TL;DR: If mediastinal staging is improved, more patients should receive optimal treatment and might survive longer and the current post hoc analysis evaluated survival in ASTER.
Abstract: Five-Year Survival After Endosonography vs Mediastinoscopy for Mediastinal Nodal Staging of Lung Cancer Lung cancer accounts for the highest cancer-related mortality rate worldwide.1 Accurate mediastinal nodal staging is crucial in the management of non–small cell lung cancer (NSCLC) because it directs therapy and has prognostic value.2,3 The Assessment of Surgical Staging vs Endosonographic Ultrasound in Lung Cancer (ASTER) trial compared mediastinoscopy (surgical staging) with an endosonographic staging strategy (which combined the use of endobronchial and transesophageal ultrasound followed by mediastinoscopy if negative).4 The endosonographic strategy was significantly more sensitive for diagnosing mediastinal nodal metastases than surgical staging (94% endosonographic strategy vs 79% surgical strategy). If mediastinal staging is improved, more patients should receive optimal treatment and might survive longer. The current post hoc analysis evaluated survival in ASTER.
TL;DR: It is hypothesized that omitting mediastinoscopy after negative endosonography in mediastinal staging of NSCLC does not result in an unacceptable percentage of unforeseen N2 disease at surgical resection, and may be associated with lower morbidity and comparable survival.
Abstract: In case of suspicious lymph nodes on computed tomography (CT) or fluorodeoxyglucose positron emission tomography (FDG-PET), advanced tumour size or central tumour location in patients with suspected non-small cell lung cancer (NSCLC), Dutch and European guidelines recommend mediastinal staging by endosonography (endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS)) with sampling of mediastinal lymph nodes. If biopsy results from endosonography turn out negative, additional surgical staging of the mediastinum by mediastinoscopy is advised to prevent unnecessary lung resection due to false negative endosonography findings. We hypothesize that omitting mediastinoscopy after negative endosonography in mediastinal staging of NSCLC does not result in an unacceptable percentage of unforeseen N2 disease at surgical resection. In addition, omitting mediastinoscopy comprises no extra waiting time until definite surgery, omits one extra general anaesthesia and hospital admission, and may be associated with lower morbidity and comparable survival. Therefore, this strategy may reduce health care costs and increase quality of life. The aim of this study is to compare the cost-effectiveness and cost-utility of mediastinal staging strategies including and excluding mediastinoscopy. This study is a multicenter parallel randomized non-inferiority trial comparing two diagnostic strategies (with or without mediastinoscopy) for mediastinal staging in 360 patients with suspected resectable NSCLC. Patients are eligible for inclusion when they underwent systematic endosonography to evaluate mediastinal lymph nodes including tissue sampling with negative endosonography results. Patients will not be eligible for inclusion when PET/CT demonstrates ‘bulky N2-N3’ disease or the combination of a highly suspicious as well as irresectable mediastinal lymph node. Primary outcome measure for non-inferiority is the proportion of patients with unforeseen N2 disease at surgery. Secondary outcome measures are hospitalization, morbidity, overall 2-year survival, quality of life, cost-effectiveness and cost-utility. Patients will be followed up 2 years after start of treatment. Results of the MEDIASTrial will have immediate impact on national and international guidelines, which are accessible to public, possibly reducing mediastinoscopy as a commonly performed invasive procedure for NSCLC staging and diminishing variation in clinical practice. The trial is registered at the Netherlands Trial Register on July 6th, 2017 (
TL;DR: EBUS-TBNA is more cost-effective than Med and it is currently recommended as the test of first choice for invasive mediastinal LN staging in lung cancer.
Abstract: This review provides an update on the current role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and mediastinoscopy (Med) in assessment of patients with non-small cell lung cancer (NSCLC). Invasive mediastinal lymph node (LN) staging is the major application for both of these techniques. Up until recently, Med was the gold standard for invasive mediastinal LN staging in NSCLC. However, EBUS-TBNA has shown to be equivalent, and in some studies better than Med for invasive staging of lung cancer. EBUS-TBNA offers access to N1 LNs and development of the thin convex probe EBUS (TCP-EBUS) will expand EBUS-TBNA access from the paratracheal region and central airways to more distal parabronchial regions allowing for more extensive N1 LN assessment and sampling more distal lung tumors. EBUS-TBNA is more cost-effective than Med and it is currently recommended as the test of first choice for invasive mediastinal LN staging in lung cancer. Confirmatory Med should be performed selectively in patients with high pretest probability of metastatic disease. Addition of esophageal ultrasound fine needle aspiration (EUS-FNA) may increase diagnostic yield of EBUS-TBNA mediastinal staging. Both Med and EBUS-TBNA can be used in primary lung cancer diagnosis, restaging of the mediastinum following neoadjuvant therapy and in diagnosis of lung cancer recurrence. In the future, a combination of EBUS-TBNA with or without EUS-FNA and Med is most likely going to provide the most optimal invasive assessment of the mediastinum in patients with lung cancer. The decision on test choice and sequence should be made on a case-by-case basis and factoring in local resources and expertise.
TL;DR: The latest findings regarding the benefits of EBUS are outlined in this review, which is the first to emphasise the impact of the procedure, both on timing and costs of lung cancer staging, as well as on survival.
Abstract: The use of endobronchial ultrasound trans-bronchial needle aspiration (EBUS-TBNA) as the initial diagnostic and staging procedure in patients with suspected, non-metastatic lung cancer has gained substantial support, and is now recommended by numerous guidelines. Whereas considerable attention has been pointed to the reductions in costs achieved by EBUS-TBNA, that has not been the case for some of its more significant benefits, namely the reduction of the diagnostic work-up time and its ability to accurately assess and restage lymph nodes, which were previously stated incorrectly by CT or PET scan. Both these benefits translate into improved outcomes for patients, as delays are reduced, futile surgeries are prevented and curable operations can be performed on patients previously excluded by CT or PET scan. Indeed, the use of EBUS as the initial diagnostic and staging procedure has been proven to significantly increase survival, compared with conventional diagnostic and staging procedures, in a pragmatic, randomised controlled trial (Navani N. et al, 2015). The instalment of EBUS will have the greatest effect on overwhelmed, suboptimally functioning national healthcare systems, by decreasing the number of required diagnostic and staging procedures, therefore reducing both treatment delays and costs. The improved selection of surgical candidates by EBUS will result in improved patient outcomes. The latest findings regarding the benefits of EBUS are outlined in this review, which, to the best of our knowledge, is the first to emphasise the impact of the procedure, both on timing and costs of lung cancer staging, as well as on survival.
TL;DR: The rate of unforeseen N2 disease after negative endosonography findings was similar in patients undergoing immediate lung tumor resection to those undergoing confirmatory mediastinoscopy first, at the cost of 6.0% rate of complications by mediastinescopy.
Abstract: Introduction Confirmatory mediastinoscopy after negative endosonography findings is advised by the guidelines on patients with resectable NSCLC and suspected intrathoracic nodes on fludeoxyglucose F 18 positron emission tomography–computed tomography. Its role however is under debate owing to its limited nodal metastasis detection rate, morbidity, associated treatment delay, and unknown impact on survival. Methods Systematic review and meta-analysis of studies on invasive mediastinal staging in patients with (suspected) NSCLC. The Medline, Embase, and Cochrane databases were searched until September 19, 2018, without year or language restrictions. The Quality Assessment Tool for Diagnostic Accuracy Studies, version 2, was used to evaluate the risk of bias and applicability of the included studies. Rates of unforeseen N2 disease were assessed for endobronchial ultrasound and/or endoscopic ultrasound staging strategies with or without confirmatory mediastinoscopy. Additionally, the complication rates of cervical video mediastinoscopy for mediastinal staging of NSCLC were investigated. Results A total of 5073 articles were found, of which 42 studies or subgroups (covering a total of 3248 patients undergoing the surgical reference standard of treatment) were considered in the analysis. Random effects meta-analysis of endosonography with or without confirmatory mediastinoscopy showed rates of unforeseen N2 disease of 9.6% (95% confidence interval [CI]: 7.8%–11.7%, I2 = 30%) versus 9.9% (95% CI: 6.3%–15.2%, I2 = 73%), respectively. Random effects meta-analysis of mediastinoscopy (eight studies [1245 patients in total]) showed a complication rate of 6.0% (95% CI: 4.8%–7.5%), with laryngeal recurrent nerve palsy accounting for 2.8% (95% CI: 2.0%–4.0%). Conclusion The rate of unforeseen N2 disease after negative endosonography findings was similar in patients undergoing immediate lung tumor resection to those undergoing confirmatory mediastinoscopy first, at the cost of 6.0% rate of complications by mediastinoscopy.
TL;DR: Transvascular endosonographic-guided biopsy is an important adjunct to conventional endoscopic techniques and allows the thoracic endoscopist to obtain biopsy specimens from intrathoracic lesions that are not accessible without vascular puncture.
Abstract: Background Endoscopic ultrasound–guided biopsy techniques, including endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA), are currently the standard of care for the assessment of mediastinal lymphadenopathy. Traditionally, passing the needle through and through vascular structures has been avoided owing to the risk of bleeding. In this study, we evaluated the safety and diagnostic accuracy of transvascular endosonographic-guided biopsies of mediastinal, hilar and lung lesions. Our hypothesis is that the approach is safe and adds to the endoscopic armamentarium, avoiding the need for surgical biopsy in specifically selected cases. Methods One hundred patients who underwent transvascular EBUS- or EUS-guided biopsy between 2012 and 2018 were identified from a prospective interventional endoscopy database. Results Biopsy was performed under EUS guidance in 65 patients and under EBUS guidance in 35 patients. The most frequent targets were the mediastinum (60 patients), lung (21 patients), and hilar lymph nodes (16 patients). The aorta was the vessel most commonly traversed (n = 57), followed by the pulmonary artery (n = 33). A median of 2 passes were performed per target (range, 1-5). The samples were adequate to make a diagnosis in 80 patients, and the endoscopic diagnosis was a malignancy in 62 patients. The overall sensitivity was 71.5%, and the accuracy was 74.5%. There were no observed intraoperative or immediate postoperative complications. A delayed complication, aortic pseudoaneurysm, was observed in 1 patient. Follow-up was completed in 84 patients, with a median duration of 12.3 ± 18 months. Conclusions Transvascular endosonographic-guided biopsy is an important adjunct to conventional endoscopic techniques and allows the thoracic endoscopist to obtain biopsy specimens from intrathoracic lesions that are not accessible without vascular puncture.
TL;DR: A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests.
Abstract: Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests.
TL;DR: Urinary albumin excretion is a predictor of all-cause mortality in the general population and the excess risk was more attributable to death from CV causes, independent of the effects of other CV risk factors.
Abstract: Background— For the general population, the clinical relevance of an increased urinary albumin excretion rate is still debated. Therefore, we examined the relationship between urinary albumin excretion and all-cause mortality and mortality caused by cardiovascular (CV) disease and non-CV disease in the general population. Methods and Results— In the period 1997 to 1998, all inhabitants of the city of Groningen, the Netherlands, aged between 28 and 75 years (n=85 421) were sent a postal questionnaire collecting information about risk factors for CV disease and CV morbidity and a vial to collect an early morning urine sample for measurement of urinary albumin concentration (UAC). The vital status of the cohort was subsequently obtained from the municipal register, and the cause of death was obtained from the Central Bureau of Statistics. Of these 85 421 subjects, 40 856 (47.8%) responded, and 40 548 could be included in the analysis. During a median follow-up period of 961 days (maximum 1139 days), 516 deat...
TL;DR: It is demonstrated that PET scanning is more accurate than CT scanning, but tissue biopsy is still required to confirm PET scan findings, and evidence suggests that more complete staging improves patient outcomes.
Abstract: Background Correctly staging lung cancer is important because the treatment options and prognosis differ significantly by stage. Several noninvasive imaging studies and invasive tests are available. Understanding the accuracy, advantages, and disadvantages of the available methods for staging non-small cell lung cancer is critical to decision-making. Methods Test accuracies for the available staging studies were updated from the second iteration of the American College of Chest Physicians Lung Cancer Guidelines. Systematic searches of the MEDLINE database were performed up to June 2012 with the inclusion of selected meta-analyses, practice guidelines, and reviews. Study designs and results are summarized in evidence tables. Results The sensitivity and specificity of CT scanning for identifying mediastinal lymph node metastasis were approximately 55% and 81%, respectively, confirming that CT scanning has limited ability either to rule in or exclude mediastinal metastasis. For PET scanning, estimates of sensitivity and specificity for identifying mediastinal metastasis were approximately 77% and 86%, respectively. These findings demonstrate that PET scanning is more accurate than CT scanning, but tissue biopsy is still required to confirm PET scan findings. The needle techniques endobronchial ultrasound-needle aspiration, endoscopic ultrasound-needle aspiration, and combined endobronchial ultrasound/endoscopic ultrasound-needle aspiration have sensitivities of approximately 89%, 89%, and 91%, respectively. In direct comparison with surgical staging, needle techniques have emerged as the best first diagnostic tools to obtain tissue. Based on randomized controlled trials, PET or PET-CT scanning is recommended for staging and to detect unsuspected metastatic disease and avoid noncurative resections. Conclusions Since the last iteration of the staging guidelines, PET scanning has assumed a more prominent role both in its use prior to surgery and when evaluating for metastatic disease. Minimally invasive needle techniques to stage the mediastinum have become increasingly accepted and are the tests of first choice to confirm mediastinal disease in accessible lymph node stations. If negative, these needle techniques should be followed by surgical biopsy. All abnormal scans should be confirmed by tissue biopsy (by whatever method is available) to ensure accurate staging. Evidence suggests that more complete staging improves patient outcomes.
TL;DR: The risks of mortality, myocardial infarction, and progression to kidney failure associated with a given level of eGFR are independently increased in patients with higher levels of proteinuria.
Abstract: Context The current staging system for chronic kidney disease is based primarily on estimated glomerular filtration rate (eGFR) with lower eGFR associated with higher risk of adverse outcomes. Although proteinuria is also associated with adverse out- comes, it is not used to refine risk estimates of adverse events in this current system. Objective To determine the association between reduced GFR, proteinuria, and ad- verse clinical outcomes. Design, Setting, and Participants Community-based cohort study with partici- pants identified from a province-wide laboratory registry that includes eGFR and pro- teinuria measurements from Alberta, Canada, between 2002 and 2007. There were 920985 adults who had at least 1 outpatient serum creatinine measurement and who did not require renal replacement treatment at baseline. Proteinuria was assessed by urine dipstick or albumin-creatinine ratio (ACR). Main Outcome Measures All-cause mortality, myocardial infarction, and progres- sion to kidney failure. Results The majority of individuals (89.1%) had an eGFR of 60 mL/min/1.73 m 2 or greater. Over median follow-up of 35 months (range, 0-59 months), 27959 participants (3.0%)died.Thefullyadjustedrateofall-causemortalitywashigherinstudyparticipants with lower eGFRs or heavier proteinuria. Adjusted mortality rates were more than 2-fold higher among individuals with heavy proteinuria measured by urine dipstick and eGFR of 60mL/min/1.73m 2 orgreater,ascomparedwiththosewitheGFRof45to59.9mL/min/ 1.73 m 2 and normal protein excretion (rate, 7.2 (95% CI, 6.6-7.8) vs 2.9 (95% CI, 2.7- 3.0)per1000person-years,respectively;rateratio,2.5(95%CI,2.3-2.7)).Similarresults were observed when proteinuria was measured by ACR (15.9 (95% CI, 14.0-18.1) and 7.0 (95% CI, 6.4-7.6) per 1000 person-years for heavy and absent proteinuria, respec- tively;rateratio,2.3(95%CI,2.0-2.6))andfortheoutcomesofhospitalizationwithacute myocardial infarction, end-stage renal disease, and doubling of serum creatinine level. Conclusion The risks of mortality, myocardial infarction, and progression to kidney failure associated with a given level of eGFR are independently increased in patients with higher levels of proteinuria.
TL;DR: The precise relationship between sodium and potassium intake and cardiovascular (CV) risk remains uncertain, especially in patients with CV disease or diabetes mellitus, and Cox proportional hazards multivariable models were used to determine the association.
Abstract: [HR], 1.53; 95% CI, 1.26-1.86; and 11.2% for 8 g/day; HR, 1.66; 95% CI, 1.312.10), MI (6.8%; HR, 1.48; 95% CI, 1.11-1.98 for 8 g/day), stroke (6.6%; HR, 1.48; 95% CI, 1.09-2.01 for 8 g/day), and hospitalization for CHF (6.5%; HR, 1.51; 1.122.05 for 8 g/day). Lower sodium excretion was associated with an increased risk of CV death (8.6%; HR, 1.19; 95% CI, 1.02-1.39 for 2-2.99 g/day; 10.6%; HR, 1.37; 95% CI, 1.09-1.73 for 2 g/day), and hospitalization for CHF (5.2%; HR, 1.23; 95% CI, 1.01-1.49 for 2-2.99 g/day) on multivariable analysis. Compared with an estimated potassium excretion of less than 1.5 g per day (n=2194; 6.2% with stroke), higher potassium excretion was associated with a reduced risk of stroke (4.7% [HR, 0.77; 95% CI, 0.63-0.94] for 1.5-1.99 g/day; 4.3% [HR, 0.73; 95% CI, 0.59-0.90] for 2-2.49 g/day; 3.9% [HR, 0.71; 95% CI, 0.56-0.91] for 2.5-3 g/day; and 3.5% [HR, 0.68; 95% CI, 0.49-0.92] for 3 g/day) on multivariable analysis. Conclusions The association between estimated sodium excretion and CV events was J-shaped. Compared with baseline sodium excretion of 4 to 5.99 g per day, sodium excretion of greater than 7 g per day was associated with an increased risk of all CV events, and a sodium excretion of less than 3 g per day was associated with increased risk of CV mortality and hospitalization for CHF. Higher estimated potassium excretion was associated with a reduced risk of stroke.