External-beam radiation therapy in the treatment of diffuse tracheobronchial amyloidosis.

Tracheobronchial amyloidosis is characterized by deposits of amyloid in airway walls. No effective treatment is known. We describe a 59-year-old woman who presented with increasing symptoms of airway obstruction due to diffuse deposition of amyloid throughout her tracheobronchial tree. She was treated with external-beam radiation therapy (20 Gy) with marked improvement in her symptoms, effort tolerance, bronchoscopic appearance, and forced expiratory volume in 1 second (1.39 L to 1.97 L [42%]). This improvement was maintained during 21 months of follow-up.

Tracheobronchial foreign bodies.

Aspiration of tracheobronchial foreign bodies occurs more commonly in children, but under certain circumstances, it also can occur in adults. The most common symptoms are choking followed by a protracted cough. Physical examination findings include fever, stridor, retractions, and decreased breath sounds. Radiographic imaging can be helpful if the object aspirated is radiopaque or if there are signs of hyperexpansion on expiration. Negative-imaging studies, however, do not exclude the presence of a foreign body in the airway. The longer a foreign body resides in the airway, the more likely it is to migrate distally. When this occurs, symptoms of chronic cough and wheezing may mimic an asthmalike condition. Bronchoscopy is indicated in this situation to evaluate the airway thoroughly. If a foreign body is present, extraction can be performed with flexible or rigid bronchoscopy. If flexible bronchoscopy is attempted, it is imperative that the bronchoscopist is familiar with rigid bronchoscopy and has the equipment immediately available should danger to the airway occur. The procedure is generally safe and well tolerated. Many patients are managed under general anesthesia, but foreign bodies often can be removed with a flexible bronchoscope with the patient under local anesthesia. Surgery should be performed only as a last resort and rarely is necessary.

Strategic performance management: development of a performance measurement system at the Mayo Clinic.

Managing and measuring performance become exceedingly complex as healthcare institutions evolve into integrated health systems comprised of hospitals, outpatient clinics and surgery centers, nursing homes, and home health services. Leaders of integrated health systems need to develop a methodology and system that align organizational strategies with performance measurement and management. To meet this end, multiple healthcare organizations embrace the performance-indicators reporting system known as a "balanced scorecard" or a "dashboard report." This discrete set of macrolevel indicators gives senior management a fast but comprehensive glimpse of the organization's performance in meeting its quality, operational, and financial goals. The leadership of outpatient operations for Mayo Clinic in Rochester, Minnesota built on this concept by creating a performance management and measurement system that monitors and reports how well the organization achieves its performance goals. Internal stakeholders identified metrics to measure performance in each key category. Through these metrics, the organization links Mayo Clinic's vision, primary value, core principles, and day-to-day operations by monitoring key performance indicators on a weekly, monthly, or quarterly basis.

Solitary pulmonary nodules: clinical prediction model versus physicians.

OBJECTIVE: To determine whether a clinical prediction model developed to identify malignant lung nodules based on clinical data and radiologic lung nodule characteristics could predict a malignant lung nodule diagnosis with higher accuracy than physicians. MATERIAL AND METHODS: One hundred cases were obtained by using a stratified random sample from a retrospective cohort of 629 patients with newly discovered 4- to 30-mm radiologically indeterminate solitary pulmonary nodules (SPNs) on chest radiography. A chest radiologist, pulmonologist, thoracic surgeon, and general internist made predictions of a malignant lesion and recommendations for management (thoracotomy, transthoracic needle aspiration biopsy, or observation) on the basis of radiologic and clinical data used to develop the clinical prediction rule. The predictions of a malignant lung nodule were compared with the probability of malignant involvement from a previously validated clinical prediction model to identify malignant nodules on the basis of three clinical characteristics (age, smoking status, and history of cancer greater than or equal to 5 years previously) and three radiologic characteristics (nodule diameter, spiculation, and upper lobe location). RESULTS: Receiver operating characteristic analysis showed no significant difference between the logistic model and the physicians' predictions. Calibration curves revealed that physicians overestimated the probability of a malignant lesion in patients with low risk of malignant disease by the prediction rule; this finding suggests a potential for the decision rule to improve the management of patients with SPNs that are likely to be benign. CONCLUSION: The prediction model was not better than physicians' predictions of malignant SPNs. The prediction rule may have potential to improve the management of patients with SPNs that are likely to be benign.

Human immunodeficiency virus infection and pulmonary hypertension: two new cases and a review of 86 reported cases.

In this article, we describe pulmonary hypertension in two men (31 and 43 years of age) with human immunodeficiency virus (HIV) infection who were examined at Mayo Clinic Rochester. Among 88 reported cases (including the two current ones) of HIV- or acquired immunodeficiency syndrome (AIDS)-associated pulmonary hypertension, 61% were male; the age range was 2 to 56 years (mean, 32). Dyspnea was the usual initial symptom. Of the 74 patients in whom pulmonary artery pressure was recorded or calculated by echocardiography, systolic pressures ranged from 49 to 118 mm Hg (mean, 68). Of the 33 cases in which lung tissue was evaluated microscopically, 28 (85%) were of the plexogenic variant of pulmonary arterial hypertension. Of the other five cases examined histologically, three consisted of thrombotic pulmonary arteriopathy (one was due to recurrent thromboembolism, and the other two were due to in situ thrombosis), and two were of pulmonary venoocclusive disease. No correlation existed between either CD4 counts or a history of pulmonary infections and the development of pulmonary hypertension. In 15 of the 88 patients (17%), confounding factors for hypertensive pulmonary vascular disease were present, including coexisting liver disease in 13 and coagulation abnormalities in 2. In 83% of the patients, the development of pulmonary hypertension seems to have been related primarily to the chronic HIV infection. Pulmonary hypertension was more rapidly progressive in patients with HIV or AIDS than in those with primary pulmonary hypertension; the reported time intervals between onset of symptoms and diagnosis were 6 months and 30 months, respectively. The 1-year survival rate for patients with HIV and pulmonary hypertension was 51%, based on the follow-up data compiled from the 63 patients in whom it was described; this compares with a 1-year survival rate of 68% for patients with primary pulmonary hypertension. Death was considered a direct consequence of pulmonary hypertension in 29 (76%) of the 38 fatal cases.

Photodynamic therapy for bronchogenic carcinoma.

Photodynamic therapy has been used in the management of early lung cancer since the 1980s. It appears to be effective as a curative therapy for superficial squamous cell carcinomas and as palliative therapy in obstructive cancers of the tracheobronchial tree. New photosensitizers that have a deeper penetration and less photosensitivity are needed.

Photodynamic therapy for early stage squamous cell carcinoma of the lung.

OBJECTIVE: To study the effectiveness of photodynamic therapy (PDT) as a therapeutic strategy in roentgenographically occult squamous cell carcinoma of the lung. MATERIAL AND METHODS: A carefully selected group of 21 patients (with 23 cancers) who had early stage squamous cell carcinoma of the lung and were eligible for surgical treatment were offered PDT as an alternative to resection. Patients underwent close follow-up with bronchoscopic surveillance and were offered resection if cancer persisted after no more than two sessions of PDT. RESULTS: A complete response was identified in 15 patients (16 cancers) after an initial PDT session. A complete response that lasted longer than 12 months was noted in 11 patients (52%). After PDT, the minimal follow-up period was 24 months. A subsequent primary lung cancer developed in 5 of the 21 patients (24%). Ten patients ultimately had surgical treatment, in 3 (30%) of whom N1 disease was identified at the time of resection. Two patients refused a surgical procedure and received alternative therapy. Therefore, nine patients (43%) were spared an operation (95% confidence interval, 21.8 to 66.6%). The mean duration of follow-up for these nine patients was 68 months (range, 24 to 116). CONCLUSION: On the basis of this investigation, we can conclude with 95% confidence that at least 22% of patients with early stage squamous cell lung cancer who are candidates for PDT can be spared surgical resection.

Diagnostic tests for lung cancer.

Bronchogenic carcinoma is the leading cause of cancer death in both men and women in the United States. There has been little impact on the overall mortality from lung cancer in the past 20 years. Diagnostic tests such as routine chest x-ray and sputum cytology have proven to be ineffective in altering this mortality. The identification of risk factors, including obstructive lung disease and familial tendencies to develop lung cancer, may allow for specific strategies that will impact this mortality. Additionally, biological markers are being identified in sputum specimens that may allow identification of premalignant changes prior to morphologic changes seen in sputum cytology. Radiologic testing such as CT scans with contrast enhancement and positive emission tomography may also aid in the early detection of peripheral lung nodules. It is through the development of these new technologies that we have an opportunity to alter overall lung cancer mortality. Here we review several articles reporting exciting new diagnostic technology.

The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules.

BACKGROUND: A clinical prediction model to identify malignant nodules based on clinical data and radiological characteristics of lung nodules was derived using logistic regression from a random sample of patients (n = 419) and tested on data from a separate group of patients (n = 210). OBJECTIVE: To use multivariate logistic regression to estimate the probability of malignancy in radiologically indeterminate solitary pulmonary nodules (SPNs) in a clinically relevant subset of patients with SPNs that measured between 4 and 30 mm in diameter. PATIENTS AND METHODS: A retrospective cohort study at a multispecialty group practice included 629 patients (320 men, 309 women) with newly discovered (between January 1, 1984, and May 1, 1986) 4- to 30-mm radiologically indeterminate SPNs on chest radiography. Patients with a diagnosis of cancer within 5 years prior to the discovery of the nodule were excluded. Clinical data included age, sex, cigarette-smoking status, and history of extrathoracic malignant neoplasm, asbestos exposure, and chronic interstitial or obstructive lung disease; chest radiological data included the diameter, location, edge characteristics (eg, lobulation, spiculation, and shagginess), and other characteristics (eg, cavitation) of the SPNs. Predictors were identified in a random sample of two thirds of the patients and tested in the remaining one third. RESULTS: Sixty-five percent of the nodules were benign, 23% were malignant, and 12% were indeterminate. Three clinical characteristics (age, cigarette-smoking status, and history of cancer [diagnosis, > or = 5 years ago]) and 3 radiological characteristics (diameter, spiculation, and upper lobe location of the SPNs) were independent predictors of malignancy. The area (+/-SE) under the evaluated receiver operating characteristic curve was 0.8328 +/- 0.0226. CONCLUSION: Three clinical and 3 radiographic characteristics predicted the malignancy in radiologically indeterminate SPNs.

The documentation of thoracic endoscopy.

Thoracic endoscopy encompasses bronchoscopy, esophagoscopy, laryngoscopy, mediastinoscopy, and thoracoscopy (pleuroscopy). In this article, the role of documentation as it applies to bronchoscopy is discussed. However, the discussion is generally applicable to other thoracic endoscopy procedures.

Future therapeutic procedures.

Management of disorders of the tracheobronchial tree have advanced significantly since the first use of the rigid bronchoscope by Gustav Killian. The addition of the flexible bronchofiberscope by Shigeto Ikeda offered a second generation of new therapeutic opportunities. The future use of thoracic endoscopy will depend upon the application and improvement of technologies that currently exist in addition to those not yet developed. There are three current technologies which are being improved and may be applicable in the future management of diseases of the tracheobronchial tree and these include cryotherapy, electrosurgery, and photodynamic therapy.

Cytokine production at the site of disease in chronic eosinophilic pneumonitis.

Chronic eosinophilic pneumonitis (CEP) is characterized by longstanding respiratory symptoms accompanied by a massive pulmonary eosinophil infiltration. We hypothesized that cytokine(s) produced in the disease sites are implicated in the pathophysiology of CEP. We studied peripheral blood and bronchoalveolar lavage fluids (BALF) obtained from two lung segments of a patient with CEP. Seventy times more eosinophils were found in the BALF from an involved lung segment (showing patchy opacification on a chest roentgenogram) than from an uninvolved segment. The eosinophil-active cytokines interleukin-5 (IL-5), IL-6, and IL-10 were strikingly elevated in the BALF from the involved lung segment, whereas no or minimal levels of these cytokines were detectable in the BALF from the uninvolved segment or serum, respectively. Leukocytes in the involved lung segment, but not those in peripheral blood, expressed messenger ribonucleic acid (mRNA) for IL-5, IL-6, and IL-10. In contrast, IL-2, IL-3, IL-4, interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha) were not detected in any sample. These findings suggest that increased production of several cytokines, such as IL-5, IL-6, and IL-10, in the involved lung segment, but not in the uninvolved lung segment or peripheral blood, is a critical pathophysiologic feature of CEP.

Photodynamic therapy. Its use in the management of bronchogenic carcinoma.

Photodynamic therapy is an investigational treatment of various types of carcinoma. It involves a photosensitizing agent which, when exposed to light of the proper wavelength, forms toxic oxygen radicals that result in cell death. This article describes its current use in the management of bronchogenic carcinoma.

Tests for diagnosis and staging of bronchogenic carcinoma.

Bronchogenic carcinoma continues to be a significant cause of both morbidity and mortality. Despite the attempts to reduce exposure to known causative agents, such as tobacco, the incidence of lung cancer continues to rise. New methods are being developed to aid in the early detection and localization of lung cancer in hopes that overall survival can be improved. More accurate staging may prevent patients who have advanced disease from encountering the morbidity associated with thoracotomy. This review summarizes some of the new methods being evaluated to assist in the early diagnosis and staging of bronchogenic carcinoma.

Extrapulmonary lymphangioleiomyomatosis and lymphangiomatous cysts in tuberous sclerosis complex.

OBJECTIVE: To describe the clinical manifestations, imaging findings, and histologic features of extrapulmonary lymphangioleiomyomatosis (LAM) in the tuberous sclerosis complex (TSC). DESIGN: We retrospectively reviewed institutional medical records since 1940 to identify patients with TSC and extrapulmonary LAM. MATERIAL AND METHODS: Of 403 patients with TSC, 3 had pulmonary and extrapulmonary LAM and retroperitoneal lymphangiomatous cysts. The clinical, imaging, and histologic features of these three patients were summarized, including analysis of biopsy specimens by conventional histology, immunohistology, radiolabeled ligand-binding assays, and tissue culture. RESULTS: The three young women had characteristic dermatologic findings of TSC and pulmonary LAM. Two patients were of normal intelligence, and one had a recent history of contraceptive use. All three patients had intra-abdominal lymphangiomatous cysts, uterine LAM, and renal angiomyolipomas. Renal and uterine biopsy specimens demonstrated positive immunostaining for melanoma-related antigens and expression of estrogen and progesterone receptors by ligand-binding assay and immunohistology. Cells cultured from LAM tissue of one of the patients exhibited a mitogenic response to estradiol. CONCLUSION: Clinically significant extrapulmonary LAM is a rare manifestation of TSC and may occur in women with this disease who also have pulmonary LAM. The clinical features of these patients confirm the importance of sex steroids in the development of these lesions. Immunohistochemical findings suggest that LAM and angiomyolipomas have a neuroectodermal origin. The development of lymphangiomatous cysts in these patients is probably due to smooth muscle proliferation in lymph vessels, which can result in lymphatic obstruction.

Tracheobronchial involvement in Wegener's granulomatosis.

This study was designed to characterize the clinical spectrum and course of tracheobronchial involvement in Wegener's granulomatosis (WG). Of the 51 patients with biopsy-proven WG who underwent bronchoscopy at least once at our institution between January 1982 and November 1993, 30 (59%) had endobronchial abnormalities due to WG. Initial findings included subglottic stenosis in five (17%), ulcerating tracheobronchitis with or without inflammatory pseudotumors in 18 (60%), tracheal or bronchial stenosis without inflammation in four (13%), and hemorrhage without identifiable source in two (4%) patients. Nine patients with ulcerating tracheobronchitis on initial study had subsequent bronchoscopies for continued symptoms, which in seven cases documented the progression from ulcerating tracheobronchitis to stenosis without inflammation. Bronchoscopic interventions included dilation by rigid bronchoscope in three, YAG-laser treatment in one, and placement of silastic airway stents in three patients. Only the stents provided persistent airway patency. Endobronchial biopsies were performed on 21 occasions in 17 patients. Half of the specimens were helpful in establishing the diagnosis and in all but three in assessing disease activity. While antineutrophil cytoplasmic antibody titers reflect overall disease activity, no correlation with endobronchial inflammatory activity was apparent.

The use of prosthetic stents in tracheobronchial, gastrointestinal, and genitourinary diseases.

The concept of using a stent to maintain patency of a lumen is not new. As early as 1969, stents were being investigated in the peripheral arterial system as a means of preventing restenosis after dilatation by balloon angioplasty (Dotter, 1969). Since then, numerous reports have demonstrated the use of stents in both the peripheral and coronary artery systems (Maass et al., 1982; Dotter et al., 1983; Wright et al., 1985; Palmaz et al., 1987). Concomitant with the investigation of expandable endovascular metal prosthesis has been the development of prosthetic devices for management of tracheobronchial, gastrointestinal, and genitourinary diseases. We will review the use of endoscopically placed prosthetic devices in the management of diseases affecting these systems.

The role of transcarinal needle aspiration in the staging of bronchogenic carcinoma.

Metastatic spread to subcarinal lymph nodes in patients with bronchogenic carcinoma generally indicates unresectability. Transcarinal needle aspiration of the main carina (TCNA) has been used to obviate the need for more invasive procedures, particularly thoracic surgery. Of 510 transbronchial needle aspirations performed at our institution from 1983 to 1991, 88 (17 percent) were from the main carina in patients with bronchogenic carcinoma. We reviewed these 88 TCNA procedures to assess our experience with TCNA in the staging of lung cancer. The TCNA results were positive in 32 of 88 (36 percent) patients (20 non-small-cell cancers, 12 small-cell lung cancers). Following bronchoscopy, TCNA was the only evidence of unresectability in all 20 patients with non-small-cell lung cancer and was the only mode of diagnosis in 5 of 12 (42 percent) patients with small-cell lung cancer. Thirteen patients with non-small-cell lung cancer and positive TCNA also had positive bronchial secretion cytologic studies. Five of these patients had further subcarinal sampling and in all cases metastatic involvement was confirmed. TCNA was positive in 29 of 67 (43 percent) patients with radiographic evidence of mediastinal adenopathy. Of the remaining 38 patients with radiographic evidence of mediastinal adenopathy and negative TCNA results, 23 patients had further mediastinal sampling with mediastinoscopy or thoracotomy and in all cases mediastinal spread of cancer was established. Nineteen of 58 (33 percent) patients with an endoscopically normal-appearing main carina had a positive TCNA, while 13 of 30 (43 percent) patients with broadening or widening of the main carina had positive TCNA results. There were no complications. We conclude that TCNA is often a safe and useful staging modality in patients with bronchogenic carcinoma.