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.

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.

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.

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.

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.

Patients experiencing early acute respiratory failure have high postoperative mortality after pneumonectomy.

OBJECTIVE: Post-pneumonectomy acute respiratory failure leading to invasive mechanical ventilation carries a severe prognosis especially when acute respiratory distress syndrome occurs. The aim of this study was to describe risk factors and outcome of acute respiratory failure. METHODS: We retrospectively reviewed clinical files of all patients who underwent pneumonectomy in a single center between 2005 and 2015. Risk factors and outcome of acute respiratory failure were assessed in univariate and multivariate analysis. RESULTS: Among the 543 patients who underwent pneumonectomy in the period of study, 89 (16.4%) needed reintubation within the 30th postoperative day and 60 of these (11% of all pneumonectomies) developed acute respiratory distress syndrome. In multivariate analysis, right-side of pneumonectomy (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.24-4.22), chronic cardiac disease (OR, 2.15; 95% CI, 1.08-4.25), Charlson Comorbidity Index (OR, 1.35; 95% CI, 1.14-1.61), carinal resection (OR, 3.23; 95% CI, 1.26-8.29), and extrapleural pneumonectomy (OR, 8.36; 95% CI, 3.31-21.11) were identified as independent risk factors of reintubation. Thirty-day mortality was 7.7% for all pneumonectomies, 41.6% (37/89) in the invasive ventilation group, and 53.3% (32/60) in patients with acute respiratory distress syndrome. In non-reintubated patients, 30-day mortality was 1.1% (5/454). In reintubated patients, 5-year survival was 27.1% (95% CI, 17.8-41.4). CONCLUSIONS: Early acute respiratory failure requiring reintubation remains a severe complication of pneumonectomy with a poor outcome.

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.

Regulatory B cells in myasthenia gravis are differentially affected by therapies.

We analyzed the number and functionality of regulatory B (Breg) cells in well-defined myasthenia gravis patients. We first showed a decreased number of circulating CD19+ CD24++ CD38++ Breg cells and an altered functionality of Breg cells in untreated myasthenia gravis patients. Next, we demonstrated that the proportion of circulating Breg cells was restored in myasthenia gravis patients after thymectomy, probably as Breg cells could be sequestered in the myasthenia gravis thymus. In contrast, corticosteroid treatments did not restore and decreased even more the proportion of Breg cells in myasthenia gravis patients. These results clearly demonstrated that two distinct immunomodulatory therapies affect differentially Breg cells.

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.

Oropharyngeal and nasopharyngeal decontamination with chlorhexidine gluconate in lung cancer surgery: a randomized clinical trial.

PURPOSE: Respiratory complications are the leading causes of morbidity and mortality after lung cancer surgery. We hypothesized that oropharyngeal and nasopharyngeal decontamination with chlorhexidine gluconate (CHG) would be an effective method to reduce these complications as reported in cardiac surgery. METHODS: In this multicenter parallel-group randomized double-blind placebo-controlled trial, we enrolled consecutive adults scheduled for anatomical pulmonary resection for lung cancer. Perioperative decontamination consisted in oropharyngeal rinse solution (0.12% CHG) and nasopharyngeal soap (4% CHG) or a placebo. The primary outcome measure was the proportion of patients requiring postoperative invasive and/or noninvasive mechanical ventilation (MV). Secondary outcome measures included occurrence of respiratory and non-respiratory healthcare-associated infections (HAIs) and outcomes within 90 days. RESULTS: Between July 2012 and April 2015, 474 patients were randomized. Of them, 24 had their surgical procedure cancelled or withdrew consent. The remaining 450 patients were included in a modified intention-to-treat analysis: 226 were allocated to CHG and 224 to the placebo. Proportions of patients requiring postoperative MV were not significantly different [CHG 14.2%; placebo 15.2%; relative risks (RRs) 0.93; 95% confidence interval (CI) 0.59-1.45; P = 0.76]. Neither of the proportions of patients with respiratory HAIs were different (CHG 13.7%; placebo 12.9%; RRs 1.06; 95% CI 0.66-1.69; P = 0.81). The CHG group had significantly decreased incidence of bacteremia, surgical-site infection and overall Staphylococcus aureus infections. However, there were no significant between-group differences for hospital stay length, change in tracheal microbiota, postoperative antibiotic utilization and outcomes by day 90. CONCLUSIONS: CHG decontamination decreased neither MV requirements nor respiratory infections after lung cancer surgery. Additionally, CHG did not change tracheal microbiota or postoperative antibiotic utilization. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, number NCT01613365.

Prognostic factors after pulmonary metastasectomy of colorectal cancers: a single-center experience.

BACKGROUND: Surgical resection has been widely admitted as the treatment of choice for pulmonary metastases of colorectal cancer (CRC). Nevertheless, this practice is not supported by high level of evidence and patients' eligibility remains controversial. Aim of this study was to evaluate long terms results and factors influencing survival after lung metastasectomy of CRC. METHODS: A single-center retrospective analysis of patients with pathologically proven colorectal metastasis, operated from 2004 to 2013, was performed. Patients were treated with a multidisciplinary approach and selected for surgery if complete resection was considered feasible. RESULTS: Three hundred and six patients were considered for analysis. Mean number of lesions at CT scan was 2.6±2.3. Ratios of each largest resection type at first side surgery were: segmentectomy 20.6%, lobectomy 12.9%, bilobectomy 1.2%, pneumonectomy 1.2% and sub-lobar resection 64.1%, respectively. No in-hospital death occurred. At pathology, mean number of resected metastasis was 2.6±2.3, ranging from 1 to 12. Resection was complete in 92.5% of patients. Nodal involvement was proven in 40 (12.9%) patients. The initially planned complete resection could not be achieved in 23 (7.5%) cases. Mean follow-up was 3.06±2.36 years. Kaplan-Meier analysis revealed that recurrence-free survival (RFS) was 76.3% [95% confidence interval (95% CI), 71-80.7%], 38.9% (95% CI, 33-44.7%), 28.3% (95% CI, 22.5-34.4%) and 22.7% (95% CI, 16.5-29.5%) at 1, 3, 5 and 7 years, respectively. Overall survival (OS) estimates were 77.8% (95% CI, 72.7-82.7%), 59.0% (95% CI, 51.2-66.4%), and 56.9% (95% CI, 48.4-65.0%) at 3, 5 and 7 years, respectively. Multivariate analysis, including pT parameter of the primary tumor, number of lesions, one-sided versus bilateral lung disease, and body mass index (BMI) (all significant at univariate analysis), showed that bilateral disease (P<0.001) and pT4 primary (P=0.005) were independent pejorative predictors of OS, whereas BMI ≥25 was protective (P=0.028). CONCLUSIONS: Bilateralism and primary tumor local extension influence the prognosis of patients surgically treated for pulmonary colorectal metastases. Specifically designed randomized trials are necessary.

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.

Thoracic Endometriosis Syndrome Other Than Pneumothorax: Clinical and Pathological Findings.

BACKGROUND: Thoracic endometriosis syndrome refers to a broad spectrum of clinical manifestations related to the presence of ectopic intrathoracic endometrial tissue. Few studies have reported on manifestations other than pneumothorax. METHODS: Clinical, surgical, and pathology records of all consecutive women of reproductive age referred to our institution from September 2001 to August 2016 for clinically suspected thoracic endometriosis syndrome were retrospectively reviewed. After excluding women with pneumothorax, we enrolled 31 patients, divided into three subgroups: catamenial chest pain (n = 20), endometriosis-related diaphragmatic hernia (n = 6), and endometriosis-related pleural effusion (n = 5). RESULTS: Surgery was performed in 11 patients with catamenial thoracic pain (median age, 30 years; range, 23 to 42). Median pain intensity assessed on the 0 to 10 Visual Analogue Scale was 8 (range, 8 to 9) before surgery. At surgery, 8 patients had diaphragmatic endometriosis implants, which were resected with direct suture of diaphragm. At follow-up, median pain score was 3 (range, 0 to 8). In the group presenting with diaphragmatic hernia (median age, 36 years; range, 29 to 50), diaphragm was repaired by direct suture or placement of prosthesis in 4 and 2 cases, respectively. At follow-up, no sign of recurrent hernia was observed. Finally, among women with endometriosis-related pleural effusion (median age, 30 years; range, 25 to 42), surgical treatment was represented by evacuation of the pleural effusion and biopsy (n = 4) or removal (n = 1) of visible endometrial foci. CONCLUSIONS: Thoracic endometriosis syndrome is a poorly recognized entity responsible for various manifestations other than pneumothorax. In case of catamenial thoracic pain, diaphragmatic hernia and catamenial pleural effusion surgery should be advised in a multidisciplinary setting.

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.

Body Mass Index and Total Psoas Area Affect Outcomes in Patients Undergoing Pneumonectomy for Cancer.

BACKGROUND: Hypothesizing that morphometric measurements are reliable markers of fitness in patients with lung cancer requiring aggressive surgical intervention, the purpose of this study was to assess their impact on postoperative outcome and long-term survival in patients with non-small cell lung cancer (NSCLC) requiring pneumonectomy. METHODS: Height, weight, and body mass index (BMI), as well as usual clinical, laboratory (including C-reactive protein [CRP] concentrations), and pathologic data were retrospectively retrieved from files of 161 consecutive patients treated by pneumonectomy for NSCLC, whose preoperative computed tomographic (CT) scans were available in the Picture Archive and Communication System (PACS) of the hospital. Cross-sectional areas of right and left psoas areas (measured by CT scan at the L3 level), perirenal fat thickness, and anterior subcutaneous tissue thickness at the left renal vein level were also assessed. RESULTS: BMI and total psoas area were strongly and directly correlated (p = 0.0000001), whereas BMI was inversely related to CRP levels. Sarcopenia (total psoas area ≤33rd percentile) was associated with high CRP levels (>20 mg/L) (p = 0.010). Factors associated with 90-day mortality included older age (p = 0.000045), lower body weight (p = 0.032), and BMI less than or equal to 25 kg/m2 (p = 0.013). At univariate analysis, long-term outcome was negatively affected by a nonsquamous cell histologic type (p = 0.011), pathologic stage IIIB-IV (p =0.026), CRP levels greater than 20 mg/L (p = 0.017), BMI less than or equal to 25 kg/m2 (p = 0.010), and total psoas area less than or equal to the 33rd percentile (p = 0.029). Multivariate analysis showed the independent prognostic value of both BMI and total psoas area. CONCLUSIONS: BMI less than or equal to 25 kg/m2 and total psoas cross-sectional area less than or equal to the 33rd percentile are prognostic determinants in patients with NSCLC requiring pneumonectomy.

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.

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.