Markus Solèr

Prediction of functional reserves after lung resection: comparison between quantitative computed tomography, scintigraphy, and anatomy.

Background and Objectives: We prospectively compared five techniques to estimate predicted postoperative function (ppo F) after lung resection: recently proposed quantitative CT scans (CT), perfusion scans (Q), and three anatomical formulae based on the number of segments (S), functional segments (FS), and subsegments (SS) to be removed. Methods: Four parameters were assessed: FEV1, FVC, DLCO and VO2max, measured preoperatively and 6 months postoperatively in 44 patients undergoing pulmonary resection, comparing their ppo value to the postoperatively measured value. Results: The correlations (r) obtained with the five methods were for CT: FEV1 = 0.91, FVC = 0.86, DLCO = 0.84, VO2max = 0.77; for Q: 0.92, 0.90, 0.85, 0.85; for S: 0.88, 0.86, 0.84, 0.75; for FS: 0.88, 0.85, 0.85, 0.75, and for SS: 0.88, 0.86, 0.85, 0.75, respectively. The mean difference between ppo values and postoperatively measured values was smallest for Q estimates and largest for anatomical estimates using S. Stratification of the extent of resection into lobectomy (n = 30) + wedge resections (n = 4) versus pneumonectomy (n = 10) resulted in persistently high correlations for Q and CT estimates, whereas all anatomical correlations were lower after pneumonectomy. Conclusions: We conclude that both Q- and CT-based predictions of postoperative cardiopulmonary function are useful irrespective of the extent of resection, but Q-based results were the most accurate. Anatomically based calculations of ppo F using FS or SS should be reserved for resections not exceeding one lobe.

CT-Guided Radiofrequency Ablation of a Pulmonary Metastasis Followed by Surgical Resection

Outpatient CT-guided radiofrequency ablation (RFA) of a pulmonary metastasis followed by surgical resection and histopathological analysis was performed in a 72-year-old lady suffering from a peritoneal leiomyosarcoma. Histological workup 3 weeks post-ablation showed complete devitalization of the metastasis. This case report demonstrates that complete thermal destruction of a pulmonary metastasis by percutaneous image-guided RFA is possible.

Transbronchial Needle Aspiration in Routine Fiberoptic Bronchoscopy

The objective of this study was to evaluate the yield of transbronchial needle aspiration (TBNA) in a clinical routine setting of a teaching hospital for the diagnosis and staging of bronchogenic carcinoma in comparison to the results of controlled clinical studies. We reviewed our results with Wang retractable needle catheters during a 9-month period. The needle catheters were used in 72 patients. 43 patients had a final diagnosis of bronchogenic carcinoma. Classical bronchial washes, brushings and forceps biopsies led to the diagnosis in 28 patients (65%). The addition of TBNA increased the diagnostic yield by 14% (6 patients) to 79% overall. In 32 patients staging of mediastinal lymph nodes was attempted. Positive TBNA proved inoperability in 9 patients. In 7 patients TBNA was used to investigate peripheral masses. Two patients had a malignant tumor, of which one was diagnosed by TBNA. Overall, TBNA revealed important information with clinical consequences in 16 of 72 patients (22%). There were no complications. We conclude that TBNA significantly increases the diagnostic yield of fiberoptic bronchoscopy and carries only a minimal risk. Our results, obtained in the clinical routine setting of a teaching hospital, are comparable to the reported results of controlled studies.

Regular follow-up after curative resection of nonsmall cell lung cancer: a real benefit for patients?

Even though complete resection is regarded as the only curative treatment for nonsmall cell lung cancer (NSCLC), >50% of resected patients die from a recurrence or a second primary tumour of the lung within 5 yrs. It remains unclear, whether follow-up in these patients is cost-effective and whether it can improve the outcome due to early detection of recurrent tumour. The benefit of regular follow-up in a consecutive series of 563 patients, who had undergone potentially curative resection for NSCLC at the University Hospital, was analysed. The follow-up consisted of clinical visits and chest radiography according to a standard protocol for up to 10 yrs. Survival rates were estimated using the Kaplan-Meier analysis method and the cost-effectiveness of the follow-up programme was assessed. A total of 23 patients (6.4% of the group with lobectomy) underwent further operation with curative intent for a second pulmonary malignancy. The regular follow-up over a 10-yr period provided the chance for a second curative treatment to 3.8% of all patients. The calculated costs per life-yr gained were 90,000 Swiss Francs. The cost-effectiveness of the follow-up protocol was far above those of comparable large-scale surveillance programmes. Based on these data, the intensity and duration of the follow-up was reduced.

Evaluation of High-Risk Lung Resection Candidates: Pulmonary Haemodynamics versus Exercise Testing

We compared the value of exercise testing and measurement of pulmonary haemodynamics (PH) in the pre-operative assessment of 5 patients (mean age: 64 years, 3 men) with clinical stage I or II bronchogenic carcinoma and severe chronic obstructive pulmonary disease. They were considered at high risk due to poor pulmonary function tests (PFT); (one or more of the following): (1) radionuclide calculated postlobectomy FEV1 < 30% predicted, (2) diffusion capacity or transfer factor < 60% predicted, combined with a fall in PaO2 on maximal exercise of > 5 mm Hg, (3) a PaCO2 at rest of > 45 mm Hg. Maximal oxygen uptake (VO2max) during symptom-limited cycle ergometry and PH were measured in these 5 patients. They were considered eligible for lobectomy if they fulfilled at least one of the two criteria: (1) mean pulmonary artery pressure (PAP) of < 35 mm Hg and pulmonary vascular resistance of < 190 dyn.s.cm-5 at moderate exercise (40 W), (2) a VO2max of > or = 15 ml/kg/min. Six months postoperatively PFT and VO2max were measured again. PAP40W was 21, 38, 38, 46 and 52 mm Hg, respectively, which would have excluded 4/5 patients from surgery. VO2max was 21.7, 14.9, 13.4, 19.2 and 18.6 ml/kg/min, respectively, which would have excluded 2/5 patients. Expressed in percent predicted, however, VO2max was > or = 69% in all 5 patients, indicating only mild impairment of exercise capacity in the 2 patients with < 15 ml/kg/min VO2max. Therefore all 5 patients were offered surgery and underwent lobectomy. Apart from 1 prolonged air leak no complications occurred, the mean hospital stay was 16 days (13-21).(ABSTRACT TRUNCATED AT 250 WORDS)

Nuclear and cytoplasmic Maspin expression in primary non-small cell lung cancer

Aim: To investigate whether nuclear and cytoplasmic Maspin expression is associated with distinct clinicopathological parameters and TP53 expression in a representative series of primary non-small cell lung cancer (NSCLC). Methods: Tissue microarrays (n = 487) were used to immunohistochemically analyse expression of Maspin and TP53. Cytoplasmic and nuclear expression of Maspin was scored on the basis of the percentage of positive tumour cells. Univariate analysis of clinicopathological variables potentially affecting tumour-specific survival was performed. Results: Immunohistochemical Maspin expression (nuclear and cytoplasmic) was informative in 72.3% (352/487) of cases. Cytoplasmic and nuclear Maspin immunoreactivity in ⩾10% of tumour cells was detected in 37.8% (133/352) and 65.3% (230/352) of informative cases, respectively. Nuclear and cytoplasmic Maspin staining was observed more frequently in primary squamous cell carcinomas than in other lung cancer types. Only nuclear Maspin immunoreactivity was significantly associated with positive TP53 staining. Cytoplasmic or nuclear Maspin expression was not associated with tumour-specific survival. Conclusion: Maspin expression was found both in the nucleus and the cytoplasm of NSCLC, more frequently in squamous cell carcinomas. However, no association with tumour-specific survival could be demonstrated.

Takayasu disease with predominant pulmonary involvement

We report a case of Takayasu’s arteritis with predominant pulmonary involvement, which led eventually to complete obliteration of the right pulmonary artery. Subsequently, cavitation and chronic inflammation developed in the nonperfused right lung. A right pneumonectomy was performed to control the infectious process, leading to functional improvement and better control of the underlying immunologic disorder.

DNA aneuploidy, S-phase fraction, nuclear p53 positivity, and survival in non-small-cell lung carcinoma.

Abstract Inactivation of the p53 gene plays a key role in tumour biology, probably through a disturbed cell cycle control and an increased genetic instability in p53-inactivated tumours. To learn more about the relationship between p53 alterations, proliferation and genetic instability (DNA aneuploidy) in lung cancer patients, specimens of 220 surgically resected lung carcinomas with clinical follow-up information were examined by immunohistochemistry (p53; CM1) and flow cytometry. Nuclear p53 positivity – found in 49.5% of the tumours – was associated with both high S-phase fraction (SPF) and DNA ploidy aberrations. SPF was higher in p53-positive tumours (15.9 ± 10.2) than in p53-negative tumours (10.3 ± 8.7; P = 0.03). The rate of p53 positivity was higher in 101 DNA-aneuploid and DNA-multiploid tumours (55%) than in 27 diploid and peridiploid carcinomas (33%; P = 0.0512). These results are consistent with an in vivo role of p53 inactivation for increased proliferative activity and development of genomic instability in lung cancer. There was no association between SPF and prognosis. Although prognosis was worse in DNA-aneuploid and multiploid tumours than in diploid, peridiploid and tetraploid carcinomas (P = 0.029), DNA ploidy was not an independent predictor of poor prognosis in multivariate analysis. These data show that DNA-flow cytometry has little prognostic value for patients with resected non-small-cell lung carcinoma.

Cell cultures from cryopreserved human lung tissue.

To assess gene induction in primary human fibroblasts, we have developed a method for cryopreservation of lung biopsies in liquid nitrogen. Fresh biopsies (n = 10) were chopped into 5 x 5 mm pieces and transferred into an ice-cold freezing medium. Biopsies were kept on ice for 15 min, followed by further cooling of the tissue to -70 degrees C. With this method, lung biopsies were preserved for more than 1 year before they were used for generating cell cultures. There was no significant difference in the biological responsiveness of fibroblasts generated from immediately cultured lung biopsies compared with those from cryopreserved tissue. The doubling rate of fibroblasts from fresh tissue was 23.6 +/- 1.1 hr; compared to 23.5 +/- 1.5 hr for fibroblasts generated from cryopreserved tissue. PDGF-BB enhanced de novo synthesis of DNA 100 times, in both the immediately cultured fibroblasts and those generated from cryopreserved biopsies. Macrophages, dendritic cells and endothelial cells could also be recovered from cryopreserved lung tissue. This method permits long-term storage of lung tissue and the possibility of establishing primary cell lines from the same tissue at later times without appreciable changes in their cellular biological characteristics.

Granulomatous Pneumocystis carinii pneumonia in Wegener′s granulomatosis

This study reports on a first case of granulomatous Pneumocystis carinii pneumonia (PCP) in a human immunodeficiency virus-negative patient with antineutrophil cytoplasmic antibody-positive Wegeners granulomatosis whilst receiving immunosuppressive treatment. The patient presented with diffuse alveolar haemorrhage, pauci-immune rapid progressive glomerulonephritis and leukocytoclastic vasculitis of the skin. Granulomatous Pneumocystis carinii pneumonia developed under immunosuppressive treatment with cyclophosphamide and prednisone. At the time Pneumocystis carinii pneumonia developed, there was a marked lymphopenia with a very low CD8+ cell count in the blood. Grocott staining in bronchoalveolar lavage fluid revealed no Pneumocystis carinii. The diagnosis was made via a video-assisted thoracoscopic lung biopsy which showed granulomas containing high numbers of Pneumocystis carinii cysts.