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Biomedical subjects

Walter Weder

Publications and source records attributed to Walter Weder.

17 recordsLinked to original sources
PubMed2003

Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography.

BACKGROUND: We compared the diagnostic accuracy of integrated positron-emission tomography (PET) and computed tomography (CT) with that of CT alone, that of PET alone, and that of conventional visual correlation of PET and CT in determining the stage of disease in non-small-cell lung cancer. METHODS: In a prospective study, integrated PET-CT was performed in 50 patients with proven or suspected non-small-cell lung cancer. CT and PET alone, visually correlated PET and CT, and integrated PET-CT were evaluated separately, and a tumor-node-metastasis (TNM) stage was assigned on the basis of image analysis. Nodal stations were identified according to the mapping system of the American Thoracic Society. The standard of reference was histopathological assessment of tumor stage and node stage. Extrathoracic metastases were confirmed histopathologically or by at least one other imaging method. A paired sign test was used to compare integrated PET-CT with the other imaging methods. RESULTS: Integrated PET-CT provided additional information in 20 of 49 patients (41 percent), beyond that provided by conventional visual correlation of PET and CT. Integrated PET-CT had better diagnostic accuracy than the other imaging methods. Tumor staging was significantly more accurate with integrated PET-CT than with CT alone (P=0.001), PET alone (P<0.001), or visual correlation of PET and CT (P=0.013); node staging was also significantly more accurate with integrated PET-CT than with PET alone (P=0.013). In metastasis staging, integrated PET-CT increased the diagnostic certainty in two of eight patients. CONCLUSIONS: Integrated PET-CT improves the diagnostic accuracy of the staging of non-small-cell lung cancer.

Aged↗
PubMed2003

Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial.

PURPOSE: A multicenter, phase II trial investigated the efficacy and toxicity of neoadjuvant docetaxel-cisplatin in locally advanced non-small-cell lung cancer (NSCLC) and examined prognostic factors for patients not benefiting from surgery. PATIENTS AND METHODS: Ninety patients with previously untreated, potentially operable stage IIIA (mediastinoscopically pN2) NSCLC received three cycles of docetaxel 85 mg/m2 day 1 plus cisplatin 40 mg/m2 days 1 and 2, with subsequent surgical resection. RESULTS: Administered dose-intensities were docetaxel 85 mg/m2/3 weeks (range, 53 to 96) and cisplatin 95 mg/m2/3 weeks (range, 0 to 104). The 265 cycles were well tolerated, and the overall response rate was 66% (95% confidence interval [CI], 55% to 75%). Seventy-five patients underwent tumor resection with positive resection margin and involvement of the uppermost mediastinal lymph node in 16% and 35% of patients, respectively (perioperative mortality, 3%; morbidity, 17%). Pathologic complete response occurred in 19% of patients with tumor resection. In patients with tumor resection, downstaging to N0-1 at surgery was prognostic and significantly prolonged event-free survival (EFS) and overall survival (OS; P =.0001). At median follow-up of 32 months, the median EFS and OS were 14.8 months (range, 2.4 to 53.4) and 33 months (range, 2.4 to 53.4), respectively. Local relapse occurred in 27% of patients with tumor resection, with distant metastases in 37%. Multivariate analyses identified mediastinal clearance (hazard ratio, 0.22; P =.0003) and complete resection (hazard ratio, 0.26; P =.0006) as strongly prognostic for increased survival. CONCLUSION: Neoadjuvant docetaxel-cisplatin is effective and tolerable in stage IIIA pN2 NSCLC. Resection is recommended only for patients with mediastinal downstaging after chemotherapy.

Adult↗
PubMed2003

Haemolytic anaemia after lung transplantation: an immune-mediated phenomenon?

BACKGROUND: Haemolytic anaemia is believed to occur only rarely after solid organ transplantation. During the past eight years we have repeatedly observed cases with otherwise unexplained haemolysis in our lung transplant recipients. METHODS: We conducted a retrospective cohort analysis to determine the prevalence of haemolytic anaemia after lung transplantation and to elucidate possible pathogenetic mechanisms. RESULTS: Whereas in three cases haemolytic anaemia was possibly caused by cytomegalovirus disease or drug-related side effects, sixteen out of the remaining 81 lung transplant recipients at risk (20 percent) developed otherwise unexplained haemolysis. All except one haemolytic episode occurred during the first postoperative year and their degree was mild to moderate in 14 cases. A case control study of these patients with those who did not develop haemolysis revealed that this phenomenon occurred less often in patients receiving immunosuppressive therapy with mycophenolate mofetil and prophylaxis for cytomegalovirus disease with intravenous immune globulin. CONCLUSIONS: We found a high prevalence of otherwise unexplained, mostly mild to moderate episodes of haemolytic anaemia after lung transplantation occurring predominantly during the first year after transplantation. The fact that this phenomenon was observed less often in patients receiving mycophenolate mofetil instead of azathioprine as well as in those receiving regular immune globulin prophylaxis with potentially immunomodulatory effects may indicate an immunemediated pathogenesis.

Adolescent↗
PubMed2003

The influence of the rapamycin-derivate SDZ RAD on the healing of airway anastomoses.

OBJECTIVE: Among the many immunosuppressive effects of SDZ RAD (40-0(2-hydroxyethyl)-rapamycin), a rapamycin derivative, is the inhibition of fibroblast proliferation. Since the long-term success of lung transplantation is limited by the development of bronchiolitis obliterans, a fibroblast-associated progressive luminal obstruction of the terminal bronchioli, the use of SDZ RAD as immunosuppressive in pulmonary graft recipients may counteract this process. However, reduction of fibroblast activity, posttransplant, may impair the healing of the bronchial anastomoses. MATERIALS AND METHODS: The cervical trachea in pigs was denuded, divided and re-anastomosed with Prolene 4-0 single stitches. Control animals (group 1, n=4) were without, and study animals (group 2, n=6) were with SDZ RAD therapy (1.25 mg/kg/day, p.o., 14 days). After 14 days, the pigs were sacrificed. The anastomoses were examined histologically, and breaking strength of tracheal strips of 5-mm width was measured. RESULTS: All animals survived without complications. Serum levels of SDZ RAD were 30.9+/-8.7 ng/ml (recommended level 20-40 ng/ml). All anastomoses healed macroscopically without difference between the two groups. Breaking strength was significantly lower in the treated animals (group 1 vs. group 2: 11.75+/-0.35 vs. 7.69+/-1.39 N, P=0.01). Histology did not show a significant change in histoarchitecture between the groups. CONCLUSIONS: Although SDZ RAD significantly reduced the breaking strength of the tracheal anastomosis, no obvious histological differences between treated and untreated animals could be detected. Since this model does not reflect the clinical situation, further investigations are necessary to reveal the effect of SDZ RAD on airway wound healing in concert with a contemporary clinically used multidrug immunosuppressive regimen in allograft recipients.

Anastomosis, Surgical↗
PubMed2003

Tissue engineered cartilage generated from human trachea using DegraPol scaffold.

OBJECTIVE: To date numerous attempts have been undertaken to conquer the challenging problem of reconstructing long segmental tracheal defects, as yet without lasting success. Recently, employing concepts of tissue engineering in animals, cartilage-like constructs were transplanted in vivo. However, both the feasibility of fabricating tracheal replacements and the use of human tracheal chondrocytes (HTC) for tissue engineering are still under investigation. In this study, we optimized isolation and cultivation techniques for human tracheal cartilage, assessing the feasibility of seeding these cells onto a novel, three-dimensional (3-D) polyester-urethane polymer (DegraPol). METHODS: Human tracheal cartilage was harvested from the trachea of lung donors, digested in 0.3% collagenase II, and the condrocytes serially passaged every 7-9 days. Cells were also cultivated over agar plate during the total 6-8 weeks expansion phase. Thereafter, chondrocytes were seeded onto DegraPol (pore sizes 150-200 microm) with a seeding density of 2.4 x 10(7)/ml, and chondrocyte-polymer constructs maintained during in vitro static culture. RESULTS: HTC displayed stable proliferation kinetics in monolayer culture with positive expression of collagen type II. Following polymer seeding, both cellular proliferation and extracellular matrix (ECM) production, as measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and glycosaminoglycan assays, continued over extended culture. Active growth of HTC on DegraPol was further demonstrated by Alcian blue staining, with the histomorphological appearance of the construct resembling that of native cartilage. Scanning electron microscopy showed chondrocyte growth and ECM synthesis both on the surface and inside the porous scaffold, with a dense cell layer on the surface of the scaffold and a lower cell distribution in the scaffold's interior. CONCLUSIONS: The harvested chondrocytes from human trachea cartilage expand well in vitro and possess the ability to form new cartilage-like tissue when seeded onto DegraPol matrix. However, improved culture conditions are needed to permit cellular growth throughout cell-polymer constructs.

Absorbable Implants↗
PubMed2002

News on lung volume reduction surgery.

Lung volume reduction surgery (LVRS) is an established therapeutic option for patients with advanced pulmonary emphysema after all conservative measures, including comprehensive pulmonary rehabilitation, have been exhausted. LVRS improves pulmonary function, shortness of breath, exercise capacity and hence quality of life in some 80% of cases for up to four years. Even patients with homogeneous types of pulmonary emphysema improve if those with extremely low FEV1 and/or very low diffusion capacity are excluded. At experienced centres perioperative mortality is less than 2% in appropriately selected patients, and current results suggest that the five-year survival in COPD patients may even be improved by this palliative surgical intervention. In patients under 60 LVRS may serve as a bridging procedure to lung transplantation. Bronchoscopic creation of extraanatomic bronchopulmonary passages--endoscopic LVRS--is a novel approach now under investigation.

Follow-Up Studies↗
PubMed2002

Tolerability, safety and efficacy of conventional amphotericin B administered by 24-hour infusion to lung transplant recipients.

BACKGROUND: Fungal infections cause serious morbidity and mortality in lung transplant recipients. Expensive lipid formulations of amphotericin B (AmB) are generally used because of fear of adverse effects due to concomitant cyclosporine A and other nephrotoxic drugs. However, a 24-hour dosing regimen of AmB may be well tolerated even in these patients. METHODS: In an open pilot study 6 out of 94 lung transplant recipients with invasive or semi-invasive bronchopulmonary azole-resistant candidal infections (3 paraspilosis, 2 glabrata, 1 krusei) were treated for 40 (17-73) days by 24-hour continuous infusions of AmB 1 mg/kg. Additionally, patients received at least 1000 ml of 0.9% saline intravenously per day. Beside cyclosporine A at serum trough levels of 240 (195-273) microg/l, five patients additionally received aminoglycosides for at least 2 weeks, and 4 were treated with ganciclovir. RESULTS: Calculated creatinine clearance decreased from 57 (43-73) ml/min to a nadir of 35 (28-39) and recovered to 52 (33-60) after cessation of therapy. One patient needed temporary haemofiltration for 7 days after 30 days of AmB, most probably because of the use of contrast media in conjunction with furosemide and hypovolaemia. Besides three episodes of mild hypokalaemia no other side effects attributable to AmB were recorded. While in one case an asymptomatic candidal colonisation persisted for 10 months, the other 5 were cured from their infection. CONCLUSION: These preliminary data show that conventional AmB administered by 24-hour infusion is well tolerated, safe, and efficacious in lung transplant recipients receiving cyclosporine A and other nephrotoxic substances.

Adolescent↗
PubMed2002

Melatonin attenuates posttransplant lung ischemia-reperfusion injury.

BACKGROUND: Melatonin, a pineal hormone, is a free radical scavenger and an antioxidant. The purpose of this study was to assess the protective effect of melatonin on posttransplant lung ischemia-reperfusion injury. METHODS: Rat single-lung transplantation was performed in two (n = 10) experimental groups after 18 hours of cold (4 degrees C) ischemia. Group I animals consisted of the ischemic control group. In group II, donor and recipient animals were treated with intraperitoneal injection of 10 mg/kg melatonin 10 minutes before harvest and reperfusion, respectively. After 2 hours of reperfusion, oxygenation, plasma, and bronchoalveolar lavage nitrite levels were measured. Lung tissue was assessed for thiobarbituric acid reactive substances and myeloperoxidase activity. Peak airway pressure was recorded throughout the reperfusion period. RESULTS: The melatonin-treated group showed significantly better oxygenation (321.8+/-33.8 mm Hg versus 86.1+/-17.4 mm Hg; p < 0.001), reduced lipid peroxidation (0.65+/-0.3 nmol/g versus 1.63+/-0.8 nmol/g; p = 0.032), and reduced myeloperoxidase activity (0.56+/-0.1 deltaOD x mg(-1) x min(-1) versus 1.01+/-0.2 deltaOD x mg(-1) x min(-1); p = 0.032). Bronchoalveolar lavage nitrite levels in the transplanted lungs were significantly lower in group II than in group I (0.34+/-0.06 micromol/L versus 1.65+/-0.6 micromol/L; p = 0.016). In group II significant reduction in peak airway pressure was noted compared with group I (p = 0.002). CONCLUSIONS: In this model, exogenously administered melatonin effectively protected lungs from reperfusion injury after prolonged ischemia.

Animals↗
PubMed2002

Prevention of recurrent empyema after pneumonectomy for chronic infection.

OBJECTIVES: Pneumonectomy in chronic pulmonary infection with empyema is associated with a high mortality rate and an increased risk of recurrent empyema. The surgical resection is technically demanding, and successful management continues to be a challenge. METHODS: We evaluated a concept which combines (pleuro-)pneumonectomy or completion pneumonectomy with surgical debridement of the pleural cavity and packing with povidine-iodine soaked dressings. The debridement and packing is repeated in the operating theater after 48 h until the chest cavity is macroscopically clean. Finally, the pleural space is obliterated with antibiotic solution. RESULTS: Between February 1997 and October 2000, 11 patients (average age of 59 years, ranging from 25 to 84) with destroyed lung caused by tuberculosis (six), aspergilloma (two), bronchiectasis (one), esophago-pleural fistula (one) or broncho-pleural fistula after lobectomy for bronchial carcinoma (one) and ongoing chronic infection with acute empyema (ten) (25-2500 days between first and definitive therapy) were treated. Pleural culture findings showed Aspergillus in four, Mycobacterium in two, Enterococcus in two, Candida in one and Staphylococcus in one, respectively. The mean number of interventions was 2.9 (2-4). The chest was definitively closed in all patients within 1 week. The mean hospitalization time was 19 days (9-31 days). In the follow-up (10-54 months), there was no recurrence of empyema. One patient (84 years) died at day 31, due to sepsis. CONCLUSIONS: Pneumonectomy combined with repeated surgical debridement and antimicrobial therapy enables the successful treatment of chronic pulmonary infection with empyema within a short time period.

Adult↗
PubMed2002

Osteoporosis before lung transplantation: association with low body mass index, but not with underlying disease.

Due to progress in lung transplantation, post-transplantation osteoporosis becomes an important problem. We determined bone mineral density (BMD) in 74 lung transplantation candidates, among them 24 patients with cysticfibrosis, 16 with chronic obstructive pulmonary disease, 14 with pulmonary fibrosis, and 11 with pulmonary hypertension. The mean T score (+/- SD) was -2.6 +/- 1.3 at femoral neck (FN), -2.2 +/- 1.6 at Ward's triangle (WT) and -2.3 +/- 1.5 at lumbar spine (LS). Osteoporosis was found in 61% of the patients at FN, 45% at WT and 50% at LS. Patients with different underlying lung diseases were similarly affected, not only those with cystic fibrosis but also others, including patients with pulmonary hypertension. No association was found between BMD and age, gender, menstrual condition in women and testosterone level in men. A negative correlation was found between chronic glucocorticoid use and T scores. Body mass index correlated positively (p < 0.01) with T scores at any site and the correlation was also significant for the 2 largest subgroups. Loss of lung function (FEV1) also was associated with lower T scores. No correlation was found between BMD and biochemical indices of bone turnover. Multivariate analysis revealed BMI and glucocorticoid use as independent risk factors. We conclude that osteoporosis is a very common condition in patients with end-stage pulmonary disease, independent of the underlying diagnosis. In view of additional bone loss under immunosuppressive treatment after lung transplantation, early diagnosis and prevention of osteoporosis in the pretransplant period should receive high priority.

Absorptiometry, Photon↗
PubMed2002

Patient selection for lung volume reduction surgery: is outcome predictable?

Patient selection for lung volume reduction surgery (LVRS) relies on sound physiologic concepts and experience from large case series. LVRS should be considered in severely symptomatic emphysema with marked airflow obstruction and hyperinflation despite optimal medical management, and in the absence of major comorbidities associated with excessive perioperative risks. Qualitative estimation of functional benefit from LVRS in suitable candidates has been based on functional criteria (e.g., high inspiratory conductance, high residual volume/total lung capacity ratio), on heterogeneity of emphysema assessed by computed tomography (CT) or perfusion scans, and on severity of emphysema assessed by CT or impaired diffusing capacity. Selection strategies relying on such criteria have provided favorable functional results at a low mortality, but further validation of potential outcome predictors in prospective trials is needed.

Adult↗
PubMed2002

Gain and subsequent loss of lung function after lung volume reduction surgery in cases of severe emphysema with different morphologic patterns.

OBJECTIVE: Surgical lung volume reduction improves lung function and dyspnea in advanced emphysema to a variable degree. Because long-term results with this procedure are scant, we prospectively investigated lung function over several years after lung volume reduction surgery with regard to emphysema morphology. METHODS: Bilateral video-assisted thoracoscopic lung volume reduction surgery was performed in severely symptomatic patients with marked hyperinflation caused by advanced nonbullous emphysema. Emphysema heterogeneity was visually graded on chest computed tomography. Symptoms and lung function were assessed before the operation and 3, 6, and then every 6 months after the operation. RESULTS: A total of 115 patients with a median forced expiratory volume in 1 second of 0.73 L (27% of predicted value) underwent lung volume reduction surgery. Follow-up extended over a median of 37 months. Median forced expiratory volume in 1 second significantly increased within 6 months after the operation by 37% in homogeneous (n = 27), by 38% in intermediately heterogeneous (n = 37), and by 63% in markedly heterogeneous emphysema (n = 51, P <.05 vs. other morphologies). Maximal forced expiratory volume in 1 second was reached within 6 months after lung volume reduction surgery and decreased in the first postoperative year by 0.16 L per year in homogeneous, by 0.19 L per year in intermediately heterogenous, and by 0.32 L per year in markedly heterogeneous emphysema (P <.01 vs. other morphologies). The decline in forced expiratory volume in 1 second over subsequent years decelerated according to an exponential decay and was similar for all morphologic types (median annual decrease of 0.09 L [9%]). CONCLUSIONS: Lung volume reduction surgery improves lung function in severe homogeneous and, to an even greater extent, heterogeneous emphysema. Forced expiratory volume in 1 second peaks within 6 months postoperatively. The subsequent decline is most rapid in the first year and slows down in succeeding years according to an exponential decay. Therefore, long-term functional results of lung volume reduction surgery may be more favorable than expected from linear extrapolations of short-term observations.

Adult↗
PubMed2002

Successful lung volume reduction surgery in a child with severe airflow obstruction and hyperinflation due to constrictive bronchiolitis.

Lung volume reduction surgery (LVRS) may improve pulmonary function in patients with severe emphysema. However, its effects in other types of obstructive lung disease are unknown. To delay the need for lung transplantation, we performed LVRS in a 14-year-old boy with disabling airflow obstruction/hyperinflation secondary to postinfectious bronchiolitis nonresponsive to medical therapy. Within days after LVRS, a major improvement of symptoms and lung function occurred and persisted for > 1 year. Our observation suggests that LVRS may be a novel treatment option in selected patients with extreme hyperinflation even if the underlying disease is not emphysema.

Adolescent↗
PubMedDate not supplied

Acute amiodarone-induced pulmonary toxicity following lung resection.

Amiodarone-induced pulmonary toxicity has been described mostly in patients receiving large doses of the drug over prolonged periods. In this report, we describe the early onset of acute pulmonary toxicity leading to acute respiratory distress syndrome after a short course of amiodarone treatment following middle-lobe non-small-cell lung cancer resection.

Aged↗