Rob Lamers

Does the cellular bronchoalveolar lavage fluid profile reflect the severity of sarcoidosis

The aim of this study was to assess whether the cellular bronchoalveolar lavage fluid (BALF) profile, particularly the number of polymorphonuclear neutrophils (PMNs), is associated with disease severity of sarcoidosis and its usefulness in determining remission. Twenty-six nonsmoking outpatients with sarcoidosis were included in this study. The patients were divided into two subgroups according to the absolute number of PMNs in BALF: < or =0.2x10(4) cells x mL(-1) (group 1; n = 15) and >0.2x10(4) cells x mL(-1) (group 2; n = 11). The radiographic stage, high-resolution computed tomography (HRCT) findings, 67Ga lung uptake as well as lung function tests differed significantly between group 1 and 2. Follow-up revealed that 14 (93.3%) patients of group 1 compared to four (36.4%) of group 2 recovered spontaneously without the help of corticosteroids. In contrast, no differences were found in the number of lymphocytes in BALF nor in the serum angiotensin converting enzyme (sACE) level between both groups. The number of PMNs, the transfer factor of the lungs for carbon monoxide (TL,CO), the forced expiratory volume in one second (FEV1) and one of the HRCT subscores discriminated between patients with different disease progression. Of these parameters the PMNs appeared to be the only one which differentiated patients who demonstrated remission and those who deteriorated. In conclusion, these results indicate that the number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid distinguish between sarcoidosis patients who demonstrated remission and those having a more severe course of the disease. Whether polymorphonuclear neutrophils may be considered as markers of disease activity and/or prognosis in sarcoidosis needs further investigation.

External irradiation versus external irradiation plus endobronchial brachytherapy in inoperable non-small cell lung cancer: a prospective randomized study.

Abstract Purpose : No randomized studies are available on the additional value of endobronchial brachytherapy (EBB) to external irradiation (XRT) regarding palliation of respiratory symptoms (RS). A prospective randomized study was initiated to test the hypothesis that the addition of EBB to XRT provides higher levels of palliation of dyspnea and other RS and improvement of quality of life (QoL) in patients with non-small cell lung cancer (NSCLC) with endobronchial tumour. Materials and methods : Patients with previously untreated NSCLC, stages I-IIIb, WHO-performance status of 0–3 and with biopsy proven endobronchial tumour in the proximal airways were eligible. EBB consisted of two fractions of 7.5 Gy at 1 cm on day 1 and 8. XRT started at day 2. The XRT dose was 30 Gy (2 weeks) or 60 Gy (6 weeks). The EORTC QLQ-C30 and QLQ-LC13 were assessed before treatment and 2 weeks, 6 weeks, 3, 6 and 12 months after treatment. Re-expansion of collapsed lung was tested by the inspiratory vital capacity (IVC) and CT scan of the chest. Results : Ninety-five patients were randomized between arm 1 (XRT alone) ( n =48) or arm 2 (XRT+EBB) ( n =47). The arms were well balanced regarding pre-treatment characteristics and QoL scores. The compliance for QoL-assessment was >90% at all times. No significant difference between the trial arms was observed with respect to response of dyspnea. However, a beneficial effect of EBB was noted concerning the mean scores of dyspnea over time ( P =0.02), which lasted for 3 months. This benefit was only observed among patients with an obstructing tumour of the main bronchus. A higher rate of re-expansion of collapsed lung was observed in arm 2 (57%) compared to arm 1 (35%) ( P =0.01). The inspiratory vital capacity (IVC) assessed 2 weeks after radiotherapy improved with 493 cm 3 in arm 2 and decreased 50 cm 3 in arm 1 ( P =0.03). No difference was noted regarding the incidence of massive haemoptysis (13 vs. 15%). Conclusion : The addition of EBB to XRT in NSCLC is safe and provides higher rates of re-expansion of collapsed lung resulting in a transient lower levels of dyspnea. This beneficial effect was only observed among patients with obstructing tumours in the main bronchus.

Sarcoidosis: assessment of disease severity using HRCT

The value of high-resolution computed tomography (HRCT) in diagnosing and assessing inflammatory activity in sarcoidosis is well established. The aim of the present study was to address the intra- and inter-observer agreements of the HRCT score by Oberstein et al. [8], and to evaluate the relationship between HRCT findings and disease severity expressed in respiratory functional impairment in sarcoidosis. The clinical records of 80 known sarcoidosis patients visiting the outpatient clinic between January 2000 and August 2001, who underwent a HRCT as well as lung function tests (including exercise testing), were reviewed. Two readers scored the first 60 HRCT images twice. Weighted kappa and intra-class correlation coefficient were used to assess the reliability of the HRCT scoring system. Spearmans rank correlation coefficients and multiple regression analyses were performed to evaluate the relationship between HRCT findings (first reading, reader A) and respiratory functional impairment. Intra- and inter-reader reliability demonstrated good agreement. All HRCT subscores, except enlargement of lymph nodes, were correlated to the FEV1, FVC, DLco, Pao2max (all p<0.05) and A-aPo2 max (p<0.001). Furthermore, HRCT abnormalities, but not the chest radiographic stage, were strongly associated with functional parameters. Abnormal changes of lung parenchyma, established by HRCT features, were associated with respiratory functional impairment in sarcoidosis. Moreover, compared with the radiographic stages, HRCT findings appeared to be much more sensitive in depicting respiratory disability, especially abnormal gas exchange.

Interobserver variability and accuracy of computed tomographic assessment of nodal status in lung cancer

To assess the interobserver variability of computed tomography in determining nodal status in non-small cell lung carcinoma, four experienced radiologists reviewed the computed tomographic scans of 147 patients. Interobserver variability was calculated using the kappa statistic. In addition, the accuracy of CT assessment of the nodal status by the four observers was measured by comparing their findings with thorough mediastinal exploration at both mediastinoscopy (n = 35) and thoracotomy (n = 112). Interobserver variability was large between the four radiologists regarding nodal status on a per-patient basis (kappa = 0.38). Sensitivity of computed tomography for the observers on a per-patient basis ranged from 40% to 69% with a 1.0-cm criterion and from 28% to 56% with a 1.5-cm criterion. From the large interobserver variability and the low sensitivities in this study it can be concluded that a negative result of computed tomography regarding mediastinal lymph nodes does not eliminate the need for mediastinoscopy or exploration of the mediastinum at the time of operation in patients with non-small cell lung cancer.

The prognostic significance of accumulation of p53 protein in stage III non-small cell lung cancer treated by radiotherapy

In the present study the prognostic significance of accumulation of nuclear p53 protein on survival and freedom from local progression was investigated. Formalin-fixed, paraffin-embedded sections obtained by bronchoscopy or mediastinoscopy were used to examine the expression of nuclear p53 protein using immunohistochemistry. In 37 cases (57%), overexpression of the p53 protein was detected. No relation was found between p53 expression and other pretreatment variables. Response to radiotherapy was found in 11 p53-negative cases (65%) versus 10 p53-positive cases (42%). Freedom from local progression was significantly better in the p53-negative cases as compared with the p53-positive cases. The p53-negative cases who responded to radiotherapy showed an excellent freedom from local progression rate after 2 years of 100%, whereas all p53-positive cases without response to radiotherapy showed local progression within 24 months. Overall survival between p53-negative and -positive cases did not differ, however the disease-specific survival was found to be worse in the p53-positive cases as compared to the negative cases (median survival 8.4 vs. 14.4 months (P < 0.05)). No correlation was found between p53 expression and the frequency of distant metastases. In conclusion, the results of this study suggest that p53 protein expression may be of prognostic value on freedom from local progression in non-small cell lung carcinoma.

Cell proliferation and apoptosis in stage III inoperable non-small cell lung carcinoma treated by radiotherapy

PURPOSE The purpose of this study was to assess the prognostic value of the expression of p53 and bcl-2, the apoptotic index and the expression of topoisomerase II alpha in patients with inoperable non-small cell lung cancer (NSCLC) treated with high dose radiotherapy. PATIENTS AND METHODS A number of 161 patients with inoperable NSCLC treated with high dose radiotherapy (60 Gy) were included. Immunohistochemical analysis was used to assess the expression of nuclear p53-protein, topoisomerase II alpha and cytoplasmatic expression of bcl-2, while spontaneous apoptosis was assessed using in situ labeling. The minimal follow up period was 2 years. RESULTS Local control did not only depend on the presence of p53 expression, but also on the proportion of p53 positive cells. The most important prognostic factor was the apoptotic index. A high apoptotic index was associated with worse local control, more distant metastases and a significantly worse overall survival. No association was noted between the expression of bcl-2 and topoisomerase II alpha with any of the endpoints. CONCLUSION This study indicates that p53 expression and the apoptotic index are prognostic factors with regard to local control in patients with inoperable NSCLC treated with radiotherapy and by combining these 2 factors, a clinically relevant estimation of the local control probability can be made. The apoptotic index turned out to be the only factor significantly related to survival.

Serum LDH : a marker of disease activity and its response to therapy in idiopathic pulmonary fibrosis

In the following case report the determination of serum lactate dehydrogenase (LDH)-a simple though non-specific test-reflects changes of disease activity and clinical improvement during treatment with cyclophosphamide and a tapered dose of prednisone from 100 to 0 mg daily in a 43-year-old woman with idiopathic pulmonary fibrosis. The trend observed in this case indicates that the serum LDH-activity may be directly proportional to the extent of this diffuse inflammatory pulmonary disease.

Is the chest radiograph a reliable tool in the assessment of tumor response after radiotherapy in nonsmall cell lung carcinoma

BACKGROUND The purpose of this study was to evaluate whether the chest radiograph is a reliable tool to assess response to radiotherapy. MATERIALS AND METHODS Pre- and post-treatment chest radiographs and computed tomographs (CT) of 63 patients with nonsmall cell lung cancer (NSCLC) treated by radiotherapy were reviewed by four observers with regard to suitability for tumor measurement, and response. Suitability for tumor measurement was expressed as the number of measurable diameters. In addition, the consequences to clinical outcome were studied by survival analysis. RESULTS The CT turned out to be more suited for tumor measurement before as well as after radiotherapy, resulting in an increase of the number of measurable cases. The number of measurable cases with CT was 52 (83%) as compared to 28 (44%) with chest radiography. Especially in case of centrally localized tumors, the presence of an atelectasis, or squamous cell carcinoma, CT contributed to a higher rate of measurable cases. The interobserver agreement with regard to response using chest radiograph was good (mean kappa = 0.74). In 25 of 28 cases (89%) measurable with CT as well as with chest radiograph, response was equally classified. When CT was used, the median survival of the responders was 14.2 months as compared to 6.8 months of the nonresponders. When chest radiograph was used, the median survival of these groups was 12.0 and 6.6 months respectively, which was not significantly different when response was assessed by CT. CONCLUSION We conclude that CT is more suited for tumor measurement because more measurable lesions can be found and more evaluable lesions on chest radiograph become measurable on CT. The chest radiograph does have a valuable role to play in those lesions that are measurable because of the good interobserver agreement with regard to the response classification, the high overall agreement between CT and chest radiograph in case of measurable cases, and the lack of important differences with regard to survival.

Computed tomographic staging of esophageal carcinoma: a study on interobserver variation and correlation with pathological findings

Despite numerous reports on the efficacy of CT in the staging of esophageal carcinoma, no data are available on the reproducibility of the procedure. Three experienced radiologists independently reviewed the CT scans of 35 patients retrospectively. Calculation of interobserver variation was performed using the kappa statistic. The CT findings of each observer were subsequently correlated with the surgical and pathological findings of 17 patients. There was a large interobserver variation concerning involvement of the aorta, pulmonary vessels, vertebral column, stomach and lymph nodes, ranging from poor to excellent agreement. Agreement between observers on extension of the disease to the tracheobronchial tree, pericardium and liver was good or excellent. Agreement between the CT findings of all observers and the surgical findings for invasive growth was poor. CT pathological correlation of the three observers showed sensitivities ranging from 50 to 57%, specificities ranging from 50 to 60% and accuracies ranging from 46 to 71%. It can be concluded from this study that patients with positive CT findings for involvement of the tracheobronchial tree, the pericardium and the liver should be considered unresectable for cure. Negative findings, however, should be interpreted with caution, because involvement of other structures may still be present. Despite optimistic reports on the efficacy of CT in the pretherapy staging of esophageal neoplasms, this modality has its limitations.

Mediastinal staging of lung cancer with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography and a dual-head coincidence gamma camera.

Abstract. The aims of the present study were (a) to evaluate mediastinal staging in patients with lung cancer with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) using a coincidence gamma camera (hybrid PET) in comparison with dedicated positron emission tomography (PET) and computed tomography (CT), and (b) to assess the feasibility to determine standardized uptake values (SUV) with hybrid PET. Forty patients were included in the study. Hybrid PET was performed without and with attenuation correction. Data were rebinned with single-slice (SSRB) or Fourier rebinning (FORE). The SUVs of primary tumors were calculated with hybrid PET and compared with SUVs determined by dedicated PET. Diagnostic accuracy for hybrid with or without attenuation correction was 80 or 74% compared with 82% for dedicated PET, and 63% for CT. Attenuation-corrected hybrid PET revealed a higher specificity than CT (83 vs 52%; p<0.05). The SUVs of primary tumors were similar to those of hybrid PET and dedicated PET with a mean relative difference of 20.8±16.4%. The FORE improved the agreement of SUVs with a mean relative difference of 13.8±9.9 vs 36.0±17.9% for SSRB (p<0.001). Hybrid PET with attenuation correction is more specific than CT for mediastinal staging in patients with lung cancer (p<0.05). It reveals similar results in comparison with dedicated PET. Calculation of SUVs with hybrid PET is feasible.