Jeffrey L. Myers

Efficacy of Bilateral Prophylactic Mastectomy in Women with a Family History of Breast Cancer

BACKGROUND Options for women at high risk for breast cancer include surveillance, chemoprevention, and prophylactic mastectomy. The data on the outcomes for surveillance and prophylactic mastectomy are incomplete. METHODS We conducted a retrospective study of all women with a family history of breast cancer who underwent bilateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. The women were divided into two groups - high risk and moderate risk - on the basis of family history. A control study of the sisters of the high-risk probands and the Gail model were used to predict the number of breast cancers expected in these two groups in the absence of prophylactic mastectomy. RESULTS We identified 639 women with a family history of breast cancer who had undergone bilateral prophylactic mastectomy: 214 at high risk and 425 at moderate risk. The median length of follow-up was 14 years. The median age at prophylactic mastectomy was 42 years. According to the Gall model, 37.4 breast cancers were expected in the moderate-risk group; 4 breast cancers occurred (reduction in risk, 89.5 percent; P<0.001). We compared the numbers of breast cancers among the 214 high-risk probands with the numbers among their 403 sisters who had not undergone prophylactic mastectomy. Of these sisters, 38.7 percent (156) had been given a diagnosis of breast cancer (115 cases were diagnosed before the respective probands prophylactic mastectomy, 38 were diagnosed afterward, and the time of the diagnosis was unknown in 3 cases). By contrast, breast cancer was diagnosed in 1.4 percent (3 of 214) of the probands. Thus, prophylactic mastectomy was associated with a reduction in the incidence of breast cancer of at least 90 percent. CONCLUSIONS In women with a high risk of breast cancer on the basis of family history, prophylactic mastectomy can significantly reduce the incidence of breast cancer.

An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline

BACKGROUND This document updates the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guideline on idiopathic pulmonary fibrosis treatment. METHODS Systematic reviews and, when appropriate, meta-analyses were performed to summarize all available evidence pertinent to our questions. The evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and then discussed by a multidisciplinary panel. Predetermined conflict-of-interest management strategies were applied, and recommendations were formulated, written, and graded exclusively by the nonconflicted panelists. RESULTS After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications to health equity, recommendations were made for or against specific treatment interventions. CONCLUSIONS The panel formulated and provided the rationale for recommendations in favor of or against treatment interventions for idiopathic pulmonary fibrosis.

Acute interstitial pneumonia. A clinicopathologic, ultrastructural, and cell kinetic study

Eight cases of acute interstitial pneumonia were studied to define the clinical and pathologic features and to determine the relationship to chronic interstitial pneumonia. Clinically, this disease differs from the chronic interstitial pneumonias by a sudden onset and a rapid course. Five patients died of respiratory failure after 23 days to 2 months, and two died of other complications after 3½—6 months. An etiologic agent could not be identified in any case. The histologic hallmark was interstitial fibrosis and edema associated with type II pneumocyte hyperplasia. The fibrosis differed from that seen in the chronic interstitial pneumonias by extensive fibroblast proliferation and relatively little collagen deposition. Autoradiographic studies of tritiated thymidine (3H-TdR) uptake showed high labeling indices in interstitial cells and type II pneumocytes. Evidence of acute lung injury, including both endothelial and epithelial cell damage, was a prominent ultrastructural feature. These findings emphasize that acute interstitial pneumonia is a clinically and pathologically distinct form of interstitial pneumonia that should be separated from the group of chronic interstitial pneumonias.

Efficacy of Contralateral Prophylactic Mastectomy in Women With a Personal and Family History of Breast Cancer

PURPOSE To estimate the efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer. PATIENTS AND METHODS We followed the course of 745 women with a first breast cancer and a family history of breast and/or ovarian cancer who underwent contralateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. Family history information and cancer follow-up information were obtained from the medical record, a study-specific questionnaire, and telephone follow-up. Life-tables for contralateral breast cancers, which consider age at first breast cancer, current age, and type of family history, were used to calculate the number of breast cancers expected in our cohort had they not had a prophylactic mastectomy. RESULTS Of the 745 women in our cohort, 388 were premenopausal (age < 50 years) and 357 were post- menopausal. Eight women developed a contralateral breast cancer. Six events were observed among the premenopausal women, compared with 106.2 predicted, resulting in a risk reduction of 94.4% (95% confidence interval [CI], 87.7% to 97.9%). For the 357 postmenopausal women, 50.3 contralateral breast cancers were predicted, whereas only two were observed, representing a 96.0% risk reduction (95% CI, 85.6% to 99.5%). CONCLUSION The incidence of contralateral breast cancer seems to be reduced significantly after contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.

High short-term mortality following lung biopsy for usual interstitial pneumonia

Usual interstitial pneumonia (UIP) is a specific histological pattern of interstitial pneumonia most often associated with the clinical syndrome of idiopathic pulmonary fibrosis (IPF). There is controversy regarding the use of surgical lung biopsy in the diagnosis of UIP, and the risk of lung biopsy in these patients is largely unknown. This study investigated the 30 day surgical mortality rate in patients undergoing surgical lung biopsy for UIP. Patients undergoing surgical lung biopsy over a 10-yr period from 1986-1995 with the ultimate diagnosis of UIP (with or without underlying connective tissue disease) were identified. Pathology, computed tomography, medical records, and survival were assessed. Ten of sixty patients with usual interstitial pneumonia were found to be dead within 30 days of surgical biopsy. All of these were patients with idiopathic UIP, unassociated with connective tissue disease (clinical condition of IPF). In conclusion, patients with usual interstitial pneumonia of the idiopathic type, who present with atypical features, may be at higher risk for death following surgical biopsy than patients presenting with more typical features or patients with other interstitial illnesses.

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.

Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report

Acute exacerbation of idiopathic pulmonary fibrosis has been defined as an acute, clinically significant, respiratory deterioration of unidentifiable cause. The objective of this international working group report on acute exacerbation of idiopathic pulmonary fibrosis was to provide a comprehensive update on the topic. A literature review was conducted to identify all relevant English text publications and abstracts. Evidence-based updates on the epidemiology, etiology, risk factors, prognosis, and management of acute exacerbations of idiopathic pulmonary fibrosis are provided. Finally, to better reflect the current state of knowledge and improve the feasibility of future research into its etiology and treatment, the working group proposes a new conceptual framework for acute respiratory deterioration in idiopathic pulmonary fibrosis and a revised definition and diagnostic criteria for acute exacerbation of idiopathic pulmonary fibrosis.

Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites.

Metastatic neuroendocrine neoplasms can have similar histologic appearances, and without an obvious primary, it may be difficult to determine the site of origin of the metastasis. Thyroid transcription factor-1 (TTF-1) is a nuclear protein expressed during the development of thyroid, lung, and forebrain. The clinical utility of TTF-1 to distinguishing between metastatic pulmonary and nonpulmonary well-differentiated neuroendocrine tumors (WDNET) has not been previously studied. One hundred fifty-eight primary and metastatic WDNET were evaluated for TTF-1 expression. The tumors included 20 pulmonary WDNET, including 17 typical and 3 atypical carcinoid tumors, 10 metastatic pulmonary WDNET, 26 intestinal WDNET, 24 metastatic intestinal WDNET, 3 thymic mediastinal WDNET, 30 thyroid tumors (10 medullary carcinomas, 5 follicular carcinomas, 5 follicular adenomas, 5 papillary carcinomas, and 5 anaplastic carcinomas), 10 parathyroid adenomas, 20 pituitary adenomas, 10 pancreatic WDNET, and 5 pheochromocytomas. TTF-1 expression was found in 19 of 20 (95%) pulmonary WDNET, 8 of 10 (80%) metastatic pulmonary WDNET, and in 0 of 50 (0%) intestinal WDNET. All thyroid tumors were diffusely positive for TTF-1, except for three anaplastic carcinomas. All parathyroid and pituitary adenomas, pancreatic and thymic WDNET, and pheochromocytomas were uniformly negative for TTF-1. These results indicate that TTF-1 is clinically useful in distinguishing metastatic pulmonary from metastatic WDNET of extrapulmonary origin.

Pathologic and clinical features of primary pulmonary extranodal marginal zone B-cell lymphoma of MALT type

We reviewed pathologic, phenotypic, and clinical features of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type primarily involving lung to address unresolved questions regarding behavior and pathologic features of unambiguously diagnosed pulmonary MALT lymphoma. Lung specimens from 50 patients were reviewed. Forty-one had low-grade MALT lymphoma. Nine had low-grade MALT lymphoma and diffuse large B-cell lymphoma. The patients included 32 women and 18 men with a median age of 68 years (range 34–88 years). Half of the patients were asymptomatic at the time lymphoma was diagnosed. Radiographic abnormalities were more commonly unilateral (37 patients) than bilateral (12 patients). Localized masses or nodules occurred in 39 patients. Associated autoimmune disorders (29%) and monoclonal gammopathies (43%) were common. Low-grade lymphomas formed intraparenchymal masses composed of centrocyte-like cells, plasmacytoid lymphocytes, and plasma cells that formed lymphoepithelial lesions and exhibited a lymphangitic growth pattern. Mediastinal lymph nodes were involved histologically in 44% of cases. Lymphoma-specific survival was 71.7% at 10 years, and overall survival was significantly worse than age-and gender-matched control patients. None of the following features predicted those patients who had an adverse outcome: systemic symptoms, presence of autoimmune disorders or paraproteinemia, anatomic distribution and number of pulmonary lesions, lymph node involvement, or presence of anthracycline-treated large B-cell lymphoma.

Bronchiolitis obliterans and usual interstitial pneumonia. A comparative clinicopathologic study.

The clinical, radiographic, and pathologic features were studied in 24 cases of bronchiolitis obliterans and 16 cases of usual interstitial pneumonia, to define better their distinguishing characteristics. Bronchiolitis obliterans had a more acute onset often associated with fever, while the presentation of usual interstitial pneumonia was insidious with dyspnea and cough. The radiographs in usual interstitial pneumonia uniformly showed bilateral interstitial opacities, while they were more variable in bronchiolitis obliterans, with air space densities in 15 and interstitial opacities in nine. Prognosis was considerably better for bronchiolitis obliterans patients. Resolution of disease occurred in nearly half, while no patient with usual interstitial pneumonia recovered. Three individuals with bronchiolitis obliterans (12.5%) died of progressive disease, compared to 10 with usual interstitial pneumonia (62.5%). Pathologically, the lesion in bronchiolitis obliterans affected mainly air spaces in a peribronchiolar distribution, while the changes in usual interstitial pneumonia were mainly interstitial and randomly distributed. The fibrosis in bronchiolitis obliterans was composed of proliferating fibroblasts, compared to collagen deposition in usual interstitial pneumonia. These findings emphasize that bronchiolitis obliterans and usual interstitial pneumonia represent separate and distinct clinicopathologic entities.