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Walter Weder

Publications and source records attributed to Walter Weder.

At least 19 recordsLinked to original sources
PubMed2006

Tissue-engineered trachea: History, problems and the future.

This review tries to summarize the efforts over the past 20 years to construct a tissue-engineered trachea. After illustrating the main technical bottlenecks faced nowadays, we discuss what might be the solutions to these bottlenecks. You may find out why the focus in this research field shifts dramatically from the construction of a tubular cartilage tissue to reepithelialization and revascularization of the prosthesis. In the end we propose a novel concept of 'in vivo bioreactor', defined as the design of a perfusion system inside the scaffold, and explain its potential application in the construction of a tissue-engineered trachea.

Animals↗
PubMed2006

ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer.

The European Society of Thoracic Surgeons (ESTS) organized a workshop dealing with lymph node staging in non-small cell lung cancer. The objective of this workshop was to develop guidelines for definitions and the surgical procedures of intraoperative lymph node staging, and the pathologic evaluation of resected lymph nodes in patients with non-small cell lung cancer (NSCLC). Relevant peer-reviewed publications on the subjects, the experience of the participants, and the opinion of the ESTS members contributing on line, were used to reach a consensus. Systematic nodal dissection is recommended in all cases to ensure complete resection. Lobe-specific systematic nodal dissection is acceptable for peripheral squamous T1 tumors, if hilar and interlobar nodes are negative on frozen section studies; it implies removal of, at least, three hilar and interlobar nodes and three mediastinal nodes from three stations in which the subcarinal is always included. Selected lymph node biopsies and sampling are justified to prove nodal involvement when resection is not possible. Pathologic evaluation includes all lymph nodes resected separately and those remaining in the lung specimen. Sections are done at the site of gross abnormalities. If macroscopic inspection does not detect any abnormal site, 2-mm slices of the nodes in the longitudinal plane are recommended. Routine search for micrometastases or isolated tumor cells in hematoxylin-eosin negative nodes would be desirable. Randomized controlled trials to evaluate adjuvant therapies for patients with these conditions are recommended. The adherence to these guidelines will standardize the intraoperative lymph node staging and pathologic evaluation, and improve pathologic staging, which will help decide on the best adjuvant therapy.

Biopsy↗
PubMed2006

Human monoclonal antibodies to domain C of tenascin-C selectively target solid tumors in vivo.

We had previously reported that splice isoforms of tenascin-C containing the extra-domain C are virtually absent in normal adult tissues but are highly abundant in high-grade astrocytomas, with a prominent peri-vascular pattern of expression. We now report that the extra-domain C of tenascin-C is strongly expressed in the majority of lung cancers, with a vascular and stromal pattern of expression. Using antibody phage technology, we have generated a human monoclonal antibody (G11), with a dissociation constant K(D) = 4.2 nM for the human domain C. The G11 antibody, expressed in scFv and in mini-antibody (SIP) format, as well as a scFv-interleukin-2 fusion protein, was then characterized in quantitative biodistribution studies using mice grafted subcutaneously with U87 gliomas, revealing a selective tumor uptake, with tumor/blood ratios up to 11.8:1 at 24 h. A radioiodinated preparation of SIP(G11) was also investigated in a double tracer study using an orthotopic rat glioma model, confirming the antibody's ability to preferentially localize at the tumor site, with tumor/brain ratios superior to the ones observed with (18)F-fluorodeoxyglucose. These tumor-targeting properties, together with the strong immunohistochemical staining of human tumor sections, indicate that the G11 antibody may be used as a portable targeting moiety for the selective delivery of imaging and therapeutic agents to gliomas and lung tumors.

Amino Acid Sequence↗
PubMed2006

CD26/dipeptidylpeptidase IV-targeted therapy of acute lung rejection in rats.

BACKGROUND: CD26 is a T-cell co-stimulator, and interacts with adenosine deaminase, human immunodeficiency virus (HIV) Tat-1 protein and extracellular matrix. It possesses dipeptidylpeptidase IV (DPP IV) catalytic activity, which is linked to its co-stimulatory efficacy. We investigated the effect of specific DPP IV systemic activity inhibition on acute pulmonary rejection. METHODS: Rat single-lung transplantation (Tx) was performed (LBNF1/LEW donor/recipient) in two groups (n = 12). Group I (n = 6) received daily treatment with a Pro-Pro-diphenylphosphonate derivative (AB197), and Group II served as an untreated control. At Day 5 post-Tx, ventilatory parameters, cytotoxicity and mixed lymphocyte reaction were analyzed and staining for ISHLT rejection grade and proliferating cell nuclear antigen (PCNA) was performed. RESULTS: Treatment with AB192 abrogated acute rejection and preserved pulmonary function up to Day 5 post-Tx for PO2 (Group II: 24.9 +/- 6.9 mm Hg; Group I: 149.5 +/- 24.3 mm Hg; p < 0.001), PCO2 (Group II: 53.3 +/- 13.6 mm Hg; Group I: 39.0 +/- 9.8 mm Hg; p < 0.05) and peak airway pressure (Group II: 50.7 +/- 17.2 mm Hg; Group I: 20.2 +/- 10.0 mm Hg; p < 0.01). Controls showed moderate/severe rejection (ISHLT Grade A2 or 3), grafts from inhibited hosts revealed no/mild rejection (Grade A0 to 2: Group II: 2.8 +/- 0.3; Group I: 1.25 +/- 1.0; p < 0.005). Proliferating cell nuclear antigen (PCNA) staining of rejection-associated cellular infiltrates showed a significant reduction in positivity in perivascular infiltrates (34 +/- 11.5%; p < 0.05) and bronchial surface epithelium (31.7 +/- 10.6%; p < 0.05) in Group I vs Group II (55.9 +/- 8.4% and 57.2 +/- 4.5%). CONCLUSIONS: Irreversible enzymatic inhibition of DPP IV has been shown to abrogate acute pulmonary rejection, maintain pulmonary function, and preserve histomorphologic architecture. These results extend earlier findings and illustrate the role of CD26/DPP IV in alloantigen-mediated immune responses.

Animals↗
PubMed2006

Thoracoscopic treatment of pulmonary sequestration.

OBJECTIVE: Pulmonary sequestration is a rare congenital malformation and may be the cause of recurrent infections or hemoptysis. It has been shown in case reports that resection by video-assisted thoracic surgery (VATS) is feasible despite the possible technical difficulties due to inflammatory changes, but its role has not been evaluated yet in a larger series of consecutively treated patients. METHODS: Retrospective analysis of all consecutively thoracoscopically treated patients (between January 1991 and January 2005) with pulmonary sequestration in a single center. We included 14 patients in the study who fulfilled the criteria; seven were women. Median age was 33 years (20-64 years). The following data were analyzed for all patients: major symptoms, diagnostic procedures, treatment, and outcome. Operative parameters and findings including operating time, blood loss, anatomical location of the sequestration, and feeding vessels were evaluated. RESULTS: Leading symptoms were recurrent infections (10), hemoptysis (3), and chest discomfort (1). The diagnosis was made by CT scan. Additionally, an arteriography or an angio-MRI was done in three patients and one patient, respectively. Thirteen intralobar (all lower lobes, eight on the right) and one left-sided extralobar pulmonary sequestration were resected. We performed eight lobectomies, four atypical segmentectomies, one extralobar resection, and one occlusion of the aberrant artery. One case had to be converted to a thoracotomy due to bleeding from the aberrant artery. There was no mortality. Complications included pneumonia in three cases, one hemothorax, one pneumothorax after removing the chest tube, and one wound infection. All were treated conservatively. CONCLUSION: Thoracoscopic treatment of pulmonary sequestration is feasible in experienced hands. The aberrant systemic artery can be freed and dissected safely despite the frequently occurring inflammatory changes. Conversion rate to thoracotomy is low.

Adult↗
PubMed2006

Incidence and management of complications after neoadjuvant chemotherapy followed by extrapleural pneumonectomy for malignant pleural mesothelioma.

OBJECTIVE: To investigate the incidence and management of postoperative complications after neoadjuvant chemotherapy followed by extrapleural pneumonectomy for malignant pleural mesothelioma. METHODS: Patients with histologically proven mesothelioma of clinical stages T1-3, N0-2, M0 and considered to be completely resectable received neoadjuvant chemotherapy (cisplatin+gemcitabine or cisplatin+pemetrexed) followed by extrapleural pneumonectomy and postoperative radiotherapy. The incidence and management of postoperative complications in general and of bronchopleural fistula and postpneumonectomy-empyema in particular were analyzed. Univariate analysis was performed to identify prognostic factors [sex, age, side of operation, weight loss, smoking, chemotherapy, EORTC-score (European Organization for Research and Treatment of Cancer-classification) and duration of operation]. RESULTS: Between 1st May 1999 and 15th August 2005, 63 patients underwent complete extrapleural pneumonectomy after neoadjuvant chemotherapy. Postoperative complications were observed in 39 cases (62%) and 2 patients died within 30 days (3.2%). Postpneumonectomy-empyema occurred in 15.8% of the patients (n=10), six with a bronchopleural fistula on the right side. All empyemas were treated successfully. Five patients developed chylothorax (7.9%) and four patients had complications due to a patch failure: cardiac herniation (n=2), restriction of cardiac output (n=1) or gastric herniation (n=1). Patients with higher EORTC-score presented significantly more postoperative complications (p=0.03). A longer duration of surgery tended to be associated with a higher incidence of postoperative complications, especially of empyemas. CONCLUSIONS: Extrapleural pneumonectomy after neoadjuvant chemotherapy can be performed with mortality rates comparable to standard pneumonectomies. Complications are frequent but can be successfully managed; the EORTC-score seems to be a predictor for postoperative complications.

Adult↗
PubMed2006

Sildenafil extends survival and graft function in a large animal lung transplantation model.

OBJECTIVE: Restoring intracellular cGMP and inducing NO-synthesis attenuates ischemia-associated early pulmonary allograft dysfunction. Phosphodiesterase-5 (PDE), predominantly expressed in lung tissue, plays a pivotal role in modulating the cGMP/NO-synthase pathway in endothelial and epithelial cells. In this study, we evaluate the effect of employing sildenafil (Viagra), a specific inhibitor of PDE-5, to counteract ischemia/reperfusion (I/R) injury in a single lung transplantation model of extended ischemia. METHODS: Donor animals (weight matched outbred pigs, 28-35 kg) in the treatment group (I) (n=5) were injected with 0.7 mg sildenafil/kg into the pulmonary artery (PA) prior to inflow occlusion. For perfusion, Perfadex, containing 0.7 mg sildenafil/l was used, and the graft stored at 1 degrees C in the perfusion solution. After 24h ischemia, unilateral left lung transplantation was performed. Starting at reperfusion, group I received continuous sildenafil (0.7 mg sildenafil/kg), over 6h. Except for the sildenafil application, the control group (II) (n=4) was treated identically (PGE1 was injected into the PA). One hour after reperfusion, the right main bronchus (MB) and right PA were occluded. Over the next 5h, cardiopulmonary parameters (systemic atrial, PA, central venous, left atrial pressure, pCO(2), pO(2)) were measured, including extravascular lung water (EVLW). Thiobarbituric acid-reactive substance assay (TBARS) and myeloperoxidase (MPO) analysis from lung tissue were run. RESULTS: All recipients of group I survived the 6-h reperfusion period; in contrast, all control animals died within 1-2h after occlusion of the right side. In comparison to a marked rise in pulmonary vascular resistance (PVR) in group II (>1000 dynescm(-5)), PVR in group I remained stable, moderately elevated from baseline (baseline: 150-180 dynescm(-5) vs endpoint: 1000 dynescm(-5)). EVLW in group I did not increase during reperfusion (baseline: 6.75+/-1.4 mg/kg vs endpoint: 6.7+/-1.0mg/kg), in contrast to group II, where pulmonary edema at 2-h reperfusion preceded terminal graft failure (group I: 9.7+/-0.1mg/kg vs group II: 6.48+/-1.8 mg/kg). Tissue reactive free radicals at endpoint measurement in group I did not differ significantly from native tissue. Yet, when compared to specimen taken from group II at time of terminal graft failure, a significant increase in free radicals was noted (group I: 13.8+/-1.6 pmol/g vs group II: 18.5+/-3.0 pmol/g, p<0.05). CONCLUSION: Sildenafil treatment prevents terminal early graft failure, allowing lung transplantation after 24-h ischemia time. Reperfusion edema was strikingly diminished, preserving pulmonary structural and functional integrity while prolonging graft ischemia time. Employing the established PDE-5 inhibitor sildenafil during lung perfusion, storage, and implantation, ischemic tolerance may be extended and early graft function improved.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2006

Lung-volume reduction surgery as an alternative or bridging procedure to lung transplantation.

BACKGROUND: In this study, we prospectively analyzed the functional outcome and the survival after lung-volume reduction surgery (LVRS) in patients with end-stage emphysema who were initially potential candidates for lung transplantation (LTX), and investigated the impact of LVRS on posttransplant course in patients who underwent LTX after LVRS. METHODS: Of the 216 patients who underwent LVRS between 1994 and 2005, 58 were potential candidates for LTX at the time of LVRS (age 65 years or younger, forced expiratory volume in 1 second 25% of predicted or less; LVRS/LTX group). Lung-volume reduction surgery was performed by means of video-assisted, bilateral stapled resection of target areas. During the same period, 31 patients underwent primary LTX for end-stage emphysema (LTX group). Spirometry, plethysmography, carbon monoxide diffusing capacity, 6-minute walking distance, and dyspnea score were assessed preoperatively and at predetermined times after operation. Survival analysis was performed by use of the Kaplan-Meier method. RESULTS: All the functional variables significantly improved after LVRS and peaked within the first year. Subjective improvement was observed for up to 5 years after LVRS, and 53% (31 of 58) of the patients were still alive and had not undergone transplantation after a median follow-up of 44 months. Fourteen percent (8 of 58) of the patients underwent secondary LTX because of progressive worsening of the respiratory function after a median bridging time between LVRS and LTX of 33 months. Postoperative recovery after transplantation and median survival time were comparable between the 8 patients of the LVRS/LTX group and the 31 patients of the LTX group (96.5 months versus 118.5 months, p = 0.9). CONCLUSIONS: Lung-volume reduction surgery can significantly improve symptoms and lung function in selected patients who are initially potential candidates for LTX. Lung-volume reduction surgery can allow the postponement of LTX for up to 4 to 5 years and does not impair the chances for a subsequent successful LTX.

Adult↗
PubMed2006

The BODE index after lung volume reduction surgery correlates with survival.

STUDY OBJECTIVE: A recently introduced, multidimensional index called BODE (body mass index [BMI], degree of airflow obstruction assessed by spirometry, grade of dyspnea, and exercise capacity), quantified by 6-min walking distance (6MWD), has excellent predictive power with respect to outcome in COPD. We investigated whether the BODE index is able to predict survival after lung volume reduction surgery (LVRS). DESIGN: Retrospective study. SETTING: Tertiary university hospital. PATIENTS: One hundred eight-six COPD patients (76 women) with severe emphysema (mean +/- SD age, 64 +/- 8 years; mean FEV(1), 28 +/- 8% of predicted). INTERVENTION: Bilateral thoracoscopic LVRS. MEASUREMENTS AND RESULTS: BMI, pulmonary function, 6MWD, and the modified Medical Research Council dyspnea score were assessed before and 3 months after LVRS, and the BODE index was calculated. The patients were followed up with respect to survival for a median time of 40 months (range, 3 to 116 months) after surgery. The mean BODE index decreased from 7.2 +/- 1.6 preoperatively to 4.0 +/- 2.0 at 3 months after LVRS (p < 0.001). The postoperative but not the preoperative BODE correlated with survival, although preoperative patient characteristics were comparable between short-term (< 5 years) and long-term (> 5 years) survivors. A decrease to a lower BODE score class was associated with a reduced mortality (hazard ratio, 0.497, 95% confidence interval, 0.375 to 0.659; p < 0.001). The C statistic for the ability of the BODE index to predict the risk of death was larger (0.74) than that for the FEV(1) (0.63), the degree of dyspnea (0.64), or the 6MWD (0.62). CONCLUSIONS: The postoperative BODE index is a powerful predictor of survival in COPD patients after LVRS.

Aged↗
PubMed2005

Etiology of solitary extrapulmonary positron emission tomography and computed tomography findings in patients with lung cancer.

PURPOSE: The aim of this prospective study was to assess the incidence and the nature of solitary extrapulmonary [18F] fluorodeoxyglucose (FDG) accumulations in patients with non-small-cell lung cancer (NSCLC) staged with integrated positron emission tomography and computed tomography (PET/CT) and to evaluate the impact on management. PATIENTS AND METHODS: A total of 350 patients with NSCLC underwent whole-body PET/CT imaging. All solitary extrapulmonary FDG accumulations were evaluated by histopathology, further imaging, or clinical follow-up. RESULTS: PET/CT imaging revealed extrapulmonary lesions in 110 patients. In 72 patients (21%), solitary lesions were present. A diagnosis was obtained in 69 of these patients, including 37 (54%) with solitary metastases and 32 (46%) with lesions unrelated to the lung primary. Histopathologic examinations of these 32 lesions revealed a second clinically unsuspected malignancy or a recurrence of a previous diagnosed carcinoma in six patients (19%) and a benign tumor or inflammatory lesion in 26 patients (81%). The six malignancies consisted of carcinoma of the breast in two patients, and carcinoma of the orbit, esophagus, prostate, and non-Hodgkin's lymphoma in one patient each. Benign tumors and inflammatory lesions included eight colon adenomas, four Warthin's tumors, one granuloma of the lower jaw, one adenoma of the thyroid gland, one compensatory muscle activity due to vocal chord palsy, two occurrences of arthritis, three occurrences of reflux esophagitis, two occurrences of pancreatitis, two occurrences of diverticulitis, one hemorrhoidal inflammation, and one rib fracture. CONCLUSION: Solitary extrapulmonary FDG accumulations in patients with newly diagnosed lung cancer should be analyzed critically for correct staging and optimal therapy, given that up to half of the lesions may represent unrelated malignancies or benign disease.

Adult↗
PubMed2005

Extended donor lungs: eleven years experience in a consecutive series.

OBJECTIVE: The aim of this study was to delineate the profile of extended donor lungs in comparison to ideal donor lungs and to analyse their outcome. Particular attention was given to donor lungs with a low PaO(2) (<250mmHg) before harvesting or with multiple extended criteria. METHODS: Between 1993 and 2003, 148 patients (79 women, 69 men, mean age 39.9 years) underwent lung transplantation. Indications were cystic fibrosis in 35.8%, emphysema in 26.4%, pulmonary fibrosis in 12.2%, pulmonary hypertension in 9.5%, and others in 16.1%. Donor data and recipients medical files were reviewed. Criteria for donor lungs were considered extended if one or more of the following criteria were met: age >55 years, smoking >20 pack-years, PaO(2) before harvesting <300mmHg, pathologic chest X-ray, and purulent secretion at bronchoscopy. A comparison between recipients from ideal and from extended donor lungs was performed with respect to the median duration of mechanical ventilation, the median length of stay at the intensive care unit, postoperative complications, the 30-day and the 1-year survival, and the 6-month follow-up spirometry. RESULTS: Sixty-three (42.6%) donor lungs were considered extended and 20 (31.7%) met more than one criteria. Outcome comparison between recipients from ideal (I) and extended (II) donor lungs did not statistically differ in postoperative complications (18.8% (I) vs. 26.9% (II), P=0.32), mean duration of mechanical ventilation (d) (4.4+/-2.7 (I) vs. 2.6+/-2.1 (II), P=0.2), mean length of stay at the ICU (d) (11.5+/-8.8 (I) vs. 9.2+/-6.9 (II), P=0.4), 6-month pulmonary function (FEV1=83+/-23% of the predicted value (I) vs. 82+/-18% (II), P=0.81), 30-day survival (90.6% (I) vs. 93.7% (II), P=0.56), 1-year survival (83.5% (I) vs. 81% (II), P=0.83). Thirty-day survival was also comparable even in recipients from donor lungs with PaO(2)<250mmHg (n=8) (90.6% (I) vs. 87.5%, P=0.57). The number of extended criteria had no impact on the outcome. The combination of PaO(2)<300mmHg with purulent secretion at bronchoscopy seemed to influence the early outcome of recipients from extended donor lungs negatively. CONCLUSIONS: Our results suggest that the use of selected extended donor lungs does not compromise the outcome after transplantation. PaO(2) <250mmHg before harvesting of the lungs is not an absolute contra-indication for transplantation.

Adult↗
PubMed2005

Patterns of changes in arterial PO2 during one-lung ventilation: a comparison between patients with severe pulmonary emphysema and patients with preserved lung function.

OBJECTIVES: One-lung ventilation (OLV) during thoracoscopic surgery is associated with a significant decline in arterial PO(2) in patients with severe pulmonary emphysema and patients with preserved lung function. The authors hypothesized that patterns of arterial PO(2) changes are different in these 2 patient groups. DESIGN: Prospective nonrandomized study. SETTING: University hospital. PARTICIPANTS: Twenty-five patients undergoing thoracoscopic interventions: 16 with severe pulmonary emphysema and 9 patients without emphysema. INTERVENTIONS: Continuous arterial blood gas measurement (PaO(2), PaCO(2), pHa) during OLV of the left lung in left lateral position using the Paratrend 7 blood gas monitoring system (PT7; Pfizer Hospital Products Group, High Wycombe, UK). MAIN RESULTS: The decrease of PaO(2) was delayed in patients with severe emphysema. Steady state (defined as DeltaPaO(2) <7.5 mmHg/min) was reached after 18 +/- 4 minutes compared with 11 +/- 3 minutes (mean +/- standard deviation) in patients with normal lung function (p = 0.0002). PaO(2) values at steady state were comparable (p = 0.49); the pattern of changes in PaO(2) for the first 15 minutes of left-sided OLV was significantly different between the groups (p = 0.0004). The difference of predicted versus measured PaO(2) at steady state was -48 +/- 160 mmHg for patients with emphysema and -51 +/- 60 mmHg for patients with normal lung function (p = 0.019). CONCLUSION: During OLV, oxygenation is better preserved for a longer period of time in patients with severe pulmonary emphysema as compared with patients with normal lung function. In contrast to patients without emphysema, prediction of oxygenation during OLV for the individual patient with emphysema is unreliable because of large interindividual differences.

Adolescent↗
PubMed2005

Inflammation patterns in allogeneic and autologous airway tissue of lung transplant recipients.

Inflammatory injuries directed toward airway structures play a key role in lung allograft rejection. However, data relating to the inflammation patterns of large airways are scarce and, in particular, the relation between autologous and allogeneic parts is unknown. For the first time, in this study, simultaneously collected endobronchial biopsies from the main (autologous) and upper lobe (allogeneic) carina of lung transplant recipients were assessed immunohistologically. A total of 27 pairs of EBBs were taken. Twelve endoscopies documented acute rejection and four examinations of patients with BOS were performed. Patients with acute rejection had more CD8-positive cells in the allogeneic parts compared with patients without acute rejection. Patients with BOS had more CD4- and CD45-positive cells in the autologous airways than stable patients. We conclude that distinct inflammatory changes do occur in large airways of lung transplant recipients and are not limited to the donor parts of airways.

Adult↗
PubMed2005

Iron accumulation in lung allografts is associated with acute rejection but not with adverse outcome.

BACKGROUND: Iron content in lung allografts is increased after transplantation. It was hypothesized that this may lead to fibrosis and posttransplant bronchiolitis obliterans syndrome (BOS). METHODS: In a prospective study, we evaluated 399 BAL fluid (BALF) and transbronchial lung biopsy samples obtained concurrently from 72 consecutive lung transplant recipients. RESULTS: The hemosiderin scores (HSs) of the BALF samples increased steadily during the postoperative period (p < 0.001). Patients with at least one acute rejection episode (AR) grade > or = A2 event had higher mean HSs, the difference being significant after the second (p < 0.008) and the sixth postoperative months (p < 0.05). The HS correlated with the number of ARs (p < 0.004), and it significantly increased after the first AR (p < 0.04). Except for oral anticoagulation, no other risk factors for elevated iron content were found. There was no correlation between HS or number of ARs and the development of BOS or survival, respectively. CONCLUSIONS: Progressive iron accumulation in lung allografts seems to be caused mainly by an AR, possibly due to perivascular leakage of erythrocytes. Neither increased HS nor the frequency of ARs were risk factors for subsequent development of BOS. Early detection and treatment of ARs might uncouple their association with BOS.

Acute Disease↗
PubMed2004

Circulating deoxyribonucleic Acid as prognostic marker in non-small-cell lung cancer patients undergoing chemotherapy.

PURPOSE: Circulating cell-free DNA is present in increased amounts in the blood of cancer patients, but the clinical relevance of this phenomenon remains unclear. We conducted a clinical study to assess the value of circulating DNA as a prognostic marker in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A standard protocol for the quantification of circulating DNA by real-time polymerase chain reaction was set up and validated at two oncology units. One hundred eighty-five informed patients with NSCLC and 46 healthy controls were included in the study. DNA concentrations were determined in paired plasma and serum samples and analyzed for a relationship with leukocyte counts and lactate dehydrogenase (LDH) levels. DNA concentrations in healthy controls and in patients were compared, and cutoff levels for plasma and serum DNA were determined. Patient survival was analyzed relative to baseline DNA concentrations, and the relationship between tumor responses and changes in DNA concentrations was assessed in patients receiving chemotherapy. RESULTS: We found a significant correlation between increased plasma DNA concentrations and elevated LDH levels (P = .009), advanced tumor stage (P < .003), and poor survival (P < .001). Tumor progression after chemotherapy was significantly (P = .006) associated with increasing plasma DNA concentrations. Serum DNA concentrations strongly correlated (P < .001) with leukocyte counts. CONCLUSION: Our data demonstrate that quantification of plasma DNA is an accurate technique amenable to standardization, which might complement current methods for the prediction of patient survival. This approach might be considered for evaluation in large prospective studies.

Adult↗
PubMed2004

Neoadjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma.

PURPOSE: To investigate neoadjuvant chemotherapy with cisplatin and gemcitabine followed by extrapleural pneumonectomy with or without radiation therapy in patients with potentially resectable malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Eligible patients had MPM with clinical stage T1-3, N0-2, M0 disease considered to be completely resectable and a WHO performance status of 0 to 2. Neoadjuvant chemotherapy consisted of three cycles of cisplatin 80 mg/m2 on day 1 and gemcitabine 1,000 mg/m2 on days 1, 8, and 15, given every 28 days. Surgery had to consist of a complete extrapleural pneumonectomy, including resection of pericardium and diaphragm. Postoperative radiotherapy was to be considered for all patients. RESULTS: Nineteen patients with MPM were included in this pilot study. According to the European Organization for Research and Treatment of Cancer prognostic score, two patients were in the good prognosis group, and 17 patients were in the poor prognosis group. The response rate to neoadjuvant chemotherapy was 32%. The major toxicity was thrombocytopenia. Extrapleural pneumonectomy was performed in 16 patients with no perioperative mortality. Major surgical complications occurred in six patients, and all were treated successfully. Thirteen patients received postoperative radiotherapy. The median survival time was 23 months. Two patients remain alive and free of disease 41 and 38 months after initiation of therapy. CONCLUSION: For patients with potentially operable MPM, the availability of active and well-tolerated chemotherapy regimens, the fact that extrapleural pneumonectomy can be safely performed after neoadjuvant chemotherapy in an experienced center, and the promising results regarding survival in our pilot study warrant further investigation of the role of neoadjuvant chemotherapy in a multimodality strategy.

Aged↗