G.P.M. Ten Velde

Flow cytometric analysis of DNA ploidy level in paraffin-embedded tissue of non-small-cell lung cancer

Investigations regarding the prognostic value of DNA content (ploidy) and proliferative characteristics [percentage of cells in S-phase or S-phase fraction (SPF)] have been greatly facilitated by the application of flow cytometry (FCM) using nuclei isolated from paraffin-embedded tissue. We have applied this technique to tumor sections from patients presenting with non-small-cell lung cancer (NSCLC) in 1980 and 1981. From 67 out of 115 patients material of sufficient quantity and quality was obtained to perform DNA-FCM. A multivariate analysis including stage of disease (UICC), age, tumor histology and treatment modality was performed to examine the prognostic significance of DNA-FCM in NSCLC. Aneuploidy was found in 65% of cases. In our study, the DNA content was not related to histology, stage of disease or treatment modality, nor to the length of survival (log rank test P = 0.62). Calculation of SPF was possible in 49/67 cases. The SPF was not related to histology, stage of disease or treatment modality, but a significant prognostic value was found for survival; patients with a high SPF died earlier (P = 0.04) and this was especially true for squamous cell carcinoma (P = 0.02). This study demonstrates the prognostic importance of DNA-FCM-derived information in NSCLC using a multivariate analysis; however further prospective studies in larger patient populations are needed.

MR-imaging of the brain of neurologic asymptomatic patients with large cell or adenocarcinoma of the lung. Does it influence prognosis and treatment?

Magnetic resonance imaging (MRI) of the brain and extensive neurological examination by a neurologist was performed as part of initial staging evaluation of 91 neurologic asymptomatic patients with large cell carcinoma or adenocarcinoma of the lung. Patients were followed up for at least 6 months. Evidence of metastatic brain disease was documented in 13 (14%) patients. Two of these patients were found suspective of brain metastases (BM) by the neurologist. The detection of BM resulted in upstaging of 1 (3%) patient in stage I/II, 4 (21%) patients in stage IIIA and 2 (11%) patients in IIIB. Especially for patients in stage III this upstaging is of importance as aggressive locoregional treatment can be abandoned. Evaluation of the brain with MRI is a sensitive method of detecting BM in neurologic asymptomatic patients and is recommended as part of the initial staging of patients with large cell carcinoma or adenocarcinoma of the lung in stage III. Additional examination by the neurologist is of little value to provide information of the neurologic status.

Neurotoxicity of prophylactic cranial irradiation in patients with small cell carcinoma of the lung

This study is concerned with effects of prophylactic cranial irradiation on neurological and mental functioning of patients with small cell cancer of the lung. Results are reported of a pilot study in two parts. In a prospective clinical-neurological study, 14 patients with small cell cancer of the lung were evaluated with standard neurological and bedside mental status examinations, before and after irradiation. Their performance was compared with evaluation results of seven small cell cancer of the lung patients who received no irradiation. Dysfunctions were exclusively found in the irradiated patients, which are interpreted as a contributional effect of prophylactic cranial irradiation. Results are reported of further neuropsychological investigation in a sample of five prophylactic cranial irradiation patients. The presence of a rather specific pattern of neuropsychic deficits was confirmed. Areas of malfunctioning were described with some clinical and research implications.

Bioelectrical impedance analysis to assess changes in total body water in patients with cancer

Predominantly based on studies in obese individuals, the applicability of single-frequency bioelectrical impedance analysis (BIA) to measure changes in total body water and fat-free mass has been questioned. To further clarify this issue, we compared changes in BIA-derived height(2)/resistance (ht(2)/R) with changes in total body water (deuterium dilution, delta-TBWdeu) in cancer patients participating in a clinical trial. Thirty-three patients (mean body mass index 23.2 +/- 3.5 kg/m(2)) were studied after an average follow-up of 11 weeks. Changes in TBWdeu occurred in both directions (mean +0.2 +/- 1.6 L, range -3.3 to +3.1 L). These changes were significantly predicted by changes in ht(2)/R (r(2)0.43, P < 0.0001, SEE 1.22 L), although precision was poor (residual SD 1. 2 L). There were in this regard no significant differences between patients with and without underweight. We conclude that in underweight and normal-weight cancer patients, BIA-derived changes in ht(2)/R significantly predict changes in total body water assessed by deuterium dilution.

The enhanced inflammatory response in non-small cell lung carcinoma is not reflected in the alveolar compartment

An inflammatory response has been observed in lung cancer both locally and systemically. The aim of the present study was to investigate whether the alveolar compartment was involved in the inflammatory response in non-small cell lung carcinoma (NSCLC). Both inflammatory mediators in bronchoalveolar lavage fluid (BALF) and cytokines produced by alveolar macrophages (AM) were investigated. Twenty patients with newly detected NSCLC and nine control subjects were studied. The patients had not been treated with chemotherapy, radiotherapy or with systemic or inhaled corticosteroids. All patients and control subjects were current smokers or stopped smoking recently. BAL was performed in the affected lung as well as in the contralateral lung of NSCLC patients, and only unilaterally in control subjects. Comparable results were demonstrated for the levels of the of the inflammatory mediators TNF-a, Interleukin (IL)-6, IL-8, both soluble TNF receptors and the soluble adhesion molecules E-selectin and intercellular adhesion molecule (ICAM)-1 between the affected lung and the contralateral lung in the NSCLC population as well as between the NSCLC population and the control subjects. Moreover, no significant differences in cytokine profiles of AM were found between AM obtained from the affected lung and from the contralateral lung. Although BAL is a useful tool in the diagnostic procedure for NSCLC, the present findings suggest that BAL does not reflect the enhanced inflammatory state, as reported in plasma and in the interstitial compartment around the tumour cells in NSCLC.

A solitary pulmonary nodule due to eosinophilic granuloma

A symptomless 42 year old man with a smoking history of 40 pack-years presented with a solitary pulmonary nodule highly suggestive of lung cancer. Wedge resection proved it to be an eosinophilic granuloma. No other localizations of eosinophilic granuloma were found, and none developed during a 3 yr follow-up.

Examination of bone marrow biopsy specimens and staging of small cell lung cancer

Bone marrow biopsy specimens were evaluated retrospectively in 63 of 88 (72%) patients with small cell lung cancer (SCLC). Significant differences were not found between extensive disease (ED) patients with or without bone marrow metastases in survival nor in nadirs of leucocytes or platelets subsequent to chemotherapy. A panel of antibodies was used to investigate whether immunohistochemical analysis on routinely processed bone marrow biopsy specimens could detect marrow metastases more effectively than conventional microscopy. In histologically proven marrow metastases and in control SCLC sections a combination of an antibody against cytokeratin 8, 18 and 19 (NCL5D3) and an antibody against neurone specific enolase was validated for detection of metastases. In histologically negative marrow biopsy samples, however, this combination did not yield any additional tumour positive cases. Therefore, histological evaluation of a bone marrow biopsy specimen, even when analysed by immunohistochemistry, does not contribute information relevant for staging, therapy evaluation or prognosis in SCLC.

Complete metabolic remission of an irresectable mediastinal solitary fibrous tumour with concurrent chemoradiation

Solitary fibrous tumour is a rare mesenchymal tumour of uncertain origin that occurs most frequently in the pleura, although it has also been described in extraserosal sites. The biological behaviour of the tumour is unpredictable. The case history is described of a patient diagnosed with a large symptomatic irresectable mediastinal solitary fibrous tumour who achieved a clinical, radiological and metabolic response after concurrent chemotherapy and radiotherapy.

Antimicrobial Treatment of Respiratory Tract Infections

Summary77 patients with a bacteriologically proven respiratory tract infection were admitted to a study in which a retrospective comparison of the efficacy and tolerability of 3 antimicrobial regimens was made. The first regimen comprised oral amoxicillin 1g four times daily, the second oral ciprofloxacin 500mg twice daily, and the third oral ciprofloxacin 750mg twice daily. All agents were given for 10 days, and the age, sex and underlying disease states of the 3 groups were comparable.The best clinical, bacteriological, and overall results were obtained with the third regimen. Adverse reactions were seen only in the second group (receiving ciprofloxacin 500mg twice daily); nausea, dizziness and visual disturbances were reported in 5 patients, 8 had slight liver test abnormalities, and 2 patients had seizures. All adverse events were transient.

Two different dosages of ciprofloxacin in patients with respiratory tract infections

Fifty-one patients with chronic obstructive lung disease with a proven bacterial respiratory tract infection were treated with ciprofloxacin 500 mg twice daily or 750 mg twice daily. Both dosages were given orally for approximately 10 days. The higher dosage showed a reduced amount of reinfections and relapses (19% and 16% versus 5% and 0%). The overall results were the same in both groups. Adverse reactions were mild: nausea and visual disturbances were seen in five patients. Eights patients had slight liver test abnormalities. In one patient a seizure occurred. All adverse reactions were of a temporary nature.