Treatment of lung cancer with conventional radiation therapy is associated with suboptimal local tumor control and poor long-term survival. Poor local tumor control may result from inaccurate tumor targeting, failure to satisfactorily conform to dose distribution with the target volume, and/or inadequate radiation doses. Three-dimensional treatment planning is a radiotherapy technique that provides more accurate dose targeting via the direct transfer of three-dimensional anatomic information from diagnostic scans into the planning process. This technology can assist treatment planning by providing dose-volume histograms, an estimation of normal tissue complication probabilities, and facilitate dose escalation. Preliminary clinical studies suggest that this is a feasible approach worthy of additional study. The three-dimensional tools provide new opportunities to better understand radiation-induced changes in pulmonary function.

Treatment for small cell lung cancer has not improved substantially in the past 15 years. Some advances are being made in supportive care and by use of more intense concurrent thoracic radiotherapy. New agents such as the taxanes and the topoisomerase I inhibitors hold promise and are currently in phase III evaluation. The question whether dose intensity can improve the outcome of patients with small cell lung cancer has been raised for many years. Improving supportive care enhances our ability to test this question more thoroughly. This paper reviews the historical and current experience using high-dose therapy with hematopoietic stem cell support for the treatment of small lung cancer. Future directions are identified.

Small cell lung cancer (SCLC) is a common malignancy that is rapidly fatal if left untreated, with most patients surviving < 6 months. Currently, patients with SCLC are treated with chemotherapy with or without thoracic radiotherapy. Randomized trials have demonstrated the superiority of multiagent regimens over single-agent therapies, with the combination of cisplatin and etoposide being the initial regimen of choice for most patients, regardless of stage at presentation. Dose escalation, weekly chemotherapy, alternating noncross-resistant chemotherapy, and maintenance chemotherapy have been evaluated in SCLC, with no convincing data to date demonstrating an advantage for these strategies over conventional treatment strategies. Second-line therapy may be effective in selected patients, depending on the interval between primary treatment and recurrence, response to primary therapy, and the agents used for initial treatment. Radiotherapy is generally accepted as an essential component of optimal management of limited-stage disease, although sequencing, timing, fractionation, dose, and field size remain less than adequately defined. Finally, the routine use of prophylactic cranial irradiation remains controversial, and currently should be reserved for patients in complete remission.

Both imaging and image-directed biopsy play a major role in evaluating solitary pulmonary nodules. Imaging is used to determine whether the nodule is actually solitary or if multiple nodules are present. Once a nodule has been detected, imaging techniques can be used to characterize the nodule in terms of whether it is likely benign or malignant. As technology has improved, smaller nodules are now more easily detected, which may create a management dilemma. With the advent of video-assisted thoracoscopic techniques, however, sampling of these lesions has become much easier. Once a solitary pulmonary nodule is detected, image-guided biopsy is often considered, which can be undertaken using CT or fluoroscopy. Technical limitations, the location of the solitary pulmonary nodules, and clinical conditions must be considered when determining the role of image-guided biopsy. Other concerns include the role of on-site cytology and the use of more recent technical advances. Image-guided biopsy should be used as part of a multimodality approach to patient management, and decisions should be discussed with the radiologist and other caregivers to determine the cost-effectiveness and safety of the procedure for each patient.

The management of resectable non-small cell lung cancer (NSCLC) has been the focus of extensive investigation over the last decade. Nonetheless, existing management strategies are suboptimal for all stage groupings. The only exception is complete resection for stage IA NSCLC, in which a cure is achieved in 70 to 85% of patients. A number of studies demonstrate that adjuvant chemotherapy may be associated with some biological effect. Nonetheless, chemotherapy remains experimental and cannot be definitively recommended outside the context of a randomized trial. Radiation therapy appears to be associated with a reduction in local recurrence in stage II NSCLC. With regard to potentially resectable stage IIIA NSCLC, the results of randomized trials support the conclusion that induction chemotherapy followed by resection (with or without postoperative radiation) may enhance survival compared to that achieved with resection alone. Among patients with stage IIIA and IIIB NSCLC who are treated without resection, numerous phase III studies demonstrate that induction chemotherapy with definitive radiation improves outcome when compared to thoracic radiation therapy alone. While there may be an advantage for concurrent chemoradiation compared to sequential therapy, definitive results are not yet available to support this conclusion. While the magnitude of benefit associated with induction chemotherapy or chemoradiation in regionally advanced NSCLC is debatable, the results of multimodality studies provide a basis for optimism that real therapeutic progress is being achieved. Further study of therapeutic strategies that incorporate aggressive systemic treatment and local-regional therapy in stage IIIA and IIIB NSCLC is warranted. Moreover, completion of randomized studies focusing on the role of adjuvant chemotherapy in stage IB and stage II NSCLC should be given priority.

Most patients who receive a diagnosis of non-small cell lung cancer (NSCLC) have advanced disease and are not curable with surgery. Developments in the technology of radiation therapy (RT) have contributed to the broad utility of this treatment modality in both a curative and palliative capacity. Many patients at all stages, including those who are medically inoperable, may benefit from RT. Locally advanced NSCLC is treated commonly with combined modality therapy. Novel RT administration schedules and chemotherapy regimens for combined modality therapy are essential for improving the management of NSCLC. Additional benefits can be foreseen as new strategies for patient selection emerge.

Survival following surgical resection of non-small cell lung cancer (NSCLC) has improved since the 1960s, although the 5-year survival rate remains low. This article provides an overview of the role of surgery for NSCLC stages I-III, with a focus on optimizing long-term survival in those patients with resectable disease. Topics explored include diagnosis and staging, indications for resection, types of resection, and indications for adjuvant therapy. A review of the literature indicates a clear survival advantage for complete resection, and is suggestive of an advantage for mediastinal lymph node dissection (vs lymph node sampling) and neoadjuvant therapy (vs adjuvant therapy).

Strategies for the early detection of lung cancer are being investigated in an attempt to improve the poor prognosis associated with the disease. Such approaches, which include the identification of biomarkers for preclinical disease, must be integrated into multimodal cancer prevention strategies. Recent investigations have identified potential markers of early disease, including heterogeneous nuclear ribonucleoprotein, although the use of multiple markers may be required to provide the sensitivity and specificity necessary for mass screening. Early detection necessitates the development of effective chemoprevention strategies for the airway-confined phase of lung cancer. Current research efforts explore the utility of direct drug delivery, such as with the use of aerosolized delivery of retinoids, to maximize delivery of the active agent to the site of early lung cancer while avoiding systemic adverse effects.

Cigarette smoking is an intractable public health problem and the single largest risk factor for a variety of malignancies, including lung cancer. Worldwide, about 3 million people die each year of smoking-related disease, and this is expected to increase to > 10 million deaths per year. The Agency for Health Care Policy and Research has published a clinical practice guideline detailing available outcome data for various smoking cessation strategies. In particular, it has been recommended that all patients be screened for smoking status on every health-care visit, and that all patients who smoke be strongly advised to quit and offered assistance to do so. Health-care providers play a vital role in the effort to reduce the prevalence of smoking by delivering smoking cessation advice, supporting community-based efforts to control tobacco, and becoming involved in the tobacco control debate.

The definition of a standard therapy for resectable esophageal cancer remains a clinical controversy. In the past decade, a variety of strategies have been developed in an attempt to improve local control and decrease the all too common problem of distant metastases. Preoperative treatment with radiotherapy or chemotherapy has been proved to be feasible, although neither strategy has resulted in improved survival rates. More recently, concurrent, neoadjuvant chemoradiation has been utilized with encouraging pathologic responses. Equally important is the recognition that such aggressive therapy does not lead to worse surgical outcomes. The evidence for the safety, feasibility, and efficacy of induction therapy followed by esophagectomy is presented in the context of developing a rational methodology to allow for the ongoing modification of standards of care in the management of this difficult disease.

Cancer of the esophagus and gastroesophageal junction remains a virulent malignancy with an overall poor prognosis. Especially in the Western hemisphere, the incidence of adenocarcinoma is sharply rising. Over the last two decades, surgery has become the mainstay of treatment. Decreased surgical mortality and standardization of oncologic principles focusing on the completeness of resection are believed to be responsible for the improved 5-year survival rates, which are reaching > or = 30%. Until now, there has been no proven benefit from combined neoadjuvant treatment modalities using chemotherapy or chemoradiotherapy except for the subset of patients showing a complete response at pathologic examination. Further research should focus on new chemotherapeutic agents and the development of molecular markers that allow better identification of candidates for multimodality regimens.

Malignant pleural mesothelioma remains a therapeutic and diagnostic problem. Translational mechanisms for treatment of the disease are emerging from newly learned characteristics of the tumor on a molecular, cellular, and extracellular basis. Although slow to reach the clinical arena, these potential strategies do show proof of principle in the in vitro and in vivo settings, and some, including adenoviral molecular chemotherapy, have completed phase I testing. This review describes the rationale and status of these newer treatment ideas.

Long-term glucocorticoid (GC) therapy has been instrumental in decreasing morbidity and mortality in a variety of chronic inflammatory diseases, including persistent asthma. Long-term GC therapy is also widely prescribed for COPD. One of the important and often unrecognized side effects of chronic GC therapy is secondary osteoporosis. The risk of GC-induced bone loss is roughly correlated with daily dose, duration, and total cumulative lifetime dose of GC treatment. Oral prednisone increases the risk of bone loss and fracture. High doses of inhaled GCs may also increase the risk of osteopenia/osteoporosis, but the risk appears to be less than that associated with oral GCs. Hormone replacement therapy, oral and parenteral bisphosphonates, supplemental calcium and vitamin D, calcitonin, and fluoride compounds have been used, experimentally, in the management of GC-induced bone loss. Asthma and COPD specialists are key prescribers of oral and inhaled steroids and are likely to encounter patients with significant bone loss. Despite known risk factors and the availability of reliable diagnostic tools to recognize bone loss, the opportunity to slow, reverse, and treat bone loss is often missed. We present a review of the current literature regarding the incidence, treatment, and prevention of osteopenia/osteoporosis secondary to chronic GC therapy in adult asthma and COPD patients. Guidelines are presented regarding the identification of patients at risk for developing GC-induced secondary bone loss, and therapeutic alternatives are discussed.

To report the first series of patients with severe airway manifestations of relapsing polychondritis (RP) that were managed successfully with self-expandable metallic stents, and to review the literature.

Skeletal muscle plays an important role in respiratory and cardiovascular physiology. The ability to measure metabolic changes in skeletal muscle has been enhanced with the advent of magnetic resonance spectroscopy (MRS). MRS measurements have been used to understand the metabolic control of respiration and to evaluate metabolic changes in the muscle in patients with respiratory and cardiac diseases. The key to the respiratory control measurements is the ability to measure intracellular pH with MRS. Muscle oxidative metabolism has been measured in two ways: during steady-state exercise and using recovery kinetics. The similarities in the metabolic findings for pulmonary and coronary disease suggest the potential for some interesting common pathways.

Among adult patients with obstructive sleep apnea syndrome (OSAS), adherence to continuous positive airway pressure (CPAP) treatment is approximately 40%, according to recent well-designed studies that evaluated outcomes other than adherence as a primary end point. This finding suggests the need for the improvement of the adult OSAS treatment approach, either by improving adherence to CPAP treatment or by developing effective alternatives to CPAP. Technologic advances have allowed for the development of new treatments for OSAS that include automatic CPAP and innovative airway procedures. Studies evaluating the application of these new technologies are reviewed. These technologic advances can be viewed as possible improvements over the existing treatment approach only if the risks and benefits of each new treatment are well understood by OSAS patients and their physicians.

This review provides an update on the various techniques that are available to monitor patients during mechanical ventilation with an emphasis on clinical observations and applications in critically ill patients.