Severity of Atelectasis during Bronchoscopy: Descriptions of a New Grading System (AtelectasisSeverity Scoring System-"ASSESS") and At-Risk-Lung Zones.

Atelectasis during bronchoscopy under general anesthesia is very common and can have a detrimental effect on navigational and diagnostic outcomes. While the intraprocedural incidence and anatomic location have been previously described, the severity of atelectasis has not. We reviewed chest CT images of patients who developed atelectasis in the VESPA trial (Ventilatory Strategy to Prevent Atelectasis). By drawing boundaries at the posterior chest wall (A), the anterior aspect of the vertebral body (C), and mid-way between these two lines (B), we delineated at-risk lung zones 1, 2, and 3 (from posterior to anterior). An Atelectasis Severity Score System ("ASSESS") was created, classifying atelectasis as "mild" (zone 1), "moderate" (zones 1-2), and "severe" (zones 1-2-3). A total of 43 patients who developed atelectasis were included in this study. A total of 32 patients were in the control arm, and 11 were in the VESPA arm; 20 patients (47%) had mild atelectasis, 20 (47%) had moderate atelectasis, and 3 (6%) had severe atelectasis. A higher BMI was associated with increased odds (1.5 per 1 unit change; 95% CI, 1.10-2.04) (p = 0.0098), and VESPA was associated with decreased odds (0.05; 95% CI, 0.01-0.47) (p = 0.0080) of developing moderate to severe atelectasis. ASSESS is a simple method used to categorize intra-bronchoscopy atelectasis, which allows for a qualitative description of this phenomenon to be developed. In the VESPA trial, a higher BMI was not only associated with increased incidence but also increased severity of atelectasis, while VESPA had the opposite effect. Preventive strategies should be strongly considered in patients with risk factors for atelectasis who have lesions located in zones 1 and 2, but not in zone 3.

Preventing atelectasis during bronchoscopy under general anesthesia.

Atelectasis is a well-defined phenomenon in patients having surgery under general anesthesia. Recently, this phenomenon was also reported in patients having bronchoscopy under general anesthesia, with dedicated studies demonstrating a high incidence of up to 89%. Not surprisingly, time under general anesthesia and a higher body mass index (BMI) were found to be two significant factors that influenced the development of intraprocedural atelectasis. Atelectasis poses a significant obstacle in peripheral bronchoscopy since it can result in false positive radial probe ultrasound images, create computed tomography to body divergence, as well as obscure the target lesion on intraprocedural cone beam computed tomography (CBCT) images, thereby affecting both the navigational and diagnostic yield of the procedure. Bronchoscopists should be aware of this phenomenon and make efforts to prevent it when peripheral bronchoscopy under general anesthesia is planned. Ventilatory strategies to reduce intraprocedural atelectasis have been studied and proven to be effective and well-tolerated. Other strategies, such as patient positioning and preprocedural strategies have also been described but need further investigation. This article aims to summarize the recent history regarding the discovery and significance of intraprocedural atelectasis during bronchoscopy under general anesthesia and the various state-of-the-art strategies that have been proposed to mitigate the development of this entity.

An update on bronchopleural fistulae following cancer-related surgery.

PURPOSE OF REVIEW: Bronchopleural fistulae (BPF) are rare complications in cancer-related surgery but impart significant morbidity and mortality. BPF may be difficult to identify, with a broad differential diagnosis at presentation, so it is critical to be aware of newer diagnostic and therapeutic approaches for this disease entity. RECENT FINDINGS: Multiple novel diagnostic and therapeutic interventions are featured in this review. Reports of newer bronchoscopic techniques to localize BPF, as well as approaches for bronchoscopic management, like stent deployment, endobronchial valve placement, or alternative interventions when indicated are discussed, paying particular attention to factors that influence procedure selection. SUMMARY: Management of BPF remains highly variable, but several novel approaches have shown improved identification and outcomes. Although a multidisciplinary approach is imperative, an understanding of these newer techniques is important to provide optimal care for patients.

Mobile Cone-Beam CT-Assisted Bronchoscopy for Peripheral Lung Lesions.

Peripheral bronchoscopy with the use of thin/ultrathin bronchoscopes and radial-probe endobronchial ultrasound (RP-EBUS) has been associated with a fair diagnostic yield. Mobile cone-beam CT (m-CBCT) could potentially improve the performance of these readily available technologies. We retrospectively reviewed the records of patients undergoing bronchoscopy for peripheral lung lesions with thin/ultrathin scope, RP-EBUS, and m-CBCT guidance. We studied the performance (diagnostic yield and sensitivity for malignancy) and safety (complications, radiation exposure) of this combined approach. A total of 51 patients were studied. The mean target size was 2.6 cm (SD, 1.3 cm) and the mean distance to the pleura was 1.5 cm (SD, 1.4 cm). The diagnostic yield was 78.4% (95 CI, 67.1-89.7%), and the sensitivity for malignancy was 77.4% (95 CI, 62.7-92.1%). The only complication was one pneumothorax. The median fluoroscopy time was 11.2 min (range, 2.9-42.1) and the median number of CT spins was 1 (range, 1-5). The mean Dose Area Product from the total exposure was 41.92 Gy·cm2 (SD, 11.35 Gy·cm2). Mobile CBCT guidance may increase the performance of thin/ultrathin bronchoscopy for peripheral lung lesions in a safe manner. Further prospective studies are needed to corroborate these findings.

Therapeutic bronchoscopy for malignant central airway obstruction: impact on quality of life and risk-benefit analysis.

PURPOSE OF REVIEW: Malignant central airway obstruction (CAO) is a common complication in cancer and confers significant symptom burden and reduction in quality of life. Multiple bronchoscopic interventions exist for malignant CAO. In this review, we discuss the role of therapeutic bronchoscopy in the management of malignant CAO, emphasizing its impact on symptom control and quality of life while balancing the risks and benefits of intervention. RECENT FINDINGS: Significant practice variations exist among practitioners of therapeutic bronchoscopy, and limited data exist to guide real-time clinical decision-making. Recent analyses demonstrate that therapeutic bronchoscopy is effective for symptoms associated with malignant CAO with infrequent complications. These studies also show that many of the improvements in symptoms and quality of life are sustained after intervention and are associated with improved overall survival in patients with malignant CAO. Recent data have also shown that the improvement in symptoms associated with therapeutic bronchoscopy may enable more definitive cancer treatment, further improving patient outcomes. SUMMARY: Therapeutic bronchoscopy is safe and effective at improving patient-centered outcomes in malignant CAO. Research is ongoing to better understand its optimal role in this setting, refine decision-making regarding advanced bronchoscopic interventions, and further improve patient outcomes.

Update on the diagnosis and management of malignant pleural effusions.

Roughly 150,000 malignant pleural effusions (MPE) are diagnosed in the United States each year. The majority of cases are caused by lung and breast cancer, and since MPE represents advanced disease, the prognosis is generally poor. In this article we review the pathophysiology, epidemiology, and prognosis of MPE. We then discuss the approach to diagnosis of MPE including the role of imaging, pleural fluid analysis, and medical thoracoscopy. Current management strategies for symptomatic MPE include repeated thoracentesis for patients with very limited life expectancy as well as more definitive procedures such as chemical pleurodesis, tunneled indwelling pleural catheters, and novel combined approaches. The choice of intervention is guided by the efficacy, local expertise, and risk, as well as patient factors and preferences.

Central nervous system miliary metastasis in breast cancer: a case series analysis and proposed identification criteria of a rare metastasis subtype.

BACKGROUND: CNS miliary metastasis (MiM) is poorly recognised in breast and other malignancies. Given its rarity, little epidemiologic, radiographic and clinical data are known. Although usually identified on neuroimaging, criteria for radiographic diagnosis do not exist. In this analysis, we establish its presence in breast cancer and identify factors contributing to outcome. METHODS: We identified 546 female patients with brain metastasis from breast cancer between 2000 and 2015. Radiographic criteria were established through review of neuroimages by a senior Neuroradiologist, and defined as: (1) ≥20 lesions per image on ≥2 non-contiguous MRI images or ≥10 lesions per image on ≥2 non-contiguous CT images, and (2) bilateral lesions located in both the supratentorial and infratentorial compartments. RESULTS: Twenty-one MiM cases were identified (3.8%). Number and anatomical distribution of metastases best identified MiM, while lesion size did not. Ten patients were diagnosed with MiM as initial CNS metastasis; 11 developed MiM following known CNS metastasis. Breast cancer subtype did not influence MiM development before or after other CNS metastasis. CONCLUSIONS: This is the first study to propose radiographic criteria for MiM diagnosis. Additional analysis is needed to verify data, but our results may enable a standardised approach for future MiM research.

Effect of neoadjuvant chemotherapy regimen on relapse-free survival among patients with breast cancer achieving a pathologic complete response: an early step in the de-escalation of neoadjuvant chemotherapy.

BACKGROUND: Patients with breast cancer who have a pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) have improved survival. We hypothesize that once pCR has been achieved, there is no difference in subsequent postsurgical recurrence-free survival (RFS), whichever NACT regimen is used. METHODS: Data from patients with breast cancer who achieved pCR after NACT between 1996 and 2011 were reviewed. RFS was estimated by the Kaplan-Meier method, and differences between groups were assessed using log-rank testing. Cox proportional hazards regression analysis adjusted for age, menopausal status, stage, grade, tumor subtype, and adjuvant endocrine HER2-targeted radiation treatment. RESULTS: Among 721 patients who achieved pCR after NACT, 157 (21.8%) were hormone receptor-positive (HR), 310 (43.3%) were HER2-amplified, and 236 (32.7%) were triple-negative; 292 (40.5%) were stage IIA, 153 (21.2%) were stage IIB, 78 (10.8%) were stage IIIA, 66 (9.2%) were stage IIIB, and 132 (18.3%) were stage IIIC. Most patients (367 [50.9%]) had been treated with adriamycin-based chemotherapy plus taxane (A + T), 56 (7.8%) without taxane (A no T), 227 (31.5%) with HER2-targeted therapy, and 71 (9.8%) provider choice. Median follow-up was 7.1 years. Adjuvant chemotherapy was employed in 196 (27%) patients, adjuvant endocrine in 261 (36%), and adjuvant radiation in the majority (559 [77.5%]). There was no statistically significant difference in RFS by NACT group. Adjusted RFS hazard ratios, comparing each treatment with the reference group A + T, were 1.25 (95% CI 0.47-3.35) for A no T, 0.90 (95% CI 0.37-2.20) for HER2-targeted therapy, and 1.28 (95% CI 0.55-2.98) for provider choice. CONCLUSIONS: These data suggest that postsurgical RFS is not significantly influenced by the choice of NACT or cancer subtype among patients achieving pCR.

Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inhibitor Discontinuation.

Background: CDK 4 and 6 inhibitors (CDK4/6i), which arrest unregulated cancer cell proliferation, show clinical efficacy in breast cancer. Unexpectedly, a patient treated on a CDK4/6i-based trial, as first-line therapy in metastatic breast cancer, developed rapid disease progression following discontinuation of study drug while receiving standard second-line therapy off trial. We thus sought to expand this observation within a population of patients treated similarly at The University of Texas MD Anderson Cancer Center. Methods: Using an IRB-approved protocol, 4 patients previously enrolled on CDK4/6i trials were analyzed for outcomes after discontinuing study drug. These patients were treated on a randomized trial of first-line endocrine therapy +/- a CDK4/6i. Rapid disease progression was defined as progression occurring within 4 months of CDK4/6i discontinuation. Results: In total, 4 patients developed rapid disease progression and died; 2 of whom died within 6 months of CDK4/6i discontinuation. Conclusion: This case series suggests a potential for rapid disease progression following CDK4/6i discontinuation. However, the clinical course following progression must be validated in large CDK4/6i clinical trials and standard-of-care cohorts. If confirmed, such observations may alter the algorithm for subsequent therapy in patients with disease progression on CDK4/6i. Nevertheless, the need remains to define a mechanistic basis for this rapid progression and formulate alternative therapeutic strategies.

CDK4/6 and autophagy inhibitors synergistically induce senescence in Rb positive cytoplasmic cyclin E negative cancers.

Deregulation of the cell cycle machinery is a hallmark of cancer. While CDK4/6 inhibitors are FDA approved (palbociclib) for treating advanced estrogen receptor-positive breast cancer, two major clinical challenges remain: (i) adverse events leading to therapy discontinuation and (ii) lack of reliable biomarkers. Here we report that breast cancer cells activate autophagy in response to palbociclib, and that the combination of autophagy and CDK4/6 inhibitors induces irreversible growth inhibition and senescence in vitro, and diminishes growth of cell line and patient-derived xenograft tumours in vivo. Furthermore, intact G1/S transition (Rb-positive and low-molecular-weight isoform of cyclin E (cytoplasmic)-negative) is a reliable prognostic biomarker in ER positive breast cancer patients, and predictive of preclinical sensitivity to this drug combination. Inhibition of CDK4/6 and autophagy is also synergistic in other solid cancers with an intact G1/S checkpoint, providing a novel and promising biomarker-driven combination therapeutic strategy to treat breast and other solid tumours.

Clinical nomogram to predict bone-only metastasis in patients with early breast carcinoma.

BACKGROUND: Bone is one of the most common sites of distant metastasis in breast cancer. The purpose of this study was to combine selected clinical and pathologic variables to develop a nomogram that can predict the likelihood of bone-only metastasis (BOM) as the first site of recurrence in patients with early breast cancer. METHODS: Medical records of patients with non-metastatic breast cancer were retrospectively collected. On the basis of the analysis of patient and tumour characteristics using the Cox proportional hazards regression model, a nomogram to predict BOM was constructed for a 4175-patient-training cohort. The nomogram was validated in an independent cohort of 579 patients. RESULTS: Among 4175 patients with non-metastatic breast cancer, 314 developed subsequent BOM. Age, T classification, lymph node status, lymphovascular space invasion, and hormone receptor status were significantly and independently associated with subsequent BOM. The nomogram had a concordance index of 0.69 in the training set and 0.73 in the validation set. CONCLUSIONS: We have developed a clinical nomogram to predict subsequent BOM in patients with non-metastatic breast cancer. Selection of a patient population at high risk for BOM could facilitate research of more specific staging approaches or the selective use of bone-targeted therapy.

CCR 20th Anniversary Commentary: Setting the Stage for Nanoparticle Albumin-Bound Paclitaxel-How Far Science Has Come.

In this phase I pharmacokinetic study of ABI-007, which was published in the May 1, 2002, issue of Clinical Cancer Research, Ibrahim and colleagues provided the framework needed for subsequent studies to confirm the benefits of ABI-007 over solvent-based formulations. Since the study's publication, experiments have highlighted the importance of drug-delivery systems, the immune system in cancer biology, and immunoregulatory properties of taxane compounds.

Sulfate-driven elemental sparing is regulated at the transcriptional and posttranscriptional levels in a filamentous cyanobacterium.

Sulfur is an essential nutrient that can exist at growth-limiting concentrations in freshwater environments. The freshwater cyanobacterium Fremyella diplosiphon (also known as Tolypothrix sp. PCC 7601) is capable of remodeling the composition of its light-harvesting antennae, or phycobilisomes, in response to changes in the sulfur levels in its environment. Depletion of sulfur causes these cells to cease the accumulation of two forms of a major phycobilisome protein called phycocyanin and initiate the production of a third form of phycocyanin, which possesses a minimal number of sulfur-containing amino acids. Since phycobilisomes make up approximately 50% of the total protein in these cells, this elemental sparing response has the potential to significantly influence the fitness of this species under low-sulfur conditions. This response is specific for sulfate and occurs over the physiological range of sulfate concentrations likely to be encountered by this organism in its natural environment. F. diplosiphon has two separate sulfur deprivation responses, with low sulfate levels activating the phycobilisome remodeling response and low sulfur levels activating the chlorosis or bleaching response. The phycobilisome remodeling response results from changes in RNA abundance that are regulated at both the transcriptional and posttranscriptional levels. The potential of this response, and the more general bleaching response of cyanobacteria, to provide sulfur-containing amino acids during periods of sulfur deprivation is examined.