David E. Midthun

Primary salivary gland-type lung cancer: spectrum of clinical presentation, histopathologic and prognostic factors.

Primary salivary‐type lung cancers are rare tumors that include adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC). The clinicopathologic profiles, symptoms on presentation, and long‐term outcomes of patients with ACC and MEC as an overall group have not been defined recently.

Alpha1-antitrypsin deficiency carriers, tobacco smoke, chronic obstructive pulmonary disease, and lung cancer risk.

BACKGROUND Genetic susceptibility in lung cancer risk has long been recognized but remains ill defined, as does the role of tobacco smoke exposure and chronic obstructive pulmonary disease (COPD). METHODS Using a dual case-control design, we tested whether alpha(1)-antitrypsin deficiency (alpha(1)ATD) carriers are predisposed to a higher risk of lung cancer, adjusting for the effects of tobacco smoke exposure and COPD. A total of 1856 patients with incident lung cancer were included in the study; 1585 community residents served as controls. A second control group was composed of 902 full siblings of the patients. We first modeled 1585 case-control pairs without the alpha(1)ATD variable using multiple logistic regression analysis and then modeled the alpha(1)ATD allele type in the presence of other known risk factors of lung cancer. RESULTS We found a significantly increased lung cancer risk among alpha(1)ATD carriers from 2 parallel case-control comparisons: when patients were compared with unrelated controls, alpha(1)ATD carriers had a 70% higher risk of developing lung cancer than noncarriers (odds ratio, 1.7; 95% confidence interval, 1.2-2.4). In a further comparison of patients with their cancer-free siblings, we found a 2-fold increased lung cancer risk in alpha(1)ATD carriers (95% confidence interval, 1.4-2.7). Stratified analysis by tumor histologic subtypes showed a significant increase for adenocarcinoma and squamous cell carcinoma among alpha(1)ATD carriers. CONCLUSION Our results suggest that alpha(1)ATD carriers are at a 70% to 100% increased risk of lung cancer and may account for 11% to 12% of the patients with lung cancer in our study.

Approach to the Solitary Pulmonary Nodule

Because many malignant and benign processes may manifest as a solitary pulmonary nodule on a chest roentgenogram, this finding presents a diagnostic challenge. The major concern is whether the lesion is malignant. The likelihood of a malignant tumor correlates with the age of the patient, the size of the nodule, a history of a prior malignant lesion, and a history of smoking. Recent advances in radiologic techniques, such as the detection of calcium or the inference of the presence of calcium by high attenuation values on computed tomography, provide assistance in identifying benign lesions. The history, physical examination, and radiographic information can help determine an appropriate course of action. The goals are to remove malignant nodules promptly and to avoid surgical intervention in patients whose nodules are benign.

Are airflow obstruction and radiographic evidence of emphysema risk factors for lung cancer? A nested case-control study using quantitative emphysema analysis.

OBJECTIVES Several studies have identified airflow obstruction as a risk factor for lung cancer independent of smoking history, but the risk associated with the presence of radiographic evidence of emphysema has not been extensively studied. We proposed to assess this risk using a quantitative volumetric CT scan analysis. METHODS Sixty-four cases of lung cancer were identified from a prospective cohort of 1,520 participants enrolled in a spiral CT scan lung cancer screening trial. Each case was matched to six control subjects for age, sex, and smoking history. Quantitative CT scan analysis of emphysema was performed. Spirometric measures were also conducted. Data were analyzed using conditional logistic regression making use of the 1:6 set groups of 64 cases and 377 matched control subjects. RESULTS Decreased FEV(1) and FEV(1)/FVC were significantly associated with a diagnosis of lung cancer with ORs of 1.15 (95% CI, 1.00-1.32; P = .046) and 1.29 (95% CI, 1.02-1.62; P = .031), respectively. The quantity of radiographic evidence of emphysema was not found to be a significant risk for lung cancer with OR of 1.042 (95% CI, 0.816-1.329; P = .743). Additionally, there was no significant association between severe emphysema and lung cancer with OR of 1.57 (95% CI, 0.73-3.37). CONCLUSIONS We confirm previous observations that airflow obstruction is an independent risk factor for lung cancer. The absence of a clear relationship between radiographic evidence of emphysema and lung cancer using an automated quantitative volumetric analysis may result from different population characteristics than those of prior studies, radiographic evidence of emphysema quantitation methodology, or absence of any relationship between emphysema and lung cancer risk.

An official American Thoracic Society/American College of Chest Physicians policy statement: implementation of low-dose computed tomography lung cancer screening programs in clinical practice.

RATIONALE Annual low-radiation-dose computed tomography (LDCT) screening for lung cancer has been shown to reduce lung cancer mortality among high-risk individuals and is now recommended by multiple organizations. However, LDCT screening is complex, and implementation requires careful planning to ensure benefits outweigh harms. Little guidance has been provided for sites wishing to develop and implement lung cancer screening programs. OBJECTIVES To promote successful implementation of comprehensive LDCT screening programs that are safe, effective, and sustainable. METHODS The American Thoracic Society (ATS) and American College of Chest Physicians (ACCP) convened a committee with expertise in lung cancer screening, pulmonary nodule evaluation, and implementation science. The committee reviewed the evidence from systematic reviews, clinical practice guidelines, surveys, and the experience of early-adopting LDCT screening programs and summarized potential strategies to implement LDCT screening programs successfully. MEASUREMENTS AND MAIN RESULTS We address steps that sites should consider during the main three phases of developing an LDCT screening program: planning, implementation, and maintenance. We present multiple strategies to implement the nine core elements of comprehensive lung cancer screening programs enumerated in a recent ACCP/ATS statement, which will allow sites to select the strategy that best fits with their local context and workflow patterns. Although we do not comment on cost-effectiveness of LDCT screening, we outline the necessary costs associated with starting and sustaining a high-quality LDCT screening program. CONCLUSIONS Following the strategies delineated in this policy statement may help sites to develop comprehensive LDCT screening programs that are safe and effective.

5-Year Lung Cancer Screening Experience: Growth Curves of 18 Lung Cancers Compared to Histologic Type, CT Attenuation, Stage, Survival, and Size

BACKGROUND Although no study has prospectively documented the rate at which lung cancers grow, many have assumed exponential growth. The purpose of this study was to document the growth of lung cancers detected in high-risk participants receiving annual screening chest CT scans. METHODS Eighteen lung cancers were evaluated by at least four serial CT scans (4 men, 14 women; age range, 53 to 79 years; mean age, 66 years). CT scans were retrospectively reviewed for appearance, size, and volume (volume [v] = pi/6[ab(2)]). Growth curves (x = time [in days]; y = volume [cubic millimeters]) were plotted and subcategorized by histology, CT scan attenuation, stage, survival, and initial size. RESULTS Inclusion criteria favored smaller, less aggressive cancers. Growth curves varied, even when subcategorized by histology, CT scan attenuation, stage, survival, or initial size. Cancers associated with higher stages, mortality, or recurrence showed fairly steady growth or accelerated growth compared with earlier growth, although these growth patterns also were seen in lesser-stage lung cancers. Most lung cancers enlarged at fairly steady increments, but several demonstrated fairly flat growth curves, and others demonstrated periods of accelerated growth. CONCLUSIONS This study is the first to plot individual lung cancer growth curves. Although parameters favored smaller, less aggressive cancers in women, it showed that lung cancers are not limited to exponential growth. Tumor size at one point or growth between two points did not appear to predict future growth. Studies and equations assuming exponential growth may potentially misrepresent an indeterminate nodule or the aggressiveness of a lung cancer.

Quality of Life and Symptom Burden among Long-Term Lung Cancer Survivors

Introduction: Information is limited regarding health-related quality of life (QOL) status of long-term (greater than 5 years) lung cancer survivors (LTLCS). Obtaining knowledge about their QOL changes over time is a critical step toward improving poor and maintaining good QOL. The primary aim of this study was to conduct a 7-year longitudinal study in survivors of primary lung cancer which identified factors associated with either decline or improvement in QOL over time. Methods: Between 1997 and 2003, 447 LTLCS were identified and followed through 2007 using validated questionnaires; data on overall QOL and specific symptoms were at two periods: short-term (less than 3 years) and long-term postdiagnosis. The main analyses were of clinically significant changes (greater than 10%) and factors associated with overall QOL and symptom burden for each period and for changes over time. Results: Three hundred two (68%) underwent surgical resection only and 122 (27%) received surgical resection and radiation/chemotherapy. Recurrent or new lung malignancies were observed in 84 (19%) survivors. Significant decline or improvement in overall QOL over time were reported in 155 (35%) and 67 (15%) of 447 survivors, respectively. Among the 155 whose QOL declined, significantly worsened symptoms were fatigue (69%), pain (59%), dyspnea (58%), depressed appetite (49%), and coughing (42%). The symptom burden did not lessen among the 67 who reported improvement in overall QOL, suggesting that survivors had adapted to their compromised physical condition. Conclusions: LTLCS suffered substantial symptom burden that significantly impaired their QOL, indicating a need for targeted interventions to alleviate their symptoms.

Fibrosing Mediastinitis Clinical Presentation, Therapeutic Outcomes, and Adaptive Immune Response

Fibrosing mediastinitis (FM) is a rare disorder characterized by the invasive proliferation of fibrous tissue within the mediastinum. FM frequently results in the compression of vital mediastinal structures and has been associated with substantial morbidity and mortality. Its pathogenesis remains unknown. However, in North America most cases are thought to represent an immune-mediated hypersensitivity response to Histoplasma capsulatum infection. To characterize the clinical disease spectrum, natural disease progression, responses to therapy, and overall survival, we retrospectively analyzed all 80 consecutive patients with a diagnosis of FM evaluated at Mayo Clinic, Rochester, MN, from 1998 to 2007. Furthermore, we characterized the adaptive immune response in 15 representative patients by immunohistochemistry. The majority of patients presented with nonspecific respiratory symptoms due to the compression of mediastinal broncho-vascular structures. Chest radiographic imaging most frequently revealed localized, invasive, and frequently calcified right-sided mediastinal masses. Most patients had radiographic or serologic evidence of previous histoplasmosis. In contrast to earlier reports summarizing previously reported FM cases, the clinical course of our patients appeared to be more benign and less progressive. The overall survival was similar to that of age-matched controls. There were only 5 deaths, 2 of which were attributed to FM. These differences may reflect publication bias associated with the preferential reporting of more severely affected FM patients in the medical literature, as well as the more inclusive case definition used in our consecutive case series. Surgical and nonsurgical interventions effectively relieved symptoms caused by the compression of mediastinal vascular structures in these carefully selected patients. In contrast, antifungal and antiinflammatory agents appeared ineffective. Histologic examination and immunostaining revealed mixed inflammatory infiltrates consistent with a fibroinflammatory tissue response in these histoplasmosis-associated FM cases. The immune cell infiltrates included large numbers of CD20-positive B lymphocytes. As B lymphocytes may contribute to the pathogenesis of the disease, therapeutic B-cell depletion should be investigated as a therapeutic strategy for FM. Abbreviations: CT = computed tomography, FM = fibrosing mediastinitis, PET = positron emission tomography, SVC = superior vena cava.

Diagnostic approach to the patient with diffuse lung disease.

Detecting diffuse lung infiltrates on chest radiography is a common clinical problem. Many diverse pathological processes can cause diffuse lung disease. The presentation of these diseases can vary from acute to chronic and includes a side array of radiological patterns that are optimally evaluated on high-resolution computed tomography of the chest. In diagnosing diffuse lung disease, it is helpful to focus on a few pivotal parameters to narrow the broad differential diagnosis. We describe the diagnostic approach to a patient with diffuse lung disease usingthe following key parameters: tempo of the pathological process, characteristics of the radiological pattern, and clinical context.

Mediastinal Lymphangioma: Mayo Clinic Experience of 25 Cases

OBJECTIVE To describe the clinical findings, treatment outcomes, disease recurrence rates, and survival of patients with pathologically confirmed mediastinal and cervicomediastinal lymphangioma. PATIENTS AND METHODS There are 2 patient cohorts. Cohort A consisted of 12 Mayo Clinic patients with pathologically confirmed medilastinal or cervicomediastinal lymphangioma identified from 1986 to 1999. Cohort B consisted of 13 additional patients with mediastinal lymphangioma who had been previously reported from the Mayo Clinic (from 1976 to 1986). All patients were retrospectively identified, and follow-up was performed by either telephone or medical record review. RESULTS The mean age at the time of diagnosis was 36.5 years, with a male-female ratio of 1:3. All but 3 patients were symptomatic at presentation, with dyspnea being the most common symptom. Computed tomographic scans commonly revealed a homogeneous, low-attenuation mass that often Involved vascular or airway structures. Although 3 patients were initially observed, all patients had surgical intervention because of symptoms or enlargement of the mass. Thoracotomy with resection was the most common surgical intervention. Five recurrences were noted. Recurrence was minimized by complete excision of the lymphangioma. On follow-up that spanned 23 years, 75% of patients were alive. These survival rates were not statistically different from the expected survival rates of the same age- and sex-matched controls. Only 1 death was attributed to complication from lymphangioma. CONCLUSION Mediastinal and cervicomediastinal lymphangioma are rare lesions that can be treated successfully with surgical excision. Prognosis appears to be excellent because no difference in survival was found between patients and age- and sex-matched controls.