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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.

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 9 /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.

In the healthy lung, airway epithelial cells (AEC) regulate fibroblast proliferation through release of soluble factors, such as prostaglandins and proteins. Fibroproliferative diseases and airway remodelling may result from an inadequate generation of suppressive factors by AEC or the inability of fibroblasts to respond to them appropriately.The aim of this study was to study the effect of primary human AEC on the proliferation of fibroblasts obtained from healthy and fibrotic lungs in an interactive cell culture model.Conditioned medium (CM) from 14 out of 16 AEC lines significantly inhibited proliferation of normal human lung fibroblasts by 51.2+/-6.0%. The proliferation of fibroblasts derived from patients with lung fibrosis was equally inhibited by CM of AEC. The inhibitory effect of AEC-CM was completely reversed when fibroblasts were pre-incubated with 2.5 microm indomethacin. Furthermore, primary human AEC, but not fibroblasts, secrete TGF-beta, and the inhibitory effect of the AEC-CM was blocked by neutralizing anti-TGF-beta antibodies.These results demonstrate that AEC actively inhibit the proliferation of both normal and fibrotic fibroblasts via TGF-beta, which induces the prostaglandin E(2) synthesis in fibroblasts. The data indicate that proliferative lung diseases may be treated using the epithelial cell as the target of medication.

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.

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.

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.

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).Seventy-four consecutive patients (29 men; mean age, 64 years) with a pulmonary noduleor = 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.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).Combining bronchoscopy and PET scanning has an useful role in the diagnosis of noncalcified chest radiologic lesionsor = 3 cm in size. Bronchoscopy has a diagnostic yield of50% and also allows the diagnosis of endobronchial lesions. If bronchoscopy is nondiagnostic, a PET scan should be performed.

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-γ 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.

Background Lung resection for invasive pulmonary aspergillosis (IPA) is controversial. Neutropenia, thrombopenia and poor general condition may increase perioperative morbidity and mortality, and the redeeming benefit is questionable. Therefore we analyzed short- and long-term outcome after lung resection for IPA. Methods 41 patients with hematological disease underwent lung resection for suspected IPA: lobectomy (23 patients), wedge-resection (16) and enucleation (2). Results 4 (10%) patients developed major complications: pleural aspergillosis, bronchial stump insufficiency, severe bleeding, ARDS. 11 (27%) patients showed minor complications: pleural effusion (6), pneumothorax (2), seroma (2) and hematothorax (1). 30-day mortality was 10 % (4 of 41 patients): two died of bacterial septicemia, two of disseminated aspergillosis. One (2%) death was possibly surgery-related. IPA was cleared in 87% of patients, fungal relapse occurred in 4 (10%) patients. Overall survival was 65%, 58% and 40% at 6 months, 12 months and 5 years. Conclusion Lung resection for IPA even in profound cytopenia is feasible with acceptable morbidity and mortality. Fungal infection can be cured in more than 80 % of patients. Long-term outcome can be achieved if the hematological disease is under control.

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.

Background. Results of medialization thyroplasty for treatment of unilateral vocal fold paralysis are often unsatis- factory. 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 paraly- sis following thoracic surgery underwent medialization thyro- plasty. 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 clo- sure and voice function were assessed with videostroboscopy, perceptual and objective voice measures, and the Voice Dys- function 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. V C 2010 Wiley Periodicals, Inc. Head Neck 32: 1605-1612, 2010

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.

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.Retrospective single-center study.University hospital hemato-oncologic isolation unit and division of thoracic surgery.Forty-one patients with hematologic disease and suspected IPA who underwent lung resection.Lobectomy (n = 23), wedge resection (n = 16), and enucleation (n = 2).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; p0.0001), fungal relapse (RR, 5.06; 95% CI, 3.83 to 6.28; p0.0001), and to a minor extent the type of the underlying hematologic disease (p0.018) were the most important predictors of patient survival.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 in80% 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.

a rib segment to an intact portion of the same or adjacent ribs. Our patient’s injuries precluded other described techniques owing to the lack of intact structures to anchor stabilizing components. Our novel use of Nuss bars enabled us to create a viable superstructure to suspend the chest wall and allow full re-expansion of the lung. This technique will be useful in patients whose severity of injury precludes stabilization by previously described methods. We corresponded with Dr Donald Nuss for his thoughts. He wrote

1010-7940/$ see front matter Q 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.ejcts.2005.03.045 * Corresponding author. Tel.: C41 61 265 71 99; fax: C41 61 265 73 24. E-mail address: fgambazzi@uhbs.ch (F. Gambazzi). avoiding dissemination. Surprisingly, the cyst contained hair and seborrhoeic liquid. Histological confirmation of a mature teratoma. European Journal of Cardio-thoracic Surgery 28 (2005) 334 www.elsevier.com/locate/ejcts