A Nomogram for Predicting Cancer-Specific Survival of TNM 8th Edition Stage I Non-small-cell Lung Cancer.

BACKGROUND: Models for predicting the survival outcomes of stage I non-small-cell lung cancer (NSCLC) defined by the newly released 8th edition TNM staging system are scarce. This study aimed to develop a nomogram for predicting the cancer-specific survival (CSS) of these patients and identifying individuals with a higher risk for CSS. METHODS: A total of 30,475 NSCLC cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified and integrated the risk factors to build a nomogram. The model was subjected to bootstrap internal validation with the SEER database, and external validation with a multicenter cohort of 1133 patients from China. The difference in the impact of adjuvant chemotherapy on model-defined high- and low-risk patients was examined using the National Cancer Database (NCDB). RESULTS: Eight independent prognostic factors were identified and integrated into the model. The calibration curves showed good agreement. The concordance index (C-index) of the nomogram was higher than that of the staging system (IA1, IA2, IA3, and IB) (internal validation set 0.63 vs. 0.56; external validation set 0.66 vs. 0.55; both p < 0.01). Specifically, 21.7% of stage IB patients (7.5% of all stage I) were categorized into the high-risk group (score > 30). There was a significant interaction effect between the adjuvant chemotherapy and risk groups in the NCDB cohort (p = 0.003). CONCLUSIONS: We established a practical nomogram to predict CSS for 8th edition stage I NSCLC. A prospective study is warranted to determine its role in identifying adjuvant chemotherapy candidates.

Lung cancer in Spanish women: The WORLD07 project.

The WORLD07 study was a female-specific database, to prospectively characterise the clinical, histological, molecular and treatment-related features in Spanish women with lung cancer. Data were collected from patients' medical records and patient interviews from October 2007 to December 2012. A total of 2,060 women were analysed: median age, 61.3 years; white, 98.6%; postmenopausal, 80.2%; and no smokers, 55% including never smokers and ex-smokers. A family history of cancer was found in 42.5% of patients, 12.0% of patients had had a previous history of cancer (breast cancer, 39.7%). Most patients (85.8%) were diagnosed of non-small-cell lung cancer (NSCLC), most commonly reported with adenocarcinoma (71.4%), which was stage IV at diagnosis in 57.6%. Median overall survival (OS) for the entire population was 24.0 months, with a 1- and 2-year survival rate of 70.7% and 50.0% respectively. Median OS in patients with small-cell lung cancer was 18.8 months versus 25.0 months in patients with NSCLC (p = 0.011). Lung cancer appears to be a biologically different disease in women. By collecting prospective information about characteristics of women with lung cancer attending university hospitals in Spain, we hope to highlight the need to develop strategies based on gender differences and influence future healthcare policy.

Managing multifocal bronchioloalveolar carcinoma/lepidic predominant adenocarcinoma: changing rules for an evolving clinical entity.

Although the clinical entity of bronchioloalveolar carcinoma (BAC) has been reclassified into adenocarcinoma in situ, lepidic predominant adenocarcinoma, and mucinous adenocarcinoma, it continues to merit special consideration based on its distinct natural history and response to therapy. The clinical behavior of multifocal BAC is highly variable, as is its response to various treatments. This characteristic should encourage latitude for individualized judgment rather than reliance on dogma about how advanced non-small cell lung cancer (NSCLC) should be managed. Specifically, it is worth first questioning whether any of the visible disease is progressing at a clinically significant pace. If clear progression is unlikely to occur over several months or longer, an appropriate option is attentive clinical and radiographic follow-up with no intervention. If significant progression is demonstrated in an isolated area, it is very reasonable to consider local therapy-whether surgery or radiation-in this area alone. If progression is clearly apparent, then optimal systemic therapy should be used based on molecular findings. This is the same approach that is generally recommended for other forms of advanced NSCLC, with the presence or absence of a driver mutation used to guide the selection of an epidermal growth factor receptor inhibitor, an anaplastic lymphoma kinase inhibitor, or conventional platinum-based chemotherapy (with the potential addition of bevacizumab).

Using macrophage activation to augment immunotherapy of established tumours.

BACKGROUND: Successful immunotherapy will require alteration of the tumour microenvironment and/or decreased immune suppression. Tumour-associated macrophages (TAMs) are one major factor affecting tumour microenvironment. We hypothesised that altering TAM phenotype would augment the efficacy of immunotherapy. METHODS: We and others have reported that 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA, Vadimezan) has the ability to change TAM phenotypes, inducing a tumour microenvironment conducive to antitumour immune responses. We therefore combined DMXAA with active immunotherapies, and evaluated anti-tumour efficacy, immune cell phenotypes (flow cytometry), and tumour microenvironment (RT-PCR). RESULTS: In several different murine models of immunotherapy for lung cancer, DMXAA-induced macrophage activation significantly augmented the therapeutic effects of immunotherapy. By increasing influx of neutrophils and anti-tumour (M1) macrophages to the tumour, DMXAA altered myeloid cell phenotypes, thus changing the intratumoural M2/non-M2 TAM immunoinhibitory ratio. It also altered the tumour microenvironment to be more pro-inflammatory. Modulating macrophages during immunotherapy resulted in increased numbers, activity, and antigen-specificity of intratumoural CD8(+) T cells. Macrophage depletion reduced the effect of combining immunotherapy with macrophage activation, supporting the importance of TAMs in the combined effect. CONCLUSION: Modulating intratumoural macrophages dramatically augmented the effect of immunotherapy. Our observations suggest that addition of agents that activate TAMs to immunotherapy should be considered in future trials.

Well-differentiated adenocarcinoma-bronchioloalveolar carcinoma-in situ adenocarcinoma: a conundrum.

Over the last decade, considerable changes have been made to the classification of pulmonary adenocarcinoma, mainly with respect to the classification of small solitary tumors. The main goal seems to have been the identification of tumors that not only follow an indolent clinical course but that can also be treated more conservatively. Thus, the most important change to the classification of lung adenocarcinoma was proposed for a tumor no greater than 3.0 cm in size with a pure lepidic growth pattern and lacking stromal, vascular, or pleural invasion, which should now be categorized as in situ adenocarcinoma. At the same time, a category of minimally invasive adenocarcinoma was proposed for tumors with a predominantly lepidic growth pattern, <3 cm in size, and with <5 mm invasion in greatest dimension in any 1 focus. What is interesting about all these developments is the fact that all the publications on this issue have been presented under the terms of small adenocarcinomas or bronchioloalveolar carcinoma. Unfortunately, the literature reviews that have proposed the change in nomenclature to in situ adenocarcinoma have not offered a more in-depth assessment of these neoplasms. More recently, a publication of a large series of cases of small adenocarcinomas has offered a different view and underscored some of the important issues that need to be taken into account before a serious change in the nomenclature can be considered.

Prolonged remission of advanced bronchoalveolar adenocarcinoma in a dog treated with autologous, tumour-derived chaperone-rich cell lysate (CRCL) vaccine.

PURPOSE: This paper presents the treatment of a 12-year-old female spayed Great Dane who presented with vestibular signs (ataxia, nystagmus, hind end collapse). Thoracic radiographs revealed a discrete pulmonary nodule in the right cranial lung lobe. Ultrasound-guided fine needle aspirate detected primary bronchoalveolar adenocarcinoma, verified via computed tomography, with a second smaller nodule discovered in the right cranial lung lobe. MATERIALS AND METHODS: A lateral thoracotomy with right cranial lung lobectomy was performed. Histopathological analysis of the nodules and an excised lymph node identified grade III bronchoalveolar adenocarcinoma with vascular infiltration and lymph node metastasis - a grim diagnosis with a reported median survival time of 6-27 days. A 10-g sample of the tumour was processed into a chaperone-rich cell lysate (CRCL) vaccine, which was administered weekly to the patient. Imiquimod - a Toll-like receptor 7 (TLR7) agonist - was applied topically for the first 12 treatments to stimulate local Langerhans cells. A single injection of bacillus Calmette-Guerin (BCG) was administered for additional immune stimulation at week 30 of treatment. RESULTS: The dog remained stable and in otherwise good health until diffuse relapse occurred 44 weeks after the initial treatment; following gastrointestinal bleeding, the dog was euthanised 50+ weeks post diagnosis. CONCLUSION: To the authors' knowledge, this is the first report of significantly prolonged survival following a diagnosis of grade III/stage III bronchoalveolar adenocarcinoma in a canine patient. This case report suggests that CRCL vaccine combined with topical imiquimod is a safe, effective treatment for canine tumours.

Bronchioloalveolar carcinoma.

This review focuses on aspects of bronchioloalveolar carcinoma (BAC) in which it differs importantly from other forms of non-small-cell lung cancer. BAC is a form of adenocarcinoma with unique clinical, radiological, and epidemiological features. With the notable exception of a lower likelihood of a positive positron-emission tomographic (PET) scan in BAC, staging, diagnosis, and treatment are largely the same as for other histological subtypes of lung cancer. However, additional treatment options exist that are equivalent, if not more effective, for many patients with BAC. The diagnosis of BAC should be reserved for those tumors meeting the 1999/2004 criteria set forth by the World Health Organization. Revised nomenclature proposed by an expert consensus panel may change how this disease is viewed. Additional clinical trials are needed on patients with BAC, employing strict definitions and enrollment criteria to allow the results to be applied to appropriate patient populations.

MHC II lung cancer vaccines prime and boost tumor-specific CD4+ T cells that cross-react with multiple histologic subtypes of nonsmall cell lung cancer cells.

Nonsmall cell lung cancer (NSCLC) is the major cause of lung cancer-related deaths in the United States. We are developing cell-based vaccines as a new approach for the treatment of NSCLC. NSCLC is broadly divided into 3 histologic subtypes: adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Since these subtypes are derived from the same progenitor cells, we hypothesized that they share common tumor antigens, and vaccines that induce immune reactivity against 1 subtype may also induce immunity against other subtypes. Our vaccine strategy has focused on activating tumor-specific CD4(+) T cells, a population of lymphocytes that facilitates the optimal activation of effector and memory cytotoxic CD8(+) T cells. We now report that our NSCLC MHC II vaccines prepared from adeno, squamous or large cell carcinomas each activate CD4(+) T cells that cross-react with the other NSCLC subtypes and do not react with HLA-DR-matched normal lung fibroblasts or other HLA-DR-matched nonlung tumor cells. Using MHC II NSCLC vaccines expressing the DR1, DR4, DR7 or DR15 alleles, we also demonstrate that antigens shared among the different subtypes are presented by multiple HLA-DR alleles. Therefore, MHC II NSCLC vaccines expressing a single HLA-DR allele activate NSCLC-specific CD4(+) T cells that react with the 3 major classes of NSCLC, and the antigens recognized by the activated T cells are presented by several common HLA-DR alleles, suggesting that the MHC II NSCLC vaccines are potential immunotherapeutics for a range of NSCLC patients.

Systemic approaches for multifocal bronchioloalveolar carcinoma: is there an appropriate target?

Bronchioloalveolar carcinoma (BAC) is a subset of pulmonary adenocarcinoma characterized by distinct and unique pathological, molecular, radiographic, and clinical features. While the incidence of pure BAC is rare, comprising only 1% to 4% of non-small-cell lung cancer (NSCLC), mixed subtypes (including BAC with focal invasion and adenocarcinoma with BAC features) represent as much as 20% of adenocarcinomas--and that figure may be increasing. Despite the longstanding recognition of this entity, there is no established treatment paradigm for patients with multifocal BAC, resulting in competing approaches and treatment controversies. Current options for multifocal BAC include both surgery and systemic therapies. Unfortunately, prospective data on systemic approaches are limited by study design and small patient numbers; there are only seven phase II studies involving four therapies. This article evaluates key characteristics of BAC, including the current understanding of histopathology and tumor biology. In addition, it comprehensively reviews the systemic phase II studies in an attempt to clarify the therapeutic challenges in this disease. It also includes the first proposed treatment paradigm that integrates both EGFR mutational status and the sub-histologies, mucinous and nonmucinous BAC.

Preclinical evaluation of synergistic effect of telomerase-specific oncolytic virotherapy and gemcitabine for human lung cancer.

A phase I dose-escalation study of telomerase-specific oncolytic adenovirus, OBP-301 (Telomelysin), is now under way in the United States to assess feasibility and to characterize its pharmacokinetics in patients with advanced solid tumors. The present preclinical study investigates whether OBP-301 and a chemotherapeutic agent that is commonly used for lung cancer treatment, gemcitabine, are able to enhance antitumor effects in vitro and in vivo. The antitumor effects of OBP-301 infection and gemcitabine were evaluated by 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt assay. In vivo antitumor effects of intratumoral injection of OBP-301 in combination with systemic administration of gemcitabine were assessed on nu/nu mice s.c. xenografted with human lung tumors. OBP-301 infection combined with gemcitabine resulted in very potent synergistic cytotoxicity in human lung cancer cells. The three human lung cancer cell lines treated with OBP-301 for 24 hours tended to accumulate in S phase compared with controls. The proportion of cells in S phase increased from 43.85% to 56.41% in H460 cells, from 46.72% to 67.09% in H322 cells, and from 38.22% to 57.67% in H358 cells. Intratumoral injection of OBP-301 combined with systemic administration of gemcitabine showed therapeutic synergism in human lung tumor xenografts. Our data suggest that the combination of OBP-301 and gemcitabine enhances the antitumor effects against human lung cancer. We also found that the synergistic mechanism may be due to OBP-301-mediated cell cycle accumulation in S phase. These results have important implications for the treatment of human lung cancer.

Initial treatment strategies and outcomes for multifocal bronchioloalveolar carcinoma.

BACKGROUND: Bronchioloalveolar carcinoma (BAC) commonly presents as multifocal disease. Management of multifocal BAC remains controversial and may include surgical resection, systemic therapy, surveillance, or a combination of these strategies. Knowledge of current practice patterns and outcomes could help to inform future research. MATERIALS AND METHODS: Medical records of patients with BAC were retrospectively reviewed, and regression analyses were conducted to correlate demographic parameters, disease characteristics, and treatment modality with clinical outcomes. RESULTS: Of the 109 cases identified, 85 patients were eligible for study, 26% with unifocal and 74% with multifocal BAC. Median age at diagnosis was 65 years; the majority of the patients were female (64%), were non-Asian (82%), and had a smoking history (66%). In the subset with multifocal BAC, 24% of the cases were confined to one lobe, 76% affected multiple lobes, and 40% involved both lungs. The primary treatment modality for multifocal disease included surgical resection (78%), systemic therapy (14%), and observation (8%). In multivariate analyses, extensive disease (> or = 3 lobes involved) and medical oncology assessment predicted treatment with systemic therapy (odds ratio [OR], 8.68; P = .03 and OR, 1.68; P < .01, respectively). The presence of extensive disease and the receipt of systemic therapy were associated with higher likelihood of disease progression (hazard ratio [HR], 8.62; P = .02 and HR, 8.46; P = .02, respectively). CONCLUSION: Initial treatment choices and referral patterns for multifocal BAC were diverse and influenced by clinical selection, whereby patients with extensive disease were more likely to discuss and receive systemic therapy. Surgery and surveillance were reasonable treatment options for selected patients. The precise roles of the various treatment strategies for multifocal BAC require further evaluation.

Bronchioloalveolar carcinoma: the case for two diseases.

By current criteria, bronchioloalveolar carcinoma (BAC) is a subtype of pulmonary adenocarcinoma, developing from terminal bronchiolar and acinar epithelia and progressing in a lepidic and/or aerogenous manner on intact alveolar walls but without stromal, vascular, or pleural invasion. Evidence suggests that the 2 main cytologic types of BAC, ie, nonmucinous and mucinous, have some differing characteristics. The more frequent nonmucinous BAC directly evolves from the terminal respiratory unit cells, the type II pneumocyte, and Clara cells. This form predominates in smokers, presents more frequently as a ground-glass opacity, and frequently harbors epidermal growth factor receptor (EGFR) polysomy/mutations, believed to be the driver of its malignant process. The less frequent mucinous BAC, on the other hand, derived from metaplasia of bronchiolar epithelia, presents more frequently as a pneumonic-type infiltrate, rarely demonstrates EGFR polysomy/mutations, and much more frequently harbors and is driven by a K-ras mutation. These mutational oncogenic differences could lead to different therapeutic responses: nonmucinous BAC has been found to be sensitive to EGFR tyrosine kinase inhibitors, while mucinous BAC might be more responsive to taxane-based chemotherapy. In fact, there might be more differences than similarities, suggesting 2 distinct phenotypes that might need to be treated differently in order to optimize our management of the range of clinical disease that is often currently broadly classified as BAC.

[Other thoracic cancers. Bronchioloalveolar carcinoma and adenocarcinoma with bronchioloalveolar carcinoma feature: a clinico-pathological spectrum]. / Carcinome bronchioloalvéolaire (CBA) et adénocarcinome pulmonaire avec composante bronchioloalvéolaire (ADC-CBA): un continuum anatomoclinique.

Bronchioloalveolar carcinoma (BAC) is a primary pulmonary adenocarcinoma (ADC) developed from the terminal respiratory unit. Its restrictive definition adopted by the 1999 WHO pathological classification needs a complete tumor resection to exclude any signs of histological invasion. Although IIIB-IV tumors were excluded from the strict WHO definition of BAC, the first international workshop on BAC in 2004 had focussed on the need to include in the same spectrum of disease pure BAC and ADC with BAC feature (ADC-WBF). BAC and ADC-WBF affect more frequently women, non-smokers and Asian people than other non small cell carcinoma. Their predominant lepidic and aerogenous tumor progression results in a frequent pneumonic, multifocal or diffuse presentation and explains why death is more frequently related to bilateral pulmonary involvement than extra-thoracic metastasis. Natural history is slower and prognosis better than for other ADC. Surgical resection remains the best therapeutic option for localized tumors. High frequency of epidermal growth factor receptor (EGFR) expression on tumor cells and its gene amplification and/or mutation as well as a particular sensitivity of this entity to EGFR tyrosine kinase inhibitors offer new strategy of therapeutical management in patients with non resectable tumor. However, the place of chemotherapy has recently been revisited.

Intrapulmonary administration of CCL21 gene-modified dendritic cells reduces tumor burden in spontaneous murine bronchoalveolar cell carcinoma.

The antitumor efficiency of dendritic cells transduced with an adenovirus vector expressing secondary lymphoid chemokine (CCL21) was evaluated in a murine model of spontaneous bronchoalveolar cell carcinoma. The transgenic mice (CC-10 TAg) express the SV40 large T antigen (TAg) under the Clara cell promoter, develop bilateral, multifocal, and pulmonary adenocarcinomas, and die at 4 months as a result of progressive pulmonary tumor burden. A single intratracheal administration of CCL21 gene-modified dendritic cells (DC-AdCCL21) led to a marked reduction in tumor burden with extensive mononuclear cell infiltration of the tumors. The reduction in tumor burden was accompanied by the enhanced elaboration of type 1 cytokines [IFN-gamma, interleukin (IL)-12, and granulocyte macrophage colony-stimulating factor] and antiangiogenic chemokines (CXCL9 and CXCL10) but a concomitant decrease in the immunosuppressive molecules (IL-10, transforming growth factor-beta, prostaglandin E(2)) in the tumor microenvironment. The DC-AdCCL21 therapy group revealed a significantly greater frequency of tumor-specific T cells releasing IFN-gamma compared with the controls. Continuous therapy with weekly intranasal delivery of DC-AdCCL21 significantly prolonged median survival by >7 weeks in CC-10 TAg mice. Both innate natural killer and specific T-cell antitumor responses significantly increased following DC-AdCCL21 therapy. Significant reduction in tumor burden in a model in which tumors develop in an organ-specific manner provides a strong rationale for further evaluation of intrapulmonary-administered DC-AdCCL21 in regulation of tumor immunity and genetic immunotherapy for lung cancer.

Bronchioloalveolar lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition).

OBJECTIVES: To review the current evidence on special issues relating to the diagnosis, imaging, prognosis, and treatment of bronchioloalveolar carcinoma (BAC). METHODS: This guideline focuses on aspects of BAC that are unique and ways in which BAC differs importantly from other forms of non-small cell lung cancer (NSCLC). The author reviewed published literature reporting on BAC using key words "histology," "CT scans," "fluorodeoxyglucose positron emission tomography scan," "sensitivity," "specificity," "surgical resection," "sublobar resection," and "epidermal growth factor receptor tyrosine kinase inhibitor" and selected references from published review articles. Also included was a review of the 1999 World Health Organization (WHO) revised classification system for lung tumors, which established a more restrictive definition of BAC to tumors with a pure lepidic spreading pattern and no evidence of stromal, vascular, or pleural invasion. RESULTS: With the notable exception of a lower likelihood of a positive positron emission tomography finding in the presence of BAC, staging, diagnosis, and treatment are the same as for other histologic subtypes of NSCLC, but additional treatment options that may prove to be equivalent, if not more effective, for more patients exist (eg, epidermal growth factor receptor tyrosine kinase inhibitor therapy, sublobar resection). CONCLUSIONS: BAC is a form of adenocarcinoma with unique clinical, radiologic, and epidemiologic features. The diagnosis of BAC should be reserved for tumors that meet the WHO criteria. Additional clinical trials are needed on this population of patients, using strict definitions and enrollment criteria to allow the results to be applied to appropriate patient populations.

Clinical presentation, treatment options and outcome in patients with bronchioloalveolar carcinoma.

PURPOSE: To determine the characteristics of bronchioloalveolar carcinoma (BAC) as a special clinical and pathological entity and to evaluate the effects of treatment options on survival of BAC patients. PATIENTS AND METHODS: The study was partially retrospective and partially prospective, non randomized. We evaluated the clinical presentation, smoking habits, radiographic findings, treatment and survival of 21 patients with BAC treated at our Institute from 2000-2004. RESULTS: Registered were 16 (76.2%) male and 5 (23.8%) female patients, most of them in the 6th and 7th decade of life. Among younger patients females prevailed. Most common symptoms were dyspnoea 15 (71.4%), cough 14 (66.6%) and bronchial hypersecretion 9 (42.8%). There were 5 (23.8%) smokers, 6 (28.6%) ex-smokers and 10 (47.6%) nonsmokers. Main radiographic findings were lung consolidation (9; 42.8%), diffuse interstitial infiltrates (6; 28.6%), solitary (4; 19.0%) and multiple pulmonary lesions (2; 9.5%). Surgery was performed in 8 (38.0%) patients and 5 of them received adjuvant radio- and chemotherapy, while the remaining received chemotherapy alone (9; 42.8%) and symptomatic treatment (4; 19.0%). The median survival was 25 months and 1-year survival 70%, regardless of stage. In the group of patients treated surgically 1- and 2-year survival rate was 100% and the median survival 33 months. In non-operated patients the median survival was 18 months and 1- and 2-year survival 55% and 25%, respectively. CONCLUSION: BAC is a special clinical and pathological form of adenocarcinoma of the lung. Surgical treatment is the best option for selected BAC patients. Survival is associated with the treatment modality. Larger scale studies are necessary to confirm these findings.

Bronchioloalveolar carcinoma: a review.

Bronchioloalveolar carcinoma (BAC) is classified as a subset of lung adenocarcinoma but has a distinct clinical presentation, tumor biology, response to therapy, and prognosis compared with other subtypes of non-small-cell lung carcinoma (NSCLC). Bronchioloalveolar carcinoma disproportionately affects women, never-smokers, and Asians and is characterized by growth along alveolar septae without evidence of stromal, vascular, or pleural invasion. Although pure BAC accounts for approximately 4% of lung cancers, tumors with histologically mixed BAC and adenocarcinoma account for > 20% of all NSCLCs, and the incidence of BAC might be increasing. Bronchioloalveolar carcinoma histology is most commonly found in small lesions identified incidentally on chest radiographs or computed tomography scans and might represent a precursor lesion to invasive adenocarcinoma. As with other subsets of NSCLC, surgical resection is the only potentially curative treatment. Patients with unresectable BAC are more likely to respond to the epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib than patients with other subtypes of NSCLC. Stage for stage, patients with BAC have a higher rate of long-term survival but might have an increased rate of intrathoracic recurrence than patients with other subtypes of NSCLC.

Bronchioloalveolar carcinoma.

PURPOSE: To review bronchioloalveolar carcinoma (BAC). MATERIALS AND METHODS: English language articles were identified through a Melvyl Medline Search (1966 to 1995) and through the bibliographies of selected articles. RESULTS: An increase in BAC appears to be responsible for the observed rise in the incidence of adenocarcinoma of the lung. Patients with BAC tend to be younger at diagnosis, are more likely to be female, and less likely to be cigarette smokers when compared with other patients with non-small-cell lung cancer (NSCLC). The etiology of this disease is unclear, but multiple environmental insults have been implicated. There are three subtypes of BAC and the symptoms and prognosis of the disease depend on the subtype and extent of disease, but are generally similar to other histologic types of NSCLC. The radiographic differential diagnosis is broad and includes both benign and malignant diseases. The treatment approach to patients with BAC is similar to those with other types of NSCLC. CONCLUSION: BAC appears to be increasing in incidence, especially in young, nonsmoking females. Three subtypes of the disease exist and are responsible for the variable clinical presentations. Further epidemiologic investigation is needed to elucidate the etiology and pathogenesis of this unique disease.

Sublobar resection for the subcentimeter pulmonary nodule.

Several studies have demonstrated an increased local recurrence rate with sublobar resection (SR) when compared with lobar resection for the treatment of non-small-cell lung cancer (NSCLC). Therefore, lobectomy has remained the gold standard therapy for NSCLC with lesser resection reserved as a compromise operation for high-risk patients. The increased identification of small NSCLC tumors by CT scan is leading many surgeons to question the appropriateness of lobectomy for these tumors. There has been increasing interest by many surgeons to use SR as intentional therapy for patients with small peripheral NSCLC. This article reviews the recent literature and evidence supporting intentional SR for NSCLC. Although lobectomy should continue to be regarded as the procedure of choice for NSCLC, we believe that a subset of patients with favorable characteristics may be appropriately treated with intentional SR as long as good assessment of nodal involvement is made. Future investigation is required to better define when SR is appropriate.