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Citrate is a key metabolite of the Krebs cycle that can also be exported in the cytosol, where it performs several functions. In normal cells, citrate sustains protein acetylation, lipid synthesis, gluconeogenesis, insulin secretion, bone tissues formation, spermatozoid mobility, and immune response. Dysregulation of citrate metabolism is implicated in several pathologies, including cancer. Here we discuss how cancer cells use citrate to sustain their proliferation, survival, and metastatic progression. Also, we propose two paradoxically opposite strategies to reduce tumour growth by targeting citrate metabolism in preclinical models. In the first strategy, we propose to administer in the tumor microenvironment a high amount of citrate, which can then act as a glycolysis inhibitor and apoptosis inducer, whereas the other strategy targets citrate transporters to starve cancer cells from citrate. These strategies, effective in several preclinical in vitro and in vivo cancer models, could be exploited in clinics, particularly to increase sensibility to current anti-cancer agents., Competing Interests: Declaration of Competing Interest MEM is an inventor on the Patent Application no. EP15767532.3 and US15/514,255 (status patent pending) “The plasma membrane citrate transporter for use in the diagnosis and treatment of cancer” owned by the University Hospital Regensburg. GZ is an employee and shareholder of Eternygen GmbH. PI, MA and LS have no conflict of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background & Aims: Sarcopenia has long been associated with higher toxicity induced by anti-cancer treatments and shorter survival in patients with solid tumors. The creatinine-to-cystatin ratio (CC ratio, serum creatinine/cystatin C × 100) and the sarcopenia index (SI, serum creatinine × cystatin C (CysC)-based glomerular filtration rate (eGFR CysC )) are have been reported to be correlated with skeletal muscle mass. The aim of this study is to assess primarily whether the CC ratio and the SI could predict mortality in metastatic non-small cell lung cancer (NSCLC) patients treated with PD-1 inhibitors, and secondarily their impact on severe immune-related adverse effects (irAEs)., Methods: From the prospective CERTIM cohort, we analyzed retrospectively stage IV NSCLC patients, who received PD-1 inhibitors between June 2015 and November 2020 in Cochin Hospital (Paris, France). We assessed sarcopenia measuring skeletal muscle area (SMA) by computed tomography and handgrip strength (HGS) by a hand dynamometer., Results: In total, 200 patients were analyzed. The CC ratio and the IS were significantly correlated with SMA and HGS: r CC/SMA  = 0.360, r SI/SMA  = 0.407, r CC/HGS  = 0.331, r SI/HGS  = 0.370. In multivariate analysis of overall survival, a lower CC ratio (HR 1.73, P = 0.033) and a lower SI (HR 1.89, P = 0.019) were independent predictors of poor prognosis. In univariate analysis of severe irAEs, CC ratio (OR 1.01, P = 0.628) and SI (OR 0.99, P = 0.595) were not associated with a higher risk of severe irAEs., Conclusions: In metastatic NSCLC patients treated with PD-1 inhibitors, a lower CC ratio and a lower SI are independent predictors of mortality. However, they are not associated with severe irAEs., Competing Interests: Conflicts of interest Jérôme Alexandre received honoraria from Astra Zeneca, MSD, GSK, Eisai, Clovis and Novartis. Marco Alifano received consulting fees from Roche and Astra Zaneca, honoraria from Roche, Astra Zaneca and AMGEN and travel accommodation from Medtronic. Jennifer Arrondeau received honoraria from BMS and Astra Zaneca and meeting accommodation from Pfizer. Pascaline Boudou-Rouquette received personal fees from Takeda, Pharmama and IPSEN. Diane Damotte received a research grant from Astra Zaneca. François Goldwasser served on advisory board for Fresenius Kabi and Nutricia and received research grant from Baxter International Inc, USA. Olivier Huillard received honoraria from Bristol-Myers Squibb, Astellas, IPSEN, MSD, Pfizer, Janssen, Astra Zaneca, Bayer and AAA Novartis and travel accommodation from IPSEN and AAA Novartis. Elisabeth Ashton, Laure Hirsch, Anne Jouinot, Audrey Lupo-Mansuet, Guillaume Ulmann and Marie Wislez have no conflict of interest to declare., (Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Obesity is a well-established risk factor for pancreatic cancer. Bariatric surgery has demonstrated superior results in terms of weight loss and obesity-related comorbidities compared to medical and behavioral treatments. The aim of this study is to evaluate the effect of bariatric surgery on pancreatic cancer incidence in individuals with obesity., Method: Individuals with a diagnosis of obesity were retrieved from the French national hospital discharge database. We conducted a cohort study comparing the risk to develop pancreatic cancer in individuals with obesity with and without history of bariatric surgery; the inverse probability of treatment weighting (IPTW) method was performed to assess the uncertainty around the results. Moreover, a subgroup analysis according to age at the time of bariatric surgery was performed to study its impact on the risk of pancreatic cancer. Finally, possible differences depending on the type of bariatric procedure (sleeve gastrectomy vs Roux-en-Y gastric bypass) were also explored., Results: 160,129 (Bariatric Surgery group) and 1,263,804 (control group) patients with 5.2 ± 1.9 and 6.0 ± 1.9 years of follow-up respectively were included. A significant reduced risk to develop pancreatic cancer during follow-up was identified for the bariatric surgery group in the overall population (HR: 0.567). However, this reduced risk was only observed in the 18-50 years group. These results were furtherly confirmed after IPTW analysis. No difference was found between different bariatric procedures., Conclusion: Bariatric surgery has a protective effect against pancreatic cancer in the 18-50 years population. High-quality prospective studies are needed to confirm these results., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Surgical lung biopsy is essential in the diagnostic algorithm of interstitial lung disease (ILD) of unknown cause. Safety concerns have been recently reiterated. This study prospectively assessed the yield of diagnosis and safety of video-assisted thoracoscopic surgical lung biopsy (VATS-LB) for ILD diagnosis., Methods: This prospective study, conducted in 6 ILD-referral Paris hospitals, included 103 patients with ILD. VATS-LB was proposed after initial multidisciplinary discussion. A final diagnosis was made after the procedure, during a second multidisciplinary discussion. The main outcome was to determine the final diagnoses and their proportion after VATS-LB. Other outcomes were the percentage of change in diagnosis and treatment propositions after VATS-LB and adverse events during 3 months after the operation, postoperative pulmonary function, quality of life, and pain., Results: A definite diagnosis was reached in 87 patients (84.4%), and 16 remained unclassifiable (15.6%). After VATS-LB, the hypothesized diagnosis changed in 65 patients (63.1%) and treatment changed in 41 patients (39.8%). One patient died of acute exacerbation. In-hospital complications were predicted by a shorter preoperative 6-minute walking test distance and by forced vital capacity lower than 77%. Postoperative quality of life was not modified at 3 months, whereas forced vital capacity decreased slightly. Postoperative neuropathic pain was revealed in 5% of patients at 1 month and in 2% at 3 months., Conclusions: VATS-LB dramatically changed preoperative hypothetical diagnoses and treatment in ILD of unknown cause, with good patient survival in ILD referral centers., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The tumor microenvironment is a complex mix of cancerous and noncancerous cells (especially immune cells and fibroblasts) with distinct metabolisms. These cells interact with each other and are influenced by the metabolic disorders of the host. In this review, we discuss how metabolic pathways that sustain biosynthesis in cancer cells could be targeted to increase the effectiveness of cancer therapies by limiting the nutrient uptake of the cell, inactivating metabolic enzymes (key regulatory ones or those linked to cell cycle progression), and inhibiting ATP production to induce cell death. Furthermore, we describe how the microenvironment could be targeted to activate the immune response by redirecting nutrients toward cytotoxic immune cells or inhibiting the release of waste products by cancer cells that stimulate immunosuppressive cells. We also examine metabolic disorders in the host that could be targeted to inhibit cancer development. To create future personalized therapies for targeting each cancer tumor, novel techniques must be developed, such as new tracers for positron emission tomography/computed tomography scan and immunohistochemical markers to characterize the metabolic phenotype of cancer cells and their microenvironment. Pending personalized strategies that specifically target all metabolic components of cancer development in a patient, simple metabolic interventions could be tested in clinical trials in combination with standard cancer therapies, such as short cycles of fasting or the administration of sodium citrate or weakly toxic compounds (such as curcumin, metformin, lipoic acid) that target autophagy and biosynthetic or signaling pathways., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: The coronavirus disease 2019 (COVID-19) outbreak was officially declared in France on March 14, 2020. The objective of this study is to report the incidence and outcome of COVID-19 after surgical resection of non-small cell lung cancer in Paris Public Hospitals during the pandemic., Methods: We retrospective analyzed a prospective database including all patients who underwent non-small cell lung cancer resection between March 14, 2020, and May 11, 2020, in the 5 thoracic surgery units of Paris Public Hospitals. The primary endpoint was the occurrence of SARS-CoV-2 infection during the first 30 days after surgery., Results: Study group included 115 patients (male 57%, age 64.6 ± 10.7 years, adenocarcinoma 66%, cT1 62%, cN0 82%). During the first month after surgery, 6 patients (5%) were diagnosed with COVID-19. As compared with COVID-negative patients, COVID-positive patients were more likely to be operated on during the first month of the pandemic (100% vs 54%, P = .03) and to be on corticosteroids preoperatively (33% vs 4%, P = .03). Postoperative COVID-19 was associated with an increased rate of readmission (50% vs 5%, P = .004), but no difference in 30-day morbidity (for the study group: grade 2, 24%; grade 3, 7%; grade 4, 1%) or mortality (n = 1 COVID-negative patient, 0.9%). Immediate oncologic outcomes did not differ significantly between groups (R0 resection 99%, nodal upstaging 14%, adjuvant chemotherapy 29%)., Conclusions: During the COVID-19 pandemic, surgical treatment of non-small cell lung cancer was associated with a rate of postoperative COVID-19 of 5% with a significant impact on readmissions but not on other outcomes studied., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Adapting therapies and providing personalized care for patients with resectable non-small cell lung cancer represent major challenges. This involves integrating several parameters into the patient's management, not only crude pathologic results, but also a better understanding of the mechanisms involved in tumor progression. Many studies have looked at the impact of host and tumor characteristics and their interactions through inflammatory processes or tumor immune environment. Beyond tumor stage, poor nutrition, sarcopenia and inflammatory state have been identified as independent factors that can directly impact postoperative outcome. The development of Enhanced Recovery After Surgery (ERAS), in which patient becomes the main player in their own management, seems to be an interesting answer since it seems to allow a reduction in postoperative complications, length of stay and indirectly reduction in costs. A broader and more complete vision including morphometric evaluation of the patient, physical performances, inflammatory state and nutritional state would provide additional discriminating information which can predict postoperative outcome and help in adapting therapies in a personalized way., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Five to ten percent of lung adenocarcinoma harbor chromosomal rearrangements affecting the ALK, ROS1, NTRK and RET genes. These rearrangements are associated with the production of fusion transcripts that lead to the synthesis of chimeric proteins with constitutive kinase activity. These abnormal proteins induce an oncogenic dependency that may be targeted by tyrosine kinase inhibitors. In this review, we will summarize the clinical and molecular epidemiology of chromosomal rearrangements affecting ALK, ROS1, NTRK and RET genes. We will describe the mechanisms of resistance to tyrosine kinase inhibitors that have been reported. We will present the molecular techniques that can be used to detect these rearrangements and the strategies set-up by the molecular oncology laboratories to diagnose these genetic alterations., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Caloric starvation, as well as various diets, has been proposed to increase the oxidative DNA damage induced by radiotherapy (RT). However, some diets could have dual effects, sometimes promoting cancer growth, whereas proposing caloric restriction may appear counterproductive during RT considering that the maintenance of weight is a major factor for the success of this therapy. A systematic review was performed via a PubMed search on RT and fasting, or caloric restriction, ketogenic diet (>75% of fat-derived energy intake), protein starvation, amino acid restriction, as well as the Warburg effect. Twenty-six eligible original articles (17 preclinical studies and 9 clinical noncontrolled studies on low-carbohydrate, high-fat diets popularized as ketogenic diets, representing a total of 77 patients) were included. Preclinical experiments suggest that a short period of fasting prior to radiation, and/or transient caloric restriction during treatment course, can increase tumor responsiveness. These regimens promote accumulation of oxidative lesions and insufficient repair, subsequently leading to cancer cell death. Due to their more flexible metabolism, healthy cells should be less sensitive, shifting their metabolism to support survival and repair. Interestingly, these regimens might stimulate an acute anticancer immune response, and may be of particular interest in tumors with high glucose uptake on positron emission tomography scan, a phenotype associated with poor survival and resistance to RT. Preclinical studies with ketogenic diets yielded more conflicting results, perhaps because cancer cells can sometimes metabolize fatty acids and/or ketone bodies. Randomized trials are awaited to specify the role of each strategy according to the clinical setting, although more stringent definitions of proposed diet, nutritional status, and consensual criteria for tumor response assessment are needed. In conclusion, dietary interventions during RT could be a simple and medically economical and inexpensive method that may deserve to be tested to improve efficiency of radiation., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background & Aims: Metastatic non-small cell lung cancer (NSCLC) is the first cause of cancer death worldwide. Increased resting energy expenditure (REE) is frequent among cancer patients and may contribute to cancer cachexia. The aim of this study was to examine the prognostic value of increased REE in metastatic NSCLC patients., Methods: This observational study was conducted between June 2012 and November 2017 in the outpatient unit of the oncology department of Cochin hospital, Paris. Consecutive patients with newly diagnosed stage IV NSCLC underwent measurement of REE by indirect calorimetry before treatment initiation. Uni- and multivariate analysis of overall survival (OS, Cox models) included age, sex, smoking habit, histological subtype, performance status, body mass index, weight loss, albumin and CRP levels and the ratio of measured REE to the REE predicted by the Harris Benedict formula (mREE/pREE)., Results: 144 patients were enrolled: mean age 64 years, 63% male, 90% non-squamous carcinoma, including 17% with ALK/EGFR alteration. In univariate analysis, tobacco consumption (p = 0.007), histo-molecular subtype (p < 10 -3 ), performance status (p = 0.04), weight loss (p < 10 -4 ), albumin (p < 10 -4 ), CRP (p = 0.001) and mREE/pREE ratio (>vs ≤ 120%: HR = 2.16, p < 10 -3 ) were significant prognostic factors of OS. Median OS were 6.1 and 17.3 months in patients with mREE/pREE ratio > and ≤120%, respectively. In multivariate analysis, histo-molecular subtype (non-squamous ALK/EGFR mutated vs squamous carcinoma: HR = 0.25, p = 0.006), weight loss (>vs ≤ 5%: HR = 1.98, p = 0.004), albumin (≥vs < 35 g/L: HR = 0.56, p = 0.02) and mREE/pREE ratio (> vs ≤120%: HR = 1.90, p = 0.004) were identified as independent prognostic factors., Conclusions: Elevated resting energy expenditure emerges as an independent prognostic factor in metastatic NSCLC., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Paraneoplastic leukemoid reaction is a challenging differential diagnosis when it presents at the time of diagnosis of cancer. Severe hyperleukocytosis with elevation of blood neutrophils and monocytes counts can evoke myeloid hematologic malignancies. We report the case of a patient who presented with blood and bone marrow features highly suggestive of chronic myelomonocytic leukemia. The diagnosis of primary lung sarcomatoid carcinoma was performed. Surgical removal of this tumor which will always remain the priority led to full normalization of blood cell count., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A growing number of studies suggest a tumor suppressor role for the SWI/SNF complex involved in the remodeling of chromatin. Alterations of this complex have been found in many tumors of different origins, with topographic, morphologic and phenotypic diversity. Notably, they define 2 types of thoracic tumors: SMARCA4-deficient non-small cell lung carcinoma and SMARCA4-deficient sarcoma. Some clinical features appear to be common to both, such as intrathoracic localization, smoking exposure, male predominance and poor prognosis. However, the histological distinction between these two entities is sometimes difficult and it is not excluded that these entities belong to the same tumor spectrum with different degrees of differentiation. The therapy of these tumors is not yet codified. These tumors do not seem associated with oncogenic driver mutations allowing the prescription of targeted therapy, but immunotherapy has been shown to be effective in rare reported cases. More specific treatments using EZH2 inhibitors also seem promising in SMARCA4 deficient sarcomas., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Adrenal gland metastases occur in up to 20% of patients with non-small-lung cancer. In selected cases with limited burden of disease, surgery may be offered to improve patient outcome; furthermore, tissue analysis would provide useful information on genotype of primary and secondary neoplasms., Materials and Methods: We report our experience in the management of adrenal metastasis by retrospectively reviewing data of 21 consecutive patients treated with curative intent to the primary tumor followed by adrenalectomy in a 15-year time span. Targeted next generation sequencing was performed to compare molecular profile of primary lung cancers and adrenal metastases. Patient overall survival was assessed by Kaplan-Meier method, using adrenalectomy as time zero. Survival rates were compared by log rank test., Results: No surgery-related mortality or morbidity was observed. Median survival was 50 months; 5-year overall survival was 34.5% (95% confidence interval, 12%-66%). No significant survival difference was observed with respect to timing of onset (synchronous vs. metachronous) or side (homolateral vs. contralateral) of adrenal metastasis, T or N status of primary lung cancer, mutational asset, and histologic type. Mutations in TP53 genes were found in 61% and 85% of primary and metastatic tumors, respectively. In 3 of 15 cases, we found differences between molecular mutation patterns in primary lung cancer and corresponding adrenal metastasis., Conclusions: Adrenalectomy is a safe and effective approach in selected cases. Discordance between primary and secondary tumor mutational profile was found in 20% of assessable patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

An unusual case of pleural empyema related to Nocardia farcinica and Ureaplasma urealyticum, occurring after autologous haematopoietic stem cell transplantation in a 30-year-old patient with lymphoma, is reported. This case illustrates the role of repeated and comprehensive microbiological investigations and the contribution of molecular techniques in reaching the aetiological diagnosis., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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/m 2 (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/m 2 (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/m 2 and total psoas cross-sectional area less than or equal to the 33rd percentile are prognostic determinants in patients with NSCLC requiring pneumonectomy., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Surgery is still the best treatment option of lung cancer but only one third of patients are operable and prognosis remains mediocre in operated patients, with the exception of initial stages. Medical treatment is fast moving toward new frontiers. New insights in the biology of cancer development led to discovery of new drugs, which are more effective as compared to conventional platinum based chemotherapy. A new approach to immunotherapy based on immune-check point represents a remarkable innovation in lung cancer treatment. Initial trials with anti PD-1 antibodies in metastatic patients provided results never observed with previously known drug categories. Several key question need to be answered to identify patients most likely to respond to anti PD-1/anti PD-L1 treatments, to assess the role of combined treatment modalities including immune check point receptor block (associations with surgery, chemotherapy, ITKs), and to boost host immune response, possibly by lowering his systemic inflammation and improving nutritional status., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Tumors of the posterior mediastinum are mostly neurogenic and could involve the intervertebral foramen and the medullary canal. We describe the case of a patient who underwent surgery for a nerve sheet tumor originating at the level of the right second neural root. Resection was associated with an incidental dural tear and cerebrospinal fluid leak that was promptly repaired. One week after surgery, horizontal diplopia occurred. A palsy of the left abducens nerve secondary to intracranial hypotension was diagnosed. We present the pathogenic cascade leading to this ocular complication after posterior mediastinal surgery. The surgical techniques to prevent this complication are discussed., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The treatment for recurrent thymoma remains a very controversial issue. This study aims to investigate the long-term outcomes in patients with relapse according to treatment strategies and clinicopathological features., Methods: We retrospectively analyzed the database of three tertiary centers of thoracic surgery with the aim of reviewing the clinical records of 81 patients who experienced a recurrent thymoma after radical thymectomy, in the period between January 2001 and June 2013. The staging of both primitive and recurrent thymomas were based on the surgical and pathological criteria described by Masaoka. Experienced pathologists reassessed independently the histology of the initial thymoma and its relapse, according to the WHO classification. To the purposes of this study R+ resection or thymic carcinoma were considered as exclusion criteria. The overall outcome for long-term (5 years and 10 years) survival and disease-free survival after initial thymectomy and after treatment of recurrent thymoma were analyzed using standard statistics., Results: The population was gender balanced (41 M, 40 F), mean age: 46.4 ± 12.3 years. Fifty-four patients (66.7%) were affected by myasthenia gravis, while the other 14 by other paraneoplastic conditions. Surgery was performed in 61 patients (75.3%,), and radiotherapy and/or chemotherapy in 14 patients (17.3%). The mean follow-up duration after recurrence onset was 66.3 ± 56.4 months. Adjuvant therapy had no effect on prolonging the disease-free survival: no differences were found when investigating the administration of adjuvant chemotherapy (no CHT = 91.5 ± 76.4 months versus yes CHT=64.0 ± 41.3) and radiotherapy (no RT=86.2 ± 72.8 months versus yes RT= 93.0 ± 62.3; p = 0.8). Relapses were mostly local (mediastinum: 15 cases, pleura: 44 cases); hematogenous distant recurrences were observed in 15 cases (lung: 12; liver: 1; bone: 2 cases). An upgrade in the WHO class (defined as the "migration" of WHO class at initial thymectomy to more aggressive WHO class assigned at thymic recurrence resection) was found in 25/61 cases (40.9%), but this phenomenon apparently did not influence patient's prognosis. Overall, the 5- and 10-year survival rates after the initial thymectomy were 94.8% and 71.7%, respectively, while the 5- and 10-year survival rates after the treatment of the recurrence at the thymic level were 73.6% and 48.3%, respectively (82.4% at 5 years and 65.4% at 10 years when a R0-re-resection was obtained). The analysis on the trends of disease-free survival indicated that the site of recurrence (hematogenous diffusion) seems to be associated to a higher risk of re-relapse (p = 0.01)., Conclusions: Even following a thymectomy performed with radical intent, thymoma may recur several years later, usually as a locoregional relapse. A rewarding long-term survival may be expected after treatment, especially when a re-resection (radical) is performed (82.4% at 5 years). An histopathological "WHO upgrade" (from "low-risk" WHO classes at thymectomy to "high-risk classes" at relapse) may be observed in a remarkable percentage of patients (nearly 40% in this series), but this phenomenon seems to be not correlated with any worsening of the prognosis.

Background: Histologic classification of lung adenocarcinoma subtype has a prognostic value in most studies. However, lung adenocarcinoma characteristics differ across countries. Here, we aimed at validating the prognostic value of this classification in a large French series of lung adenocarcinoma., Methods: We reviewed 407 consecutive lung adenocarcinomas operated on between 2001 and 2005 and reclassified them according to the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification and subsequently graded them into low, intermediate, and high grade. We analyzed the relevance of this classification according to clinical, pathologic, and molecular analysis., Results: Patients (median age, 61 years; 288 men) underwent lobectomy (n = 378) or pneumonectomy (n = 29). Patients' overall survival at 5 and 10 years was 53.2% and 32.6%, respectively. Union for International Cancer Control stage distribution was 189 stage I, 104 stage II, 107 stage III, and seven stage IV. Low-grade tumor was found in one patient, intermediate grade in 275 patients, and high grade in 131 patients. KRAS and EGFR mutations were detected in 34% and 9.6%, respectively. Histologic grade was significantly correlated with extent of resection (P = .01), thyroid transcriptional factor-1 expression (P = .00000001), vascular emboli (P = .03), and EGFR mutations (P = .01). Mucinous adenocarcinomas were associated with KRAS mutations (P = .003). At univariate analysis, age, extent of resection, histologic grade, pleural invasion, vascular emboli, pathologic T and N, and stage were predictive of survival. At multivariate analysis, age (P = .0001), histologic grade (P = .03), and stage (P = .000003) were independent prognostic factors., Conclusions: IASLC/ATS/ERS classification of lung adenocarcinomas predicts survival in French population. Histologic grade correlates with clinical, pathologic and molecular parameters suggesting different oncogenic pathways.

Background: A significant percentage of pneumothorax in women is due to thoracic endometriosis. Pathophysiologic mechanisms continue to be debated, and pathologic aspects are poorly known., Methods: Clinical and pathologic records of all consecutive women of reproductive age operated on for pneumothorax between 2000 and 2011 were retrospectively reviewed., Results: Two hundred twenty-nine women (mean age, 33 years) underwent surgery. One hundred forty-four cases (63%) were right-sided, and pneumothoraces were catamenial for 80 women (35%). Diagnosed pelvic endometriosis was associated in 29 cases. At pathology, thoracic endometriosis was diagnosed in 54 cases (24%). Endometrial glands were observed in 33 of 54 cases and were often cystic (16 of 33). Stroma was observed in 51 of 54 cases and endometrial stroma without glands in 21 cases. Hemosiderin-laden macrophages were observed in 27 of 54 cases. All cases of thoracic endometriosis were positive for progesterone and/or estrogen receptors (intense and nuclear). Catamenial pneumothoraces (n = 80, 34.9%) were endometriosis related in 50% of cases (n = 40, 17% of the whole population). Pneumothoraces were noncatamenial but endometriosis related in 6% of cases (n = 14) and merely idiopathic in 60% of patients (n = 135). Multivariate analysis showed that right side, presence of diaphragmatic abnormalities, relapse after unilateral surgery, and presence of hemosiderin-laden macrophages were independent variables associated with thoracic endometriosis (all, P &lt; .02). Apical emphysema-like changes were found in 184 of the 213 patients (86%) with apical resection and were significantly associated with the absence of thoracic endometriosis (P &lt; .001)., Conclusions: In women with surgically treated pneumothorax, prevalence of catamenial/endometriosis-related pneumothorax is high. Clinicians and pathologists must be aware to recognize such a difficult diagnosis.

Background: The incidence of vascular and lymphatic emboli in a specimen of resected non-small cell lung cancer is variable according to different authors' experience as well as prognostic significance in patients treated by surgery. We aimed at evaluating these factors in an unselected population of patients with primary pulmonary adenocarcinoma treated by major surgical resection., Methods: Clinical and pathology records of all patients treated by lobectomy or pneumonectomy and nodal dissection for pulmonary adenocarcinoma between June 2001 and June 2006 were retrospectively reviewed. Impact on survival of age, sex, tobacco use, history of chronic obstructive pulmonary disease, extent of resection, pathologic stage, and presence of vascular and lymphatic emboli was studied by univariate analysis and multivariate analysis (for factors significantly associated with survival at univariate analysis)., Results: Five hundred three patients underwent lobectomy or pneumonectomy with nodal dissection for pathologically proven lung adenocarcinoma. There were 355 men and 148 women; mean age was 61.1 years, and 181 patients were 65 years old or older; 87% were current or former smokers; 90.3% had pulmonary lobectomy; and 9.7% had pneumonectomy. Pathologic stages were I, II, and III/IV in 45%, 17.9%, and 37.1%, respectively. Vascular emboli and lymphatic emboli were found in 183 of 503 patients (36.4%) and 149 of 503 (29.6%), respectively. Overall 5-year survival for the whole population was 50.7%. At univariate analysis, age more than 65 years (p=0.0019), chronic obstructive pulmonary disease (p=0.042), extent of resection (p=0.047), pathologic stage (p<0.0000001), T size (p=0.0020), T and N variables (p=0.0000016 and p<0.0000001, respectively), presence of vascular emboli (p=0.026), and presence of lymphatic emboli (p=0.000021) were associated with worse prognosis. At multivariate analysis, age more than 65 years (p=0.0047, relative risk 1.5), stage I versus II versus III versus IV (p=0.00000032), and presence of lymphatic emboli (p=0.05, relative risk 1.34) were identified as independent negative prognostic factors., Conclusions: In an unselected population of patients with pulmonary adenocarcinoma treated by lobectomy or pneumonectomy, the presence of lymphatic emboli is an independent negative prognostic factor., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Scimitar syndrome is one of the large congenital pulmonary venolobar syndromes and is defined as hypogenetic lung associated with partial anomalous pulmonary venous return. We report the case of a 25-year-old man with complex and exceptional variant scimitar syndrome. A chest CT scan with three-dimensional (3-D) reconstruction led us to identify hypoplastic right lung with homolateral hemidiaphragm agenesis and hypogenetic right pulmonary artery. There was a large and sinuous systemic arterial supply and anomalous venous return directed into the left atrium (venous return being usually directed into the right atrium or inferior vena cava in scimitar syndrome). Hyperoxia test showed no shunt. This variant scimitar syndrome has been previously reported and anomalous venous return called "meandering" pulmonary vein. Diagnosis and management of these patients with complex congenital anomalies are difficult because of their exceptional condition. Chest CT scan with 3-D reconstruction offers an accurate noninvasive diagnosis.

Surgical treatment of lung diseases is based on removal of the affected lung tissue, achieved by atypical or anatomic lung resection. Infectious lung diseases are generally treated by medical therapy, including medications, chest physiotherapy, bronchoscopic toilet, and respiratory rehabilitation. Surgical management of infectious disease of the lung is integrated in the multispecialty care. This article focuses exclusively on nonresectional surgery and other alternatives to lung resection and addresses bacterial infection and fungal disease of the lung., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Our aim was to study the clinical, surgical, and pathological characteristic of women with homolateral recurrence of pneumothorax despite previous surgery., Methods: This study is a retrospective analysis of the clinical and pathological records of all consecutive women of reproductive age hospitalized in a thoracic surgery department for surgical treatment of pneumothorax recurrence despite previous surgery between 2000 and 2009., Results: During the study period, 35 women were operated on. Their mean age was 37 years. Twenty-nine pneumothoraces (83%) were right sided. In 20 women, the recurrence occurred during the menstrual period. At initial surgery, 5 cases had been catamenial with evidence of thoracic endometriosis, 12 were catamenial with no evidence of endometriosis, 5 were noncatamenial with thoracic endometriosis, and 13 were idiopathic. At repeat surgery the figures were 18, 4, 5, and 8 cases, respectively. Repeat operation was carried out by video-assisted thoracoscopy in 13 cases, video-assisted minithoracotomy in 10, and standard thoracotomy in 12. Partial diaphragmatic resection was performed at repeat surgery in 16 patients (45.7%). Talc pleurodesis and pleural abrasion were carried out in 20 (57.1%) and 15 patients (42.9%), respectively. No major morbidity was observed. After repeat surgery, hormonal treatment was prescribed in 24 cases. Median follow-up was 40 months (range, 1.5 to 138 months). In 6 women, further homolateral recurrence of pneumothorax occurred (17.1%) and required surgery in 3 cases., Conclusions: Repeat surgery can be safely performed in women with recurrence of pneumothorax despite previous surgery, and frequently shows initially missed endometriosis., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We retrospectively reviewed our recent experience with thoracoplasty to define its role in the context of current surgical practice., Methods: Twenty-six patients underwent thoracoplasty in the last 10 years with the aim of obliterating a residual pleural space or pulmonary cavity. Twenty-one patients had a postresectional empyema, 3 had a primary empyema and 2 had a cavernostomy performed for a pulmonary aspergilloma. A bronchopleural fistula was present in 10 cases. Infection had been previously controlled in all cases by intercostal drainage, open-window thoracostomy, or cavernostomy (in 4, 20, and 2 patients, respectively). Twenty-two extramuscoloperiosteal thoracoplasties, 3 thoracomyoplasties, and 1 Andrews thoracoplasty were performed. Intrathoracic flap transposition followed thoracoplasty in 9 cases; a second step of the Clagett procedure followed thoracoplasty in 2 cases., Results: One patient died postoperatively (3.8%). Thoracoplasty alone (n=6) or combined with a procedure to fill the residual space (n=14) was successful in achieving complete obliteration of the residual space in 77% of patients (n=20). In 4 patients thoracoplasty alone reduced the residual cavity but filling procedures were not feasible. In 1 patient thoracoplasty failed to obliterate the cavity and infection recurred. Three patients experienced chronic thoracic sequelae., Conclusions: Thoracoplasty remains an option for the treatment of residual pleural or pulmonary spaces (with or without bronchopleural fistula) once infection has been controlled, when other more conservative procedures are not effective or feasible. In our experience it was effective both when used alone in favorable conditions and when combined with other procedures to fill the residual cavity., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We report the case of a 79-year-old woman referred to our institution for persistent cough and right-sided chest pain. A computed tomographic scan revealed a 2-cm round nodule in the right lower lobe. A wedge resection of the lesion was achieved by video-assisted thoracic surgery. Pathologic examination was consistent with the diagnosis of chordoma. Magnetic resonance imaging of the whole spine and skull basis was normal. Therefore, a diagnosis of primary lung chordoma, an exceptional condition, could be established., (2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The recommended antibiotic prophylaxis by second-generation cephalosporins reduces the incidence of wound infection and empyema, but its effectiveness on postoperative pneumonias (POPs) after major lung resection lacks demonstration. We investigated risk factors and characteristics of POPs occurring when antibiotic prophylaxis by second-generation cephalosporin or an alternative prophylaxis targeting organisms responsible for bronchial colonization was used., Methods: An 18-month prospective study on all patients undergoing lung resections for noninfectious disease was performed. Prophylaxis by cefamandole (3 g/24 h, over 48 hours) was used during the first 6 months, whereas amoxicillin-clavulanate (6 g/24 h, over 24 hours) was used during the subsequent 12 months. Intraoperative bronchial aspirates were systematically cultured. Patients with suspicion of pneumonia underwent bronchoscopic sampling for culture., Results: Included were 168 patients in the first period and 277 patients in the second period. The incidence of POP decreased by 45% during the second period (P = 0.0027). A significant reduction in antibiotic therapy requirement for postoperative infections (P = 0.0044) was also observed. Thirty-day mortality decreased from 6.5% to 2.9% (P = 0.06). Multivariate analysis showed that type of resection, intraoperative colonization, chronic obstructive pulmonary disease, gender, body mass index, and type of prophylaxis were independent risk factors of POP. A case control-study that matched patients of the two periods according to these risk factors (except for antibiotic prophylaxis) confirmed that the incidence of POP was lowered during the second period., Conclusions: Targeted antibiotic prophylaxis may decrease the rate of POPs after lung resection and improve outcome.

Background: Results of pneumonectomy after chemotherapy are controversial, and the procedure is often considered as potentially dangerous., Methods: Records of patients who underwent pneumonectomy after chemotherapy for non-small cell lung cancer in a single institution in a 6-year period were reviewed retrospectively., Results: One hundred eighteen patients had pneumonectomy after chemotherapy. Indications for preoperative chemotherapy were N2 disease, 74; potentially resectable T4 disease, 17; doubtful resectability, 18; stage IV disease (nodule on another ipsilateral lobe), 4; and participation in a randomized trial on induction chemotherapy in initial stages, 5. Chemotherapy protocols were platinum-based. Imaging reevaluation showed complete, partial, minor response, and disease stability in 0, 24, 39, and 55 patients, respectively. Operative mortality was 5.9% (7 of 118), consisting of 4 of 54 after pneumonectomy, and 3 of 64 after left pneumonectomy. Bronchopleural fistula caused one death. No factor among those evaluated (sex, age, comorbidities, forced expiratory volume in 1 second, symptoms, side and location of tumor; indication for operation, number of cycles, and response to chemotherapy; extent of resection, TNM status, pathologic stage) predicted postoperative death. Median and overall 5-year survival was 22 months and 23.7%, respectively. At univariate analysis, pathologic stage, T status, and the occurrence of postoperative complications influenced 5-year survival. At multivariate analysis, T status (p = 0.0054), the occurrence of postoperative complications (p = 0.0015), and clinical response to induction chemotherapy (p = 0.028) were identified as independent predictors of 5-year survival., Conclusions: Pneumonectomy after chemotherapy has acceptable mortality. Long-term results are encouraging.

Background: Idiopathic spontaneous pneumothorax (ISP) results from rupture of blebs, bullas, or diseased alveolar walls. Initiating mechanisms may relate to increased transpulmonary pressure. The possible impact of changes in atmospheric pressure (Patm) on the occurrence of ISP remains uncertain., Methods: We studied the relationship between the occurrence of ISP and meteorological conditions during a 4-year period in the urban area of Bologna, Italy, in which all cases of pneumothorax can be exhaustively identified. For each day of the study period, Patm and ambient temperature were obtained from the local meteorological institute. A cluster was defined as the admission of at least two patients with pneumothorax within 3 days of each other., Results: There were 294 episodes of ISP; 247 (84%) occurred in 76 clusters. Clusters were significantly associated with wider differences in Patm between the index day (ie, the first day of the cluster) and the previous day (ie, the difference in mean [+/- SEM] Patm, -1.23 +/- 0.45 vs + 0.04 +/- 0.12 mm Hg, respectively; p = 0.01[analysis of variance]). Similarly, pneumothorax and storms (but not temperature) were significantly associated (p < 0.0001 [chi(2) test])., Conclusions: This large-scale study shows that patients with ISP are hospitalized in clusters and suggests that important variations in Patm may be involved. The knowledge of this relationship may help to understand the pathophysiology of the disease.

Catamenial pneumothorax is a relatively rare condition, generally of mild to moderate severity. We report the case of a 29-year-old woman who experienced an episode of life threatening right-sided hemopneumothorax in association with menses. She had already been operated on for recurrent pneumothorax. Treatment of the current episode included urgent tube thoracostomy and iterative thoracotomy, together with lung wedge resection, parietal pleurectomy, and partial diaphragmatic excision. Pathologic examination revealed endometrial implants massively involving the diaphragm, the pleura, and the lung parenchyma. The present report shows that endometriosis-related pneumothorax may be extremely severe. The multiple localizations of endometrial implants in this case may provide a support to the different pathogenic theories of endometriosis-related pneumothorax.

Thoracic endometriosis syndrome includes four well-recognized clinical entities, namely catamenial pneumothorax, catamenial hemothorax, catamenial hemoptysis and lung nodules, as well as some exceptional presentations. The etiological mechanisms of this syndrome are not well understood, and different theories have been proposed. Controversies exist about optimal management, as experience has been drawn from case reports and small clinical series. Surgery, hormonal treatments and combined approaches have all been proposed, with variable results in terms of short and long term outcome.

Background: Resection of tumors with carinal involvement remains a challenge because of specific problems of operative technique and airway management. We reviewed our experience with carinal resection and studied factors influencing postoperative course and long-term survival., Methods: Between 1983 and 2002, 65 patients underwent a carinal resection for non-small-cell lung cancers involving the carina (54 squamous cell carcinomas and 11 adenocarcinomas)., Results: Fifty-eight right sleeve pneumonectomies and 2 left sleeve pneumonectomies were performed. In addition, five tracheocarinal resections with double bronchial reimplantation (no lung resection) were also performed. The intraoperative airway management consisted of high-frequency jet ventilation in 83% of patients and intermittent conventional ventilation through the operative field in the remaining 17% of patients. Operative mortality was 7.7%. Resection was complete in 61 patients. The overall 5-year and 10-year survival rates were 26.5% and 10.6%, respectively. Patients with N0 or N1 disease had a 5-year survival of 38% compared with 5.3% for those with N2 disease (p < 0.01). At multivariate analysis only nodal status (N0, N1 versus N2; p = 0.0046) had a significant impact on long-term survival., Conclusions: Carinal resection provides acceptable results in terms of operative mortality and long-term survival rates. Patients should be carefully selected and probably enrolled in a multimodality treatment program in case of anticipated mediastinal lymph node involvement.

Background: This study seeks to evaluate results regarding the repair of diaphragmatic eventration using video-assisted thoracic surgery (VATS)., Methods: We performed a prospective observational study including patients referred to us for surgical treatment of diaphragmatic eventration during a 12-year period. Clinical, radiologic, and functional data were prospectively recorded. VATS was performed with two thoracoports and a 4-cm mini-thoracotomy. Diaphragmatic plication was performed using two nonresorbable running sutures from periphery to the cardio-phrenic angle. Follow-up data (clinical examination, chest roentgenogram, lung function tests at 3, 6, 12 months, and annually thereafter) were also prospectively recorded., Results: Twelve patients (4 male adults, mean age 57.7 +/- 14.8 years) were operated on between 1992 and 2003. The left side was involved in 8 patients and the mean height of diaphragm elevation was 7.5 +/- 1.8 cm. All patients experienced symptoms related to the disease; in 2 patients the operation was carried out to achieve weaning from mechanical ventilation. The etiologic mechanism could be identified in 11 out of 12 patients (trauma, n = 9; Charcot-Marie disease, n = 1; calcified para-aortic nodes, n = 1). Mean operative time, drainage output, and hospital stay were 77 +/- 15 minutes, 0.8 +/- 04 L, and 3.4 +/- 0.7 days, respectively. No mortality was observed; 1 patient experienced postoperative pneumonia, which was treated using antibiotics. All patients experienced amelioration of symptoms and long-term lung function tests revealed a marked improvement of both the forced volume capacity and the forced expiratory volume at 1 second. No relapses were observed at follow-up chest roentgenogram., Conclusions: Treatment using VATS is a safe and effective alternative to conventional surgery. Functional improvement persists at long-term follow-up.

Background: No specific data are available in the literature on the bronchoalveolar Lavage (BAL) findings of Legionella pneumophila pneumonia. We report on the cytological and immunophenotypical BAL data of three immunocompetent patients with severe community-acquired pneumonia due to L. pneumophila serogroup 1., Methods: Retrospective chart review. The microbiologial diagnosis was obtained by BAL culture or/and urinary antigen assay., Results: All patients presented with high-grade fever, bilateral chest infiltrates and severe respiratory failure requiring ventilatory support. The cytological BAL pattern at presentation showed in all patients the association of a marked neutrophilia with a variable but remarkable percentage of lymphoblasts. Increased levels of activated T-Lymphocytes (both HLA-DR + and CD25 + cells) and, in 2 out of 3 patients, of T-cells bearing the gamma/delta T-cell receptor were the main immunophenotypical findings on flow cytometric analysis., Conclusions: We suggest that the association of lymphoblasts with a marked neutrophilia in BAL fluid of patients with a clinical-radiological setting compatible with acute pneumonia should suggest L. pneumophila as a possible etiologic agent.

Objectives: To evaluate the incidence of catamenial pneumothorax (CP) among women who have been referred for the surgical treatment of spontaneous pneumothorax (SP) and to study its pathogenic mechanisms., Design: A prospective study of women of reproductive age who have been referred to our center for the surgical treatment of SP. Patients with pneumothorax secondary to a known lung disease were excluded., Setting: A university hospital., Methods: At the preoperative evaluation, special attention was given to the investigation of a possible temporal relationship between pneumothorax and menses. Video-assisted thoracoscopy constituted the operative technique of choice. The lung was inspected to identify blebs or bullae and the origin of possible air leaks. Signs of thoracic endometriosis were also carefully searched for. The diaphragm was systematically inspected to search for holes and/or endometrial implants. When limited diaphragmatic abnormalities were found, a partial diaphragmatic resection was carried out using an endoscopic stapler. In case of lesions that were not accessible by a purely endoscopic approach, a utility minithoracotomy was used., Results: In an 18-month period, 32 women with SP were referred for surgery. In eight cases, the catamenial character of the pneumothorax was recognized by clinical history. In all these patients, the following diaphragmatic abnormalities were found at surgery: holes (one patient); endometrial implants (three patients); and both (four patients). Visceral pleural endometriosis was found in one patient. During pathologic examination, diaphragmatic endometriosis was confirmed in seven of the eight cases. In one patient, it was associated with pulmonary and pleural endometriosis. In only one patient (with multiple diaphragmatic holes and a pulmonary nodular brown lesion), endometriosis could not be confirmed at histology, but signs of parenchymal focal hemorrhages were found., Conclusions: Our experience shows that (1) CP is more frequent than expected and (2) diaphragmatic abnormalities seem to play a fundamental role in its pathogenesis.

Objectives: To study the clinical characteristics, treatment modalities, and outcome of patients with superior sulcus tumors who underwent surgery over a 15-year period., Design: Retrospective clinical study., Methods: Clinical records of all patients operated on for superior sulcus tumors by the same surgical team between 1988 and 2002 were reviewed retrospectively., Results: Sixty-seven patients were operated on in this period. All the patients underwent en bloc lung and chest wall resection. Surgical approaches were as follows: posterolateral thoracotomy according to Paulson (n = 33), combined transcervical and transthoracic approach (n = 33), and isolated transcervical approach (n = 1). Types of pulmonary resection included lobectomies (n = 59), pneumonectomies (n = 2), and wedge resections (n = 6). Pathologic stages were IIB, IIIA, and IIIB in 49 cases, 12 cases, and 6 cases, respectively. Resection was complete in 55 patients (82%). Operative mortality was 8.9% (n = 6). Postoperative treatment was administered in 53 patients (radiotherapy, n = 42; chemoradiotherapy, n = 9; and chemotherapy, n = 2). Overall 2-year and 5-year survival rates were 54.2% and 36.2%, respectively. Five-year survival was significantly higher after complete resection than after incomplete resection (44.9% vs 0%, p = 0.000065). The presence of associated major illness negatively affected the outcome (5-year survival, 16.9% vs 52%; p = 0.043). Age, weight loss, respiratory impairment, tumor size, presence of nodal disease, and histologic type did not influence the long-term outcome. At multivariate analysis, only the completeness of resection and the absence of associated major comorbidities had an independent positive prognostic value., Conclusions: Superior sulcus tumor remains an extremely severe condition, but long-term survivals may be achieved in a large percentage of cases. The presence of associated major illness and the completeness of resection are the two most important factors affecting the long-term outcome.