Malcolm M. DeCamp

Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma : results in 183 patients

OBJECTIVESnOur aim was to identify prognostic variables for long-term postoperative survival in trimodality management of malignant pleural mesothelioma.nnnMETHODSnFrom 1980 to 1997, 183 patients underwent extrapleural pneumonectomy followed by adjuvant chemotherapy and radiotherapy.nnnRESULTSnForty-three women and 140 men (age range 31-76 years) had a median follow-up of 13 months. The perioperative mortality rate was 3.8% (7 deaths) and the morbidity, 50%. Survival in the 176 remaining patients was 38% at 2 years and 15% at 5 years (median 19 months). Univariate analysis identified 3 prognostic variables associated with improved survival: epithelial cell type (52% 2-year survival, 21% 5-year survival, 26-month median survival; P =.0001), negative resection margins (44% at 2 years, 25% at 5 years, median 23 months; P =.02), and extrapleural nodes without metastases (42% at 2 years, 17% at 5 years, median 21 months; P =.004). Using the Cox proportional hazards, the relative risk of death was calculated for nonepithelial cell type (OR 3.0, CI 2.0-4.5; P <.0001), positive resection margins (OR 1.7, CI 1.2-2.6; P =.0082), and metastatic extrapleural nodes (OR 2.0, CI 1.3-3.2; P =.0026). Thirty-one patients with 3 positive variables had the best survival (68% 2-year survival, 46% 5-year survival, median 51 months; P =.013). A previously published staging system using these variables stratified survival (P <.05).nnnCONCLUSIONSn(1) Multimodality therapy including extrapleural pneumonectomy is feasible in selected patients with malignant pleural mesotheliomas, (2) pre-resectional evaluation of extrapleural nodes may select patients for radical therapy, (3) microscopic resection margins affect long-term survival, highlighting the need for further investigation of locoregional control, and (4) patients with epithelial, margin-negative, extrapleural node-negative resection had extended survival.

Prognostic models of thirty-day mortality and morbidity after major pulmonary resection ☆ ☆☆ ★

BACKGROUNDnA part of the prospective, multi-institutional National Veterans Affairs Surgical Quality Improvement Program was developed to predict 30-day mortality and morbidity for patients undergoing a major pulmonary resection.nnnMETHODSnPerioperative data were acquired from 194,319 noncardiac surgical operations at 123 Veterans Affairs Medical Centers between October 1, 1991, and August 31, 1995. Current Procedural Terminology code-based analysis was undertaken for major pulmonary resections (lobectomy and pneumonectomy). Preoperative, intraoperative, and outcome variables were collected. The 30-day mortality and morbidity models were developed by means of multivariable stepwise logistic regression with the preoperative and intraoperative variables used as independent predictors of outcome.nnnRESULTSnA total of 3516 patients (mean age 64 9 years) underwent either lobectomy (n = 2949) or pneumonectomy (n = 567). Thirty-day mortality was 4.0% for lobectomy (119/2949) and 11.5% for pneumonectomy (65/567). The preoperative predictors of 30-day mortality were albumin, do not resuscitate status, transfusion of more than 4 units, age, disseminated cancer, impaired sensorium, prothrombin time more than 12 seconds, type of operation, and dyspnea. When the intraoperative variables were considered, intraoperative blood loss was added to the preoperative model. In the presence of these intraoperative variables in the model, do not resuscitate status and prothrombin time more than 12 seconds were only marginally significant. Thirty-day morbidity, defined as the presence of 1 or more of the 21 predefined complications, was 23.8% for lobectomy (703/2949) and 25.7% for pneumonectomy (146/567). In multivariable models, independent preoperative predictors (P <.05) of 30-day morbidity were age, weight loss greater than 10% in the 6 months before surgery, history of chronic obstructive pulmonary disease, transfusion of more than 4 units, albumin, hemiplegia, smoking, and dyspnea. When intraoperative variables were added to the preoperative model, the duration of operation time and intraoperative transfusions were included in the model and albumin became marginally significant.nnnCONCLUSIONSnThis analysis identifies independent patient risk factors that are associated with 30-day mortality and morbidity for patients undergoing a major pulmonary resection. This series provides an initial risk-adjustment model for major pulmonary resections. Future refinements will allow comparative assessment of surgical outcomes and quality of care at many institutions.

Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma. Results in 120 consecutive patients.

OBJECTIVEnThe authors examine the feasibility and efficacy of trimodality therapy in the treatment of malignant pleural mesothelioma and identify prognostic factors.nnnBACKGROUNDnMesothelioma is a rare, uniformly fatal disease that has increased in incidence in recent decades. Single and bimodality therapies do not improve survival.nnnMETHODSnFrom 1980 to 1995, 120 patients underwent treatment for pathologically confirmed malignant mesothelioma at Brigham and Womens Hospital and Dana-Farber Cancer Institute (Boston, MA). Initial patient evaluation was performed by a multimodality team. Patients meeting selection criteria and with resectable disease identified by computed tomography scan or magnetic resonance imaging underwent extrapleural pneumonectomy followed by combination chemotherapy and radiotherapy.nnnRESULTSnThe cohort included 27 women and 93 men with a mean age of 56 years. Operative mortality rate was 5.0%, with a major morbidity rate of 22%. Overall survival rates were 45% at 2 years and 22% at 5 years. Two and 5-year survival rates were 65% and 27%, respectively, for patients with epithelial cell type, and 20% and 0%, respectively, for patients with sarcomatous or mixed histology tumors. Nodal involvement was a significant negative prognostic factor. Patients who were node negative with epithelial histology had 2- and 5-year survival rates of 74% and 39%, respectively. Involvement of margins at time of resection did not affect survival, except in the case of full-thickness, transdiaphragmatic invasion. Classification on the basis of a revised staging system stratified median survivals, which were 22, 17, and 11 months for stages I, II, and III, respectively (p = 0.04).nnnCONCLUSIONSnExtrapleural pneumonectomy with adjuvant therapy is appropriate treatment for selected patients with malignant mesothelioma selected using a revised staging system.

Relation between Preoperative Inspiratory Lung Resistance and the Outcome of Lung-Volume–Reduction Surgery for Emphysema

BACKGROUNDnSurgery to reduce lung volume has recently been reintroduced to alleviate dyspnea and improve exercise tolerance in selected patients with emphysema. A reliable means of identifying patients who are likely to benefit from this surgery is needed.nnnMETHODSnWe measured lung resistance during inspiration, static recoil pressure at total lung capacity, static lung compliance, expiratory flow rates, and lung volumes in 29 patients with chronic obstructive lung disease before lung-volume-reduction surgery. The changes in the forced expiratory volume in one second (FEV1) six months after surgery were related to the preoperatively determined physiologic measures. A response to surgery was defined as an increase in the FEV1 of at least 0.2 liter and of at least 12 percent above base-line values.nnnRESULTSnOf the 29 patients, 23 had some improvement in FEV1 including 15 who met the criteria for a response to surgery. Among the variables considered, only preoperative lung resistance during inspiration predicted changes in expiratory flow rates after surgery. Inspiratory lung resistance correlated significantly and inversely with improvement in FEV1 after surgery (r=-0.63, P<0.001). A preoperative criterion of an inspiratory resistance of 10 cm of water per liter per second had a sensitivity of 88 percent (14 of 16 patients) and a specificity of 92 percent (12 of 13 patients) in identifying patients who were likely to have a response to surgery.nnnCONCLUSIONSnPreoperative lung resistance during inspiration appears to be a useful measure for selecting patients with emphysema for lung-volume-reduction surgery.

Pulmonary intravascular macrophages: their contribution to the mononuclear phagocyte system in 13 species

The organ uptake of intravenously injected particles was examined in 13 species. All animals were injected intravenously with 198Au colloid and magnetic iron oxide particles. Vascular clearance kinetics of 198Au colloid was similar in all species. Pulmonary uptake of 198Au colloid ranged from 17 to 60% in sheep, calves, pigs, and cats but was <1.1% in monkeys, hyraxes, rabbits, guinea pigs, rats, mice, and chickens. For iron oxide particles, pulmonary uptake ranged from 80 to 99% in sheep, calves, pigs, goats, and cats and 15 to 18% in hamsters, hyraxes, and monkeys and was <10% in rabbits, chicken, mice, rats, and guinea pigs. In all species, the bulk of the remainder of particle uptake was in the liver. Pulmonary intravascular macrophages are the cellular site of lung uptake in calves, cats, pigs, goats, and sheep, whereas monocytes and neutrophils predominate in other species. Kupffer cells were the site of uptake in the liver. Our data show marked species differences in the fate of circulating particles; ruminants, pigs, and cats have extensive pulmonary localization due to phagocytosis by pulmonary intravascular macrophages.The organ uptake of intravenously injected particles was examined in 13 species. All animals were injected intravenously with 198Au colloid and magnetic iron oxide particles. Vascular clearance kinetics of198Au colloid was similar in all species. Pulmonary uptake of 198Au colloid ranged from 17 to 60% in sheep, calves, pigs, and cats but was <1.1% in monkeys, hyraxes, rabbits, guinea pigs, rats, mice, and chickens. For iron oxide particles, pulmonary uptake ranged from 80 to 99% in sheep, calves, pigs, goats, and cats and 15 to 18% in hamsters, hyraxes, and monkeys and was <10% in rabbits, chicken, mice, rats, and guinea pigs. In all species, the bulk of the remainder of particle uptake was in the liver. Pulmonary intravascular macrophages are the cellular site of lung uptake in calves, cats, pigs, goats, and sheep, whereas monocytes and neutrophils predominate in other species. Kupffer cells were the site of uptake in the liver. Our data show marked species differences in the fate of circulating particles; ruminants, pigs, and cats have extensive pulmonary localization due to phagocytosis by pulmonary intravascular macrophages.

Longitudinal change in the BODE index predicts mortality in severe emphysema.

RATIONALEnThe predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients.nnnOBJECTIVESnTo determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival.nnnMETHODSnClinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components.nnnMEASUREMENTS AND MAIN RESULTSnThe entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components.nnnCONCLUSIONSnThe mBODE demonstrates short- and intermediate-term responsiveness to intervention in severe chronic obstructive pulmonary disease. Increase in mBODE of more than 1 point from baseline to 6, 12, and 24 months of follow-up was predictive of subsequent mortality. Change in mBODE may prove a good surrogate measure of survival in therapeutic trials in severe chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

The Role of Surgery in N2 Non ^ Small Cell Lung Cancer

Historical series document the poor survival (7-16% at 5 years) for patients with N2-positive, stage IIIA non–small cell lung cancer (NSCLC) treated with primary surgery. In 1994, two small randomized trials showed the superiority of induction chemotherapy followed by surgery over surgery alone for stage IIIA NSCLC. These findings, as well as subsequent studies showing the superiority of chemoradiotherapy over chemotherapy alone in nonoperable stage III disease, prompted investigations of preoperative chemoradiotherapy for N2-positve patients. As induction therapy improved, the use of resection in stage IIIA NSCLC was called into question. An Intergroup trial addressing this issue randomized 392 patients to induction chemoradiotherapy followed by surgery versus definitive chemoradiotherapy. Surgery following induction chemoradiotherapy was associated with a significant improvement in progression-free survival and almost a 50% reduction in local failure. As distant relapse is common, survival is likely to be enhanced only in those patients who respond to the systemic arm of treatment. Identification of genetic or biochemical markers of response, minimally invasive techniques to pathologically restage, or improved statistical or chemosensitivity analyses are needed to enhance our ability to select patients who will benefit from resection.

Lung Volume Reduction Surgery: Technique, Operative Mortality, and Morbidity

The objective of lung volume reduction surgery (LVRS) is the safe, effective, and durable palliation of dyspnea in appropriately selected patients with moderate to severe emphysema. Appropriate patient selection and preoperative preparation are prerequisites for successful LVRS. An effective LVRS program requires participation by and communication between experts from pulmonary medicine, thoracic surgery, thoracic anesthesiology, critical care medicine, rehabilitation medicine, respiratory therapy, chest radiology, and nursing. The critical analysis of perioperative outcomes has influenced details of the conduct of the procedure and has established a bilateral, stapled approach as the standard of care for LVRS. The National Emphysema Treatment Trial (NETT) remains the worlds largest multi-center, randomized trial comparing LVRS to maximal medical therapy. NETT purposely enrolled a broad spectrum of anatomic patterns of emphysema. This, along with the prospective, audited collection of extensive demographic, physiologic, radiographic, surgical and quality-of-life data, has positioned NETT as the most robust repository of evidence to guide the refinement of patient selection criteria for LVRS, to assist surgeons in providing optimal intraoperative and postoperative care, and to establish benchmarks for survival, complication rates, return to independent living, and durability of response. This article reviews the evolution of current LVRS practice with a particular emphasis on technical aspects of the operation, including the predictors and consequences of its most common complications.

Physiological and Computed Tomographic Predictors of Outcome from Lung Volume Reduction Surgery

RATIONALEnPrevious investigations have identified several potential predictors of outcomes from lung volume reduction surgery (LVRS). A concern regarding these studies has been their small sample size, which may limit generalizability. We therefore sought to examine radiographic and physiologic predictors of surgical outcomes in a large, multicenter clinical investigation, the National Emphysema Treatment Trial.nnnOBJECTIVESnTo identify objective radiographic and physiological indices of lung disease that have prognostic value in subjects with chronic obstructive pulmonary disease being evaluated for LVRS.nnnMETHODSnA subset of the subjects undergoing LVRS in the National Emphysema Treatment Trial underwent preoperative high-resolution computed tomographic (CT) scanning of the chest and measures of static lung recoil at total lung capacity (SRtlc) and inspiratory resistance (Ri). The relationship between CT measures of emphysema, the ratio of upper to lower zone emphysema, CT measures of airway disease, SRtlc, Ri, the ratio of residual volume to total lung capacity (RV/TLC), and both 6-month postoperative changes in FEV(1) and maximal exercise capacity were assessed.nnnMEASUREMENTS AND MAIN RESULTSnPhysiological measures of lung elastic recoil and inspiratory resistance were not correlated with improvement in either the FEV(1) (R = -0.03, P = 0.78 and R = -0.17, P = 0.16, respectively) or maximal exercise capacity (R = -0.02, P = 0.83 and R = 0.08, P = 0.53, respectively). The RV/TLC ratio and CT measures of emphysema and its upper to lower zone ratio were only weakly predictive of postoperative changes in both the FEV(1) (R = 0.11, P = 0.01; R = 0.2, P < 0.0001; and R = 0.23, P < 0.0001, respectively) and maximal exercise capacity (R = 0.17, P = 0.0001; R = 0.15, P = 0.002; and R = 0.15, P = 0.002, respectively). CT assessments of airway disease were not predictive of change in FEV(1) or exercise capacity in this cohort.nnnCONCLUSIONSnThe RV/TLC ratio and CT measures of emphysema and its distribution are weak but statistically significant predictors of outcome after LVRS.

Patterns of recurrence and outcome for patients with clinical stage II non-small-cell lung cancer.

Forty-six patients with pathologic clinical stage II non-small-cell lung carcinoma underwent resection with or without adjuvant radiotherapy from 1989 through 1994. These patients were analyzed to determine patterns of recurrence and survival. Surgery consisted of pneumonectomy for 11 patients, bilobectomy for two patients, lobectomy for 29 patients, and wedge or segmental resection for four patients. Adjuvant radiotherapy was delivered to 29 patients, and the median total dose was 54 Gy (range, 44-60 Gy). Median follow-up time was 23 months for all patients and 25 months for surviving patients. Twenty-six of 46 patients have had recurrence. The site of first recurrence was locoregional for 9 of 46 patients (20%) and distant for 17 of 46 patients (37%). The median time to locoregional recurrence was 18 months for patients treated with radiotherapy and 13 months for patients treated without radiotherapy. An isolated locoregional recurrence (with no simultaneous distant recurrence) was seen in 2 of 28 evaluable patients (7%) treated with radiotherapy compared with 3 of 17 patients (18%) not treated with radiotherapy. For all patients, the 3-year disease-free survival rate was 52%, and the overall survival rate was 52%. Among patients treated with radiotherapy, the 3-year disease-free survival and overall survival rates were 56% and 56%, respectively, compared with 46% and 43%, respectively, for patients who did not receive radiotherapy (p values were not significant). The locoregional recurrence rate was 33% for patients with adenocarcinoma and 15% for those with squamous cell carcinoma. The distant recurrence rates by histologic characteristic were 56% and 20%, respectively. For patients with clinical stage II non-small-cell lung cancer, postoperative radiotherapy appears to improve locoregional control. However, the preponderance of recurrences remains distant. Further study is warranted with special emphasis on control of systemic disease.