Postoperative outcomes of frequent exacerbator patients with Chronic Obstructive Pulmonary Disease after resection of Non-Small Cells Lung Cancer.

Chronic obstructive pulmonary disease (COPD) is a risk factor of post-operative complications after lung cancer resection. The influence of the "frequent exacerbator (FE)" phenotype (at least three exacerbations per year) is unknown. Postoperative outcomes of frequent exacerbators (POFE) was a prospective observational study of patients with COPD undergoing lung resection for cancer. The inclusion criteria were: age >40 years, FEV1/FVC <70%, non-urgent surgery for lung cancer, filled out self-questionnaires. The primary outcome was assessment of postoperative pulmonary complications (purulent tracheobronchitis, atelectasis, pneumonia, acute respiratory failure, need of mechanical ventilation). Secondary outcomes encompassed the prevalence of the FE phenotype and its impact on postoperative complications. A total of 682 patients were screened from June 2014 to October 2015. 93 patients with COPD were included, 21 (23%) were FE. Postoperative tracheobronchitis, atelectasis pneumonia or respiratory failure (isolated or associated) occurred in 47%, 48%, 26%, and 38% of patients, respectively. Non-invasive and invasive mechanical ventilation were necessary in 4 (4%) and 22 (23%) patients. Purulent tracheobronchitis, pneumonia and hypercapnia (this last requiring noninvasive mechanical ventilation) were more frequent in FE (p = 0.043, 0.042, 0.015); however the number of patients wth at least one respiratory complication was not different (76% vs. 52%, p = 0.056). In all patients, multivariate logistic regression identified two independent factors of postoperative respiratory complications: male sex (OR 10.6 [95% CI 1.97-57.6], p = 0.006) and the FE phenotype (OR 6.33 [1.04-38.39], p = 0.045). Occurrence of postoperative complications in patients with COPD is high. FE phenotype is an independent risk factor.

Medical and Economic Evaluation of FOREseal Bioabsorbable Reinforcement Sleeves Compared With Current Standard of Care for Reducing Air Leakage Duration After Lung Resection for Malignancy: A Randomized Trial.

OBJECTIVE: The objective of this study was to determine the efficacy of alginate staple-line reinforcement of fissure openings as compared with stapling alone, with or without tissue sealant or glue, in reducing the incidence and duration of air leakage after pulmonary lobectomy for malignancy. SUMMARY BACKGROUND DATA: No randomized trial evaluating alginate staple-line reinforcement has been performed to date. METHODS: The Staple-line Reinforcement for Prevention of Pulmonary Air Leakage study was a multicenter randomized trial, with blinded evaluation of endpoints. Patients over 18 years of age scheduled for elective open lobectomy or bilobectomy for malignancy were eligible for enrollment. At thoracotomy, patients were deemed ineligible if an unanticipated pneumonectomy was indicated, or if air leakage occurred after the liberation of pleural adhesions. Otherwise, if the fissure was incomplete or the lung had an emphysematous appearance, patients were randomized to either standard management or interventional procedure consisting of fissure opening with linear cutting staplers buttressed with paired alginate sleeves (FOREseal). The number of eligible patients necessary in each randomization arm was estimated to be 190, and an outcomes analysis was performed on an intention-to-treat basis. RESULTS: Of the 611 patients consented to study enrollment, 380 met the inclusion criteria and were randomized. Based on an intention-to-treat analysis, the primary endpoint of air leak duration was not different between the 2 groups: 1 day (range: 0-2 d) in the FOREseal group and 1 day (range: 0-3 d) in the control group (P = 0.8357). In addition, the 2 groups were similar in terms of the proportion of patients presenting with prolonged air leakage (7.8% in the FOREseal group vs 11.3% in the control group, P = 0.264) and the average duration of chest drainage (P = 0.107). Procedure costs were comparable for both groups. CONCLUSIONS: FOREseal did not demonstrate a significant advantage over standard treatment alone.

Surgical Resection for Pulmonary Carcinoid: Long-Term Results of Multicentric Study-The Importance of Pathological N Status, More Than We Thought.

BACKGROUND: Histological subdivision into typical (TC) and atypical (AC) is crucial for treatment and prognosis of lung carcinoids but can be also very challenging, even for experts. In this study, we aimed to strengthen or reduce the prognostic value of several pathological, clinical, or per-operative factors some of which are still controversial. METHODS: We retrospectively reviewed clinical records related to 195 patients affected by TC (159) or AC (36) surgically treated between 2000 and 2014, in three different centers. Survival and subtypes comparison analyses were performed to identify potential prognostic factors. RESULTS: TCs showed a lower rate of nodal involvement than ACs (N0 = 94.9%; N1 = 1.9%; N2 = 3.2% in typical and N0 = 63.8%; N1 = 16.6%; N2 = 19.4% in atypical carcinoids, respectively, p < 0.0001). Long-term oncological results of resected carcinoids were significantly better in TCs than ACs with higher 5- and 10-year overall survival rates (97.2 and 88.2% vs. 77.9 and 68.2%, respectively; p = 0.001) and disease-free survival rates (98.2 and 90.3% in typical and 80.8 and 70.7% atypical carcinoids, respectively; p = 0.001). Risk factors analysis revealed that AC subtype [HR 4.33 (95% CI 1.72-8.03), p = 0.002], pathological nodal involvement [HR 3.05 (95% CI 1.77-5.26), p < 0.0001], and higher SUVmax [HR 4.33 (95% CI 1.03-7.18), p = 0.002] were independently and pejoratively associated with overall survival. Factors associated with a higher risk of recurrence were AC subtype [HR 6.13 (95% CI 1.13-18.86), p = 0.002]; nodal involvement [HR 5.48 (95% CI 2.85-10.51), p < 0.0001]; higher Ki67 expression level [HR 1.09 (95% CI 1.01-1.20), p = 0.047]; and SUVmax [HR 1.83 (95% CI 1.04-3.23), p = 0.035]. CONCLUSION: Surgery for lung carcinoids allows satisfactory oncological results which mainly depend on carcinoid subtype dichotomy, pathological nodal status, and SUVmax.

Intratumoral Immune Cell Densities Are Associated with Lung Adenocarcinoma Gene Alterations.

RATIONALE: Tumor-infiltrating immune cells affect lung cancer outcome. However, the factors that influence the composition and function of the tumor immune environment remain poorly defined and need investigation, particularly in the era of immunotherapy. OBJECTIVES: To determine whether the tumoral immune environment is related to lung adenocarcinoma mutations. METHODS: This retrospective cohort included 316 consecutive patients with lung adenocarcinoma (225 men; 258 smokers) studied from 2001 to 2005 in a single center. We investigated the association of densities of intratumoral mature dendritic cells (mDCs), CD8+ T cells, neutrophils, and macrophages with clinical and pathological variables and tumor cell mutation profiles obtained by next-generation sequencing. MEASUREMENTS AND MAIN RESULTS: In 282 tumors, we found 460 mutations, mainly in TP53 (59%), KRAS (40%), STK11 (24%), and EGFR (14%). Intratumoral CD8+ T-cell density was high in smokers (P = 0.02) and TP53-mutated tumors (P = 0.02) and low in BRAF-mutated tumors (P = 0.005). Intratumoral mDC density was high with low pathological tumor stage (P = 0.01) and low with STK11 mutation (P = 0.004). Intratumoral neutrophil density was high and low with BRAF mutation (P = 0.04) and EGFR mutation (P = 0.02), respectively. Intratumoral macrophage density was low with EGFR mutation (P = 0.01). Intratumoral CD8+ T-cell and mDC densities remained strong independent markers of overall survival (P = 0.001 and P = 0.02, respectively). CONCLUSIONS: Intratumoral immune cell densities (mDCs, CD8+ T cells, neutrophils, macrophages) were significantly associated with molecular alterations in adenocarcinoma underlying the interactions between cancer cells and their microenvironment.

MR diagnosis of diaphragmatic endometriosis.

PURPOSE: To evaluate magnetic resonance imaging (MRI) for diaphragmatic endometriosis diagnosis. MATERIALS AND METHODS: Over a 2-year period, all diaphragmatic MRI performed in the context of diaphragmatic endometriosis were reviewed. Axial and coronal fat-suppressed T1- and T2-weighted sequences were analyzed by two independent readers for the presence of nodules, plaque lesions, micronodule clustering, or focal liver herniation. MR abnormalities were correlated to surgical findings in women surgically treated. Interobserver agreement was assessed by κ statistics. RESULTS: Twenty-three women with diaphragmatic endometriosis criteria comprised the population; 14 had surgical confirmation and nine had symptoms relief with hormonal treatment. MRI sensitivity was 83 % (19/23; 95 % confidence interval [CI]: 68, 98) for reader 1 and 78 % (18/23; 95 % CI: 61, 95) for reader 2. Kappa value was 0.86 (95 % CI: 0.47, 1.00). Readers 1 and 2 detected 35 and 36 lesions, respectively, all right-sided and agreed for 32 lesions on the type, location, and signal. Lesions were mostly nodules (23/32, 72 %), predominantly posterior (28/32, 87.5 %) and hyperintense on T1 (20/32, 63 %). MRI was negative for both readers in 2 surgically treated patients with small nodules or isolated diaphragmatic holes. CONCLUSION: MRI allows diaphragmatic endometriosis diagnosis with 78 to 83 % sensitivity and excellent interobserver agreement. KEY POINTS: • MRI allows the diagnosis of diaphragmatic endometriosis with up to 83 % sensitivity. • Diaphragmatic endometriosis lesions are better depicted on fat-suppressed T1-weighted sequences. • Diaphragmatic lesions, mostly hyperintense nodules, are right-sided and predominantly posterior. • MRI can help in timely diagnosis of diaphragmatic endometriosis.

Indications and Results of Reconstructive Techniques with Flaps Transposition in Patients Requiring Complex Thoracic Surgery: A 12-Year Experience.

BACKGROUND: Flap transposition is an infrequent but far from exceptional thoracic surgical procedure. The aim of this retrospective study was to report our experience in a referral unit of general thoracic surgery analyzing the early results after flap transposition. METHODS: We retrospectively analyzed the clinical records, surgical notes, and postoperative results of a cohort of patients who underwent flap transposition in our unit from November 2000 to February 2013. RESULTS: Overall, a surgical approach adopting flap reconstruction techniques was performed in 81 patients (54 males, 27 females) with a median age of 62 years (range 20-87). Flap transposition was necessary to reconstruct chest wall after resection for malignancy (27 patients), to repair intrathoracic viscera perforation (15 patients), and to fill residual cavities secondary to pulmonary/pleural infection (39 patients). A pedicle muscle flap was transposed in most of cases (64 pts, 79 %), while in the remaining 17 cases (11 %), an omental flap was used. There were no immediate postoperative complications, while three in-hospital deaths occurred due to respiratory or multiorgan failure. Among patients undergone flap transposition to fill a residual cavity, we observed a recurrent bronchopleural fistula in three patients (7.7 %); such patients were treated by repeat flap transposition (2 cases) and by repeat cavernostomy (1 case). CONCLUSION: Flap transposition may be indicated as part of a multimodal treatment for severely ill patients requiring complex thoracic surgery.

Epidemiology of spontaneous pneumothorax: gender-related differences.

BACKGROUND: Epidemiology of spontaneous pneumothorax has been scantily studied. We aimed to assess the incidence of spontaneous pneumothorax and describe patients' characteristics with respect to age, sex, seasonal occurrence, primary or secondary character, surgical management and rehospitalisations on a large-scale database. METHODS: Data from all patients aged ≥14 years and hospitalised with a diagnosis of non-traumatic pneumothorax in France from 2008 to 2011 were retrieved from the National Hospitalisation Database. RESULTS: There were 59 637 hospital stays corresponding to 42 595 patients. Twenty-eight per cent of patients were rehospitalised at least once during the 4-year period. Annual rate of pneumothorax could be estimated at 22.7 (95% CI 22.4 to 23.0) cases for 100 000 habitants. The women to men ratio was 1:3.3. Mean age was significantly higher in women than in men (41±19 vs 37±19 years, p<0.0001). No seasonal variation was observed. A surgical procedure was performed in 14 352 hospital stays (24%). In the group of patients aged <30 years, there was no statistical difference between men and women with regard to type of pneumothorax (primary or secondary), type of hospitalisation unit (surgery vs medicine), treatment modality (surgery or not), intensive care unit (ICU) admission and hospital stay duration. Rehospitalisation was more frequent in women than in men (56% vs 52%, p<0.0001). In the 30-49 years age group, surgery and rehospitalisation were more frequent in women than in men (each, p<0.001). In the 50-64 years age group, surgical procedures and rehospitalisations were more frequent in men than in women (p=0.002 and p<0.0001, respectively). CONCLUSIONS: Sex and age are determinant factors in the course of spontaneous pneumothorax.

Resection of Late Pulmonary Metastases from Pancreatic Adenocarcinoma: Is Surgery an Option?

Patients with recurrences from pancreas adenocarcinoma have a poor survival rate despite new chemotherapy treatment options. Recurrences are mainly hepatic metastases or peritoneal dissemination and surgical treatment is not recommended. Late and single metachronous pulmonary recurrences are uncommon and may mimic primary lung carcinoma. We report two patients with late and unique pulmonary metastasis from pancreatic cancer. These two patients underwent surgical resection; three and five years later, they did not experience recurrences. Cases called for a surgical approach in late and unique pulmonary metastases from pancreatic cancer, and paved the way for a prolonged chemotherapy free period.

Which is the Role of Pneumonectomy in the Era of Parenchymal-Sparing Procedures? Early/Long-Term Survival and Functional Results of a Single-Center Experience.

AIM: Despite the increasing adoption of parenchymal-sparing procedures, pneumonectomy is still necessary in several pleural and pulmonary (benign or malignant) diseases. We reviewed clinical data of a large cohort of patients treated by pneumonectomy with the aim of better define its impact on early and long-term results. METHODS: Clinical and pathological characteristics of all consecutive patients treated by pneumonectomy between January 2005 and May 2012 were retrospectively reviewed. Thirty- and 90-day mortality, as well as long-term survival was assessed. Factors associated to long-term survival were analyzed by univariate and multivariate analyses. Evaluation of quality of life was carried out by a standard questionnaire (SF-12) administrated by phone to patients surviving beyond 1 year. RESULTS: A total of 398 patients (293 men; mean age 61 ± 10.9 years) were operated on in the study period. Indication was malignancy in 380 patients (350 primary lung cancers). Thirty-day mortality was 9 % (right: 12.6 % vs. left: 6.3 %, p = 0.013), significantly correlating with age (p = 0.021), comorbidities (p = 0.034), PS > 1 (p = 0.018), preoperative dyspnea (p = 0.0013), and FEV1 (p = 0.0071). Overall 1-, 3-, 5-, and 7-year survival rates were 76.6, 46.6, 34.4, and 29.2 %. In case of primary lung cancer, these figures were 76.8, 46.4, 34.5, and 29.7 %. At univariate analysis, a less favorable survival was associated to PS > 1 (p = 0.0078), right side (p = 0.044), occurrence of postoperative complications (p = 0.00079), and T3-4 status (p = 0.013). At multivariate analysis, PS > 1, right side, and occurrence of postoperative complications were identified as independent worse prognostic factors. SF12 physical score was 39.1 ± 9.0 and was correlated to the presence of preoperative symptoms (p = 0.013). Mental score was 50.68 ± 9.63 and was correlated to preoperative FEV1/FVC ratio (p = 0.023) and side of disease (p = 0.023). CONCLUSION: In current practice, pneumonectomy is still performed for malignancy, sometimes after induction treatment. High postoperative morbidity and mortality are observed; however, at a farer interval time point, long-term survival with preserved quality of life can be observed.

Intertumor heterogeneity of non-small-cell lung carcinomas revealed by multiplexed mutation profiling and integrative genomics.

Non-small-cell lung cancer (NSCLC) is a heterogeneous disease, with a burden of genomic alterations exceeding most other tumors. The goal of our study was to evaluate the frequencies of co-occurring mutations and copy-number aberrations (CNAs) within the same tumor and to evaluate their potential clinical impact. Mass-spectrometry based mutation profiling using a customized lung cancer panel evaluating 214 mutations across 26 key NSCLC genes was performed on 230 nonsquamous NSCLC and integrated with genome-wide CNAs and clinical variables. Among the 138 cases having at least one mutation, one-third (41, 29.7%) showed two or more mutations, either in the same gene (double mutation) or in different genes (co-mutations). In epidermal growth factor receptor (EGFR) mutant cancers, there was a double mutation in 18% and co-mutations in the following genes: TP53 (10%), PIK3CA (8%), STK11 (6%) and MET (4%). Significant relationships were detected between EGFR mutation and 1p, 7p copy gains (harboring the EGFR gene) as well as 13q copy loss. KRAS mutation was significantly related with 1q gain and 3q loss. For Stage I, tumors harboring at least one mutation or PIK3CA mutation were significantly correlated with poor prognosis (p-value = 0.02). When combining CNAs and mutational status, patients having both KRAS mutation and the highest related CNA (3q22.3 copy loss) showed a significant poorer prognosis (p-value = 0.03). Our study highlights the clinical relevance of studying tumor complexity by integrative genomic analysis and the need for developing assays that broadly screen for both "actionable" mutations and copy-number alterations to improve precision of stratified treatment approaches.

Should we continue to offer extrapleural pneumonectomy to selected mesothelioma patients? A single center experience comparing surgical and non-surgical management.

Malignant pleural mesothelioma remains an incurable disease for which the optimal therapeutic approach remains an extremely debated issue. Though not yet clearly defined, a subset of patients may benefit from a surgery-based multimodal treatment plan, beyond what would be expected with non-surgical therapies only. Indeed, despite some disappointing results on the feasibility of a multimodality treatment (chemotherapy ± surgery and post-operative radiation therapy) based on a lung sacrificing surgery (extrapleural pleuropnemonectomy) have been recently reported, the question concerning the role of extrapleural pneumonectomy in selected mesothelioma patients is still unanswered. In the light of this, we have reviewed our mono-institutional retrospective experience in the mesothelioma management, discussing on the role of extrapleural pneumonectomy in the multimodality treatment.

Comparison of juvenile and adult myasthenia gravis in a French cohort with focus on thymic histology.

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle fatigability due to acetylcholine receptor (AChR) autoantibodies. To better characterize juvenile MG (JMG), we analyzed 85 pre- and 132 post-pubescent JMG (with a cutoff age of 13) compared to 721 adult MG patients under 40 years old using a French database. Clinical data, anti-AChR antibody titers, thymectomy, and thymic histology were analyzed. The proportion of females was higher in each subgroup. No significant difference in the anti-AChR titers was observed. Interestingly, the proportion of AChR+ MG patients was notably lower among adult MG patients aged between 30 and 40 years, at 69.7%, compared to over 82.4% in the other subgroups. Thymic histological data were examined in patients who underwent thymectomy during the year of MG onset. Notably, in pre-JMG, the percentage of thymectomized patients was significantly lower (32.9% compared to more than 42.5% in other subgroups), and the delay to thymectomy was twice as long. We found a positive correlation between anti-AChR antibodies and germinal center grade across patient categories. Additionally, only females, particularly post-JMG patients, exhibited the highest rates of lymphofollicular hyperplasia (95% of cases) and germinal center grade. These findings reveal distinct patterns in JMG patients, particularly regarding thymic follicular hyperplasia, which appears to be exacerbated in females after puberty.

Differential mutation profiles and similar intronic TP53 polymorphisms in asbestos-related lung cancer and pleural mesothelioma.

Given the interest in defining biomarkers of asbestos exposure and to provide insights into asbestos-related and cell-specific mechanisms of neoplasia, the identification of gene alterations in asbestos-related cancers can help to a better understanding of exposure risk. To understand the aetiology of asbestos-induced malignancies and to increase our knowledge of mesothelial carcinogenesis, we compared genetic alterations in relevant cancer genes between lung cancer, induced by asbestos and tobacco smoke, and malignant pleural mesothelioma (MPM), a cancer related to asbestos, but not to tobacco smoke. TP53, KRAS, EGFR and NF2 gene alteration analyses were performed in 100 non-small cell lung cancer (NSCLC) patients, 50 asbestos-exposed and 50 unexposed patients, matched for age, gender, histology and smoking habits. Detailed assessment of asbestos exposure was based on both specific questionnaires and asbestos body quantification in lung tissue. Genetic analyses were also performed in 34 MPM patients. TP53, EGFR and KRAS mutations were found in NSCLC with no link with asbestos exposure. NF2 was only altered in MPM. Significant enhancement of TP53 G:C to T:A transversions was found in NSCLC from asbestos-exposed patients when compared with unexposed patients (P = 0.037). Interestingly, TP53 polymorphisms in intron 7 (rs12947788 and rs12951053) were more frequently identified in asbestos-exposed NSCLC (P = 0.046) and MPM patients than in unexposed patients (P < 0.001 and P = 0.012, respectively). These results emphasise distinct genetic alterations between asbestos-related thoracic tumours, but identify common potential susceptibility factors, i.e. single nucleotide polymorphisms in intron 7 of TP53. While genetic changes in NSCLC are dominated by the effects of tobacco smoke, the increase of transversions in TP53 gene is consistent with a synergistic effect of asbestos. These results may help to define cell-dependent mechanisms of action of asbestos and identify susceptibility factors to asbestos.

Catamenial pneumothorax and endometriosis-related pneumothorax: clinical features and risk factors.

BACKGROUND: Catamenial pneumothorax and thoracic endometriosis (TE) are still under diagnosed. The purpose of this study is to increase the diagnostic accuracy for these conditions in patients with spontaneous pneumothorax and to identify their risk factors. METHODS: We conducted a retrospective study on all consecutive women of reproductive age referred to our Centre for surgical treatment of spontaneous pneumothorax between July 2000 and January 2009. RESULTS: The study population comprised 156 premenopausal women of whom 49 (31.4%) had catamenial and/or TE-related pneumothorax. Over a quarter of these 49 patients had a previous history of recurrent thoracic or scapular catamenial pain. They experienced their first pneumothorax episode at an older age (mean ± SD) (34.0 years ± 6.7) than women with idiopathic pneumothorax (28.7 ± 6.1 years, P < 0.001). Pelvic endometriosis was found in 51% of women with catamenial and/or TE-related pneumothorax. After adjustment for confounding factors by multiple logistic regression analysis, the results show that, infertility [odd ratio (OR) = 4.21, 95% confidence interval (CI) = 1.28-13.88] and a history of pelvic surgery with a uterine procedure and/or uterine scraping (OR = 2.85, 95% CI = 1.12-7.26) were the strongest predictors of catamenial and/or TE-related pneumothorax. CONCLUSIONS: Infertility and uterine procedures are significantly associated with catamenial and/or TE-related pneumothorax. Scapular or thoracic pain during menses often precedes the occurrence of pneumothorax and is highly specific for the diagnosis of TE. Our results suggest that in women with pelvic endometriosis, these symptoms should be systematically investigated for an earlier diagnosis of TE.

En Bloc Resection of Thoracic Tumors Invading the Spine: A Single-Center Experience.

BACKGROUND: Vertebral involvement by a thoracic tumor has long been considered as a limit to surgical treatment, and despite advances, such an invasive operation remains controversial. The aim of this study was to characterize a single-center cohort and to evaluate the outcome, focusing on survival and complications. METHODS: We retrospectively reviewed the data of all patients operated on for tumors involving the thoracic spine in an 8-year period. En bloc resection was generally performed by a double team involving thoracic and orthopedic surgeons. Distant follow-up was recorded for oncologic and functional analysis. RESULTS: There were 31 patients operated on. An induction therapy was administered in 20 patients. Spinal resection (mostly including ≥2 vertebral levels) was combined with lobectomy in 48.3% of the patients, and osteosynthesis was required in 22 patients. We observed no in-hospital death and a major complications rate of 32.3%, including 5 patients with early neurologic complications. There were 61.3% primary lung carcinomas, 12.9% extrapulmonary primaries, 9.7% metastases, and 16.1% benign tumors. Mean follow-up was 32.1 months. The 5-year overall survival rate was 81.3% in the entire cohort and 75.0% in patients with a malignant tumor. Occurrence of an early postoperative major complication was the only factor significantly associated with shorter overall survival (p = 0.03). The 5-year disease-free survival rate was 37.0% in malignancies. Delayed complications occurred in 35.5% of patients, including persistent neurologic deficit in 12.9%, instrumentation migration in 19.4%, and local infection in 12.9%. CONCLUSIONS: En bloc resection of spinal thoracic tumors offers long-term survival and few recurrences in highly selected patients but is associated with significant delayed mechanical or infectious complications.

Epidemiology and Appropriateness of Antibiotic Prescribing in Severe Pneumonia After Lung Resection.

BACKGROUND: Postoperative pneumonia (POP) is a severe complication of major lung resection. The objective of this study was to describe the current epidemiology and appropriateness of antibiotic prescriptions in severe POP, 4 years after implementation of an antimicrobial stewardship program that was based on weekly multidisciplinary review of all antibiotic therapies. METHODS: This study was a retrospective analysis of a prospectively collected database. It included all cases of severe POP occurring within 30 days after major lung resection of in a 1,500-bed hospital between 2013 and 2015. Criteria for severe POP were acute respiratory failure, severe sepsis, or a rapidly extensive pulmonary infiltrate. The study collected data on incidence, clinical outcomes, and microbiological analyses. Appropriateness of antibiotic prescribing was assessed by quality indicators previously validated in the literature. RESULTS: Over the study period, 1,555 patients underwent major lung surgery. Severe POP occurred in 91 patients (5.8%; confidence interval, 4.7%; 7.0%), with a mortality rate of 9.0% (8 of 91; confidence interval, 3.0%; 14.6%). In POP with positive microbiological results, the proportion of gram-negative bacteria other than Haemophilus was 76% (50 of 66 cases). All patients (91 of 91) had respiratory samples taken within 24 hours after the start of antibiotics; empiric therapy was concordant with the guideline in 80% (69 of 86), and it was switched to pathogen-directed therapy in 74% (46 of 62). In 71 of 91 patients (78%), the antibiotic duration was up to 7 days. CONCLUSIONS: This study reported a high proportion of gram-negative bacteria in severe POP. Four years after implementation of the program, quality indicators of antibiotic prescribing were all >70%. The rate of de-escalation to pathogen-directed therapy could be improved, however.

Synchronous Oligometastatic Lung Cancer Deserves a Dedicated Management.

BACKGROUND: Oligometastatic stage IV non-small lung cancer (NSCLC) patients have a 5-year overall survival of 30% versus 4% to 6% in historical cohorts of stage IV NSCLC patients. We reviewed data and patterns of care of patients affected by oligometastatic NSCLC in our center between 2001 and 2017. METHODS: We retrospectively reviewed clinical and pathological files of all patients with lung cancer and synchronous isolated adrenal or brain metastases, or both, treated by locally ablative treatments (surgery or radiotherapy, or both) of both primary cancer and distant metastasis. Statistical analysis was performed to assess the effect on overall survival of patient- and tumor-related characteristics and therapeutic approaches. Overall survival was assessed by the Kaplan-Meier method. Survival rates were compared by log-rank test. Significance was accepted at a level of p of less than 0.05. RESULTS: Our department treated 51 patients affected by NSCLC and synchronous brain metastasis (n = 41), adrenal metastasis (n = 9), or both (n = 1). Median survival was 42 months (95% confidence interval, 22.3 to 63.7). Overall survival was 62% at 2 years and 34.4% at 5 years. A univariate and multivariate analysis the positive prognostic factors for survival was cessation of smoking (p = 0.006) and lymphovascular and perineural spreading in the tissues (p = 0.024). CONCLUSIONS: In selected oligometastatic synchronous NSCLC patients, a multimodality approach encompassing radical treatment of the primary tumor and ablative treatment of concurrent metastases is recommended, with encouraging results. Smoking cessation is a part of the treatment sequence.

Proposal for a Combined Histomolecular Algorithm to Distinguish Multiple Primary Adenocarcinomas from Intrapulmonary Metastasis in Patients with Multiple Lung Tumors.

INTRODUCTION: Multiple nodules in the lung are being diagnosed with an increasing frequency thanks to high-quality computed tomography imaging. In patients with lung cancer, this situation represents up to 10% of patients who have an operation. For clinical management, it is important to classify the disease as intrapulmonary metastasis or multiple primary lung carcinoma to define TNM classification and optimize therapeutic options. In the present study, we evaluated the respective and combined input of histological and molecular classification to propose a classification algorithm for multiple nodules. METHODS: We studied consecutive patients undergoing an operation with curative intent for lung adenocarcinoma (N = 120) and harboring two tumors (N = 240). Histological diagnosis according to the WHO 2015 classification and molecular profiling using next-generation sequencing targeting 22 hotspot genes allowed classification of samples as multiple primary lung adenocarcinomas or as intrapulmonary metastasis. RESULTS: Next-generation sequencing identified molecular mutations in 91% of tumor pairs (109 of 120). Genomic and histological classification showed a fair agreement when the κ test was used (κ = 0.43). Discordant cases (30 of 109 [27%]) were reclassified by using a combined histomolecular algorithm. EGFR mutations (p = 0.03) and node involvement (p = 0.03) were significantly associated with intrapulmonary metastasis, whereas KRAS mutations (p = 0.00005) were significantly associated with multiple primary lung adenocarcinomas. EGFR mutations (p = 0.02) and node involvement (p = 0.004) were the only independent prognostic factors. CONCLUSION: We showed that combined histomolecular algorithm represents a relevant tool to classify multifocal lung cancers, which could guide adjuvant treatment decisions. Survival analysis underlined the good prognosis of EGFR-mutated adenocarcinoma in patients with intrapulmonary metastasis.

Catamenial and noncatamenial, endometriosis-related or nonendometriosis-related pneumothorax referred for surgery.

RATIONALE: Catamenial and endometriosis-related pneumothorax are considered relatively rare entities. Their clinical characteristics and outcome are incompletely known. OBJECTIVES: To evaluate the frequencies, clinical characteristics, and outcomes of catamenial and endometriosis-related pneumothoraces occurring in women with no underlying lung disease referred for surgical treatment. METHODS: Clinical files of all the women of reproductive age referred to our center during a 6-year period for surgical treatment of spontaneous pneumothorax were retrospectively reviewed. Catamenial pneumothorax (CP) was defined as recurrent pneumothorax occurring between the day before and within 72 hours after the onset of menses. All histologic slides were reviewed to confirm initial diagnoses. MEASUREMENTS AND MAIN RESULTS: A total of 114 women underwent video-assisted thoracic surgery; 28 women (24.6%) had CP (right-sided in all but one), and diaphragmatic abnormalities (perforations and/or nodules) were observed in 22 of them. Diaphragmatic abnormalities were seen in 21 of 86 patients with non-CP. Histologic examination found endometriosis, mainly diaphragmatic, in 18 of 28 CPs and 11 of 86 non-CPs. A 6-month antigonadotropic treatment was prescribed postoperatively to women with either CP or endometriosis-related pneumothorax. Mean follow-up was 32.7 (+/-18.5) months. Recurrence rates in CP, non-CP but endometriosis-related, and non-CP non-endometriosis-related pneumothoraces were 32, 27, and 5.3%, respectively. CONCLUSIONS: Our experience shows that (1) CP and/or endometriosis-related pneumothoraces account for an important percentage of spontaneous pneumothoraces referred for surgery, (2) diaphragmatic abnormalities seem to play a fundamental role in their pathogenesis, and (3) management is difficult because of the high recurrence rate.

Clinical presentation and treatment of catameinal pneumothorax and endometriosis-related pneumothorax.

Introduction: Catamenial pneumothorax (CP) is defined as a recurrent spontaneous pneumothorax occurring in females of reproductive age. In the 'perimenstrual period,' it is still considered relatively rare although accounting for 20-35% of spontaneous pneumothoraces occurring in premenopausal women. It is the most frequent manifestation of thoracic endometriosis, which can also cause pneumothorax during the intermenstrual period (TER non-CP). Areas covered: In this article, we review and comment the clinical presentation, etiopathogenesis, diagnostic criteria, and therapeutic management of CP and TER non-CP. We particularly emphasize on the surgical optimal treatment and associated multidisciplinary care and follow-up. Electronic databases, mostly PubMed, were used for searching terms including 'catamenial pneumothorax' and 'thoracic endometriosis.' Expert commentary: Clinical presentation and imaging of CP and TER non-CP are often unspecific except for possible visualization of endometriosis foci or diaphragmatic lesions at computed tomography-scan or magnetic resonance imaging. Thus, we recommend careful interrogatory and intraoperative inspection for appropriate diagnosis and treatment of pneumothorax in women. Despite better awareness of surgical teams, CP and TER-non CP are still associated with high rates of postoperative recurrence (around 30%). We strongly advocate for a multidisciplinary management including early surgical and chemical pleurodesis, resection of all visible endometriosis-related lesions, hormonal blockade, and prolonged follow-up.