employing the established PDE-5 inhibitor sildenafil during lung perfusion, storage, and implantation, ischemic tolerance may be extended and early graft function improved.

Role of angiopoietin-1 in experimental and human pulmonary arterial hypertension.

INTRODUCTION: The pulmonary microvasculature, consisting mainly of an endothelial cell (EC) monolayer and scant matrix support, is incompletely muscularized. Thus, the distal pulmonary arterioles may be predisposed to regression on exposure to environmental stresses (ie, hypoxia) and may be dependent on EC survival factors, like angiopoietin (Ang) 1, to attenuate the development of pulmonary arterial hypertension (PAH). In order to clarify the link between Ang1 expression and the development of PAH in patients, we also studied messenger RNA and protein expression in lung samples from healthy control subjects and patients with idiopathic PAH (IPAH) or PAH associated with other diseases (APAH). METHODS: Ang/Tie2 gene expression was assessed in rats that had been exposed to hypoxia (ie, 10% O2) for 1, 3, or 7 days. In a separate experiment, the cell-based gene transfer of Ang1/Ang2 was performed, and the effects were evaluated in rats with hypoxia-induced PAH. RESULTS: Hypoxia induced significant early increases in right ventricular systolic pressure (RVSP) and right ventricle/left ventricle-plus-septum mass ratio (RV/[LV + S]), with a significant decrease in Tie2 expression. Hypoxic rats receiving Ang1 demonstrated significant improvements in RVSP and RV/(LV + S), with a partial normalization in Tie2 protein levels. Robust Ang1 expression was observed in healthy human lungs. Furthermore, there were no significant changes in the levels of Ang1 or Ang2 in IPAH or APAH samples vs those in control subjects. CONCLUSIONS: Decreased activity of the Tie2 pathway with hypoxia may contribute to PAH, possibly by loss of EC survival signaling, which can be overcome by Ang1 gene transfer.

A novel model for post-transplant obliterative airway disease reveals angiogenesis from the pulmonary circulation.

We present a novel animal model for post-transplant obliterative airway disease in which the donor trachea is implanted into the recipient's lung parenchyma. Although this procedure is technically more challenging than the heterotopic model of implantation into a subcutaneous pouch, it has several important advantages some of which are the appropriate local environment and the possibility of local immunosuppressive therapy after transtracheal gene, cell or drug delivery. This model has revealed new insights into angiogenic potential of the pulmonary circulation.

The influence of the rapamycin-derivate SDZ RAD on the healing of airway anastomoses.

OBJECTIVE: Among the many immunosuppressive effects of SDZ RAD (40-0(2-hydroxyethyl)-rapamycin), a rapamycin derivative, is the inhibition of fibroblast proliferation. Since the long-term success of lung transplantation is limited by the development of bronchiolitis obliterans, a fibroblast-associated progressive luminal obstruction of the terminal bronchioli, the use of SDZ RAD as immunosuppressive in pulmonary graft recipients may counteract this process. However, reduction of fibroblast activity, posttransplant, may impair the healing of the bronchial anastomoses. MATERIALS AND METHODS: The cervical trachea in pigs was denuded, divided and re-anastomosed with Prolene 4-0 single stitches. Control animals (group 1, n=4) were without, and study animals (group 2, n=6) were with SDZ RAD therapy (1.25 mg/kg/day, p.o., 14 days). After 14 days, the pigs were sacrificed. The anastomoses were examined histologically, and breaking strength of tracheal strips of 5-mm width was measured. RESULTS: All animals survived without complications. Serum levels of SDZ RAD were 30.9+/-8.7 ng/ml (recommended level 20-40 ng/ml). All anastomoses healed macroscopically without difference between the two groups. Breaking strength was significantly lower in the treated animals (group 1 vs. group 2: 11.75+/-0.35 vs. 7.69+/-1.39 N, P=0.01). Histology did not show a significant change in histoarchitecture between the groups. CONCLUSIONS: Although SDZ RAD significantly reduced the breaking strength of the tracheal anastomosis, no obvious histological differences between treated and untreated animals could be detected. Since this model does not reflect the clinical situation, further investigations are necessary to reveal the effect of SDZ RAD on airway wound healing in concert with a contemporary clinically used multidrug immunosuppressive regimen in allograft recipients.