Electromagnetic navigation bronchoscopy localization of lung nodules for thoracoscopic resection.

BACKGROUND: Thoracoscopic localization of small peripheral pulmonary nodules is a concern. Failure can lead to larger parenchymal resection or conversion to thoracotomy. This study evaluates our experience in preoperative electromagnetic navigation bronchoscopy-guided localization of small peripheral lung lesions. METHODS: From January 2017 to March 2020 clinical, radiographic, surgical, and pathological data of patients who underwent electromagnetic navigation bronchoscopy (ENB)-guided methylene blue pleural marking of highly suspected pulmonary lesions before a full thoracoscopic resection were evaluated. Localization was performed for solid or mixed subpleural nodules measuring <10 mm, solid nodules measuring <20 mm located at more than 1 cm from the pleura and any pure ground glass opacity. Successful localization was defined as successful identification and thoracoscopic resection of target lesions. RESULTS: Forty-eight patients were included: 30 solid nodules (63%), 12 pure GGO (25%) and 6 mixed (13%). The median largest diameter at CT-scan was 11 mm (IQR, 9-14 mm) while the median distance from the pleural surface was 12 mm (IQR, 6-16 mm). The median ENB length was 25 min (19-33 min). Localization procedure was successful in 45 cases (94%). No procedural-related complications were reported. CONCLUSIONS: ENB is a safe and accurate preoperative procedure to localize small lung peripheral lesions. The high successful rate, the absence of related complications, the possibility of performing the procedure in the same operating room with a single general anesthesia, make ENB-guided dye marking an advantageous tool for thoracoscopic pulmonary resection.

Anti-tumour effect of low molecular weight heparin in localised lung cancer: a phase III clinical trial.

The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated.Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg-1 once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival.In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±sd age was 61.6±8.9 years, 190 (34.6%) patients had stage II-III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92-1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68-1.30; p=0.70).Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I-IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents.

Endobronchial treatment of peripheral tumors: ongoing development and perspectives.

The expanded possibilities to explore the lung deeper with new tools such as electromagnetic navigation bronchoscopy (ENB) or radial probe endobronchial ultrasonography (radial EBUS), combined with miniaturization of traditional local therapies such as radiofrequency ablation (RFA), radiotherapy, cryotherapy or photodynamic therapy, let the bronchoscopists hope for new ways of endoscopic treatments. This challenge could change the practice in the upcoming decades but raise some physical and technical issues. Safety and efficacy need to be solidly established to face the serious concurrence of stereotactic radiotherapy (SBRT) or percutaneous RFA. Here we describe ongoing development and perspectives for endobronchial treatment of peripheral lung tumors.

Early and delayed post-pneumonectomy empyemas: Microbiology, management and prognosis.

INTRODUCTION: Post-pneumonectomy empyema (PPE) is the most severe complication of pneumonectomy. Microbiology and its impact on management and prognosis have rarely been reported METHODS: We retrospectively reviewed the files of a series of 37 consecutive patients with PPE over a 10-year period with a special focus on microbiology, means used to treat empyema and prognosis. RESULTS: PPE occurred within 14 days of pneumonectomy in 17 cases (early PPE) and after postoperative day 16 in 20 patients (delayed PPE). PPE was monomicrobial in 57% of cases. The most frequent pathogens were Staphylococcus sp. and Streptococcus sp. Polymicrobial empyema was more frequent in patients with early PPE than delayed PPE (65% vs 25%; P = .02). Video-assisted thoracoscopic approach for cavity lavage was performed in 22 patients without broncho-pleural fistulae (BPF), associated with antimicrobial therapy and drainage, and was successful in 13 cases (59%). Seventeen patients (46%) underwent an open window thoracostomy. Overall 90-day post empyema mortality was 19%, with 6 deaths because of empyema in the early PPE group (35%), versus one (5%) in the delayed PPE group (P = .02). CONCLUSION: We distinguished 2 different PPE presentations: an early occurrence, mostly with polymicrobial cultures, including Gram-negative bacteria, and associated with a high mortality rate. By contrast, delayed PPEs were mostly monomicrobial with Gram-positive bacteria and associated with a better prognosis. VATS approach was successful in the majority of cases without BPF, even if some patients required secondary thoracostomy. PPE was associated with an excess of mortality especially when occurring in the early course after pneumonectomy.

Sensitivity of Cytology Specimens From Bronchial Aspirate or Washing During Bronchoscopy in the Diagnosis of Lung Malignancies: An Update.

BACKGROUND: Routine collection of cytology specimens from bronchial aspirate or washing is thought to increase the sensitivity of bronchoscopy for diagnosing malignant lung lesions. However, the added value of this practice has not been reappraised in a context of changing epidemiology. PATIENTS AND METHODS: In a retrospective monocenter study, all cytology specimens from bronchial aspirate or washing collected between May 2011 and December 2014 and the corresponding patients' files were reviewed. The final diagnosis of malignancy was based on all available pathologic information. RESULTS: Bronchoscopy was performed in 2750 patients, and bronchial cytology specimens were collected during 667 procedures, including 474 aspirate or washing cytology specimens collected during conventional (n = 366) or ultrasound-guided (EBUS) (n = 108) bronchoscopy in 455 patients with malignant lung lesion(s). The predominant histologic types were lung adenocarcinoma (43.9%) and squamous cell carcinoma (25.2%), and 271 tumors (59.6%) were endoscopically visible. At least 1 endoscopic sample (bronchial cytology and/or biopsies and/or endobronchial ultrasound-guided samples) was positive for malignancy during 329 (69.4%) of the 474 endoscopies, including 79 samples obtained in nonvisible lesions. Only 67 bronchial cytology specimens proved positive (sensitivity, 14.7%; 95% confidence interval, 11.8%-18.3%), and only 1 specimen (0.2%) produced a diagnosis not made by other samples during the same procedure. CONCLUSION: In contrast with older studies, the added value of collecting cytology specimens from bronchial aspirate or washing during bronchoscopy in this series proved negligible, reflecting mainly the increasing prevalence of adenocarcinomas. Abandoning this technique could be considered in centers with similar expertise and patient populations.

Lung fibroblasts share mesenchymal stem cell features which are altered in chronic obstructive pulmonary disease via the overactivation of the Hedgehog signaling pathway.

BACKGROUND: Alteration of functional regenerative properties of parenchymal lung fibroblasts is widely proposed as a pathogenic mechanism for chronic obstructive pulmonary disease (COPD). However, what these functions are and how they are impaired in COPD remain poorly understood. Apart from the role of fibroblasts in producing extracellular matrix, recent studies in organs different from the lung suggest that such cells might contribute to repair processes by acting like mesenchymal stem cells. In addition, several reports sustain that the Hedgehog pathway is altered in COPD patients thus aggravating the disease. Nevertheless, whether this pathway is dysregulated in COPD fibroblasts remains unknown. OBJECTIVES AND METHODS: We investigated the stem cell features and the expression of Hedgehog components in human lung fibroblasts isolated from histologically-normal parenchymal tissue from 25 patients--8 non-smokers/non-COPD, 8 smokers-non COPD and 9 smokers with COPD--who were undergoing surgery for lung tumor resection. RESULTS: We found that lung fibroblasts resemble mesenchymal stem cells in terms of cell surface marker expression, differentiation ability and immunosuppressive potential and that these properties were altered in lung fibroblasts from smokers and even more in COPD patients. Furthermore, we showed that some of these phenotypic changes can be explained by an over activation of the Hedgehog signaling in smoker and COPD fibroblasts. CONCLUSIONS: Our study reveals that lung fibroblasts possess mesenchymal stem cell-features which are impaired in COPD via the contribution of an abnormal Hedgehog signaling. These processes should constitute a novel pathomechanism accounting for disease occurrence and progression.

Air contamination for predicting wound contamination in clean surgery: A large multicenter study.

BACKGROUND: The best method to quantify air contamination in the operating room (OR) is debated, and studies in the field are controversial. We assessed the correlation between 2 types of air sampling and wound contaminations before closing and the factors affecting air contamination. METHODS: This multicenter observational study included 13 ORs of cardiac and orthopedic surgery in 10 health care facilities. For each surgical procedure, 3 microbiologic air counts, 3 particles counts of 0.3, 0.5, and 5 µm particles, and 1 bacteriologic sample of the wound before skin closure were performed. We collected data on surgical procedures and environmental characteristics. RESULTS: Of 180 particle counts during 60 procedures, the median log10 of 0.3, 0.5, and 5 µm particles was 7 (interquartile range [IQR], 6.2-7.9), 6.1 (IQR, 5.4-7), and 4.6 (IQR, 0-5.2), respectively. Of 180 air samples, 50 (28%) were sterile, 90 (50%) had 1-10 colony forming units (CFU)/m(3) and 40 (22%) >10 CFU/m(3). In orthopedic and cardiac surgery, wound cultures at closure were sterile for 24 and 9 patients, 10 and 11 had 1-10 CFU/100 cm(2), and 0 and 6 had >10 CFU/100 cm(2), respectively (P < .01). Particle sizes and a turbulent ventilation system were associated with an increased number of air microbial counts (P < .001), but they were not associated with wound contamination (P = .22). CONCLUSIONS: This study suggests that particle counting is a good surrogate of airborne microbiologic contamination in the OR.

Bulky mediastinal aspergillosis mimicking cancer in an immunocompetent patient.

We describe the case of a previously healthy 42-year-old woman who presented with a chronic cough and occasional night sweats. Radiologic exploration showed a bulky mediastinal mass surrounding the aortic arch, associated with a left subclavicular lymph node and a cerebral round lesion, mimicking a disseminated lung cancer. Surgical left subclavicular and computed tomography-guided mediastinal biopsy specimens showed granulomatous patterns. Mycologic culture of both samples grew Aspergillus flavus. Resolution was obtained after 9 months of oral voriconazole therapy.

Totally thoracoscopic major pulmonary resections: an analysis of perioperative complications.

BACKGROUND: Reports of recent large series support the safety of video-assisted thoracoscopic major pulmonary resections (MPR). However, although their rate of postoperative complications is low, the real incidence of intraoperative complications is unknown. METHODS: Clinical data from patients who underwent MPR through a full thoracoscopic approach between 2007 and 2012 were reviewed. Data were collected prospectively and analyzed retrospectively. RESULTS: A thoracoscopic MPR was attempted in 338 patients; 68.6% of the patients underwent a lobectomy and 31.4%, an anatomic segmentectomy. The mean operation time was 182 minutes (range, 80 to 300), and the mean intraoperative blood loss was 80 mL (range, 10 to 400 mL). Inhospital mortality rate was 0.3%. The overall complication rate was 32.8%. Intraoperative adverse events and conversion to open thoracotomy occurred in 2.7% and 5.6% of patients, respectively. Risk factors for conversion were preoperative forced expiratory volume of air in 1 second (p<0.001) and a fused fissure (p=0.001). A fused fissure (p=0.007) and surgical experience (p=0.022) were independent factors associated with a longer duration of operation. Major adverse events and reoperation occurred, respectively, in 8.9% and 3% of cases. Surgical complications were mostly vascular injury (n=9), laryngeal nerve palsy (n=5), chylothorax (n=3), and bronchus injury (n=1). On multivariate analysis, the only independent risk factors for major postoperative complications were smoking status and surgical experience. CONCLUSIONS: Although its overall rate of complications is low, a complete thoracoscopic approach might cause unusual adverse events. Surgeons must be aware of these complications to prevent them and anticipate their handling.

Fatal measles pneumonitis during Hodgkin's lymphoma.

The treatment of measles pneumonitis in immunocompromised adults is not established. We describe a patient with Hodgkin's lymphoma who developed acute pneumonia during a measles infection. On day 13, intravenous ribavirin and immunoglobulins were administrated. On day 18, the patient developed acute respiratory failure. An examination of transbronchial pulmonary biopsies showed Warthin-Finkeldey giant cells that are pathognomonic of measles pneumonitis. The patient died despite aggressive supportive care. Our case and a review of literature show that measles pneumonitis is routinely fatal in patients with cancer. We suggest that antiviral drugs should be considered as soon as the diagnosis has been established.

Predictive factors for complications of anatomical pulmonary segmentectomies.

OBJECTIVES: The role of anatomical pulmonary segmentectomy is increasing, but there are few data about its complication rate. We have analysed the postoperative morbidity, mortality and risk factors in a consecutive series of 228 segmentectomies performed in our department. METHODS: Between January 2007 and December 2011, 221 patients underwent 228 segmentectomies. There were 99 women (45%) and 122 men (55%). The mean age was 61 years (range 18-86 years). The mean forced expiratory volume in 1 s (FEV1) was 87%, and 30 patients had an FEV1 of ≤60%. Fifty-seven patients had a previous history of pulmonary resection. Indications for segmentectomy were: primary lung cancer (111 cases), metastases (71 cases), benign non-infectious (25 cases) and benign infectious diseases (21 cases). The approach was a posterolateral thoracotomy (Group PLT) in 146 patients (64%) and a thoracoscopy (Group TS) in 82 (36%). The two groups were homogenous in terms of age, gender, indications of surgery and type of segmentectomy. RESULTS: The mortality rate at 3 months was 1.3% (3 patients). The overall complication rate was 34%. Ten patients were reoperated for the following reasons: haemothorax (4 cases), ischaemia of the remaining segment (3 cases), active bleeding (1 case), prolonged air leak (1 case) and dehiscence of thoracotomy (1 case). The average duration of drainage was 5 days (range 1-34 days) and the average length of stay was 9 days (range 3-126 days). On univariate analysis, FEV1, male gender and thoracotomy were statistically significant risk factors for complications. On multivariate analysis, the same three predictive factors of complications independently of age were found statistically significant: preoperative FEV1 < 60% [odds ratio (OR) = 5.9, 95% CI (2.5-13.7), P < 0.001] male gender [OR = 2.04, 95% CI (1.2-3.6), P < 0.013] and thoracotomy [OR = 2.14, 95% CI (1.33-3.46), P = 0.001]. CONCLUSIONS: Pulmonary anatomical segmentectomies have an acceptable morbidity rate. Postoperative complications are more likely to develop in male gender patients, with FEV1 ≤ 60% and operated by open surgery.

The cyclooxygenase-2-prostaglandin E2 pathway maintains senescence of chronic obstructive pulmonary disease fibroblasts.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with lung fibroblast senescence, a process characterized by the irreversible loss of replicative capacity associated with the secretion of inflammatory mediators. However, the mechanisms of this phenomenon remain poorly defined. OBJECTIVES: The aim of this study was to analyze the role of prostaglandin E2 (PGE2), a prostaglandin known to be increased in COPD lung fibroblasts, in inducing senescence and related inflammation in vitro in lung fibroblasts and in vivo in mice. METHODS: Fibroblasts were isolated from patients with COPD and from smoker and nonsmoker control subjects. Senescence markers and inflammatory mediators were investigated in fibroblasts and in mice. MEASUREMENTS AND MAIN RESULTS: Lung fibroblasts from patients with COPD exhibited higher expression of PGE2 receptors EP2 and EP4 as compared with nonsmoker and smoker control subjects. Compared with both nonsmoker and smoker control subjects, during long-term culture, COPD fibroblasts displayed increased senescent markers (increased senescence associated-ß galactosidase activity, p16, and p53 expression and lower proliferative capacity), and an increased PGE2, IL-6, IL-8, growth-regulated oncogene (GRO), CX3CL1, and matrix metalloproteinase-2 protein and cyclooxygenase-2 and mPGES-1 mRNA expression. Using in vitro pharmacologic approaches and in vivo experiments in wild-type and p53(-/-) mice we demonstrated that PGE2 produced by senescent COPD fibroblasts is responsible for the increased senescence and related inflammation. PGE2 acts either in a paracrine or autocrine fashion by a pathway involving EP2 and EP4 prostaglandin receptors, cyclooxygenase-2-dependent reactive oxygen species production and signaling, and consecutive p53 activation. CONCLUSIONS: PGE2 is a critical component of an amplifying and self-perpetuating circle inducing senescence and inflammation in COPD fibroblasts. Modulating the described PGE2 signaling pathway could provide a new basis to dampen senescence and senescence-associated inflammation in COPD.

Transfusions, major bleeding, and prevention of venous thromboembolism with enoxaparin or fondaparinux in thoracic surgery.

Enoxaparin 40 mg/day (E) or fondaparinux 2.5 mg/day (F) are recommended to prevent venous thromboembolism (VTE) in medical and surgical patients at risk. Over the two years after switching from E to F in our 35-bed department of pulmonology and thoracic surgery, an increase in the number of transfusions was observed. A retrospective explanatory investigation was undertaken. Hospitalised patients in the two years before and after switching from E to F were compared. The files of all transfused patients were reviewed. A blinded independent committee adjudicated major bleeding events. In the investigated time period, the overall transfusion rate increased from 1.8% of 2,989 patients to 3.1% of 3,085 patients (p=0.002). Mean ages (58.4 vs. 59.1 years), proportions of surgical patients (63.6% vs. 58.4%), cancer patients (72.1% vs. 69.5%), and treated patients (≥ 1 dose of E or F: 51.8% vs. 52.5%) were similar. The number of medical patients transfused while receiving E or F did not increase significantly (0.9% vs. 1.3%, RR=1.45 [0.66-3.17], p=0.35). The number of surgical patients transfused postoperatively while receiving E or F increased significantly (0.7% vs. 1.9% of all surgical patients, relative risk [RR]=2.75 [1.45-5.23], p=0.001), including a significant increase in transfusions for major bleeding (0.2% vs. 0.9%, RR=5.97 [1.74-20.4], p<0.001). A multivariate analysis did not find confounding factors. The incidence of symptomatic postoperative pulmonary embolism remained very low (0.05% vs. 0.17%). In conclusion, in thoracic surgery patients, switching from enoxaparin to fondaparinux to prevent VTE was associated with a significant increase in the risk of postoperative major bleeding. A causal relationship appears plausible.

Telomere dysfunction causes sustained inflammation in chronic obstructive pulmonary disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation of unknown pathogenesis. OBJECTIVES: To investigate whether telomere dysfunction and senescence of pulmonary vascular endothelial cells (P-ECs) induce inflammation in COPD. METHODS: Prospective comparison of patients with COPD and age- and sex-matched control smokers. Investigation of mice null for telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes. MEASUREMENTS AND MAIN RESULTS: In situ lung specimen studies showed a higher percentage of senescent P-ECs stained for p16 and p21 in patients with COPD than in control subjects. Cultured P-ECs from patients with COPD exhibited early replicative senescence, with decreased cell-population doublings, a higher percentage of ß-galactosidase-positive cells, reduced telomerase activity, shorter telomeres, and higher p16 and p21 mRNA levels at an early cell passage compared with control subjects. Senescent P-ECs released cytokines and mediators: the levels of IL-6, IL-8, monocyte chemotactic protein (MCP)-1, Hu-GRO, and soluble intercellular adhesion molecule (sICAM)-1 were elevated in the media of P-ECs from patients compared with control subjects at an early cell passage, in proportion to the senescent P-EC increase and telomere shortening. Up-regulation of MCP-1 and sICAM-1 led to increased monocyte adherence and migration. The elevated MCP-1, IL-8, Hu-GROα, and ICAM-1 levels measured in lungs from patients compared with control subjects correlated with P-EC senescence criteria and telomere length. In Tert(-/-) and/or Terc(-/-) mouse lungs, levels of the corresponding cytokines (MCP-1, IL-8, Hu-GROα, and ICAM-1) were also altered, despite the absence of external stimuli and in proportion to telomere dysfunction. CONCLUSIONS: Telomere dysfunction and premature P-EC senescence are major processes perpetuating lung inflammation in COPD.

Abdominal pain and severe hyponatremia after lung cancer surgery.

We report a 54-year-old man who presented with abdominal pain and severe hyponatremia a few days after a left lower lobectomy for lung cancer. An abdominal computed tomography scan without contrast showed a bilateral adrenal hemorrhagic infarction, mainly on the right side. Serum sodium level was 113 mmol/L, and cortisol level was 0 microg/L. Anticardiolipin-type antibodies (immunoglobulin G isotype) level was 75 GPL/mL (normal value < 10). With hydrocortisone supplementation and curative doses of low-molecular-weight heparin, the patient recovered progressively and was discharged on postoperative day 17. Final diagnosis was bilateral adrenal gland hemorrhagic necrosis leading to adrenal insufficiency, associated with antiphospholipid syndrome. We discuss the mechanism and the role of the operation in the occurrence of this particularly rare and potentially life-threatening complication. Recommendations to prevent thrombosis in surgical patients who have antiphospholipid antibodies are lacking.

Thoracoscopic resection of bulky intrathoracic benign lesions.

BACKGROUND: Video-assisted thoracic surgery (VATS) is used for the diagnosis and treatment of some mediastinal lesions. However, large-size tumours are usually approached by thoracotomy or sternotomy. We report our experience of a full thoracoscopic approach for bulky intrathoracic lesions. METHODS: From November 2002 to March 2007, 14 patients with a bulky intrathoracic mass were referred for resection. The study group consisted of eight females and six males with a mean age of 44 years (range: 13-74). We defined as bulky a mass with a minimal cross-sectional diameter equal to or larger than 50 mm, as measured on the specimen by the pathologist. RESULTS: Thoracoscopic resection was completed in all patients. In 4 cases, the mass originated from the pleura, and in 10 cases from the mediastinum. The larger diameter of the lesion ranged from 50 mm to 160 mm, with a median of 90.2 mm. Operative time, calculated from insertion of the first trocar to skin closure, ranged from 40 to 190 min (mean: 102). Mean chest drain duration was 2.1 days (range: 1-4 days) and the mean hospital stay was 4.3 days (range: 3-11 days). There were no major postoperative complications. The final pathological diagnoses were the following: solitary fibrous tumours of the pleura (4), benign thymic cysts (2), teratomas (2), bronchogenic cyst (1), benign thymoma (1), pleuropericardial cyst (1) and benign neurogenic tumours (3). CONCLUSIONS: With experience and use of appropriate instrumentation, resection of bulky intrathoracic lesions by thoracoscopy is feasible and safe. It should be considered as a reliable alternate for tumours that are benign and most often asymptomatic.