Stephen J. Swensen

Late‐onset noninfectious pulmonary complications after allogeneic bone marrow transplantation

We examined the incidence and clinical outcome of late‐onset noninfectious pulmonary complications (LONIPC) in a series of 234 patients who underwent allogeneic bone marrow transplantation at our institution between April 1982 and October 1996. The 179 patients who survived 3 months or more were evaluated. Clinical, radiologic, pulmonary function, and pathologic tests were reviewed to identify 18 patients (10%) who fulfilled the diagnostic criteria of LONIPC. Accordingly, the pulmonary processes included bronchiolitis obliterans (BO, five patients), bronchiolitis obliterans with organizing pneumonia (BOOP, three patients), diffuse alveolar damage (DAD, one patient), lymphocytic interstitial pneumonia (LIP, one patient), and nonclassifiable interstitial pneumonia (NCIP, eight patients). Various methods of enhanced immunosuppressive therapy resulted in marked durable remission in nine patients (50%) (3/3 with BOOP, 3/8 with NCIP, 1/1 with DAD, 1/1 with LIP, 1/5 with BO). The presence of chronic graft‐versus‐host disease (cGVHD) and prophylaxis for GVHD with cyclosporine and prednisone were the only variables significantly associated with the development of LONIPC (P = 0.0001 and 0.008, respectively). Regardless of histology, a reduction in the forced expiratory volume to < 45% of the predicted range was associated with poor response to treatment. These findings suggest a strong association between cGVHD and LONIPC and that the risk of LONIPC development may be influenced by the particular method of GVHD prophylaxis. Most patients with BOOP or mild airflow limitation at diagnosis achieved durable remissions.

Organizing pneumonia. Features and prognosis of cryptogenic, secondary, and focal variants

BACKGROUND Organizing pneumonia (OP) is a non-specific response to many types of lung injury. Clinicians frequently encounter pathology reports of OP in patients with no underlying condition (cryptogenic OP, also known as BOOP or bronchiolitis obliterans OP) or in association with drugs or nonpulmonary disease. The goals of this study are to describe the clinical course and outcomes in patients with 3 clinical variants of OP. METHODS A retrospective study of patients with OP seen at the Mayo Clinic, Rochester, Minn, from January 1, 1984, through June 30, 1994, was conducted. Initial features were obtained from medical records. Chest radiographs and pathology specimens were reviewed for this study. Resolution, relapse, and survival were obtained from medical records and a follow-up patient questionnaire. RESULTS Seventy-four patients had pathologically confirmed OP. Organizing pneumonia was classified into 3 clinical groups: symptomatic cryptogenic OP; symptomatic OP related to underlying hematologic malignant neoplasm, collagen vascular disease, or drugs (secondary OP); and asymptomatic OP presenting as a focal nodule (focal OP). Thirty-seven patients (50%) had cryptogenic OP and 27 patients (36%) had secondary OP. No difference was found between cryptogenic and secondary OP in type or severity of symptoms, signs, laboratory and pulmonary function tests, or radiologic or pathologic findings. Corticosteroids were given at a similar initial dose (prednisone, about 50 mg/d). Resolution of symptoms was more frequent in patients with cryptogenic OP than those with secondary OP. Relapse was infrequent in both of these groups. Five-year survival was higher in patients with cryptogenic OP (73%) than in secondary OP (44%), and respiratory-related deaths were more frequent in patients with secondary OP. Organizing pneumonia was an asymptomatic focal rounded opacity in 10 patients (14%), most often detected on chest radiograph and diagnosed on lung biopsy done for suspicion of lung cancer. Patients with focal OP required no treatment and had no relapse or respiratory-related deaths. CONCLUSIONS Clinical classification of OP is useful to predict clinical course and outcome. Cryptogenic OP most often was a symptomatic bilateral lung process that had an overall favorable prognosis with prolonged corticosteroid therapy. Patients with secondary OP had a high mortality rate when the disease was associated with predisposing conditions or drugs. Patients with asymptomatic focal OP had an excellent prognosis.

Cystic and cavitary lung diseases: focal and diffuse.

Cysts and cavities are commonly encountered abnormalities on chest radiography and chest computed tomography. Occasionally, the underlying nature of the lesions can be readily apparent as in bullae associated with emphysema. Other times, cystic and cavitary lung lesions can be a diagnostic challenge. In such circumstances, distinguishing cysts (wall thickness < or = 4 mm) from cavities (wall thickness > 4 mm or a surrounding infiltrate or mass) and focal or multifocal disease from diffuse involvement facilitates the diagnostic process. Other radiological characteristics, including size, inner wall contour, nature of contents, and location, when correlated with the clinical context and tempo of the disease process provide the most helpful diagnostic clues. Focal or multifocal cystic lesions include blebs, bullae, pneumatoceles, congenital cystic lesions, traumatic lesions, and several infectious processes, including coccidioidomycosis, Pneumocystis carinii pneumonia, and hydatid disease. Malignant lesions including metastatic lesions may rarely present as cystic lesions. Focal or multifocal cavitary lesions include neoplasms such as bronchogenic carcinomas and lymphomas, many types of infections or abscesses, immunologic disorders such as Wegener granulomatosis and rheumatoid nodule, pulmonary infarct, septic embolism, progressive massive fibrosis with pneumoconiosis, lymphocytic interstitial pneumonia, localized bronchiectasis, and some congenital lesions. Diffuse involvement with cystic or cavitary lesions may be seen in pulmonary lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis, honeycomb lung associated with advanced fibrosis, diffuse bronchiectasis, and, rarely, metastatic disease. High-resolution computed tomography of the chest frequently helps define morphologic features that may serve as important clues regarding the nature of cystic and cavitary lesions in the lung.

Characterization of the Solitary Pulmonary Nodule: 18F-FDG PET Versus Nodule-Enhancement CT

OBJECTIVE The purpose of this study was to directly compare nodule-enhancement CT and 18F-FDG PET in the characterization of indeterminate solitary pulmonary nodules (SPNs) greater than 7 mm in size. MATERIALS AND METHODS Examinations from patients undergoing both nodule-enhancement CT and 18F-FDG PET to characterize the same indeterminate SPN were reviewed. For nodule-enhancement CT, an SPN was considered malignant when it showed an unenhanced to peak contrast-enhanced increase in attenuation greater than 15 H. Fluorine-18-FDG PET studies were blindly reinterpreted by two qualified nuclear radiologists. SPNs qualitatively showing hypermetabolic activity greater than the mediastinal blood pool were interpreted as malignant. These interpretations were compared with the original prospective clinical readings and to semiquantitative standardized uptake value (SUV) analysis. Results were compared with pathologic and clinical follow-up. RESULTS Forty-two pulmonary nodules were examined. Twenty-five (60%) were malignant, and 17 (40%) were benign. Nodule-enhancement CT was positive in all 25 malignant nodules and in 12 benign nodules, with sensitivity and specificity of 100% and 29%, respectively, and with a positive predictive value (PPV) and negative predictive value (NPV) of 68% and 100%, respectively. Qualitative 18F-FDG PET interpretations were positive in 24 of the 25 malignant nodules and in four benign nodules. Fluorine-18-FDG PET was considered negative in one malignant nodule and in 13 of the 17 benign nodules. This correlates with a sensitivity and specificity of 96% and 76%, respectively, and with a PPV and NPV of 86% and 93%, respectively. Original prospective 18F-FDG PET and semiquantitative SUV analysis showed sensitivity, specificity, PPV, and NPV of 88%, 76%, 85%, and 81% and 84%, 82%, 88%, and 78%, respectively. CONCLUSION Due to its much higher specificity and only slightly reduced sensitivity, 18F-FDG PET is preferable to nodule-enhancement CT in evaluating indeterminate pulmonary nodules. However, nodule-enhancement CT remains useful due to its high NPV, convenience, and lower cost. Qualitative 18F-FDG PET interpretation provided the best balance of sensitivity and specificity when compared with original prospective interpretation or SUV analysis.

Outcomes After Withholding Anticoagulation From Patients With Suspected Acute Pulmonary Embolism and Negative Computed Tomographic Findings: A Cohort Study

OBJECTIVE To determine the outcome of withholding anticoagulation from patients with suspected acute pulmonary embolism in whom computed tomographic (CT) findings are interpreted as negative for pulmonary embolism. PATIENTS AND METHODS This retrospective cohort study included 1512 consecutive patients referred from August 7, 1997, to November 30, 1998, for CT because of clinically suspected acute pulmonary embolism. All patients were examined by electron beam CT, and scanning was performed in a cephalocaudad direction from the top of the aortic arch to the base of the heart with 3-mm collimation, 2-mm table incrementation, and an exposure time of 0.2 second (130 peak kV, 620 mA, and standard reconstruction algorithm). Contrast material was infused at a rate of 3 to 4 mL/s through an antecubital vein with an automated injector. Findings on CT were interpreted as either positive or negative. The main outcome measures were deep venous thrombosis, pulmonary embolism, and vital status within 3 months after the CT scan and the cause of death based on medical record review, mailed patient questionnaires, and telephone interviews. RESULTS In 1010 patients (67%) CT scans were interpreted as negative for acute pulmonary embolism. Seventeen patients were excluded because they received anticoagulation. Of the remaining 993 patients, deep venous thrombosis or pulmonary embolism developed in 8; 118 patients died, 3 of pulmonary embolism. Nineteen patients were known to be alive, but additional clinical information could not be obtained. The 3-month cumulative incidence of overall deep venous thrombosis or pulmonary embolism was 0.5% (95% confidence interval, 0.1%-1.0%) and of fatal pulmonary embolism, 0.3% (95% confidence interval, 0.0%-0.7%). CONCLUSIONS The incidence of (1) overall deep venous thrombosis or pulmonary embolism or (2) fatal pulmonary embolism among patients with suspected acute pulmonary embolism, negative CT results, and no other evidence of venous thromboembolism is low. Withholding anticoagulation in these patients appears to be safe.

A consensus statement of the Society of Thoracic Radiology: screening for lung cancer with helical computed tomography.

This consensus statement by the Society of Thoracic Radiology is a summary of the current understanding of low dose computed tomography (CT) for screening for lung cancer. Lung cancer is the most common fatal malignancy in the industrialized world. Unlike the next three most common cancers, screening for lung cancer is not currently recommended by cancer organizations. Improvements in CT technology make lung screening feasible. Early prevalence data indicate that about two-thirds of lung cancers that are detected by CT screening are at an early stage. Other data support the postulate that patients with lung cancers detected at this early stage have better rates of survival. Whether this will translate into an improved disease specific mortality is yet to be demonstrated. The suggested technical protocols, selection criteria, and method of handling the numerous benign nodules that are detected are discussed. It is the consensus of this committee that mass screening for lung cancer with CT is not currently advocated. Suitable subjects who wish to participate should be encouraged to do so in controlled trials, so that the value of CT screening can be ascertained as soon as possible.

Impact of Organizational Leadership on Physician Burnout and Satisfaction

OBJECTIVE To evaluate the impact of organizational leadership on the professional satisfaction and burnout of individual physicians working for a large health care organization. PARTICIPANTS AND METHODS We surveyed physicians and scientists working for a large health care organization in October 2013. Validated tools were used to assess burnout. Physicians also rated the leadership qualities of their immediate supervisor in 12 specific dimensions on a 5-point Likert scale. All supervisors were themselves physicians/scientists. A composite leadership score was calculated by summing scores for the 12 individual items (range, 12-60; higher scores indicate more effective leadership). RESULTS Of the 3896 physicians surveyed, 2813 (72.2%) responded. Supervisor scores in each of the 12 leadership dimensions and composite leadership score strongly correlated with the burnout and satisfaction scores of individual physicians (all P<.001). On multivariate analysis adjusting for age, sex, duration of employment at Mayo Clinic, and specialty, each 1-point increase in composite leadership score was associated with a 3.3% decrease in the likelihood of burnout (P<.001) and a 9.0% increase in the likelihood of satisfaction (P<.001) of the physicians supervised. The mean composite leadership rating of each division/department chair (n=128) also correlated with the prevalence of burnout (correlation=-0.330; r(2)=0.11; P<.001) and satisfaction (correlation=0.684; r(2)=0.47; P<.001) at the division/department level. CONCLUSION The leadership qualities of physician supervisors appear to impact the well-being and satisfaction of individual physicians working in health care organizations. These findings have important implications for the selection and training of physician leaders and provide new insights into organizational factors that affect physician well-being.

Localized malignant mesothelioma: A clinicopathologic and flow cytometric study

Six examples of malignant mesothelioma appearing as a localized pleural mass are described. There were four women and two men, ranging in age from 42 to 76 years. A history of asbestos exposure was obtained from three patients. The tumors ranged in size from 2.8 to 10 cm. Two were pedunculated and four were sessile with broad-based pleural attachments. Histologically, three tumors were purely epithelioid and three were biphasic. Immunohistochemical stains in all six cases were positive for cytokeratin and negative for carcinoembryonic antigen. Five were also positive for epithelial membrane antigen. Five were negative for Leu-M1, while one showed focal staining in a peripheral membrane pattern. Electron microscopy in two purely epithelioid tumors showed long, thin microvilli, well-developed desmosomes, and numerous tonofilaments. Flow cytometry showed an aneuploid DNA content in four tumors and a diploid content in one. Flow cytometry in five cases identified a DNA aneuploid cell population in four tumors and a diploid population in one. Three patients showed signs of local recurrences 4, 7, and 18 months after excision and died of their disease 12, 10, and 24 months after diagnosis, respectively. Three patients are well with no evidence of disease 8, 24, and 96 months after diagnosis. These findings indicate that malignant mesotheliomas of the pleura may rarely appear as a localized mass. The biologic behavior of such tumors is difficult to predict, but some patients survive disease-free for a long time after surgical excision.

Estimating Long-term Effectiveness of Lung Cancer Screening in the Mayo CT Screening Study

PURPOSE To use individual-level data provided from the single-arm study of helical computed tomographic (CT) screening at the Mayo Clinic (Rochester, Minn) to estimate the long-term effectiveness of screening in Mayo study participants and to compare estimates from an existing lung cancer simulation model with estimates from a different modeling approach that used the same data. MATERIALS AND METHODS The study was approved by institutional review boards and was HIPAA compliant. Deidentified individual-level data from participants (1520 current or former smokers aged 50-85 years) in the Mayo Clinic helical CT screening study were used to populate the Lung Cancer Policy Model, a comprehensive microsimulation model of lung cancer development, screening findings, treatment results, and long-term outcomes. The model predicted diagnosed cases of lung cancer and deaths per simulated study arm (five annual screening examinations vs no screening). Main outcome measures were predicted changes in lung cancer-specific and all-cause mortality as functions of follow-up time after simulated enrollment and randomization. RESULTS At 6-year follow-up, the screening arm had an estimated 37% relative increase in lung cancer detection, compared with the control arm. At 15-year follow-up, five annual screening examinations yielded a 9% relative increase in lung cancer detection. The relative reduction in cumulative lung cancer-specific mortality from five annual screening examinations was 28% at 6-year follow-up (15% at 15 years). The relative reduction in cumulative all-cause mortality from five annual screening examinations was 4% at 6-year follow-up (2% at 15 years). CONCLUSION Screening may reduce lung cancer-specific mortality but may offer a smaller reduction in overall mortality because of increased competing mortality risks associated with smoking.

An Integrated Approach to Evaluation of the Solitary Pulmonary Nodule

In this article, we describe an integrated approach for detection and evaluation of solitary pulmonary nodules. Initial evaluation of the solitary pulmonary nodule includes tomography, fluoroscopy, and comparison with previously obtained roentgenograms. Subsequently, thin-section computed tomography and phantom densitometry can be used for analysis, if indicated. The rationale for the use of computed tomography in the radiologic staging of bronchogenic carcinoma is to expedite and assist in the identification of the subset of patients with resectable tumors. For nonsurgical tissue diagnosis, fiberoptic bronchoscopy is generally the initial procedure for lesions 2.0 cm or larger in diameter, and transthoracic needle biopsy is used for those smaller than 2.0 cm.