Mark K. Ferguson

ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy)

A collaboration of multidisciplinary experts on the functional evaluation of lung cancer patients has been facilitated by the European Respiratory Society (ERS) and the European Society of Thoracic Surgery (ESTS), in order to draw up recommendations and provide clinicians with clear, up-to-date guidelines on fitness for surgery and chemo-radiotherapy. The subject was divided into different topics, which were then assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. The draft reports written by the experts on each topic were reviewed, discussed and voted on by the entire expert panel. The evidence supporting each recommendation was summarised, and graded as described by the Scottish Intercollegiate Guidelines Network Grading Review Group. Clinical practice guidelines were generated and finalised in a functional algorithm for risk stratification of the lung resection candidates, emphasising cardiological evaluation, forced expiratory volume in 1 s, systematic carbon monoxide lung diffusion capacity and exercise testing. Contrary to lung resection, for which the scientific evidences are more robust, we were unable to recommend any specific test, cut-off value, or algorithm before chemo-radiotherapy due to the lack of data. We recommend that lung cancer patients should be managed in specialised settings by multidisciplinary teams.

Consensus Statements for Management of Barrett's Dysplasia and Early-Stage Esophageal Adenocarcinoma, Based on a Delphi Process

BACKGROUND & AIMS Esophageal adenocarcinoma (EA) is increasingly common among patients with Barretts esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. METHODS We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. RESULTS Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. CONCLUSIONS We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies.

Complete Barrett's Eradication Endoscopic Mucosal Resection: An Effective Treatment Modality for High-Grade Dysplasia and Intramucosal Carcinoma—An American Single-Center Experience

OBJECTIVES:Complete Barretts eradication endoscopic mucosal resection (CBE-EMR) is the endoscopic removal of all Barretts epithelium with the curative intent of eliminating high-grade dysplasia (HGD)/intramucosal carcinoma (IMC) and reducing the risk of metachronous lesion development. We report our single tertiary referral centers long-term clinical experience using this modality in HGD/IMC management.METHODS:In this study, we retrospectively reviewed all patients who had CBE-EMR for Barretts esophagus (BE) with HGD/IMC who had been entered into our centers prospectively collected database. High-definition white-light and narrow-band imaging examinations were used according to the protocol. Staging endoscopic ultrasound was done before CBE-EMR to exclude invasive disease or suspicious lymphadenopathy. High-dose proton pump inhibition was instituted after initial treatment, and Seattle-type surveillance biopsies were performed on follow-up every 6 months once the CBE-EMR procedure was completed.RESULTS:A total of 49 patients (mean age 67 years, median 65, s.d. 11; 75% men) with histologically confirmed BE and HGD (33), IMC (16), underwent CBE-EMR from August 2003 to August 2008. The mean BE segment length was 3.2 cm (median 2, s.d. 2.2); 26 patients had short-segment BE, and 30 had visible lesions. A total of 106 EMR procedures were performed. On initial EMR, two patients had superficial submucosal carcinoma invasion (sm1) and two had IMC with lymphatic channel invasion. All four patients were referred for esophagectomy, but one opted for continued endoscopic management, without evidence of residual or recurrent carcinoma. A total of 14 patients await completion of EMR (9) or first follow-up endoscopy (5). CBE-EMR therapy was completed in 32 patients by an average of 2.1 sessions (median 2, s.d. 0.9). Surveillance biopsies showed normal squamous epithelium in 31 of 32 (96.9%) patients (mean remission time 22.9 months, median 17, s.d. 16.7, interquartile range 11–38). In all, 10 of 46 patients who continued in the endoscopic protocol had subsquamous Barretts epithelium on EMR specimens and/or treatment endoscopy biopsies. Overall, 1 of these 10 patients had Barretts underneath squamous mucosa on most recent surveillance biopsies. CBE-EMR upstaged pre-EMR pathology results in 7 of 49 (14%) of patients and downstaged pathology in 15 of 49 (31%) patients. In all, 18 of 49 (37%) patients developed symptomatic esophageal stenosis after a mean of 24.4 days (median 13.5, s.d. 27.8); all were successfully managed by endoscopic treatment. No perforations or uncontrollable bleeding occurred.CONCLUSIONS:To our knowledge, this is the largest American single-center experience demonstrating that CBE-EMR with close endoscopic surveillance is an effective treatment modality for BE with HGD/IMC. Although the rate of stenosis development is significant, it is easily treated by endoscopic dilation. Patients considering endoscopic ablation should be counseled appropriately. The role of CBE-EMR in patients with lymphatic invasion or superficial submucosal invasion remains to be defined.

Safety and efficacy of video-assisted thoracic surgical techniques for the treatment of spontaneous pneumothorax

Video-assisted thoracic surgery has been widely used in the treatment of spontaneous pneumothorax despite a paucity of data regarding the relative safety and long-term efficacy for this procedure. We reviewed 113 consecutive patients (68 male and 45 female patients, aged 15 to 92 years, mean 35.1) who underwent 121 video-assisted thoracic surgical procedures during 119 hospitalizations from 1991 through 1993. Recurrent ipsilateral pneumothorax was the most frequent indication for surgery and occurred in 77 patients (65%). The most common method of management was stapling of an identified bleb in the lung, which was undertaken in 105 (87%) patients. No operative deaths occurred. Complications included an air leak lasting longer than 5 days in 10 (8%) patients, two of whom required second procedures for definitive management. No episodes of postoperative bleeding or empyema occurred. The postoperative stay ranged from 1 day to 39 days (median 3 days, average 4.3 days) and 99 patients (84%) were discharged within 5 days. Mean follow-up was 13.1 months and ranged from 1 to 34 months. Eleven patients (10%) were lost to follow-up. Ipsilateral pneumothorax recurred after five of 121 procedures (4.1%). Twelve perioperative parameters (age, gender, race, smoking history, site of pneumothorax, severity of pneumothorax, operative indications, number of blebs, site of blebs, bleb ablation, method of pleurodesis, and prolonged postoperative air leak) were entered into univariate and multivariate analysis to identify significant independent predictors of recurrence. The only independent predictor of recurrence was the failure to identify and ablate a bleb at operation, which resulted in a 23% recurrence rate versus a 1.8% rate in those with ablated blebs (p < 0.001). These data suggest that video-assisted thoracic surgery is a viable alternative to thoracotomy for the treatment of recurrent spontaneous pneumothorax. It results in a short hospital stay, low morbidity, high patient acceptance, and a low rate of recurrence.

Optimizing selection of patients for major lung resection.

OBJECTIVES It is not known whether a normal diffusing capacity for carbon monoxide permits safe lung resection in patients with marginal spirometric values, or whether normal spirometric values negate the adverse effects of a low diffusing capacity. The purposes of this study were (1) to determine the best predictors of morbidity and mortality and (2) to assess whether interactions exist between diffusing capacity and spirometry that help estimate outcome after major lung resection. DESIGN A retrospective analysis of 376 patients who underwent lung resection was performed. Three hundred three had lung cancer and 73 had other disease. Two hundred eighty-four underwent lobectomy/bilobectomy and 92 had pneumonectomy. We assessed the relationship of 23 preoperative variables to 18 postoperative events classified into categories as pulmonary or cardiac complications, overall morbidity, and operative mortality. RESULTS The best single predictor of complications was the percent predicted postoperative diffusing capacity. The incidences of pulmonary and cardiac complications, morbidity, and mortality were inversely related to predicted postoperative diffusing capacity percent (p < 0.004 for each). Multivariate logistic regression analyses identified only predicted postoperative diffusing capacity percent and age as significant independent predictors of pulmonary complications, morbidity, and death, and these with prior myocardial infarction predicted cardiac complications. There were no interactions between percent predicted postoperative forced expiratory volume in 1 second and predicted postoperative diffusing capacity percent in estimating risks of complications. CONCLUSION Predicted postoperative diffusing capacity percent is the strongest single predictor of risk of complications and mortality after lung resection. There is little interrelationship of predicted postoperative diffusing capacity percent and predicted postoperative forced expiratory volume in 1 second, indicating that these values should be assessed independently in estimating operative risk.

Mortality after Esophagectomy: Risk Factor Analysis

Abstract Esophageal resection is associated with a high incidence of operative mortality, suggesting the need for predictors of operative risk. A retrospective analysis was performed for esophagectomy patients using univariate and multivariate analyses; relative risks (RR) were calculated. Of the 269 patients, 35 (13%) died. The optimal model for the preoperative prediction of risk of mortality was defined by age ( p= 0.001; RR = 2.6) and performance status (p= 0.04; RR = 1.9). Delimiting the data pool using a calculated risk of 0.2 accurately identified outcomes in 79% of patients and predicted 41% of deaths. The optimal model for the overall prediction of risk of mortality was defined by age (p= 0.001; RR = 3.9), intraoperative blood loss (p < 0.001; RR = 1.7), pulmonary complications (p= 0.002; RR = 6.6), and the need for inotropic support (p= 0.003; RR = 10.2). The individual risk of mortality after esophagectomy can be predicted preoperatively with a model based on patient age and performance status. The findings underscore the importance of preoperative evaluation of cardiopulmonary function, meticulous operative technique, and aggressive respiratory care in the management of the esophagectomy patient.

Resection for Barrett's mucosa with high-grade dysplasia: Implications for prophylactic photodynamic therapy

OBJECTIVES Optimal therapy for Barretts mucosa is controversial. Photodynamic therapy has recently been introduced as a technique for eradicating Barretts mucosa with high-grade dysplasia. We sought to determine the incidence of invasive cancer and the outcomes after resection for high-grade dysplasia and to compare these results with published results of photodynamic therapy. METHODS We performed a retrospective review of patients who underwent esophagectomy for Barretts esophagus from 1985 to 1996 and completed a metaanalysis of published results of surgery for Barretts esophagus with high-grade dysplasia. RESULTS Thirteen men and two women with a mean age of 63 years underwent resection for Barretts esophagus with high-grade dysplasia. The operation was performed through a transhiatal approach in nine and a transthoracic approach in six patients. There was no operative mortality. The final pathologic study demonstrated dysplasia in four patients, carcinoma-in-situ in three, and invasive carcinoma in eight patients (53%). All patients are alive and none of the patients with invasive cancer has recurrent disease. A metaanalysis of published results of 119 patients undergoing resection demonstrated an operative mortality of 2.6%, an incidence of invasive cancer of 47%, and a 5-year survival in patients with invasive carcinoma of 82%. CONCLUSIONS A substantial percentage of patients with Barretts mucosa containing foci of high-grade dysplasia have invasive carcinoma at the time of diagnosis. Resection is accompanied by a low operative risk, achieves an excellent long-term outcome, and should remain the standard therapy for Barretts esophagus with high-grade dysplasia.

Sex-associated differences in presentation and survival in patients with lung cancer.

A retrospective study of 478 men and 294 women with primary lung cancer was conducted to characterize sex-associated differences in their presentation and survival. At the time of diagnosis, women were younger than men (mean age, 57.4 +/- 10.4 v 60.2 +/- 9.9 years, respective; P = .0007). Men were more likely to be current or previous smokers (94% v 84%; P less than .005), and in patients with a positive smoking history, cigarette consumption was greater in men (52.2 v 40.2 pack years; P = .0001). The proportion of adenocarcinomas compared with squamous cancers was high in women (45% v 23%), while these cell types were equally represented in men. The majority of patients in both sex groups had regionally advanced or metastatic disease at diagnosis. Survival was related to age, stage at presentation and cell type. In addition, sex was found to be an independent prognostic factor for survival. Women with tumors of all cell types lived longer than their male counterparts (P less than .0001), and survival by stage in patients with nonsmall-cell cancers was greater for women than it was for men. These data demonstrate that important sex-associated differences exist in presentation and survival from lung cancer. Such differences should be considered when planning and analyzing clinical trials.

Sleeve lobectomy or pneumonectomy: optimal management strategy using decision analysis techniques

BACKGROUND The choice between sleeve lobectomy and pneumonectomy is controversial for patients with early-stage lung cancer and who have acceptable lung function. METHODS We performed a meta-analysis of results of sleeve lobectomy and pneumonectomy published in English from 1990 to 2003. A decision model was developed with 5-year survival, quality-adjusted life years (QALY), and cost effectiveness as the outcomes, and sensitivity analyses were performed. RESULTS The model favored sleeve lobectomy (3.5 percentage point survival advantage) when the reward was 5-year survival; the results were influenced primarily by the 5-year survival rates for patients who did not develop recurrent cancer. Sleeve lobectomy was strongly favored when the reward was QALY (1.53 QALY advantage). Sleeve lobectomy was more cost effective than pneumonectomy, and had an incremental cost effectiveness ratio of

Ethnic Differences and Functional Analysis of MET Mutations in Lung Cancer

1,300/QALY. CONCLUSIONS In patients with anatomically appropriate early-stage lung cancer, sleeve lobectomy offers better long-term survival and quality of life than does pneumonectomy and is more cost effective.