Gas flow during bronchoscopic ablation therapy causes gas emboli to the heart: a comparative animal study.

BACKGROUND: Thermal ablation is one of the most commonly used modalities to treat central airway obstruction. Both laser and argon plasma coagulation (APC) have been reported to cause gas emboli and cardiac arrest. We sought to determine whether bronchoscopic ablation therapy can result in systemic gas emboli, correlate their presence with the rate of gas flow, and establish whether a zero-flow (ZF) modality would result in the significant reduction or elimination of emboli. METHODS: CO(2) laser delivered through a photonic bandgap fiber (PBF) and APC were applied in the trachea and mainstem bronchi of six anesthetized sheep at varying dosages and gas flow rates. Direct epicardial echocardiography was used to obtain a four-chamber view and detect gas emboli. RESULTS: The presence of gas flow accompanying APC and the CO(2) laser with forward flow correlated significantly with the appearance of gas bubbles in the atria. A definite dose response was observed between the gas flow rate and the number of bubbles seen. When the CO(2) laser was delivered through a PBF with ZF to the trachea or bronchi, no bubbles were observed. CONCLUSION: Bronchoscopic thermal ablation therapy using gas flow is associated with gas emboli in a dose-dependent fashion. The use of the flexible PBF with ZF is not associated with the development of gas emboli. Further study is required to determine whether a clinically safe threshold of gas emboli exists, and the relationships among the pathologic depth of tissue destruction, gas flow, pulse duration, and the development of gas emboli.

High risk of brain metastases in surgically staged IIIA non-small-cell lung cancer patients treated with surgery, chemotherapy, and radiation.

PURPOSE: Lung cancer is the leading cause of cancer mortality in the United States. We sought to review our experience with surgically staged IIIA (N2) non-small-cell lung cancer (NSCLC), focusing on the patterns of failure in consecutively treated patients from 1988 to 2000. PATIENTS AND METHODS: The records of 177 patients were reviewed. Collected data included stage, histology, use of chemotherapy and radiation, initial and subsequent sites of failure, and survival. One hundred twenty-four patients have died; follow-up time is 35 months among the remaining patients. RESULTS: The median survival from the time of surgery was 21.0 months, with a 3-year overall survival (OS) of 34%. Nodal downstaging to N0 disease correlated with OS and progression-free survival (PFS; P < .001). The most common site of recurrence was the brain. Thirty-four percent of patients recurred in the brain as their first site of failure, and 40% of patients developed brain metastases at some point in their course. In patients with nonsquamous histology and residual nodal involvement after neoadjuvant therapy, the risk of brain metastases was 53% at 3 years. CONCLUSION: Patients treated with neoadjuvant therapy for N2-positive stage IIIA NSCLC enjoy an advantage in both OS and PFS if their lymph node status is downstaged to N(0). Because brain metastases constitute the most common site of failure in these patients, future studies focusing on prophylaxis of brain metastases may improve the outcome in patients with stage IIIA NSCLC.

Induction docetaxel and carboplatin followed by weekly docetaxel and carboplatin with concurrent radiotherapy, then surgery in stage III non-small cell lung cancer: a Phase I study.

PURPOSE: To determine the maximum-tolerated dose of docetaxel (DOC) in combination with carboplatin (CAR) and thoracic radiotherapy (RT), in the setting of trimodality treatment of patients with stage III non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Thirty-two patients with biopsy-proven stage IIIA (n = 20) or IIIB (n = 12) NSCLC were given two initial cycles of CAR (area under the curve = 6) and DOC (75 mg/m(2)), subsequent RT (54 Gy) with concurrent weekly CAR (area under the curve = 2), and DOC at six dose levels from 10 to 40 mg/m(2), then surgery if the patient's disease was resectable. RESULTS: Three patients did not complete induction computed tomography (CT). Twenty-nine patients received concurrent CT/RT. Fifteen patients were eligible for surgery. Dose-limiting toxicities occurred in 2 patients, at dose levels two (atrial fibrillation) and three (transaminitis). The maximum-tolerated dose, as defined by the protocol, was not reached, although grade 3 and 4 toxicities were encountered at all dose levels. The most common more than or equal to grades 3 toxicities were neutropenia, nausea, vomiting, and fatigue. Four patients (13.3%) responded to induction CT. Ten patients (38.5%) responded to CT/RT. Eight surgical patients (57.1%) were downstaged, including 3 pathologic complete responses. Median relapse free and overall survivals are 8.5 and 12 months. One-year and estimated 2-year survival rates are 56.3 and 34.3%. CONCLUSION: This new regimen for stage III NSCLC of induction CAR/DOC, then weekly CAR/DOC with concurrent RT followed by surgery, can be safely administered and offers encouraging results. DOC at 30 mg/m(2) in combination with CAR and RT is recommended for Phase II study.

Relationship between a history of antecedent cancer and the probability of malignancy for a solitary pulmonary nodule.

STUDY OBJECTIVES: To determine the probability of malignancy for a solitary pulmonary nodule (SPN) as a function of cancer history. SETTING AND DESIGN: Patients who had undergone resection of SPNs at Brigham and Women's Hospital between August 1989 and October 1998 were analyzed. The cohort was split into the following three groups: no history of cancer; history of lung cancer; and history of extrapulmonary malignancy. The histology of the SPN was determined after excision. Logistic regression was used to evaluate the effect of covariates on the probability of malignancy. MEASUREMENTS AND RESULTS: A total of 1,104 patients (55% women; median age, 64 years; age range, 17 to 88 years) underwent removal of 353 benign lesions (32%), 638 non-small cell lung cancers (NSCLCs) [58%], and 113 metastases (10%). Antecedent cancer history was significantly associated with final diagnosis (p < 0.0001), with SPNs being malignant in 63% of patients with no previous cancer, 82% of those with a history of lung cancer (NSCLC, 80%; metastases, 2%), and 79% of patients with history of extrapulmonary cancer (NSCLC, 41%; metastases, 38%). There was no difference in the cause of SPNs between patients with a history of a single cancer and those with a history of multiple cancers. The probability of a benign cause ranged between 62% for nodules < 1 cm to 17% when nodules were > 3 cm, if the patient had no history of cancer (p < 0.0001). The probability of an SPN being benign was cut in half if there was a history of cancer. Among patients with previous extrapulmonary malignancy, age, smoking history, and histology were predictors of diagnosis (p < 0.0001). These variables were used to construct a clinical score to predict the probability of an SPN being a NSCLC or metastasis in these patients. CONCLUSIONS: A history of cancer is an important predictor of the probability of malignancy in new SPNs. Metastases from previous cancer account for almost half of SPNs seen among patients in this subgroup. Diagnosis depends on the histology of previous malignancies, smoking history, age, and size of the SPN.

Menopausal effects on presentation, treatment, and survival of women with non-small cell lung cancer.

BACKGROUND: Small population studies have reported higher survival rates for women than men with non-small cell lung carcinoma (NSCLC). Because human NSCLC cells express estrogen receptors, we evaluated hormonally active and inactive women to identify biologically mediated differences. METHODS: A total of 14,676 US women with stage I through IV primary non-small cell lung cancer (NSCLC) from the 1992 to 1997 Surveillance, Epidemiology, and End Results database were grouped into two categories based on the average menopausal age of 51 years as defined by the American College of Obstetricians and Gynecologists: ages 31 to 50 premenopausal (n = 2,230, 15%) and ages 51 to 70 postmenopausal (n = 12,446, 85%). Extreme ages were excluded. Statistics were calculated with chi(2) or Mann-Whitney tests, Kaplan-Meier estimates with log-rank tests, and Cox proportional hazards models. RESULTS: Premenopausal women more commonly presented with advanced clinical stage, less favorable histology (adenocarcinoma), and poorly differentiated tumors, and more often underwent pneumonectomies. Surgery with curative intent was performed in 31% premenopausal and 33% postmenopausal women (p = 0.03). Overall survival for premenopausal and postmenopausal women was not significantly different (median 10 and 9 months, all stages; 70 and 71 months, stages I and II). Adjusting for significant covariates (stage, histology, size, grade, extent of surgery), postmenopausal women had higher lung-cancer-related deaths (hazard ratio, 1.14; 95% confidence interval, 1.03 to 1.27). CONCLUSIONS: Premenopausal women presented more often with advanced disease and underwent more extensive resection, yet had survival advantage after covariate adjustment. Additionally, postmenopausal women had a survival advantage compared with their male counterparts. Results suggest that estrogen exposure creates a milieu that may confer a protective effect through some yet unknown mechanisms that determine outcome of the neoplastic process and warrant further investigation.

Section I: epidemiological review.

The incidence of esophageal adenocarcinoma has increased tremendously in the United States and other Western countries over the past 30 years while the incidence of esophageal squamous cell carcinoma has remained unchanged. The rate of increase in incidence is higher than for any other cancer. The reasons for this are multifactorial. Despite this, esophageal cancer remains a relatively uncommon malignancy. Barrett's esophagus (BE) is the most important risk factor for the development of esophageal adenocarcinoma and is believed to be the precursor lesion for most. The risk of developing esophageal adenocarcinoma from known BE is estimated to be 0.5% per patient year. Persistent high-grade dysplasia in BE is a sensitive indicator for the development of esophageal adenocarcinoma. However, only a minority of patients with BE are ever diagnosed and, therefore, surveillance endoscopy in Barrett's patients has failed to affect the incidence of esophageal adenocarcinoma. The relationship of Helicobacter pylori to esophageal adenocarcinoma is complex, but nonsteroidal antiinflammatory drugs may confer protection against the development of this cancer. Fortunately, improved survival is being seen with both squamous cell esophageal carcinoma and esophageal adenocarcinoma. Additional study is required to better determine the risk factors for the development of esophageal cancer, and epidemiologic understanding will prove important in developing methods of detection and therapeutic intervention for this disease.

Smoking cessation is challenging even for patients recovering from lung cancer surgery with curative intent.

BACKGROUND: Although it is recommended that smokers undergoing surgery for lung cancer quit smoking to reduce post-operative complications, few studies have examined patterns of smoking in the peri-operative period. The goals of this study were to determine: (1) patterns of smoking during post-operative recovery, (2) types of cessation strategies used to quit smoking, and (3) factors related to smoking after lung cancer surgery. METHODS: Data were collected from 94 patients through chart review, tobacco, health status, and symptom questionnaires at 1, 2, and 4 months after surgery. Smoking status was assessed through self-report and urinary cotinine measurement. RESULTS: Eighty-four patients (89%) were ever-smokers and 35 (37%) reported smoking at diagnosis. Thirty-nine (46%) ever-smokers remained abstinent, 13 (16%) continued smoking at all time-points, and 32 (38%) relapsed. Ten (46%) of those who relapsed were former-smokers and had not smoked for at least 1 year. Sixteen (46%) of those who were smoking at diagnosis received cessation assistance with pharmacotherapy being the most common strategy. Factors associated with smoking during recovery were younger age and quitting smoking < or =6 months before the diagnosis of lung cancer. Factors that were marginally significant were lower educational level, male gender, lower number of comorbidities, and the presence of pain. CONCLUSION: Only half of those who were smoking received assistance to quit prior to surgery. Some patients were unable to quit and relapse rates post-surgery were high even among those who quit more than 1 year prior. Innovative programs incorporating symptom management and relapse prevention may enhance smoking abstinence during post-operative care.

Pleural biopsy: a reliable method for determining the diagnosis but not subtype in mesothelioma.

BACKGROUND: Survival after tri-modality therapy with extrapleural pneumonectomy (EPP) and postoperative chemoradiotherapy is longer for patients with epithelial MPM versus mixed or sarcomatoid subtypes, leading some to decline aggressive therapy for patients with nonepithelial histology. However, pathologic diagnosis of malignant pleural mesothelioma (MPM) and subclassification into one of the three histologic subtypes (epithelial, mixed, sarcomatoid) can be challenging. Pleural biopsy has been proposed as the diagnostic gold standard. We investigated the accuracy of open pleural biopsy for diagnosis and subtype identification in MPM. METHODS: Patients with suspected MPM routinely undergo open pleural biopsy to establish diagnosis. Those diagnosed definitively by pleural biopsy or cytology are offered pleurectomy or EPP dependent on stage and cardiorespiratory status. We reviewed medical records for all patients undergoing EPP at our institution, comparing tissue and subtype diagnosis at initial diagnostic biopsy versus definitive resection. RESULTS: Between 1988 and 2000, 305 of 332 consecutive patients undergoing EPP had MPM. One patient diagnosed with MPM at pleural biopsy was misclassified. Subtype analysis at pleural biopsy proved correct in 80% (226/282). Most patients (174/192) with epithelial subtype at final diagnosis were diagnosed correctly at pleural biopsy. However, 44% (45/103) with pathologic diagnosis of nonepithelial subtype at resection were initially misdiagnosed with the epithelial subtype. The sensitivity of pleural biopsy for epithelial MPM was 97% with a specificity of 56%. CONCLUSIONS: Open pleural biopsy is accurate and should be considered the gold standard diagnostic method for MPM. It is less sensitive for determining histologic subclass, particularly with nonepithelial subtypes.