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Biomedical subjects

D A Waller

Publications and source records attributed to D A Waller.

At least 19 recordsLinked to original sources
PubMed2006

EGFR expression: associations with outcome and clinicopathological variables in malignant pleural mesothelioma.

Malignant mesothelioma (MM) is a fatal tumour of increasing incidence which is related to asbestos exposure. This work evaluated expression in MM of Epidermal Growth Factor Receptor (EGFR) by immunohistochemistry in 168 tumour sections and its correlations with clinicopathological and biological factors. The microvessel density (MVD) was derived from CD34 immunostained sections. Hematoxylin and eosin stained sections were examined for intratumoural necrosis. COX-2 protein expression was evaluated with semi-quantitative Western blotting of homogenised tumour supernatants (n=45). EGFR expression was correlated with survival by Kaplan-Meier and log rank analysis. Univariate and multivariate Cox proportional hazards models were used to compare the effects of EGFR with clinicopathological and biological prognostic factors and prognostic scoring systems. EGFR expression was identified in 74 cases (44%) and correlated with epithelioid cell type (p<0.0001), good performance status (p<0.0001), the absence of chest pain (p<0.0001) and the presence of TN (p=0.004), but not MVD or COX-2. EGFR expression was a good prognostic factor in univariate analysis (p=0.01). Independent indicators of poor prognosis in multivariate analysis were non-epithelioid cell type (p=0.0001), weight loss, performance status and WBC>8.3x10(9)L(-1). EGFR status was not an independent prognostic factor. EGFR expression in MM correlates with epithelioid histology and TN. EGFR may be a target for selective therapies in MM.

Biomarkers, Tumor↗
PubMed2004

The case for routine cervical mediastinoscopy prior to radical surgery for malignant pleural mesothelioma.

OBJECTIVES: To assess whether cervical mediastinoscopy is necessary before radical resection of malignant pleural mesothelioma (MPM). METHODS: Patients who underwent radical excision of MPM in a 48-month period were prospectively followed for evidence of disease recurrence and death. Histological evidence of extra pleural lymph node metastases was correlated with survival. Lymph node size at intraoperative lymphadenectomy was correlated with the presence of metastatic tumour. RESULTS: The 55 patients who underwent radical resection (51 extra pleural pneumonectomies and 4 radical pleurectomies) comprised 50 men and 5 women with a median age of 58 years, range 41-70. Histological examination revealed 50 epithelioid, four biphasic and one sarcomatoid histology. Postoperative IMIG T stage was stage I 4, II 11, III 30 and IV 10. Postoperatively the 17 patients with metastases to the extra pleural lymph nodes had significantly shorter survival (median 4.4 months, 95% CI 3.2-5.4) than those without (median survival 16.3 months, 95% CI 11.6-21.0) P=0.012 Kaplan-Meier analysis. Seventy-seven extra pleural lymph nodes without metastases were measured with a mean long axis diameter of 16.9 mm (range 4-55); 22 positive nodes had a mean long axis diameter of 15.2 mm (range 6-30). In 15 of the 17 patients with positive extra pleural nodes, the nodes could have been biopsied at cervical mediastinoscopy. CONCLUSIONS: This study confirms that extra pleural nodal metastases are related to poor survival. Pathological nodal involvement cannot be predicted from nodal dimensions. These data suggest that all patients being considered for radical resection of MPM should preferentially undergo preoperative cervical mediastinoscopy irrespective of radiological findings.

Adult↗
PubMed2004

A prospective audit evaluating the role of video-assisted cervical mediastinoscopy (VAM) as a training tool.

OBJECTIVE: Cervical mediastinoscopy is an important diagnostic and staging technique. Limited operative field and visibility have traditionally made it a difficult procedure to learn and supervise. Video-assisted techniques can aid training in the procedure. We designed a prospective study to assess the usefulness of video-assisted mediastinoscopy (VAM) as a training tool. METHODS: 43 patients were operated upon by two trainees during their initial formation in general thoracic surgery (25 patients in 15 months, and 18 patients in 9 months, respectively). INDICATIONS: staging (n = 23), diagnosis of enlarged mediastinal nodes (n = 14) and diagnosis/staging (n = 6). End-points of the study: operative time, need of consultant assistance during procedures, and ability of the trainee to identify all nodal stations independently. RESULTS: There were no complications. The mean operative time was 29 (range 18-51) min. Valid histological samples were obtained in all cases. There were no false negative results in the 13 patients who underwent subsequent lung resection (sensitivity 100%). Operative time (R2 = 0.83 and 0.77), need for consultant assistance (R2 = 0.98 and 0.94), and failure to independently reach all nodal stations (R2 = 0.95 and 0.94) significantly decreased with experience in both trainees' cases (cubic curve fit; P < 0.001 throughout). DISCUSSION: VAM permits a rapid learning and adequate supervision of the technique without compromising safety, operative time or completeness of the procedure. The main advantages are: increased visual field, image magnification, adequate light source and the ability to use two instruments simultaneously. VAM should be the technique of choice in thoracic surgical teaching units.

Adult↗
PubMed2004

Experience with video-assisted surgery for suspected mediastinal tumours.

AIM: To assess the therapeutic feasibility of video-assisted thoracoscopic surgery (VATS) in the excision of suspected mediastinal tumours. METHODS: The case notes of 24 consecutive patients referred to a single surgeon between 1997 and 2002 for excision of suspected mediastinal tumours were reviewed. The operative, post-operative and pathological characteristics of patients treated thoracoscopically and by open procedure were analysed. RESULTS: Thirteen of 24 patients underwent thoracoscopic excision. The mean age of the two groups was similar as was the mean operating time and duration of chest drainage. However, patients in the thoracoscopic group had less chest drainage, less pain and a shorter hospital stay. CONCLUSIONS: Video-assisted thoracoscopic excision of mediastinal tumours is a safe and technically feasible procedure and may offer significant post-operative advantages over open procedures.

Adult↗
PubMed2004

Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life.

BACKGROUND: In 1995 a meta-analysis of randomised trials investigating the value of adding chemotherapy to primary treatment for non-small cell lung cancer (NSCLC) suggested a small survival benefit for cisplatin-based chemotherapy in each of the primary treatment settings. However, the meta-analysis included many small trials and trials with differing eligibility criteria and chemotherapy regimens. METHODS: The aim of the Big Lung Trial was to confirm the survival benefits seen in the meta-analysis and to assess quality of life and cost in the supportive care setting. A total of 725 patients were randomised to receive supportive care alone (n = 361) or supportive care plus cisplatin-based chemotherapy (n = 364). RESULTS: 65% of patients allocated chemotherapy (C) received all three cycles of treatment and a further 27% received one or two cycles. 74% of patients allocated no chemotherapy (NoC) received thoracic radiotherapy compared with 47% of the C group. Patients allocated C had a significantly better survival than those allocated NoC: HR 0.77 (95% CI 0.66 to 0.89, p = 0.0006), median survival 8.0 months for the C group v 5.7 months for the NoC group, a difference of 9 weeks. There were 19 (5%) treatment related deaths in the C group. There was no evidence that any subgroup benefited more or less from chemotherapy. No significant differences were observed between the two groups in terms of the pre-defined primary and secondary quality of life end points, although large negative effects of chemotherapy were ruled out. The regimens used proved to be cost effective, the extra cost of chemotherapy being offset by longer survival. CONCLUSIONS: The survival benefit seen in this trial was entirely consistent with the NSCLC meta-analysis and subsequent similarly designed large trials. The information on quality of life and cost should enable patients and their clinicians to make more informed treatment choices.

Adult↗
PubMed2003

Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura.

Matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and -9), play a significant role in tumour invasion and angiogenesis. The expression and activities of MMPs have not been characterised in malignant mesothelioma (MM) tumour samples. In a prospective study, gelatinase activity was evaluated in homogenised supernatants of snap frozen MM (n=35), inflamed pleura (IP, n=12) and uninflammed pleura (UP, n=14) tissue specimens by semiquantitative gelatin zymography. Matrix metalloproteinases were correlated with clinicopathological factors and with survival using Kaplan-Meier and Cox proportional hazard models. In MM, pro- and active MMP-2 levels were significantly greater than for MMP-9 (P=0.006, P<0.001). Active MMP-2 was significantly greater in MM than in UP (P=0.04). MMP-2 activity was equivalent between IP and MM, but both pro- and active MMP-9 activities were greater in IP (P=0.02, P=0.009). While there were trends towards poor survival with increasing total and pro-MMP-2 activity (P=0.08) in univariate analysis, they were both independent poor prognostic factors in multivariate analysis in conjunction with weight loss (pro-MMP-2 P=0.03, total MMP-2 P=0.04). Total and pro-MMP-2 also contributed to the Cancer and Leukemia Group B prognostic groups. MMP-9 activities were not prognostic. Matrix metalloproteinases, and in particular MMP-2, the most abundant gelatinase, may play an important role in MM tumour growth and metastasis. Agents that reduce MMP synthesis and/or activity may have a role to play in the management of MM.

Adult↗
PubMed2003

En-bloc chest wall and lung resection for non-small cell lung cancer. Predictors of 60-day non-cancer related mortality.

OBJECTIVE: Predictors for early mortality after isolated pulmonary resection have been identified and clear guidelines regarding fitness for surgery have been produced. However, the additional risk of en-bloc chest wall resection has not been extensively studied. AIM: We analyzed our total experience of combined chest wall and lung resection for non-small-cell lung cancer (NSCLC) to identify additional risk factors for early non-tumour related mortality. PATIENTS AND METHODS: A retrospective review of 41 consecutive patients, with median age of 69 (range 37-84) years, operated by a single surgeon over a 4-year period. Univariate analysis was performed to assess the relationship of selected preoperative and operative variables on mortality within 2 months from surgery. RESULTS: Low preoperative body mass index, age over 75 years, and preoperative FEV(1) of less than 70% of predicted were associated with a significantly increased 60-day mortality. In those patients with any of these risk factors 60-day mortality was 47% (8 of 17). In those with none of the above there was no mortality (of 24 patients) (P=0.0004). DISCUSSION: En-bloc pulmonary and chest wall resection for NSCLC should be avoided in the elderly, those with limited respiratory reserve or significant weight loss. These factors render the patient highly susceptible to chest complications leading to increased mortality.

Adult↗
PubMed2003

Postoperative pain detracts from early health status improvement seen after video-assisted thoracoscopic lung volume reduction surgery.

OBJECTIVES: To assess the impact of lung volume reduction surgery (LVRS) on postoperative pain. METHODS: Fifty-two patients, 34 male/18 female, median age 59 (46-70) years, underwent unilateral video-assisted thoracoscopic (VAT) LVRS. FEV(1), TLC, RV and RV/TLC ratio were assessed preoperatively and at 3, 6, 12 and 24 months post surgery. At the same time interval health status was assessed by Euroquol and SF 36 questionnaires. RESULTS: Significant improvements in health status, as assessed by SF 36, persisted from 3 months to 1 year. However, in the pain domain there was a worsening of the mean score from 74 preoperatively to 64 at 3 months, 68 at 6 months, 73 at 12 months and 65 at 24 months. The improvements in Euroquol score were not statistically significant. However, they became significant for at least 2 years postoperatively, when those patients who had a worsening pain score postoperatively were excluded. While the percentage of patients with a worsening of pain scores measured with SF 36 remained between 40 and 45% even 2 years after LVRS, when using Euroquol this percentage did decrease from 30% at 3 months to 14% at 2 years. There was no significant correlation between the change of scores and length of operation, hospital stay or air leak. It was also not statistically significant whether these patients had an extra procedure (redo thoracotomy or insertion of extra drain postoperatively). There were some significant correlations between changes in hyperinflation and changes in pain scores but this was not consistent for Euroquol and SF 36. CONCLUSION: Postoperative pain detracts from global improvement in health status after LVRS even after unilateral VATS. There may be an influence of alterations in chest mechanics after surgery on the development of pain.

Aged↗
PubMed2002

Can pneumonectomy for non-small cell lung cancer be avoided? An audit of parenchymal sparing lung surgery.

BACKGROUND: Lung cancer resection rates are suboptimal in the UK. Pneumonectomy has a higher perioperative mortality risk than lobectomy. To increase resection rates and improve outcomes we have implemented a policy of parenchymal sparing surgery for tumours involving a main stem bronchus. METHODS: In a prospective 4 year study of 119 consecutive patients operated upon by a single surgeon the perioperative course, pathology and survival were compared for 81 patients undergoing pneumonectomy and 38 patients in whom pneumonectomy was avoided by bronchoplastic+/-angioplastic procedures. RESULTS: The rate of pneumonectomy decreased significantly with increasing experience with parenchymal sparing surgery (R(2)=0.98, P<0.001) with 21 of the last 30 patients (70%) avoiding pneumonectomy. There were no significant inter-group differences in patient characteristics, perioperative course or outcome. One-year survival was 64% after pneumonectomy and 73% after sleeve lobectomy. However the perioperative loss of respiratory function was significantly lower in the patients in whom pneumonectomy was avoided (P=0.0003). CONCLUSIONS: Pneumonectomy can be avoided in a large proportion of patients with non-small cell lung cancer of a main stem bronchus without adversely affecting outcome but with preservation of lung function

Adenocarcinoma↗
PubMed2002

Lung volume reduction surgery--a comparison of the long term outcome of unilateral vs. bilateral approaches.

OBJECTIVE: Bilateral lung volume reduction surgery (LVRS) is thought to be preferable to unilateral surgery due to greater initial benefit but the subsequent rate of decline may also be greater. We compared the long term physiological and health status outcome of LVRS performed on one or simultaneously on both lungs. METHODS: Prospective data were collected on a consecutive series of 65 patients undergoing LVRS who were all suitable for bilateral surgery. Twenty-six patients: age 59 (8) years underwent bilateral LVRS by video-assisted thoracoscopy (VAT) or sternotomy and 39 patients: age 60 (6) years underwent unilateral VAT. The perioperative effects of LVRS on spirometry were prospectively recorded at 3, 6, 12 and 24 months. RESULTS: The unilateral group had similar preoperative lung volumes to the bilateral patients: forced expiratory volume in 1s (FEV(1)) 26 vs. 30% predicted, RV 275 vs. 246% predicted and total lung capacity (TLC) 148 vs. 142% predicted. Unilateral LVRS was associated with significantly lower weight of lung resected: 80 (31) vs. 118 (46) g; hospital stay: 16 (10) days vs. 28 (22) days. Thirty-day mortality was 3% in the unilateral and 8% in the bilateral group (P=0.34). Postoperative ventilation occurred in 5% in the unilateral and in 42% in the bilateral group (P=0.0002). The decline of FEV(1) during the first postoperative year was significant in the bilateral group (-313 ml/y, P=0.04) but not significant in the unilateral group (-50 ml/y, P=0.18). SF 36 scores in all eight domains were similar in both groups preoperatively and at any postoperative interval. CONCLUSION: We have found no benefit from bilateral simultaneous LVRS and prefer unilateral LVRS because of the lower morbidity, resulting in earlier discharge, and slower decline in physiological benefit.

Aged↗
PubMed2001

Angiogenesis is an independent prognostic factor in malignant mesothelioma.

Angiogenesis is essential for tumour growth beyond 1 to 2 mm in diameter. The clinical relevance of angiogenesis, as assessed by microvessel density (MVD), is unclear in malignant mesothelioma (MM). Immunohistochemistry was performed on 104 archival, paraffin-embedded, surgically resected MM samples with an anti-CD34 monoclonal antibody, using the Streptavidin-biotin complex immunoperoxidase technique. 93 cases were suitable for microvessel quantification. MVD was obtained from 3 intratumoural hotspots, using a Chalkley eyepiece graticule at x 250 power. MVD was correlated with survival by Kaplan-Meier and log-rank analysis. A stepwise, multivariate Cox model was used to compare MVD with known prognostic factors and the EORTC and CALGB prognostic scoring systems. Overall median survival from the date of diagnosis was 5.0 months. Increasing MVD was a poor prognostic factor in univariate analysis (P = 0.02). Independent indicators of poor prognosis in multivariate analysis were non-epithelial cell type (P = 0.002), performance status > 0 (P = 0.003) and increasing MVD (P = 0.01). In multivariate Cox analysis, MVD contributed independently to the EORTC (P = 0.006), but not to the CALGB (P = 0.1), prognostic groups. Angiogenesis, as assessed by MVD, is a poor prognostic factor in MM, independent of other clinicopathological variables and the EORTC prognostic scoring system. Further work is required to assess the prognostic importance of angiogenic regulatory factors in this disease.

Age Factors↗
PubMed2001

Thoracoscopic decortication: a role for video-assisted surgery in chronic postpneumonic pleural empyema.

BACKGROUND: We evaluated a technique of video-assisted thoracoscopic (VAT) decortication of the visceral cortex to reexpand entrapped lung in cases of chronic postpneumonic pleural empyema. METHODS: A prospective cohort study of 48 consecutive patients with multiloculated postpneumonic pleural empyema in whom visceral pleural decortication was required was studied. The effect of VAT decortication on perioperative outcome and factors affecting its success were assessed. RESULTS: Before the introduction of VAT decortication 12 patients were treated by thoracotomy (group T). In the subsequent 36 patients VAT decortication was attempted with success in 21 (group VS) but lung expansion was not observed in 15 patients (group VF) who required thoracotomy. There was no difference in the age or sex distribution of the 3 groups. Operating time was significantly longer in group T than group VS, mean difference 30.3 minutes (p = 0.001) and postoperative hospital stay was longer in group T than group VS, mean difference 2.9 days (p = 0.004). The success of VAT decortication was not related to either the delay between onset of symptoms or hospital admission and surgery; indeed the operating time decreased with increasing preoperative delay. However, success was related to increasing operative experience (p = 0.001). CONCLUSIONS: VAT decortication is a feasible new technique to achieve lung reexpansion in chronic postpneumonic pleural empyema and has perioperative benefits over thoracotomy.

Adult↗
PubMed2001

Surgery for non-small cell lung cancer--new trends.

New trends in lung cancer surgery focus on new approaches to the management of the primary tumour, combined modality approaches to both local and distant control of the tumour, new approaches to ensure resectability by staging and techniques to expand the limits of operability. With new screening methods for NSCLC there is a trend toward sublobar, segmental resections of smaller tumours including an expanding use of video assisted thoracoscopy. Improvements in surgical and anaesthetic procedures have stimulated a renewed interest in the resection of locally advanced tumours. The understanding that local control alone may not give the best chance of long term survival has stimulated new trends in the use of neoadjuvant and adjuvant chemotherapy. There is a trend towards more detailed preoperative and intraoperative nodal staging in NSCLC, including video assisted techniques, and the identification of sentinel lymph node involvement to direct lymph node dissection. Increased understanding of the physiological benefits of surgery in emphysema have resulted in a re-evaluation of the selection of patients for lung cancer surgery. This together with a greater application of bronchoplastic and angioplastic techniques is leading to greater resection rates.

Carcinoma, Non-Small-Cell Lung↗