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

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

Image analysis in posttreatment non-small cell lung cancer surveillance: specialists' interpretations reviewed by the thoracic multidisciplinary tumor board.

BACKGROUND: Data show that the initial specialist's image interpretation and final multidisciplinary tumor board (MTB) assessment can vary substantially in the pretherapeutic cancer setting. The aim of this post hoc analysis was to investigate the concordance of the specialist's and MTB's image interpretations in patients undergoing systematic posttreatment lung cancer image surveillance. METHODS: In the initial prospective study, lung cancer patients who had received curative-intent treatment were randomly assigned to undergo either contrast-enhanced computed tomography (CE-CT) or integrated 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT). Imaging was performed every 6 months for 2 years, and all imaging studies were finally assessed by our MTB. This post hoc analysis assessed differences between the initial specialist's image interpretation and the final MTB's image interpretation. RESULTS: In 89 patients, 266 imaging studies (129 PET-CT, 137 CE-CT) were analyzed. In 87.2% (88.4, 86.1%) of the studies, complete concordance was found. Out of the 12.8% (11.6, 13.9%) with discordant results, 7.5% (6.9, 8.0%) had implications for alterations in patient management (major disagreements).Twenty major disagreements were detected in 17 study patients. Retrospectively, in eight out of these 17 (47%) patients, in contrast to the MTB's view, the specialist's interpretation was more appropriate, whereas in nine out of 17 patients (53%), the MTB's interpretation was more accurate. CONCLUSIONS: In an experienced MTB, the agreement between imaging specialists and the rest of the MTB with regard to the interpretation of images is high in a setting of posttreatment lung cancer image surveillance. It seems that in cases of disagreements, the rates of more accurate interpretation are well balanced between imaging specialists and the MTB. TRIAL REGISTRATION: ISRCTN16281786, Date 23. February 2017.

Comparing Two Imaging Methods for Follow-Up of Lung Cancer Treatment: A Randomized Pilot Study.

BACKGROUND: Scientific data on the image modality to be used in postcurative treatment surveillance of non-small cell lung cancer patients are scarce. This prospective randomized pilot trial compared the performance of integrated 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) and contrast-enhanced computed tomography (CE-CT). METHODS: After termination of curative-intent treatment, patients were randomly assigned to the PET-CT or the CE-CT group. Imaging was performed every 6 months for 2 years. If suspicious radiologic findings were detected or patients became symptomatic, a diagnostic workup was initiated. Sensitivity, specificity, and positive predictive value for detecting cancer recurrence were calculated for both imaging procedures. RESULTS: The study enrolled 96 patients. In 14 of 50 patients (28%) in the PET-CT group and in 14 of 46 patients (30%) in the CE-CT group, a suspicious radiologic finding was confirmed as cancer recurrence after diagnostic workup. False-positive findings were detected in 11 patients (22%) of the PET-CT group and in 8 patients (17%) of the CE-CT group. The sensitivity, specificity, and positive predictive value for detecting cancer recurrence (95% confidence interval) were 0.88 (0.62 to 0.98), 0.62 (0.42 to 0.79), and 0.56 (0.35 to 0.76) for PET-CT and 0.93 (0.68 to 1.00), 0.72 (0.53 to 0.87), and 0.64 (0.41to 0.83) for CE-CT, respectively. CONCLUSIONS: The results of our study suggest that PET-CT is not superior to CE-CT in detecting cancer recurrence during 2 years after curative-intent treatment of non-small cell lung cancer.

Procalcitonin as preoperative marker for surgery in advanced parapneumonic empyema.

BACKGROUND: The optimal time point for surgical management of advanced parapneumonic empyema in need of open pleurectomy and decortication remains unclear. We hypothesized that surgical outcomes will be better when procalcitonin (PCT) levels have dropped to normal ranges as evidence for resolution of the underlying pneumonia. METHODS: We retrospectively analyzed outcomes of 38 patients with advanced parapneumonic empyema who underwent open decortication and pleurectomy with available preoperative PCT (pPCT) values. Patients were divided into two groups based on the pPCT cut-off of 0.25 µg/L. Total length of stay was the primary endpoint. Secondary endpoints included postoperative length of stay, surgery-related complications and death. RESULTS: Patients with a pPCT ≥0.25 µg/L had a significantly longer total length of stay compared to patients with a pPCT level <0.25 µg/L [mean 22.4 vs. 15.0 days, difference -7.4 days (95% CI: -12.8 to -2.0), P=0.009]. This was also confirmed in linear regression analysis adjusting for age, gender and comorbidities [adjusted regression coefficient for log-transformed length of stay -0.27, 95% CI: -0.02 to -0.52, P=0.037]. Results for postoperative length of stay were similar. Eight patients in the pPCT ≥0.25 µg/L group had postoperative complications with two deaths while no complications occurred in the PCT <0.25 µg/L group (38% vs. 0%, P=0.004). CONCLUSIONS: These data suggest better surgical outcomes in advanced parapneumonic empyema when pneumonia has resolved with a pPCT drop of <0.25 µg/L. A larger, prospective study is needed to confirm these results.

Curative resection for lung cancer in octogenarians is justified.

BACKGROUND: Due to an increased life expectancy in a healthy aging population and a progressive incidence of lung cancer, curative pulmonary resections can be performed even in octogenarians. The present study aims to investigate whether surgery is justified in patients reaching the age of 80 years and older who undergo resection for non-small cell lung cancer (NSCLC). METHODS: In this retrospective multi-centre analysis, the morbidity, mortality and long-term survival of 88 patients (24 females) aged ≥80 who underwent complete resection for lung cancer between 2000 and 2013 were analysed. Only fit patients with few comorbidities, low cardiopulmonary risk, good quality of life and a life expectancy of at least 5 years were included. RESULTS: Curative resections from three thoracic surgery centres included 61 lobectomies, 9 bilobectomies, 6 pneumonectomies and 12 segmentectomies or wide wedge resections with additional systematic mediastinal lymphadenectomy in all cases. Final histology revealed squamous cell carcinoma [33], adenocarcinoma [41], large cell carcinoma [5] or other histological types [9]. Lung cancer stage distribution was 0 [1], I [53], II [17] and IIIA [14]. The overall 90-day mortality was 1.1%. The median hospitalisation and chest drainage times were 10 days (range, 5-27 days) and 5 days (range, 0-17 days), respectively. Thirty-six patients were complication-free (41%). In particular, pulmonary complications occurred in 25 patients (28%). In addition, 23 patients (26%) developed cardiovascular complications requiring medical intervention, while 24 patients (27%) had cerebrovascular complications, urinary tract infection and others. The median survival time was 51 months (range, 1-110 months), and the 5-year overall survival reached 45% without significance between tumour stages. CONCLUSIONS: Curative lung resections in selected octogenarians can be safely performed up to pneumonectomy for all tumour stages with a perioperative mortality, morbidity, and 5-year survival rate comparable to younger cohorts.

Pulmonary tularaemia: all that looks like cancer is not necessarily cancer - case report of four consecutive cases.

BACKGROUND: Pulmonary tularaemia is a very rare disease with only a small number of cases described in the literature. So far, to our knowledge, there exists no case report of pulmonary tularaemia where PET-CT scans and follow up CT scans are available. CASE PRESENTATION: We present four consecutive cases of pulmonary tularaemia. All patients suffered from non-specific symptoms. All patients were referred to our institution with strong suspicions of malignancy, particularly lung cancer. Diagnosis of tularaemia was made by typical findings in the aspirate of EBUS guided fine needle aspiration (necrosis, epithelioid cell aggregation) and surgical biopsy respectively, and a positive serology. In three of the four cases, the diagnosis was confirmed by positive PCR results of the tissue. PET-CT scans obtained in all four cases were indistinguishable from lesions typically seen in patients suffering from lung cancer. One of the four patients suffered from recurrence of the disease after antibiotic treatment; also this patient finally recovered after initiation of a second antibiotic regimen. One case became asymptomatic spontaneously, but this patient still received an antibiotic treatment. In one case, a follow up CT scan was unchanged compared to the initial PET-CT scan; in all other cases, the lesions disappeared almost completely. CONCLUSIONS: Symptoms of patients suffering from pulmonary tularaemia are non-specific and can be of prolonged character. PET-CT scans in these cases are indistinguishable from lung cancer. The diagnosis can be established when typical findings in EBUS guided fine needle aspirates or surgical biopsies are found in combination with a positive serology. In most cases the lesions disappear in follow up CT scans after clinically successful treatment.

Lung histology predicts outcome of bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.

Bronchiolitis obliterans (BO) is a severe complication after allogeneic hematopoietic stem cell transplantation with an unfavorable prognosis. Lung biopsy remains the gold standard for diagnosis. In this retrospective single-center study, we describe 33 patients who underwent biopsy for suspected BO. Ten patients had constrictive BO (CBO); 9 had lymphocytic bronchiolitis (LB), characterized by lymphocytic infiltration of the bronchioles. Six additional patients (4, CBO; 2, LB) had concomitant infection; 8 had other pathological diagnoses. Seven patients with CBO and 3 with LB met the National Institutes of Health consensus BO syndrome definition criteria. An additional 7 patients with histologically confirmed CBO did not meet the consensus definition, 4 of them because of concomitant airway infection. At diagnosis, there were no significant differences between the CBO and LB groups in clinical presentation; pulmonary function tests (median forced expiratory volume in one second [FEV1] at baseline, 90.4% and 99% predicted, at time of video-assisted thoracoscopic surgery, 55.1% and 60.8% for CBO and LB groups, respectively); and chest scans. Treatment was similar in both groups but outcome was different depending on histological findings. FEV1 significantly improved in LB patients compared with CBO patients. Survivals at 1 and 3 years were 77% ± 12% and 60% ± 14% for patients with CBO and 91% ± 9% for patients with LB (P = .028). Lung biopsy in patients with suspected BO enables better characterization of the pattern of BO syndrome. In contrast to CBO, LB is associated with a good long-term prognosis.

Lung resection in hematologic patients with pulmonary invasive fungal disease.

BACKGROUND: Pulmonary invasive fungal disease is a frequent complication in patients with hematologic malignancies. Surgical resection in addition to antifungal therapy is an option for selected cases but often feared because of immunosuppression. METHODS: We analyzed the outcome of 71 patients undergoing lung resection for pulmonary invasive fungal disease. Most patients had leukemia, 44 underwent high-dose chemotherapy, and 18 underwent stem cell transplantation. RESULTS: On the day of surgery, 44 patients were neutropenic, and 41 had a platelet count < 50 × 109/L. Forty-five nonanatomic (atypical) resections and 26 lobectomies were performed. Fungal infection was histologically proven in 53 patients. Reoperation was needed in four patients (bronchial stump dehiscence, persistent air leak, chylothorax, and seroma). Minor complications at the site of surgery occurred in 14 patients. In only two, there was an uncontrolled disseminated fungal infection. Overall, mortality at 30 days was 7% (five of 71). Long-term survival was mainly influenced by the underlying hematologic disease. CONCLUSIONS: Lung resection is a therapeutic option for hematologic patients with pulmonary fungal infection. Despite immunosuppression, the perioperative morbidity and mortality is acceptable, and, therefore, the prognosis is not determined by the surgical intervention.

Cytokine & chemokine response in the lungs, pleural fluid and serum in thoracic surgery using one-lung ventilation.

BACKGROUND: Thoracic surgery mandates usually a one-lung ventilation (OLV) strategy with the collapse of the operated lung and ventilation of the non-operated lung. These procedures trigger a substantial inflammatory response. The aim of this study was to analyze the cytokine and chemokine reaction in both lungs, pleural space and blood in patients undergoing lung resection with OLV with special interest in the chemokine growth-regulated peptide alpha (GROα) which is the human equivalent to the rat cytokine-induced neutrophil chemoattractant-1 (CINC-1). METHODS: Broncho-alveolar lavage (BAL) fluid of both the collapsed, operated and the ventilated, non-operated lung, respectively, pleural space drainage fluid and blood was collected and the concentrations of interleukin (IL)-6, IL-1RA and GROα were determined with enzyme-linked immunosorbent assays in 15 patients. RESULTS: Substantial inter-individual differences in the BAL fluid between patients in cytokine and chemokine levels occurred. In the pleural fluid and the blood these inter-individual differences were less pronounced. Both sides of the lung were affected and showed a significant increase in IL-6 and IL-1RA concentrations over time but not in GROα concentrations. Except for IL-6, which increased more in the collapsed, operated lung, no difference between the collapsed, operated and the ventilated, non-operated lung occurred. In the blood, IL-6 and IL-1RA increased early, already at the end of surgery. GROα was not detectable. In the pleural fluid, both cytokine and chemokine concentrations increased by day one. The increase was significantly higher in the pleural fluid compared to the blood. CONCLUSION: The inflammatory response of cytokines affects both the collapsed, operated and the ventilated, non-operated lungs. The difference in extent of response underlines the complexity of the inflammatory processes during OLV. In contrast to the cytokines, the chemokine GROα concentrations did not react in the BAL fluid or in the blood. This indicates that GROα might not be useful as marker for the inflammatory reaction in complex surgical procedures.

Hydroxyapatite versus titanium implant: Comparison of the functional outcome after vocal fold medialization in unilateral recurrent nerve paralysis.

BACKGROUND: Results of medialization thyroplasty for treatment of unilateral vocal fold paralysis are often unsatisfactory. This study compares glottal closure and voice quality after use of 2 different medialization implant types: VoCoM and TVFMI. METHODS: In all, 26 patients with unilateral vocal fold paralysis following thoracic surgery underwent medialization thyroplasty. In 11 patients (group I), a hydroxyapatite implant (VoCoM) was used. In 15 patients (group II), a titanium implant (TVFMI) was used. Preoperative and postoperative glottal closure and voice function were assessed with videostroboscopy, perceptual and objective voice measures, and the Voice Dysfunction Index (VDI). RESULTS: Group II showed a higher rate of complete glottal closure and greater improvement in perceived hoarseness, maximal phonation time, and maximal voice intensity than those in group I. CONCLUSIONS: With the individually adjustable titanium implant, better glottal closure and better functional outcome (phonation time and voice quality) were achieved.

Endoscopic management of bisected hemidiaphragm during retroperitoneoscopic donor nephrectomy.

Retroperitoneoscopy is our preferred technique for renal surgery and is routinely performed for living donor nephrectomy. We report a case of a totally bisected left hemidiaphragm during left-sided retroperitoneoscopic donor nephrectomy. This was most likely caused when creating the retroperitoneal working space by balloon dilation. Because the cardiopulmonary situation of the patient remained stable, retroperitoneoscopic donor nephrectomy was performed with the standard technique. This report describes for the first time the retroperitoneoscopic reconstruction of a diaphragmatic injury.

Opposite effect of corticosteroids and long-acting beta(2)-agonists on serum- and TGF-beta(1)-induced extracellular matrix deposition by primary human lung fibroblasts.

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by chronic airway inflammation and major structural lung tissue changes including increased extracellular matrix (ECM) deposition. Inhaled corticosteroids and long-acting beta(2)-agonists (LABA) are the basic treatment for both diseases, but their effect on airway remodeling remains unclear. In this study, we investigated the effect of corticosteroids and LABA, alone or in combination, on total ECM and collagen deposition, gene expression, cell proliferation, and IL-6, IL-8, and TGF-beta(1) levels by primary human lung fibroblasts. In our model, fibroblasts in 0.3% albumin represented a non-inflammatory condition and stimulation with 5% FCS and/or TGF-beta(1) mimicked an inflammatory environment with activation of tissue repair. FCS (5%) increased total ECM, collagen deposition, cell proliferation, and IL-6, IL-8, and TGF-beta(1) levels. In 0.3% albumin, corticosteroids reduced total ECM and collagen deposition, involving the glucocorticoid receptor (GR) and downregulation of collagen, heat shock protein 47 (Hsp47), and Fli1 mRNA expression. In 5% FCS, corticosteroids increased ECM deposition, involving upregulation of COL4A1 and CTGF mRNA expression. LABA reduced total ECM and collagen deposition under all conditions partly via the beta(2)-adrenergic receptor. In combination, the drugs had an additive effect in the presence or absence of TGF-beta(1) further decreasing ECM deposition in 0.3% albumin whereas counteracting each other in 5% FCS. These data suggest that the effect of corticosteroids, but not of LABA, on ECM deposition by fibroblasts is altered by serum. These findings imply that as soon as airway inflammation is resolved, long-term treatment with combined drugs may beneficially reduce pathological tissue remodeling.

Cancer/testis antigen expression and specific cytotoxic T lymphocyte responses in non small cell lung cancer.

Non small cell lung cancers (NSCLC) express cancer/testis antigens (CTA) genes and MAGE-A expression correlates with poor prognosis in squamous cell carcinomas. We addressed cytotoxic T lymphocytes (CTL) responses to HLA class I restricted CTA epitopes in TIL from NSCLC in an unselected group of 33 patients consecutively undergoing surgery. Expression of MAGE-A1, -A2, -A3, -A4, -A10, -A12 and NY-ESO-1 CTA genes was tested by quantitative RT-PCR. Monoclonal antibodies (MAb) recognizing MAGE-A and NY-ESO-1 CTA were used to detect CTA by immunohistochemistry. CD8(+) TIL obtained from tumors upon culture with anti CD3 and anti CD28 mAb and IL-2 were stimulated with autologous mature DC (mDC) and HLA-A*0101 restricted MAGE-A1(161-169) or MAGE-A3(168-176) peptides or HLA-A*0201 restricted MAGE-A4(230-239), MAGE-A10(254-262), NY-ESO-1(157-165) or multi-MAGE-A (YLEYRQVPV) peptides or a recombinant vaccinia virus (rVV) encoding MAGE-A and NY-ESO-1 HLA-A*0201 restricted epitopes and CD80 co-stimulatory molecule. Specificity was assessed by (51)Cr release and multimer staining. At least one CTA gene was expressed in tumors from 15/33 patients. In 10 specimens, at least 4 CTA genes were concomitantly expressed. These data were largely confirmed by immunohistochemistry. TIL were expanded from 26/33 specimens and CTA-specific CTL activity was detectable in 7/26 TIL. In 6, however, specific cytotoxicity was weak, (<40% lysis at a 50:1 E:T ratio) and multimer staining was undetectable. In one case, high (>60% lysis at 50:1 E:T ratio) MAGE-A10(254-262) specific, HLA-A*0201 restricted response was observed. Supportive evidence was provided by corresponding multimer staining. Although CTA genes are frequently expressed in NSCLC, detection of CTL reactivity against CTA epitopes in TIL from nonimmunized NSCLC patients represents a rare event.

Combining bronchoscopy and positron emission tomography for the diagnosis of the small pulmonary nodule < or = 3 cm.

AIM: To assess the role of bronchoscopy and positron emission tomography (PET) scanning in an integrated approach for the diagnosis of noncalcified, small, chest radiologic lesions (< or = 3 cm). METHODS: Seventy-four consecutive patients (29 men; mean age, 64 years) with a pulmonary nodule < or = 3 cm undergoing both combined PET and bronchoscopy were included. When bronchoscopy and PET findings were negative, a multidisciplinary decision was taken to perform further invasive diagnostics or follow-up. RESULTS: Malignancy was diagnosed in 51 patients (69%), and a positive benign diagnosis was made in 9 patients (12%). Six patients (8%) had endobronchial lesions. Bronchoscopy was diagnostic in 53% patients (cancer, n = 35; benign, n = 4). PET findings were positive in 19 of 35 patients with a nondiagnostic bronchoscopy. In these 19 patients, malignant diagnosis was made in 14 patients (CT-fine needle aspiration [FNA], n = 3; thoracoscopic biopsy, n = 3; resection, n = 7; FNA of PET-positive supraclaviclar lymph node, n = 1), and a benign diagnosis was made in 5 patients (CT-FNA, n = 1; thoracoscopic biopsy, n = 1; resection, n = 1; follow-up, n = 2). In 16 patients with nondiagnostic bronchoscopy and negative PET findings, 5 patients had a tissue diagnosis (cancer, n = 2 [< 1 cm]; benign, n = 3) and 11 patients were followed up. Sixty-seven patients had a lesion 11 mm to 3 cm; among these, all 12 patients who were bronchoscopy negative and PET negative had benign lesions. In 24 patients without mediastinal adenopathy (solitary pulmonary nodule), bronchoscopy was diagnostic in 12 patients (cancer, n = 11; bronchiolitis obliterans organizing pneumonia, n = 1). In the remaining 12 patients, PET findings were positive in 6 patients (cancer, n = 3; resection, n = 2; CT-FNA, n = 1) and negative in 6 patients (benign, n = 2, both on resection; follow-up, n = 4). CONCLUSION: Combining bronchoscopy and PET scanning has an useful role in the diagnosis of noncalcified chest radiologic lesions < or = 3 cm in size. Bronchoscopy has a diagnostic yield of > 50% and also allows the diagnosis of endobronchial lesions. If bronchoscopy is nondiagnostic, a PET scan should be performed.

Human bronchial epithelium controls TH2 responses by TH1-induced, nitric oxide-mediated STAT5 dephosphorylation: implications for the pathogenesis of asthma.

Increased levels of NO in exhaled air in association with increased NO synthetase (NOS)2 expression in bronchial epithelial are hallmark features of asthma. It has been suggested that NO contributes to asthma pathogenesis by selective down-regulation of TH1 responses. We demonstrate, however, that NO can reversibly limit in vitro expansion of both human TH1 and TH2 CD4+ T cells. Mechanistically, NO induces cGMP-mediated reversible STAT5 dephosphorylation and therefore interferes with the IL-2R activation cascade. Human bronchial epithelial cells (HBEC) up-regulate NOS2 after stimulation with IFN-gamma secreted by TH1 CD4+ T cells and release NO, which inhibits both TH1 and TH2 cell proliferation. This reversible T cell growth arrest depends on NO because T cell proliferation is completely restored after in vitro blocking of NOS2 on HBEC. HBEC thus drive the effector end of a TH1-controlled feedback loop, which protects airway mucosal tissues at the potential lesional site in asthma from overwhelming CD4+ TH2 (and potentially TH1) responses following allergen exposure. Variations in the efficiency of this feedback loop provides a plausible mechanism to explain why only a subset of atopics sensitized to ubiquitous aeroallergens progress to expression of clinically relevant levels of airways inflammation.

Predicting outcome after lung resection for invasive pulmonary aspergillosis in patients with neutropenia.

STUDY OBJECTIVES: To investigate the factors that predict survival after lung resection for invasive pulmonary aspergillosis (IPA) in patients with neutropenia, in order to assist the selection of patients who are most likely to have a successful outcome. DESIGN: Retrospective single-center study. SETTING: University hospital hemato-oncologic isolation unit and division of thoracic surgery. PATIENTS: Forty-one patients with hematologic disease and suspected IPA who underwent lung resection. INTERVENTIONS: Lobectomy (n = 23), wedge resection (n = 16), and enucleation (n = 2). RESULTS: Mortality within 30 days was 10% (4 of 41 patients). Major perioperative complications occurred in 10%. One death was possibly related to surgery (pleural aspergillosis). Of the patients with proven aspergillosis, 87.1% were cleared of infection, but fungal relapse occurred in 10%. Overall survival was 65% at 6 months, 58% at 12 months, and 40% at 5 years after surgery. Baseline characteristics and intraoperative data did not differ significantly between survivors and nonsurvivors at 6 months or 12 months after surgery. Perioperative complications did not significantly influence the outcome. Multivariate analysis of 12-month survival revealed that the variables, progression, or recurrence of the underlying hematologic disease (relative risk [RR], 4.64; 95% confidence interval [CI], 3.51 to 5.77; p < 0.0001), fungal relapse (RR, 5.06; 95% CI, 3.83 to 6.28; p < 0.0001), and to a minor extent the type of the underlying hematologic disease (p < 0.018) were the most important predictors of patient survival. CONCLUSIONS: Lung resection for IPA is feasible with an acceptable operative risk. While at 10%, the perioperative mortality is considerable; the nonsurgical mortality is reported to be between 30% and 90%. Fungal infection is cleared in > 80% of patients. Mid- to long-term survival can be achieved if the underlying hematologic disease is under control. It is not yet possible to define a group of patients with IPA who are most likely to benefit from lung resection.

Tissue microarray evaluation of Melanoma antigen E (MAGE) tumor-associated antigen expression: potential indications for specific immunotherapy and prognostic relevance in squamous cell lung carcinoma.

OBJECTIVE: To evaluate MAGE tumor-associated antigen (TAA) expression in an extensive panel of normal and neoplastic tissues. SUMMARY BACKGROUND DATA: TAAs of the MAGE family represent targets of active specific immunotherapy. Limited-size studies indicate that they are expressed in normal testis and tumors of different histologies. High-throughput tissue microarray (TMA) technology and MAGE TAA-specific monoclonal antibodies now allow us to comprehensively evaluate their expression in large numbers of tissues and to address clinical correlations. METHODS: A TMA containing 3,520 samples from 197 different tissues and a non-small-cell lung cancer TMA including 301 specimens were stained using the MAGE TAA-specific monoclonal antibody 57B. For patients with squamous cell carcinoma of the lung, the dichotomous result (positive vs. negative) of MAGE TAA staining was used as a predictor variable along with other covariates in proportional hazard regression analysis of tumor-specific survival. RESULTS: MAGE TAAs are expressed with frequencies ranging between 22.7% (larynx) and 50% of cases (lung) in squamous cell carcinomas from different anatomic areas and in large cell carcinomas of the lung (37.9%). The authors provide here the first description of MAGE TAA expression in basalioma (48.1%). To investigate the clinical significance of MAGE expression in a frequently positive tumor type, a non-small-cell lung cancer, TMA was then studied. In this TMA 43.2% of tumors were 57B positive. In patients with squamous cell carcinoma, MAGE TAA positivity was significantly correlated with a shorter tumor-specific survival in the proportional hazard regression analysis model. CONCLUSIONS: These data suggest novel potential therapeutic indications in different types of cancers. In lung squamous cell carcinoma, the significant association of MAGE TAA expression with poor prognosis suggests that patients with 57B-positive tumors may benefit from early, specific immunotherapy procedures.