Predicting Lymph Node Metastasis in Non-small Cell Lung Cancer: Prospective External and Temporal Validation of the HAL and HOMER Models.

BACKGROUND: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers. RESEARCH QUESTION: Are the HAL and HOMER models valid across multiple centers? STUDY DESIGN AND METHODS: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. HOMER was used to predict the probability of N0 vs N1 vs N2 or N3 (N2|3) disease, and HAL was used to predict the probability of N2|3 (vs N0 or N1) disease. Model discrimination was assessed using the area under the receiver operating characteristics curve (ROC-AUC), and calibration was assessed using the Brier score, calibration plots, and the Hosmer-Lemeshow test. RESULTS: Thirteen centers enrolled 1,799 patients. HAL and HOMER demonstrated good discrimination: HAL ROC-AUC = 0.873 (95%CI, 0.856-0.891) and HOMER ROC-AUC = 0.837 (95%CI, 0.814-0.859) for predicting N1 disease or higher (N1|2|3) and 0.876 (95%CI, 0.855-0.897) for predicting N2|3 disease. Brier scores were 0.117 and 0.349, respectively. Calibration plots demonstrated good calibration for both models. For HAL, the difference between forecast and observed probability of N2|3 disease was +0.012; for HOMER, the difference for N1|2|3 was -0.018 and for N2|3 was +0.002. The Hosmer-Lemeshow test was significant for both models (P = .034 and .002), indicating a small but statistically significant calibration error. INTERPRETATION: HAL and HOMER demonstrated good discrimination and calibration in multiple centers. Although calibration error was present, the magnitude of the error is small, such that the models are informative.

AABIP Evidence-informed Guidelines and Expert Panel Report for the Management of Indwelling Pleural Catheters.

BACKGROUND: While the efficacy of Indwelling pleural catheters for palliation of malignant pleural effusions is supported by relatively robust evidence, there is less clarity surrounding the postinsertion management. METHODS: The Trustworthy Consensus-Based Statement approach was utilized to develop unbiased, scientifically valid guidance for the management of patients with malignant effusions treated with indwelling pleural catheters. A comprehensive electronic database search of PubMed was performed based on a priori crafted PICO questions (Population/Intervention/Comparator/Outcomes paradigm). Manual searches of the literature were performed to identify additional relevant literature. Dual screenings at the title, abstract, and full-text levels were performed. Identified studies were then assessed for quality based on a combination of validated tools. Appropriateness for data pooling and formation of evidence-based recommendations was assessed using predetermined criteria. All panel members participated in development of the final recommendations utilizing the modified Delphi technique. RESULTS: A total of 7 studies were identified for formal quality assessment, all of which were deemed to have a high risk of bias. There was insufficient evidence to allow for data pooling and formation of any evidence-based recommendations. Panel consensus resulted in 11 ungraded consensus-based recommendations. CONCLUSION: This manuscript was developed to provide clinicians with guidance on the management of patients with indwelling pleural catheters placed for palliation of malignant pleural effusions. Through a systematic and rigorous process, management suggestions were developed based on the best available evidence with augmentation by expert opinion when necessary. In addition, these guidelines highlight important gaps in knowledge which require further study.

Risk factors for pleural effusion recurrence in patients with malignancy.

BACKGROUND AND OBJECTIVE: The main purpose of treatment in patients with malignant pleural effusion (MPE) is symptom palliation. Currently, patients undergo repeat thoracenteses prior to receiving a definitive procedure as clinicians are not aware of the risk factors associated with fluid recurrence. The primary objective of this study was to identify risk factors associated with recurrent symptomatic MPE. METHODS: Retrospective multicentre cohort study of patients who underwent first thoracentesis was performed. The primary outcome was time to fluid recurrence requiring intervention in patients with evidence of metastatic disease. We used a cause-specific hazard model to identify risk factors associated with fluid recurrence. We also developed a predictive model, utilizing Fine-Gray subdistribution hazard model, and externally validated the model. RESULTS: A total of 988 patients with diagnosed metastatic disease were included. Cumulative incidence of recurrence was high with 30% of patients recurring by day 15. On multivariate analysis, size of the effusion on chest X-ray (up to the top of the cardiac silhouette (hazard ratio (HR): 1.84, 95% CI: 1.21-2.80, P = 0.004) and above the cardiac silhouette (HR: 2.22, 95% CI: 1.43-3.46, P = 0.0004)), larger amount of pleural fluid drained (HR: 1.06, 95% CI: 1.04-1.07, P < 0.0001) and higher pleural fluid LDH (HR: 1.008, 95% CI: 1.004-1.011, P < 0.0001) were associated with increased hazard of recurrence. Negative cytology (HR: 0.52, 95% CI: 0.43-0.64, P < 0.0001) was associated with decreased hazard of recurrence. The model had low prediction accuracy. CONCLUSION: Pleural effusion size, amount of pleural fluid drained, LDH and pleural fluid cytology were found to be risk factors for recurrence.

Malignant central airway obstruction.

This review comprehensively describes recent advances in the management of malignant central airway obstruction (CAO). Malignant CAO can be a dramatic and devastating manifestation of primary lung cancer or metastatic disease. A variety of diagnostic modalities are available to provide valuable information to plan a therapeutic intervention. Clinical heterogeneity in the presentation of malignant CAO provides opportunities to adapt and utilize endoscopic technology and tools in many ways. Mechanical debulking, thermal tools, cryotherapy and airway stents are methods and instruments used to rapidly restore airway patency. Delayed bronchoscopic methods, such as photodynamic therapy (PDT) and brachytherapy can also be utilized in specific non-emergent situations to establish airway patency. Although data regarding the success and complications of therapeutic interventions are retrospective and characterized by clinical and outcome measure variability, the symptoms of malignant CAO can often be successfully palliated. Assessment of risks and benefits of interventions in each individual patient during the decision-making process forms the critical foundation of the management of malignant CAO.

Evaluation of Appropriate Mediastinal Staging among Endobronchial Ultrasound Bronchoscopists.

RATIONALE: Endobronchial ultrasound (EBUS) has transformed mediastinal staging in lung cancer. A systematic approach, beginning with lymph nodes contralateral to the primary tumor (N3), is considered superior to selective sampling of radiographically abnormal nodes. However, the extent to which this recommendation is followed in practice remains unknown. OBJECTIVES: To assess the frequency with which pulmonologists, pulmonary fellows, and interventional pulmonologists endoscopically stage lung cancer appropriately. METHODS: Bronchoscopists currently performing EBUS were surveyed about their practice patterns, procedural volume, and self-confidence in EBUS skills; they then performed a proctored simulated staging EBUS. The primary outcome was the proportion of participants who appropriately initiated ultrasonographic evaluation with the N3 nodal stations in a simulated patient undergoing EBUS for mediastinal staging. RESULTS: Sixty physicians (22 interventional pulmonologists, 18 general pulmonologists, and 20 pulmonary fellows) participated in the study. The rates of appropriate staging by study group were 95.5% (21 of 22) for interventional pulmonologists, 44.4% (8 of 18) for general pulmonologists, and 30.0% (6 of 20) for pulmonary fellows (P < 0.001). Increased procedural volume correlated with appropriate staging practices (P < 0.001). Within each group, we assessed the concordance between self-confidence in EBUS and simulation performance. Among interventional pulmonologists, the concordance was 95.4%, followed by 61.1% for general pulmonologists and 40.0% for pulmonary fellows. CONCLUSIONS: General pulmonologists and pulmonary fellows were less likely than interventional pulmonologists to perform appropriate EBUS staging. In addition, the lack of concordance between self-confidence and appropriate staging performance among noninterventionists signals a need for improved dissemination of guidelines for EBUS-guided mediastinal staging.

What Exactly Is a Centrally Located Lung Tumor? Results of an Online Survey.

RATIONALE: Accurate mediastinal staging is a cornerstone in the management of patients with lung cancer. For patients with radiographically normal mediastinum, current lung cancer guidelines recommend invasive mediastinal staging when tumors are centrally located. However, definitions of central tumors are nonspecific, and there are discrepancies among guidelines (e.g., some use the inner one-third of the hemithorax, whereas others use the inner two-thirds). OBJECTIVES: To describe the definitions of central tumors used by pulmonologists and thoracic surgeons in their practices. METHODS: An online questionnaire was e-mailed to members of the American Association for Bronchology and Interventional Pulmonology and members of the Cardiothoracic Surgery Network. MEASUREMENTS AND MAIN RESULTS: A total of 218 participants completed our survey (12% response rate). Most common definitions for central tumors were: inner one-third of the hemithorax (55%), in contact with hilar structures (29%), and inner two-thirds of the hemithorax (15%). Of note, 29% of participants chose a definition fabricated specifically for this survey and not supported by guidelines. Regarding the method to delineate the thirds of the hemithorax, 182 (84%) participants chose a system of concentric lines arising in the hilum, whereas 31 (14%) chose straight lines in the sagittal plane of the chest. We found strikingly similar responses in members of both societies. CONCLUSIONS: A uniform definition of tumor centrality is currently lacking, and should be formulated. Studies using objective measurements that evaluate the ability of these different definitions of central lung tumors to predict N2 disease are needed to construct a clear and evidence-based definition.

Safety and feasibility of prolonged bronchoscopy involving diagnosis of lung cancer, systematic nodal staging, and fiducial marker placement in a high-risk population.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is considered the standard treatment for medically inoperable early stage lung cancer. Bronchoscopy has shown to be effective in obtaining diagnosis of peripheral lung tumors, staging the mediastinum (with endobronchial ultrasound- EBUS-), and placing fiducial markers (FMs). However, the combination of these 3 procedures in a single bronchoscopy has not been studied. The aim of this study is to describe safety and feasibility of performing diagnosis, systematic nodal staging, and placement of FMs in a single bronchoscopic procedure. METHODS: Retrospective review of patients who underwent bronchoscopy with diagnosis of peripheral lung cancer, EBUS for nodal staging, and FM placement in a single procedure at Michael E. DeBakey VA Medical Center between January 2011 and July 2015. RESULTS: Twenty-one patients met our criteria, one having 2 synchronous tumors. 95% of patients had an ASA score of at least 3. Twenty-two tumors were diagnosed with a size of 2.72±1.06 cm. Distance from pleura was 1.33±1.42 cm. Median duration of bronchoscopy was 96 minutes (range, 75 to 136 minutes). Guided-bronchoscopy provided diagnosis of lung cancer in all cases. Fluoroscopy and RP-EBUS were utilized in 21 patients, "hybrid" scope in 14, and electromagnetic navigational bronchoscopy in 3. A total of 100 lymph nodes (LN) were sampled with EBUS-TBNA, with 95% of the patients having at least 4 LN sampled. A total of 71 FM were placed for 22 tumors. All markers were retained and allowed for successful SBRT. There were no pneumothoraces and no major complications. CONCLUSIONS: Although it results in lengthy procedures, a single bronchoscopy obtaining diagnosis of peripheral lung nodules, systematic nodal staging, and FM placement can be safely performed in high-risk patients. Our "all-in-one" strategy could potentially expedite treatment, decrease complications, and reduce costs. Further prospective studies are needed to corroborate our findings.

Advanced bronchoscopic techniques for the diagnosis of peripheral pulmonary lesions.

PURPOSE OF REVIEW: The review describes recent advances in bronchoscopic modalities used to diagnose peripheral pulmonary lesions. RECENT FINDINGS: The pooled diagnostic yield and sensitivity of radial probe endobronchial ultrasound (r-EBUS) has been reported to be 56% for lesions less than 2 cm and 78% for lesions more than 2 cm and 73%, respectively. The pooled diagnostic yield and sensitivity of electromagnetic navigational bronchoscopy (ENB) has been reported to be 65 and 71%, respectively. However, significant heterogeneity between studies was evident for both r-EBUS and ENB (sensitivity of r-EBUS: I = 75%; sensitivity of ENB: I = 57% and diagnostic yield of ENB: I = 66%). Recent studies show that these technologies do not perform in the clinical setting as well as reported in the literature. Conceptually, the domains of advanced bronchoscopic modalities that affect performance are navigation, maneuverability, and location verification. Combining technologies that deal with different domains, such as ENB (navigation) and r-EBUS (location verification), has led to synergistic effects with improved outcomes. SUMMARY: The performance characteristics of the different advanced bronchoscopic modalities reported in the literature may not be representative of performance in clinical practice because of clinical and statistical heterogeneity in the published literature. However, evidence is accumulating that synergistic combinations of technologies may ultimately lead to better performance.

Obstructive Sleep Apnea Is Not Associated with Higher Health Care Use after Colonoscopy under Conscious Sedation.

RATIONALE: The use of sedation allows medical procedures to be performed outside the operating room while ensuring patient comfort and a controlled environment to increase the yield of the procedure. There is concern about a higher risk of adverse events with use of sedation in patients with obstructive sleep apnea. OBJECTIVES: We aimed to determine if the presence of obstructive sleep apnea increased the risk of hospitalization and/or health care use after patients received moderate conscious sedation for an elective, ambulatory colonoscopy. METHODS: We conducted a retrospective case-control database and chart review study. We compared hospital admissions, intensive care unit (ICU) admissions, and emergency room visits at 24 hours, 7 days, and 30 days in patients with obstructive sleep apnea (n = 3,860) and without obstructive sleep apnea (n = 2,374) who had undergone an elective, ambulatory colonoscopy with sedation. MEASUREMENTS AND MAIN RESULTS: We found no significant differences in hospital admissions, ICU admissions, or emergency room visits between the two groups at any time point within the 30 days following the procedures. In a sensitivity analysis in which we compared 827 individuals with polysomnographically confirmed sleep apnea with control subjects, there was still no difference in hospital admissions, ICU admissions, or emergency room visits in the 30 days after receiving sedation for the procedure. Outcomes were not different in individuals with various severities of obstructive sleep apnea. CONCLUSIONS: The presence of obstructive sleep apnea was not associated with increased early hospital admissions, ICU admissions, or emergency room visits after colonoscopy with sedation.

Asymptomatic central pontine myelinolysis: a case report.

INTRODUCTION: Central pontine myelinolysis (CPM) is an acquired demyelinating lesion of the basis pontis that typically occurs after rapid correction of hyponatremia. There are only a few reported cases of patients without symptoms that have demonstrated CPM on imaging. CASE PRESENTATION: We report the case of a 26-year-old Hispanic male with history of alcohol abuse who was transferred to our medical center for acute onset diffuse abdominal pain. During his work up, a computed tomography scan demonstrated a large pancreatic mass. He underwent an endoscopic guided biopsy which demonstrated a rare and aggressive natural killer T cell lymphoma. His laboratory values were consistent with hyponatremia, which the medical team gently corrected. An MRI was performed for staging purposes which revealed findings consistent with CPM. A full neurological exam demonstrated no deficits. MATERIALS AND METHODS: WE CONDUCTED A PUBMED SEARCH USING THE FOLLOWING KEYWORDS: asymptomatic, central, pontine, and myelinolysis in order to find other case reports of asymptomatic CPM. RESULTS: Of the 29 results, only 6 previous case reports with English language abstracts of asymptomatic CPM were present since 1995. CONCLUSION: Despite slow correction of hyponatremia, CPM can be an important consequence, especially in patients with chronic alcoholism. Although this patient did not demonstrate any neurological deficits, the fact that there were changes seen on MRI should caution physicians in aggressively treating hyponatremia. Furthermore, if there is a decision to treat, then fluid restriction and reversal of precipitating factors (i.e. diuretics) should be used initially, unless there is concern for hypovolemia.

Etiology of syncope in patients hospitalized with syncope and predictors of mortality and rehospitalization for syncope at 27-month follow-up.

The authors investigated the etiologies of syncope and risk factors for mortality and rehospitalization for syncope at 27-month follow-up in 325 consecutive patients, mean age 66 years, hospitalized for syncope. The causes of syncope were diagnosed in 241 patients (74%). Of 325 patients, 13 (4%) were rehospitalized for syncope and 38 (12%) died. Stepwise logistic regression analysis showed that significant independent prognostic factors for rehospitalization for syncope were diabetes (odds ratio [OR], 5.7; 95% confidence interval [CI], 1.6-20.4), atrial fibrillation (OR, 4.0; 95% CI, 1.0-15.6), and smoking (OR, 4.6; 95% CI, 1.3-16.8). Stepwise Cox regression analysis showed that significant independent prognostic factors for time to mortality were diabetes (hazard ratio [HR], 2.7; 95% CI, 1.4-5.2), coronary artery bypass graft surgery (HR, 2.9; 95% CI, 1.3-6.5), malignancy history (HR, 2.5; 95% CI, 1.2-5.2), narcotics use (HR, 4.0; 95% CI, 1.7-9.8), smoking (HR, 2.8; 95% CI, 1.4-5.5), atrial fibrillation (HR, 2.4; 95% CI, 1.0-5.4), and volume depletion (HR, 2.8; 95% CI, 1.4-5.8). Copyright © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.