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.     

Antisense therapy in malignant diseases: status quo and quo vadis?

Preclinical and clinical studies indicate a role for AS ODNs (antisense oligonucleotides) as therapeutics for malignant diseases. The principle of antisense technology is the sequence-specific binding of an AS ODN to the target mRNA, resulting in a translational arrest. The specificity of hybridization makes antisense strategy attractive to selectively modulate the expression of genes involved in the pathogenesis of malignant diseases. One antisense drug has been approved for local therapy of CMV (cytomegalovirus) retinitis, and a number of AS ODNs are currently being tested in clinical trials, including AS ODN targeting Bcl-2, XIAP (X-linked inhibitor of apoptosis protein) and TGF-beta-2 (transforming growth factor beta-2). AS ODNs are well tolerated and may have therapeutic activity. In particular, an AS ODN to Bcl-2 has been tested in phase III clinical trials in chronic lymphocytic leukaemia, multiple myeloma and malignant melanoma. In this review, therapeutic concepts, clinical studies and new promising molecular targets to treat malignancies with AS ODNs are summarized.     

XIAP expression correlates with monocytic differentiation in adult de novo AML: impact on prognosis

Antiapoptotic proteins like the inhibitor of apoptosis proteins (IAPs) are molecular markers potentially useful for the characterization of acute myeloid leukemia (AML). We screened 92 adults with de novo AML for the protein expression of various IAPs, Bcl-2 family members and the proform of Caspase-3 using quantitative immunoblot and flow cytometry. XIAP expression correlated with myelomonocytic French-American-British (FAB) subtypes M4/M5 (P < 0.05) and expression of monocytic markers (CD 14, CD 36; P < 0.05; CD 4, HLA-DR; P < 0.01) in AML blasts. In addition, XIAP was overexpressed in normal monocytes but undetectable in granulocytes. In AML, XIAP expression was significantly lower in patients with favorable than intermediate or poor cytogenetics (n = 74; P < 0.05). In total, 62 of the examined patients were treated according to the German AML Cooperative Group (AMLCG) 92 protocol. These patients were analyzed for prognostic significance of apoptosis-related proteins. Patients expressing low levels of XIAP enjoyed better overall survival than patients expressing high amounts of XIAP (mean, 9 (n = 41) versus 19 months (n = 21); P < 0.05). Other IAPs, most importantly Survivin, were of no prognostic value. We conclude that XIAP but not other IAP family members is associated with monocytic differentiation in normal and malignant myelopoiesis, and may be of prognostic significance for overall survival in adult de novo AML.     

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.     

Ηeparan sulphate in infectious and non-infectious exacerbations of COPD

Background and Objective

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with worsening health outcomes and effective treatment of each episode is essential. In this study, we aimed to investigate if plasma levels of heparan sulphate (HS) are associated with the aetiology of AECOPD.

Methods

COPD patients (N = 1189), GOLD grade II–IV, from a discovery cohort (N = 638) and from a validation cohort (N = 551), were included in the study. HS and heparanase (HSPE-1) were measured longitudinally in plasma at stable state, at AECOPD and at 4 weeks follow-up.

Results

Plasma HS was higher in patients with COPD as compared with non-COPD controls and was significantly increased at AECOPD as compared to stable state (p < 0.001) in the discovery and in the validation cohorts. Four distinct exacerbation groups were classified based on aetiology (no-infection/bacterial-infection/viral-infection/bacterial and viral coinfection) in the validation cohort. The fold-increase of HS from stable state to AECOPD was associated with the aetiology of exacerbation and was higher in cases with bacterial and viral coinfections. HSPE-1 was also significantly increased at AECOPD, however, there was no association of HSPE-1 levels with the aetiology of these events. The probability of having an infection at AECOPD was raised as HS levels increased from stable state to AECOPD. This probability was higher for bacterial infections than viral infections.

Conclusion

The results of our study indicate that circulating levels of HS are increased at AECOPD and this increase may be associated with the aetiology of these events.     

Survival after reduced-intensity conditioning is not inferior to standard high-dose conditioning before allogeneic haematopoietic cell transplantation in acute leukaemias

To assess the role of allogeneic stem cell transplantation (SCT) after reduced-intensity conditioning (RIC) in acute leukaemias, we retrospectively compared 25 patients with acute lymphoblastic leukaemia or acute myelogenous leukaemia after RIC to a historical group of 50 matched controls after high-dose conditioning. Engraftment, acute GvHD and severe infections were comparable in both groups. During the observation period, 1/25 patients (4%) after RIC and 14/50 (28%) after standard SCT died due to transplant-related causes; cumulative nonrelapse mortality (NRM) was 4% after RIC and 24% after standard SCT (P=0.029). In total, 15/25 patients (60%) relapsed after RIC and 20/50 (40%) after standard SCT; probability of disease-free survival (DFS) at 3 years was 43% after RIC and 49% after standard SCT (NS). Overall survival (OS) was 40% after RIC and 37% after standard SCT (NS). Stage of disease, cytogenetic risk profile, acute and chronic GvHD, chimerism status at day 90 and severe infections after transplantation were risk factors with significant impact on DFS and/or OS. In retrospective analysis, patients with acute leukaemias who receive RIC because of contraindications against standard SCT have a comparable outcome to standard SCT, but the higher relapse rate warrants further studies.     

Guidelines for the management of traumatic dental injuries. I. Fractures and luxations of permanent teeth

Crown fractures and luxations occur most frequently of all dental injuries. An appropriate treatment plan after an injury is important for a good prognosis. Guidelines are useful for delivering the best care possible in an efficient manner. The International Association of Dental Traumatology (IADT) has developed a consensus statement after a review of the dental literature and group discussions. Experienced researchers and clinicians from various specialties were included in the group. In cases where the data did not appear conclusive, recommendations were based on the consensus opinion of the IADT board members. The guidelines represent the current best evidence, based on literature research and professional opinion. In this first article of three, the IADT Guidelines for management of fractures and luxations of permanent teeth will be presented.