Lymphoma, mediastinal cysts, and neurogenic neoplasms are the most common primary middle and posterior mediastinal tumors. Lymphoma may involve the anterior, middle and/or posterior mediastinum, frequently as lymphadenopathy or as a discrete mass. Foregut cysts are common congenital mediastinal cysts and frequently arise in the middle mediastinum. Pericardial cysts are rare. Schwannoma and neurofibroma are benign peripheral nerve neoplasms, represent the most common mediastinal neurogenic tumors, and rarely degenerate into malignant tumors of nerve sheath origin. Sympathetic ganglia tumors include benign ganglioneuroma and malignant ganglioneuroblastoma and neuroblastoma. Lateral thoracic meningocele is a rare cause of a posterior mediastinal mass.

Pulmonary alveolar microlithiasis (PAM) is characterized by deposition of calcium phosphate within the alveolar airspaces. There is currently no effective medical therapy and affected individuals may progress to end-stage lung disease requiring transplantation. Two patients with PAM underwent bilateral sequential lung transplantation. This study reviews the clinical manifestations of PAM and discusses the particular difficulties that may be encountered in the use of lung transplantation as treatment for this uncommon disease. Also addressed is the question of recurrence in the allograft.

Atrial fibrillation is the most common cardiac arrhythmia requiring treatment. Limitations of medical treatment have prompted development of nonpharmacologic therapies for this arrhythmia. These are aimed at ventricular rate control during atrial fibrillation, termination of the arrhythmia, and/or prevention of recurrences. Ventricular rate control can be achieved with transcatheter ablation or modification of the atrioventricular node. The MAZE operation is effective in preventing arrhythmia recurrence, but because it requires cardiac surgery, its appeal is limited. Development of the technique for direct transcatheter ablation of atrial fibrillation is eagerly anticipated and may represent the standard curative treatment of the future. In appropriately selected patients, implantable device therapy may play an important role in the treatment of paroxysmal atrial fibrillation.

The management of most thymomas is relatively straightforward: surgical resection remains the primary mode of therapy. However, the literature contains many contradictory points of view regarding histology and pathology, staging and its usefulness, the need for adjuvant therapy, and recently, the place of video-assisted surgery in the treatment of this tumor. This article is not a comprehensive guide to management but rather explores several of these controversial areas. Conclusions include the following: invasiveness remains the single most consistent factor in predicting outcome; surgery is the treatment of choice for thymoma whenever a complete resection can be accomplished; and incomplete resection may have some advantage over biopsy alone. The preponderance of evidence indicates that all thymomas except completely encapsulated stage I tumors should be treated with postoperative adjuvant radiation therapy in the hope of reducing the incidence of local relapse. Myasthenia can no longer be considered an adverse prognostic factor in thymoma; it may even confer a survival advantage, but this may be due to the preponderance of early-stage tumors discovered incidentally in myasthenic patients. Other associated autoimmune diseases confer a survival disadvantage. Demonstrating the equivalence of minimally invasive thoracoscopic approaches to standard thymectomy will take many years of investigation. Some promising reports on response to chemotherapy have led to the development of a phase II intergroup study to assess the value of chemotherapy in advanced thymoma.

Malignant pleural and pericardial effusions are a common problem in the treatment of patients with lung cancer, breast cancer, or lymphoma and may occur with any malignancy. These effusions are frequently symptomatic and, in the case of the pleural space, may be the presenting sign of cancer. In other patients, they represent markers of recurrent, disseminated, or advanced disease. Given the poor prognosis of most patients presenting with these effusions, reducing symptoms and improving quality of life are the primary goals of treatment. Permanent drainage and/or obliteration of the pleural or pericardial space are crucial to the effective management of the effusion and will provide long-term palliation. Immediate relief can be accomplished via external drainage, but definitive therapy may often also require interventional radiology, cardiology, and thoracic surgery, as well as medical and radiation oncology. The pathophysiology, diagnosis, and treatment of malignant pleural and pericardial effusions are discussed in this article.

The surgical management of pulmonary metastases remains controversial, as no randomized trials have compared surgical excision with nonoperative treatment (to our knowledge). A Medline-generated review of the literature was undertaken to determine the factors influencing survival following metastasectomy in published trials. In the absence of randomized comparative trials, data must remain inferential and circumstantial. However, the literature does support the anecdotal observation that patients with metastatic disease can achieve long-term survival following surgical excision, irrespective of the source of the primary neoplasm, if there is no demonstrable extrathoracic disease and complete excision of the pulmonary disease is possible. Other factors noted as influencing survival appear to be anecdotal and variable from report to report. Pulmonary metastasectomy should be considered in patients with sufficient pulmonary reserve when the lung is the only site of metastatic disease and the lesions can be totally excised. An algorithm is proposed for a logical approach to the problem.

This article reviews the indications, techniques, and results of brachytherapy in the treatment of non-small cell lung cancer (NSCLC) and selected chest neoplasms. Various isotopes and techniques are used to place radioactive sources directly into a tumor, tumor bed, or the chest. Brachytherapy techniques can be tailored to the clinical situation and can be in the form of permanent interstitial volume or planar implants (radioactive sources permanently imbedded into the tumor or tumor bed) or in the form of temporary interstitial or endoluminal implants (where radioactive sources irradiate a tumor bed over a certain length of time and then are removed). These treatments can be delivered over a short interval (high-dose rate [HDR]) or over a more protracted time (low-dose rate). HDR treatments can be used intraoperatively to deliver a large dose of radiation to a determined target area with selective sparing of surrounding normal structures. Different methods of delivering HDR intraoperative radiation are under investigation. Most reports on brachytherapy for chest malignancies are retrospective and come from a few single institutions. Most of the published data relate to the treatment of NSCLC, but other intrathoracic malignancies, such as malignant pleural mesothelioma and malignant thymoma, have been treated with brachytherapy. To our knowledge, no major randomized trials accurately assess or confirm these retrospective studies yet, complicating the interpretation of these results. Nevertheless, brachytherapy is of value in selected situations and offers the clinician and the patient an innovative method of delivering conformal high-dose radiation to a defined target with preferential sparing of normal surrounding structures. With continued innovations in the development of radioactive isotopes, computerized treatment planning and targeting, and source delivery, brachytherapy should continue to offer an attractive alternative and complement to conventional treatment approaches, and may offer patients improved local control and survival.

Prevention of cigarette smoking and early lung cancer detection remain important in our approach to the control of non-small cell lung cancer (NSCLC). In recent years, chemotherapy has emerged as a viable option in the treatment of NSCLC. The most impressive and widely confirmed evidence for this is the fact that chemotherapy can eradicate NSCLC micrometastases. Indeed, in some studies employing neoadjuvant chemotherapy followed by local surgery, pathology-confirmed complete remission rates as high as 20% have been reported. New agents showing preliminary activity in NSCLC include paclitaxel, vinorelbine, gemcitabine, and irinotecan (CPT-11). Certainly, however, there remains a need for novel, effective single-agent and combination chemotherapies. The seed/soil tumor concept, in which the seed consists of the tumor cells per se and the soil is the stroma containing the seeds, has proven helpful in devising new treatment strategies. Such strategies may include the use of antisoil agents, including antiangiogenesis, anti-invasion, and antimetastasis agents, both separately and particularly in conjunction with established antitumor agents. New therapeutic targets and methods of antitumor agent development based on modern molecular biology and pharmacology will provide a greater opportunity to improve the treatment of NSCLC.

The role of thoracic radiation therapy in the management of limited-stage small cell lung cancer (SCLC) is reviewed. Although chest irradiation has been used to treat SCLC for over four decades, its standard role in the management of limited-stage disease was established only during the last decade. Multiple prospective randomized trials have shown that the addition of thoracic radiation therapy to chemotherapy usually halves local failure rates, from >60% with chemotherapy alone to about 30% with chemoradiation therapy. Additionally, survival at 3 years is also improved by 50%, from 10% with chemotherapy alone to about 15% with chemoradiation therapy. However, issues relating to the timing, volume (ie, prechemotherapy vs postchemotherapy), and the dose fractionation scheme of thoracic radiation therapy in the treatment of limited-stage SCLC still remain unresolved. Recent review of the literature indicates the most optimal timing of thoracic radiation therapy appears to be concurrent with chemotherapy vs either a sequential or an alternating approach. Studies are currently under way evaluating the optimal volume and dose fractionation scheme to use in the delivery of thoracic radiation therapy. In summary, thoracic radiation therapy significantly improves both local chest control and survival in the treatment of limited-stage SCLC.

Small cell lung cancer (SCLC) occurs almost exclusively in smokers and represents 15 to 25% of all lung cancer histologic findings. It is distinguished from non-small cell lung cancer by its rapid tumor doubling time, high growth fraction, and early development of widespread metastases. Since patients with SCLC usually present with disseminated disease, treatment strategies have focused on systemic therapy. Single-agent and combination chemotherapy, as well as combined-modality therapy, have produced high response rates (80 to 100% for limited disease; 60 to 80% for extensive disease), but these tend to be short-lived (median duration, 6 to 8 months). Survival beyond 5 years occurs in only 3 to 8% of all patients with SCLC. At least 15 to 20 different chemotherapeutic agents have shown major activity against SCLC in both the untreated and relapsed settings, including etoposide, teniposide, cisplatin, carboplatin, ifosfamide, cyclophosphamide, vincristine, and doxorubicin. This paper reviews state-of-the-art treatment strategies being employed in the treatment of SCLC, including those incorporating high-dose intensive therapy, salvage therapy, new agents, thoracic radiotherapy, prophylactic cranial radiotherapy, surgical resection, and biologic response modifiers.

Lung cancer staging, based on anatomic extent of disease and described by the TNM staging system (T, primary tumor; N, regional lymph nodes; M, distant metastasis), is an important parameter for determining the clinical course of this disease. To evaluate the prognostic importance of TNM staging for lung cancer, we conducted a retrospective study analyzing survival rates according to TNM staging in 2,382 patients who had pulmonary resection for non-small cell lung cancer. Postoperatively, 3 patients were classified in stage 0, 796 in stage I, 304 in stage II, 719 in stage IIIA, 233 in stage IIIB, and 327 in stage IV. The 5-year survival rates for these patients were as follows: stage I, 68.5%; stage II, 46.9%; stage IIIA, 26.1%; stage IIIB, 9.0%; and stage IV, 11.2% (including ipsilateral, intrapulmonary metastases); 5-year survival rates for 140 patients with stage IV disease with intrapulmonary metastases in either the same lobe or another ipsilateral lobe were 17.8% and 8.3%, respectively. There was prognostic significance between stage I and stage II disease, stage II and stage IIIA disease, and stage IIIA and stage IIIB disease, but not between stage IIIB and stage IV disease. Only a few modifications will be required for the TNM staging system, which at present accurately reflects the prognosis of patients with lung cancer and is helpful in determining treatment.

The intrathoracic staging of lung cancer involves assessment of the primary tumor and potential sites of metastases. Imaging studies of the chest are sensitive in detecting intrathoracic abnormalities, but specific staging information generally requires a tissue biopsy. The instruments used to obtain this information include the bronchoscope, mediastinoscope, and thoracoscope. The complementary application of these instruments can provide valuable staging information while limiting the morbidity of surgical staging.

Radiology and surgery are not competing but are complementary modalities in the care of patients with lung cancer. In certain areas, such as evaluation of the solitary pulmonary nodule, radiologic studies can have an important impact on patient care. Mediastinal staging with imaging studies is inexact, and CT may be most effective as a road map for more definitive surgical staging. MRI currently offers no advantages over CT in staging of the mediastinum but can be helpful in evaluation of parts of the chest not well demonstrated on axial images. A discussion of newer nuclear medicine imaging modalities is included.

Lung cancer is now the leading cause of cancer deaths among women. In the United States, 64,300 women are expected to die of lung cancer in 1996. Smoking is responsible for about 80% of lung cancer cases. Unfortunately, the prevalence of smoking among women remains unacceptably high at about 22% and is expected to surpass the rate in men by the year 2000. Smoking rates are highest among young girls and the less educated. Whether lung cancer represents a different disease in women than in men is unclear. Data are conflicting regarding the magnitude of the relative risk of developing lung cancer due to smoking between the genders. There appears to be a difference in the relative distribution of lung cancer histologic features between men and women that is not explained entirely by differences in smoking patterns. Women who smoke appear to be at higher risk of developing small cell lung cancer than squamous cell lung cancer, whereas men who smoke have a similar risk for the two histologic conditions. Furthermore, women smokers are more likely to develop adenocarcinoma of the lung, and estrogens may play a causative role in this phenomenon. Data are unclear regarding whether the outcome of lung cancer treatment differs between genders. Solutions to the lung cancer epidemic among US women include (1) prevention of the disease by reducing smoking rates, (2) improving early detection methods, and (3) exploring new therapeutic strategies.

While intense controversy exists regarding screening for breast, colorectal, and prostate cancer, a consensus exists regarding lung cancer screening. All organizations recommend against any efforts to detect early lung cancer because each of four randomized controlled trials (RCTs) has failed to demonstrate a significant reduction in lung cancer mortality as a result of screening.

Thoracic radiotherapy is widely used in patients with non-small cell lung cancer. Its role as adjuvant treatment before or after surgery has not been established clearly. In patients with locally advanced disease, the main cause of failure is the absence of local control. Recently, three treatment approaches have shown a beneficial effect on overall survival in randomized trials conducted in this group of patients: sequential combination of thoracic radiotherapy and cisplatin-based chemotherapy, concomitant use of radiation and daily low-dose cisplatin therapy, and hyperfractionated accelerated radiotherapy. Another area that merits further investigation is the role of adjuvant surgery.

Preoperative evaluation of patients being considered for pulmonary resection is a common practice for both pulmonologists and internists. Traditionally, preoperative evaluation of this population has entailed identifying patients in whom pulmonary resection carries an unacceptably high risk of morbidity and mortality. However, recent advances in surgical technique and patient management have prompted a reconsideration of traditional preoperative approaches. This article reviews procedures currently used in the preoperative evaluation of patients considered for pulmonary resection, including the patient history, physical examination, and preoperative interventions, and addresses further evaluation of the high-risk patient.

Surgical resection remains the preferred treatment, when possible, in patients with non-small cell lung cancer (NSCLC). A complete resection is required to potentially improve survival of these patients. Lobectomy is the minimum resection of choice. En bloc resections of involved adjacent organs and structures are performed routinely with acceptable morbidity and mortality. Mediastinal lymph node dissection allows accurate surgical and pathologic staging of lymph node disease but has yet to be proven efficacious as a curative procedure. The standard approach to the hemithorax is via posterolateral thoracotomy. Recent muscle-sparing incisions and video-assisted techniques have been employed safely to accomplish goals of surgery. This article evaluates past and current approaches to the resection of NSCLC, and looks at the impact of route and extent of resection on survival of NSCLC patients.

Over the past decade and a half, several strategies have been developed to improve the survival of patients with esophageal cancer. Two strategies employ either neoadjuvant chemotherapy or chemoradiotherapy followed by surgery to improve local-regional control and decrease the incidence of distant metastases. A third strategy uses nonsurgical therapy as definitive treatment for patients without metastatic disease. Single-institution pilot trials and randomized comparative trials have been conducted evaluating each approach. The rationale for these trials, results, and current recommendations are presented.