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Biomedical subjects

Peter Goldstraw

Publications and source records attributed to Peter Goldstraw.

At least 37 records · Page 2Linked to original sources
PubMed2005

Feasibility of the detection of the sentinel lymph node in peripheral non-small cell lung cancer with radio isotopic and blue dye techniques.

STUDY OBJECTIVES: The objective of this study was to evaluate the feasibility of the sentinel lymph node (SLN) biopsy in peripheral clinically stage I or II non-small cell lung cancer (NSCLC) using (99m)Tc colloid and a hand-held gamma detection probe, associated with a blue dye technique. DESIGN: Prospective study. SETTING: Royal Brompton Hospital, London, UK; and Hopital Nord, Saint Etienne, France. METHODS: After thoracotomy, a total of 2 mL patent blue dye mixed with 1,600 muCi (99m)Tc-albumin or (99m)Tc-colloid was injected into each quadrant of lung tissue immediately surrounding the tumor. Routine lymphadenectomy was carried out. The first lymph nodes to stain blue or radioactive, if any, were considered SLNs. RESULTS: Twenty-four patients were evaluated. We successfully identified 17 SLNs in 13 patients (detection rate, 54.2%). Mean time from injection to identification of SLNs was 18 min (range, 5 to 30 min). In nine cases, the SLN was blue and radioactive, in six cases only blue, and in two cases only radioactive. The pathologic status of the SLN reflected the pathologic status of other nodes of the routine lymphadenectomy except one case of false-negative SLN (14%). Four SLNs were in N2 stations (23.5%). CONCLUSIONS: The sentinel node mapping in NSCLC with blue dye and radioisotopic techniques is feasible, but the detection rate has to be improved. This technique is an accurate method of identifying the first node draining a tumor, although it is not yet sufficiently sensitive to have a role in reducing the extent of nodal dissection.

Adult↗
PubMed2004

Primary human alveolar type II epithelial cell CCL20 (macrophage inflammatory protein-3alpha)-induced dendritic cell migration.

Inhalation of antigenic matter stimulates rapid recruitment of dendritic cells (DCs) into the lung. Recent studies propose that the chemokine CCL20 (macrophage inflammatory protein-3alpha) may play an important role in DC recruitment. We previously showed that primary human alveolar type II epithelial (ATII) cells are a rich source of chemokines and so hypothesized that the ATII cell produces CCL20 and might therefore be a key regulator of DC recruitment into the lung. Here, we show that primary human ATII cells, but not human alveolar macrophages, produce CCL20 both constitutively (403.5 +/- 85.4 pg/ml; 24 h) and in response to endotoxin (lipopolysaccharide) exposure (1,525.0 +/- 169.4 pg/ml; 1 mug/ml lipopolysaccharide; 24 h) in a time- and dose-dependent manner. In addition, we show that peripheral blood monocyte-derived CD1a+ DCs migrate in response to conditioned media from ATII cells but not those from alveolar macrophages; DC migration was significantly correlated with the amount of CCL20 (r(2) > 0.9; P < 0.05) detected in the media but not with any other chemokine measured. We therefore conclude that the alveolar epithelium is an important source of CCL20 in the lung and that the ATII cell may play a critical role in controlling the movement of DCs through the lung both under normal and inflammatory conditions.

Cell Movement↗
PubMed2004

Effect of bronchoscopic lung volume reduction on dynamic hyperinflation and exercise in emphysema.

Endobronchial valve placement improves pulmonary function in some patients with chronic obstructive pulmonary disease, but its effects on exercise physiology have not been investigated. In 19 patients with a mean (SD) FEV(1) of 28.4 (11.9)% predicted, studied before and 4 weeks after unilateral valve insertion, functional residual capacity decreased from 7.1 (1.5) to 6.6 (1.7) L (p = 0.03) and diffusing capacity rose from 3.3 (1.1) to 3.7 (1.2) mmol . minute(-1) . kPa(-1) (p = 0.03). Cycle endurance time at 80% of peak workload increased from 227 (129) to 315 (195) seconds (p = 0.03). This was associated with a reduction in end-expiratory lung volume at peak exercise from 7.6 (1.6) to 7.2 (1.7) L (p = 0.03). Using stepwise logistic regression analysis, a model containing changes in transfer factor and resting inspiratory capacity explained 81% of the variation in change in exercise time (p < 0.0001). The same variables were retained if the five patients with radiologic atelectasis were excluded from analysis. In a subgroup of patients in whom invasive measurements were performed, improvement in exercise capacity was associated with a reduction in lung compliance (r(2) = 0.43; p = 0.03) and isotime esophageal pressure-time product (r(2) = 0.47; p = 0.03). Endobronchial valve placement can improve lung volumes and gas transfer in patients with chronic obstructive pulmonary disease and prolong exercise time by reducing dynamic hyperinflation.

Bronchoscopy↗
PubMed2004

Lung cancer: intragenic ERBB2 kinase mutations in tumours.

The protein-kinase family is the most frequently mutated gene family found in human cancer and faulty kinase enzymes are being investigated as promising targets for the design of antitumour therapies. We have sequenced the gene encoding the transmembrane protein tyrosine kinase ERBB2 (also known as HER2 or Neu) from 120 primary lung tumours and identified 4% that have mutations within the kinase domain; in the adenocarcinoma subtype of lung cancer, 10% of cases had mutations. ERBB2 inhibitors, which have so far proved to be ineffective in treating lung cancer, should now be clinically re-evaluated in the specific subset of patients with lung cancer whose tumours carry ERBB2 mutations.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Detecting lung cancer in plasma with the use of multiple genetic markers.

Recent studies have demonstrated the possibility to detect genetic changes in plasma DNA of cancer patients. The goal of this study was to validate a panel of molecular markers for lung cancer detection in plasma DNA. Three markers, p53, FHIT and microsatellite alterations at loci on chromosome 3, were used to detect mutations in tumor and plasma DNA of 64 stage I-III non small cell lung cancer patients. p53 mutations were studied by direct sequencing of exons 5 through 8 in tumor DNA and by plaque hybridization assay and sequencing in plasma DNA. Allelic losses were evaluated by fluorescent PCR in tumor and plasma DNA. p53 genomic mutations were detected in 26 (40.6%) of 64 tumor DNA samples and the identical mutation was identified in plasma of 19 (73.1%) of them. Microsatellite alterations at FHIT and 3p loci were observed in 40 (62.5%) tumors and in 23 (35.9%) plasma samples. Of the 40 patients showing microsatellite alterations in tumors, 19 (47.5%) displayed the same change in plasma DNA. At least 1 of the 3 genetic markers (p53, FHIT and 3p) was altered in plasma of 51.6% of all patients and 60.7% of stage I patients. Moreover, genetic markers in plasma identified 29 of 45 (64.4%) of all stages and 15 of 22 (68.2%) of stage I patients whose tumors had an alteration. These results provide the proof of principle that plasma DNA alterations are tumor-specific in most cases and support blood testing as a noninvasive strategy for early detection.

Acid Anhydride Hydrolases↗
PubMed2004

Idiopathic tracheal and bronchial stenosis in two pediatric patients.

Idiopathic tracheal stenosis, a rare benign chronic inflammatory and fibrotic entity, has previously been reported in the literature in adults, but never in children. Here we report two pediatric cases, one with the rarer condition of idiopathic bronchial stenosis, and we discuss the management and histopathologic findings.

Bronchial Diseases↗
PubMed2004

Intraoperative pleural lavage cytology is an independent prognostic indicator for staging non-small cell lung cancer.

OBJECTIVES: For patients undergoing lung resection for cancer, macroscopic evidence of metastasis is clearly associated with adverse prognosis. However, less is known about the significance of tumor cells detected by using tests such as pleural lavage cytology. To ascertain the frequency and quantify the effect of this finding on survival, we performed a prospective study of intraoperative pleural lavage cytology. METHODS: Pleural lavage cytology consisted of cytologic analysis of 100 mL of saline irrigated over the lung surface immediately after thoracotomy. Patients were excluded if they had an existing effusion, extreme adhesions, or lateral chest wall invasion or if resection was not performed. Survival was calculated by means of Kaplan-Meier analysis and compared by using log-rank tests. Cox regression was used to ascertain independent predictors of prognosis. RESULTS: From 1995 through 2003, we performed pleural lavage cytology on 292 patients undergoing thoracotomy for lung cancer. The mean age was 64 (SD, 10) years, and 196 (67%) patients were men. Of 292 samples, 13 (4.5%) showed evidence of malignant cells. The median time to follow-up was 15 months (interquartile range, 1-40 months), with a median survival of 49 months for patients with negative pleural lavage cytology results and 13 months for patients with positive pleural lavage cytology results (P =.002). Univariate prognostic predictors were positive pleural lavage cytology status (P =.03), stage (P =.03), adenocarcinoma (P =.06), and parietal pleural involvement (P =.01). In the final multivariate model only positive pleural lavage cytology status (P =.006) and stage (P =.03) remained significant. CONCLUSIONS: Intraoperative pleural lavage cytology is a simple addition to intrathoracic staging and an independent predictor of prognosis. Positive results potentially affect survival by upstaging patients to stage IIIB or greater.

Adenocarcinoma↗
PubMed2004

Primary human alveolar type II epithelial cell chemokine release: effects of cigarette smoke and neutrophil elastase.

An early response to cigarette smoke is an influx of leukocytes into the lung. Alveolar epithelial type II (ATII) cells may contribute by releasing chemokines in response to cigarette smoke and neutrophil elastase (NE). Human ATII cells were purified from normal regions of lungs resected for carcinoma (n = 14). In vitro, these cells exhibited ATII cell characteristics: lamellar bodies, apical microvilli, tight junctions, and expressed surfactant apoprotein C. Basal ATII cell release of five chemokines ranked as follows: monocyte chemotactic protein (MCP)-1 > interleukin (IL)-8 > growth-related oncogene (GRO)-alpha > macrophage inflammatory protein (MIP)-1alpha > regulated on activation, normal T cell expressed and secreted (RANTES). MIP-1alpha and RANTES were often not detectable. After stimulation with a mixture of lipopolysaccharide/endotoxin (LPS), tumor necrosis factor-alpha, IL-1beta, and IFN-gamma, MCP-1 and IL-8 secretion rose 4-6-fold, whereas GRO-alpha rose 25-fold. NE stimulated IL-8 mRNA expression, and 10nM NE stimulated IL-8 secretion; however, 100 nM NE caused a decrease in extracellular IL-8, MCP-1, and GRO-alpha, attributed to proteolysis. Cigarette smoke extract (CSE) inhibited IL-8 mRNA expression and release of all chemokines. Glutathione protected against the effects of CSE, suggesting oxidative mechanisms. GRO-alpha, important in growth and repair, was sensitive to both stimulation, by LPS:cytokines, and inhibition, by CSE. Thus, contrary to the original hypothesis, high concentrations of NE and CSE resulted in reduced extracellular chemokine levels. We hypothesize that reduced ATII cell-derived chemokine levels compromise alveolar repair, contributing to cigarette smoke-induced alveolar damage and emphysema.

Aged↗
PubMed2003

Large cell neuroendocrine carcinoma and large cell carcinomas with neuroendocrine morphology of the lung: prognosis after complete resection and systematic nodal dissection.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) and large cell carcinoma with neuroendocrine morphology of the lung are both currently classified as subtypes of large cell carcinomas according to the World Health Organization IASLC classification system for lung and pleural tumors. Prognosis is reported as similar to that of small cell carcinomas. There is no consensus on management of this subset and adjuvant chemotherapy is recommended by some for early stage LCNEC to impact long-term prognosis. We retrospectively reviewed a cohort of patients at our institution who had this type of tumor to determine factors that might influence survival. METHODS: Twenty-one cases of LCNEC and large cell carcinoma with neuroendocrine morphology were identified in the files of the Royal Brompton Hospital between 1986 and 1999. All patient data were reviewed, and complete follow-up was achieved with 20 of these patients. RESULTS: Of the 21 patients identified, 20 underwent resection with systematic nodal dissection in 18. There was no in-hospital mortality. Of those patients fully staged by systematic nodal dissection, 9 were stage I, 5 were stage II and 4 were stage III. Median follow-up was 25 months (range, 2 to 120 months). At the time of review, 11 patients were alive and free of disease. One patient was alive and free of disease when lost to follow-up. Nine patients had died, 7 related and 2 unrelated to disease. The 5-year actuarial survival for the entire group was 47%. The actuarial survival of accurately staged, stage I patients at 5 years was 88%. The actuarial survival of patients in stage II and III was 28% at 5 years. CONCLUSIONS: LCNEC and large cell carcinoma with neuroendocrine morphology are aggressive tumors, but patients with completely resected disease after systematic nodal dissection have a better prognosis than previously described. Patients with more advanced disease have a poor prognosis.

Aged↗
PubMed2003

Liposarcoma of the thyroid gland mimicking retrosternal goiter.

Primary liposarcoma of the thyroid gland is extremely rare with only two previous reports in the literature. We report two further cases, both patients presenting with rapid airways compression. Patient 1 had clinical, radiographic, and biopsy appearances suggesting benign goiter. Patient 2 had a long-term history of benign goiter, a previous partial thyroidectomy, and more recent biopsies showing liposarcoma. The management of such rare conditions is always challenging.

Aged↗
PubMed2003

Intrapleural tumor dissemination after video-assisted thoracoscopic surgery metastasectomy.

In a 34-year-old woman extensive intrapleural disease developed within 1 year of video-assisted thoracoscopic surgery (VATS) removal of two pulmonary metastases from a previously treated synovial sarcoma. She underwent a successful complete pleurectomy through a left thoracotomy to excise the pleural tumor and remains well 6 months later. This case highlights tumor dissemination as one of the pitfalls of VATS metastasectomy and raises concerns about using VATS in this situation.

Adult↗
PubMed2003

Tracheobronchial obstruction in children: experience with endoscopic airway stenting.

BACKGROUND: We reviewed our experience to determine the role of endoscopic airway stents in children with tracheobronchial obstruction. METHODS: Seventeen children (10 boys and 7 girls) aged 2 months to 16 years underwent tracheobronchial stenting. Etiology of the tracheobronchial obstruction included external vascular compression (n = 9); tracheobronchial anastomotic strictures after heart-lung/lung transplantation (n = 4); airway compression by malignant mediastinal mass (n = 2), and subglottic/high tracheal stenosis after prolonged intubation with a tracheostomy in situ (n = 2). Indications for airway stenting were failure to wean from ventilator after a mean of 82.5 days (range, 2 to 210) in 8 children; and dyspnea or stridor in the remaining 9 children. RESULTS: Ten children had a total of 24 uncovered self-expanding metal stents (either Magic Wallstent or Ultraflex Microvasive) and 7 children had silicone stents (2 straight, 3 Y and 2 T tube stents). At follow-up at 1 week to 72 months (median 21), only 8 of 17 (47%) children were alive but all the deaths were secondary to the underlying pathology and not related to tracheobronchial stenting. Six of 8 ventilator-dependent children were extubated after a mean of 5.3 days (range, 2 to 11) after airway stenting. For the 9 children stented for dyspnea, mean Medical Research Council dyspnea score decreased from 3.0 to 1.6 after stenting. CONCLUSIONS: Tracheobronchial stenting in children is only rarely needed and often undertaken in dire circumstances. The procedure has led to significant symptomatic benefit in dyspneic children and has enabled ventilator-dependent children to be extubated. Medium-term outlook after stenting with self-expanding metal stents for vascular compression of the airway is encouraging. The long-term outcome remains uncertain, however, and is ultimately influenced by the underlying disease.

Bronchial Diseases↗
PubMed2003

Mediastinoscopy and mediastinotomy after cardiac surgery: are safety and efficacy affected by prior sternotomy?

BACKGROUND: The diagnostic and staging value of cervical mediastinoscopy is well established. Left anterior mediastinotomy is of further value in assessing left upper lobe tumors. However the efficacy and safety of both these procedures after median sternotomy for cardiac surgery is unknown. METHODS: We undertook a retrospective review of our experience of mediastinal exploration by cervical mediastinoscopy with or without left anterior mediastinotomy in patients with prior sternotomy between 1980 and 2001. RESULTS: During this period 28 patients (25 male and 3 female; mean age, 63 +/- 10 years), all with prior sternotomy for cardiac surgery (14 had left internal mammary artery graft), underwent mediastinal exploration. The mean interval between sternotomy and mediastinal exploration was 7.2 +/- 5.1 years. Additionally, 3 patients also had superior vena cava obstruction. Cervical mediastinoscopy was performed in all 28 patients and additionally left anterior mediastinotomy was undertaken in 7 of 28 patients (4 with left internal mammary artery graft). Indications for exploration were staging of lung cancer in 22 patients (cervical mediastinoscopy, n = 22; left anterior mediastinotomy, n = 7) and diagnostic biopsy of mediastinal mass in 6 patients (cervical mediastinoscopy, n = 6). Thorough mediastinal assessment was possible in all 28 patients. In the 22 patients with lung cancer the median number of lymph node stations sampled during mediastinoscopy was 3 (range, 1 to 5). A specific diagnosis was obtained in 16 patients (metastatic lung cancer, n = 10; lymphoma, n = 3; sarcoidosis, sinus histiocytosis, and metastatic melanoma, n = 1 each). The other 12 patients with negative findings underwent pulmonary resection and only 1 of 12 (8%) patients had unexpected N2 disease, a similar proportion to our overall experience with lung cancer. There were no operative complications. CONCLUSIONS: Prior sternotomy for cardiac surgery does not compromise the efficacy and the safety of mediastinoscopy and mediastinotomy.

Adult↗
PubMed2003

An assessment of the expanded classification of congenital cystic adenomatoid malformations and their relationship to malignant transformation.

The purpose of this study was to review cases of congenital cystic adenomatoid malformations (CCAMs) arising in children and adults, in order to assess the recently expanded classification system for these lesions and their association with malignant transformation. Of 28 CCAMs, there were 16 type 1, 4 type 2, and 8 type 4 lesions, 12 of which presented in adults. Five of 16 type 1 CCAMs were accompanied by microscopic foci of bronchioloalveolar carcinoma; two others showed focal mucous cell hyperplasia. In two further cases, foci of nonmucinous atypical adenomatous hyperplasia were identified in the adjacent lung parenchyma. The bronchioloalveolar carcinomas showed less cytologic atypia, proliferative activity (Ki-67), and p53 expression than a comparative group of bronchioloalveolar carcinomas arising de novo, but this was not statistically significant (p = 0.15). Neither bronchioloalveolar carcinomas nor hyperplasia was identified in type 2 or type 4 CCAMs. Four of the eight type 4 CCAMs showed focal stromal hypercellularity, and one case subsequently developed a pleuropulmonary blastoma. We conclude that classification according to the current system is of clinical value. Bronchioloalveolar carcinomas arise in association with type 1 CCAMs, but recurrence following resection is exceptional. Type 4 CCAMs show histologic overlap with grade 1 pleuropulmonary blastomas, and distinction between these entities may not be possible on histology alone. However, stromal cellularity in a type 4 CCAM should raise the possibility of blastomatous transformation.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2003

A clinicopathologic study of 12 neuroendocrine tumors arising in the thymus.

STUDY OBJECTIVES: To determine whether the new classification system for thymic carcinoid tumors/neuroendocrine carcinomas provides prognostic data, and to study the presentation, diagnosis, treatment, and prognostic factors of these rare tumors. DESIGN: Retrospective analysis. SETTING: Royal Brompton Hospital, London, UK. RESULTS: Eight men and four women with a median age of 58 years. Complete excision was possible in nine patients. Postoperative staging revealed two stage I tumors, two stage II tumors, three stage III tumors, one stage IVA tumor, and four stage IVB tumors. All tumors demonstrated the histopathologic features of neuroendocrine tumors, which were confirmed by positive immunohistochemical staining for chromogranin A in 11 of 12 tumors and for CD56 in 12 of 12 tumors, and the presence of dense core granules on ultrastructural analysis in 9 of 9 tumors. All 12 tumors did not stain positively for somatostatin receptors. Three tumors were grade 1, six cases were grade 2, and three cases were grade 3. Follow-up was available in all patients. One patient died 1 month postoperatively. Distant metastasis developed in nine patients (82%). Local recurrence was evident in six patients, of whom five had not received postoperative radiotherapy. Seven patients died of distant metastasis (22 to 83 months after surgery). Two are alive and disease-free (at 67 and 81 months), and two are alive with disease (at 60 and 86 months) CONCLUSIONS: Neither grading as neuroendocrine carcinomas nor any individual histologic parameter showed a significant association with prognosis. Initial aggressive treatment, including complete surgical excision and adjuvant radiotherapy, appears to offer the best hope for prolonged survival. Adjuvant chemotherapy also should be considered, since the incidence of distant relapse is high.

Carcinoid Tumor↗