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European Journal of Cardio-thoracic... Oct 2016The benefits of different methods of lymphadenectomy for early-stage non-small-cell lung cancer (NSCLC) remain controversial. Herein, we performed a systematic review... (Meta-Analysis)
Meta-Analysis Review
The benefits of different methods of lymphadenectomy for early-stage non-small-cell lung cancer (NSCLC) remain controversial. Herein, we performed a systematic review and meta-analysis comparing survival benefits of systematic nodal dissection (SND) with those of lymph nodal sampling (LNS) and lobe-specific nodal dissection (L-SND). PubMed, OVID, EBSCO and Springer were searched up to August 2015 for English language studies. Data of selected studies were extracted. Study quality, publication bias and heterogeneity were assessed. Analysis was performed using a random-effects model. A total of 12 studies were identified [4 randomized prospective clinical trials (RCTs) and 8 observational trials] that reported surgical outcomes of 3955 patients with resectable clinical N2 negative NSCLC: 2142 underwent SND and 1813 underwent LNS/L-SND. In the cohort studies, the SND group had a statistically significant improvement in overall survival (OS) [hazard ratios (HRs), 1.24; 95% confidence interval (CI) 1.02-1.5] and recurrence-free survival (RFS) rates (HR, 1.27; 95% CI 1.03-1.58). The pooled HR from RCTs showed a consistent tendency in terms of OS (HR = 1.13, 95% CI 0.94-1.35) and RFS (HR = 0.99, 95% CI 0.82-1.19), in spite of a non-significant difference. In subgroup analyses, the SND group had a statistically significant improvement in OS (HR, 1.40; 95% CI 1.12-1.76) and RFS (HR, 1.5; 95% CI 1.09-2.08) in cohort studies, and a consistent tendency of OS in RCTs (HR = 1.12, 95% CI 0.93-1.35) with non-significant difference. However, there was no significant difference in OS (HR, 1.02; 95% CI 0.66-1.57) and RFS (HR, 1.11; 95% CI 0.87-1.42) between the SND and L-SND group. In early-stage NSCLC patients, LNS was associated with inferior survival rates, while L-SND seemed to provide equal survival benefits compared with SND, and the indications need to be identified.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Lymph Node Excision; Neoplasm Staging; Treatment Outcome
PubMed: 27107044
DOI: 10.1093/ejcts/ezw083 -
Archivos de Bronconeumologia Feb 2016Real-time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is one of the major landmarks in the history of bronchoscopy. In the 10 years... (Review)
Review
Real-time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is one of the major landmarks in the history of bronchoscopy. In the 10 years since it was introduced, a vast body of literature on the procedure and its results support the use of this technique in the study of various mediastinal and pulmonary lesions. This article is a comprehensive, systematic review of all the available scientific evidence on the more general indications for this technique. Results of specific studies on efficacy, safety and cost-effectiveness available to date are examined. The analysis shows that EBUS-TBNA is a safe, cost-effective technique with a high grade of evidence that is a valuable tool in the diagnosis and mediastinal staging of patients with suspected or confirmed lung cancer. However, more studies are needed to guide decision-making in the case of a negative result. Evidence on the role of EBUS-TBNA in the diagnosis of sarcoidosis and extrathoracic malignancies is also high, but much lower when used in the study of tuberculosis, lymphoma and for the re-staging of lung cancer after neoadjuvant chemotherapy. Nevertheless, due to its good safety record and lack of invasiveness compared to surgical techniques, the grade of evidence for recommending EBUS-TBNA as the initial diagnostic test in patients with these diseases is very high in most cases.
Topics: Bronchoscopy; Cost-Benefit Analysis; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Lung Diseases; Lung Neoplasms; Neoplasm Staging; Time Factors
PubMed: 26565072
DOI: 10.1016/j.arbres.2015.08.007 -
Chest Mar 2016Endobronchial ultrasound (EBUS) was introduced in the last decade, enabling real-time guidance of transbronchial needle aspiration (TBNA) of mediastinal and hilar... (Review)
Review
BACKGROUND
Endobronchial ultrasound (EBUS) was introduced in the last decade, enabling real-time guidance of transbronchial needle aspiration (TBNA) of mediastinal and hilar structures and parabronchial lung masses. The many publications produced about EBUS-TBNA have led to a better understanding of the performance characteristics of this procedure. The goal of this document was to examine the current literature on the technical aspects of EBUS-TBNA as they relate to patient, technology, and proceduralist factors to provide evidence-based and expert guidance to clinicians.
METHODS
Rigorous methodology has been applied to provide a trustworthy evidence-based guideline and expert panel report. A group of approved panelists developed key clinical questions by using the PICO (population, intervention, comparator, and outcome) format that addressed specific topics on the technical aspects of EBUS-TBNA. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion, and well-recognized document evaluation tools were used to assess the quality of included studies, to extract meaningful data, and to grade the level of evidence to support each recommendation or suggestion.
RESULTS
Our systematic review and critical analysis of the literature on 15 PICO questions related to the technical aspects of EBUS-TBNA resulted in 12 statements: 7 evidence-based graded recommendations and 5 ungraded consensus-based statements. Three questions did not have sufficient evidence to generate a statement.
CONCLUSIONS
Evidence on the technical aspects of EBUS-TBNA varies in strength but is satisfactory in certain areas to guide clinicians on the best conditions to perform EBUS-guided tissue sampling. Additional research is needed to enhance our knowledge regarding the optimal performance of this effective procedure.
Topics: Bronchoscopy; Carcinoma, Non-Small-Cell Lung; Clinical Competence; Conscious Sedation; Deep Sedation; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Evidence-Based Medicine; Humans; Lung Neoplasms; Lymphatic Diseases; Lymphoma; Mediastinal Neoplasms; Needles; Pulmonary Medicine; Sarcoidosis; Simulation Training; Societies, Medical
PubMed: 26402427
DOI: 10.1378/chest.15-1216 -
Surgical Oncology Sep 2015The uptake of minimally invasive esophagectomy (MIE) has increased vastly over the last decade, with proven short-term benefits over an open approach. The aim of this... (Comparative Study)
Comparative Study Meta-Analysis Review
The uptake of minimally invasive esophagectomy (MIE) has increased vastly over the last decade, with proven short-term benefits over an open approach. The aim of this pooled analysis was to compare clinical outcomes of Minimally Invasive Esophagectomy (MIE) performed in the prone and lateral decubitus positions. A systematic literature search (2000-2015) was undertaken for publications that compared patients who underwent MIE in the lateral decubitus (LD) or prone (PR) positions. Weighted mean difference (WMD) was calculated for the effect size of LD positioning on continuous variables and Pooled odds ratios (POR) for discrete variables. Ten relevant publications comprising 723 patients who underwent minimally invasive esophagectomy were included; 387 in the LD group and 336 in the PR group. There was no significant difference between the groups in terms of in-hospital mortality, total morbidity, anastomotic leak, chylothorax, laryngeal nerve palsy, average operative time, and length hospital stay. LD MIE was associated with a non-significant increase in pulmonary complications (POR = 1.65; 95% C.I. 0.93 to 2.92; P = 0.09), and significant increases in estimated blood loss (WMD = 36.03; 95% 14.37 to 57.69; P = 0.001) and a reduced average mediastinal lymph node harvest (WMD = -2.17; 95% C.I. -3.82 to -0.52; P = 0.01) when compared to prone MIE. Pooled analysis suggests that prone MIE is superior to lateral decubitus MIE with reduced pulmonary complications, estimated blood loss and increased mediastinal lymph node harvest. Further studies are needed to explain performance-shaping factors and their influence on oncological clearance and short-term outcomes.
Topics: Esophageal Neoplasms; Esophagectomy; Humans; Minimally Invasive Surgical Procedures; Patient Positioning; Prognosis; Survival Rate
PubMed: 26096374
DOI: 10.1016/j.suronc.2015.06.001 -
Medicine Jun 2015Optimal management of clinical stage IIIA (N2) non-small cell lung cancer (NSCLC) is controversial. This study is a systematic review and meta-analysis of published... (Meta-Analysis)
Meta-Analysis Review
Is There a Survival Benefit in Patients With Stage IIIA (N2) Non-small Cell Lung Cancer Receiving Neoadjuvant Chemotherapy and/or Radiotherapy Prior to Surgical Resection: A Systematic Review and Meta-analysis.
Optimal management of clinical stage IIIA (N2) non-small cell lung cancer (NSCLC) is controversial. This study is a systematic review and meta-analysis of published randomized control trials of multimodality management strategies for NSCLC. We conducted a comprehensive literature search of the Pubmed, Embase, Medline, and CENTRAL databases for relevant studies comparing patients with stage IIIA (N2) NSCLC undergoing surgery alone, chemotherapy and/or radiotherapy alone, or surgical resection after neoadjuvant treatment with chemotherapy and/or radiotherapy. We estimated hazard ratios, odds ratios (ORs), and 95% confidence intervals (CIs) for survival data. Seven trials involving 1049 patients were included in this study. There was no significant difference in overall survival (OS) or progression-free survival (PFS) in stage IIIA (N2) NSCLC patients who received neoadjuvant chemotherapy or chemoradiotherapy prior to surgical resection compared to those who received neoadjuvant chemotherapy or chemoradiotherapy prior to radical radiotherapy. There was a significant increase in pathological complete remission in the mediastinal lymph nodes in stage IIIA (N2) NSCLC patients who received neoadjuvant chemoradiotherapy prior to surgical resection compared to those who received neoadjuvant chemotherapy (OR 3.61; 95% CI 1.07-12.15; P = 0.04), but no difference in tumor downstaging, OS, or PFS. Neoadjuvant chemotherapy and/or radiotherapy prior to surgical resection do not appear to be clinically superior to neoadjuvant chemotherapy and/or radiotherapy prior to definitive radiotherapy in IIIA (N2) NSCLC patients. Neoadjuvant chemoradiotherapy does not improve survival compared to neoadjuvant chemotherapy alone.
Topics: Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Disease-Free Survival; Humans; Lung Neoplasms; Neoadjuvant Therapy; Neoplasm Staging; Pneumonectomy; Preoperative Care; Radiotherapy, Adjuvant; Survival Rate; Treatment Outcome
PubMed: 26061306
DOI: 10.1097/MD.0000000000000879 -
Thorax Aug 2015Chemoradiotherapy is often considered the 'standard of care' for patients with N2 disease. The aim was to evaluate survival outcomes of patients with N2 disease in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Chemoradiotherapy is often considered the 'standard of care' for patients with N2 disease. The aim was to evaluate survival outcomes of patients with N2 disease in multimodality trials of chemotherapy, radiotherapy and surgery.
METHODS
Systematic review and meta-analyses (random and fixed effects) were performed. Searches of Medline and Embase (1980-2013) were conducted. Abstracts from thoracic scientific meetings were searched. Reference lists of all relevant studies were reviewed. All studies of patients with N2 disease who received induction chemotherapy or chemoradiotherapy and randomised to surgery or radiotherapy were included. No language restrictions were imposed. The main outcome was overall survival.
RESULTS
805 publications were identified. 519 and 281 were excluded because they were not primary results from randomised trials (or did not include N2 disease) or did not compare surgery with radiotherapy, respectively. The final six trials consisted of 868 patients. In four trials, patients received induction chemotherapy and in two trials patients received induction chemoradiotherapy. The HR comparing patients randomised to surgery after chemotherapy was 1.01 (95% CI 0.82 to 1.23; p=0.954) whereas for patients randomised to surgery after chemoradiotherapy was 0.87 (0.75 to 1.01; p=0.068). The overall HR of all pooled trials was 0.92 (0.81 to 1.03; p=0.157).
CONCLUSIONS
Surgery should be considered as part of multimodality treatment for patients with resectable lung cancer and ipsilateral mediastinal nodal disease. In trials where patients received surgery as part of trimodality treatment, overall survival was better than chemoradiotherapy alone.
Topics: Chemotherapy, Adjuvant; Humans; Induction Chemotherapy; Lung Neoplasms; Neoplasm Staging; Pneumonectomy; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25967753
DOI: 10.1136/thoraxjnl-2014-206292 -
Urology Journal Apr 2015There are many recent observational studies on testicular microlithiasis (TM) and risk of testicular cancer. Whether TM increases the risk of testicular cancer is still... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
There are many recent observational studies on testicular microlithiasis (TM) and risk of testicular cancer. Whether TM increases the risk of testicular cancer is still inconclusive. The objective of this updated meta-analysis was to synthesize evidence from clinical observational studies that evaluated the association between TM and testicular cancer.
MATERIALS AND METHODS
We identified eligible studies by searching the PubMed, Embase and Cochrane Library before March 2014. Adjusted relative risks (RR) with 95% confidence interval (CI) were calculated using random-or fixed-model.
RESULTS
A total of 14 studies involving 35,578 participants were included in the meta-analysis. On the basis of the Newcastle Ottawa Scale systematic review, eleven studies were identified as relatively high-quality. TM was strong association with an increased incidence of testicular cancer (RR = 12.70, 95% CI: 8.18-19.71, P < .001), with significant evidence of heterogeneity among these studies (P for heterogeneity < .001, I2 = 82.1%). The subgroup and sensitivity analysis confirmed the stability of the results and no publication bias was detected.
CONCLUSION
The present meta-analysis suggests that TM is significantly associated with risk of testicular cancer. More researches are warranted to clarify an understanding of the association between TM and risk of testicular cancer.
Topics: Calculi; Global Health; Humans; Incidence; Male; Neoplasms, Germ Cell and Embryonal; Risk Factors; Testicular Diseases; Testicular Neoplasms
PubMed: 25923148
DOI: No ID Found -
The Cochrane Database of Systematic... Nov 2014A major determinant of treatment offered to patients with non-small cell lung cancer (NSCLC) is their intrathoracic (mediastinal) nodal status. If the disease has not... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A major determinant of treatment offered to patients with non-small cell lung cancer (NSCLC) is their intrathoracic (mediastinal) nodal status. If the disease has not spread to the ipsilateral mediastinal nodes, subcarinal (N2) nodes, or both, and the patient is otherwise considered fit for surgery, resection is often the treatment of choice. Planning the optimal treatment is therefore critically dependent on accurate staging of the disease. PET-CT (positron emission tomography-computed tomography) is a non-invasive staging method of the mediastinum, which is increasingly available and used by lung cancer multidisciplinary teams. Although the non-invasive nature of PET-CT constitutes one of its major advantages, PET-CT may be suboptimal in detecting malignancy in normal-sized lymph nodes and in ruling out malignancy in patients with coexisting inflammatory or infectious diseases.
OBJECTIVES
To determine the diagnostic accuracy of integrated PET-CT for mediastinal staging of patients with suspected or confirmed NSCLC that is potentially suitable for treatment with curative intent.
SEARCH METHODS
We searched the following databases up to 30 April 2013: The Cochrane Library, MEDLINE via OvidSP (from 1946), Embase via OvidSP (from 1974), PreMEDLINE via OvidSP, OpenGrey, ProQuest Dissertations & Theses, and the trials register www.clinicaltrials.gov. There were no language or publication status restrictions on the search. We also contacted researchers in the field, checked reference lists, and conducted citation searches (with an end-date of 9 July 2013) of relevant studies.
SELECTION CRITERIA
Prospective or retrospective cross-sectional studies that assessed the diagnostic accuracy of integrated PET-CT for diagnosing N2 disease in patients with suspected resectable NSCLC. The studies must have used pathology as the reference standard and reported participants as the unit of analysis.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data pertaining to the study characteristics and the number of true and false positives and true and false negatives for the index test, and they independently assessed the quality of the included studies using QUADAS-2. We calculated sensitivity and specificity with 95% confidence intervals (CI) for each study and performed two main analyses based on the criteria for test positivity employed: Activity > background or SUVmax ≥ 2.5 (SUVmax = maximum standardised uptake value), where we fitted a summary receiver operating characteristic (ROC) curve using a hierarchical summary ROC (HSROC) model for each subset of studies. We identified the average operating point on the SROC curve and computed the average sensitivities and specificities. We checked for heterogeneity and examined the robustness of the meta-analyses through sensitivity analyses.
MAIN RESULTS
We included 45 studies, and based on the criteria for PET-CT positivity, we categorised the included studies into three groups: Activity > background (18 studies, N = 2823, prevalence of N2 and N3 nodes = 679/2328), SUVmax ≥ 2.5 (12 studies, N = 1656, prevalence of N2 and N3 nodes = 465/1656), and Other/mixed (15 studies, N = 1616, prevalence of N2 to N3 nodes = 400/1616). None of the studies reported (any) adverse events. Under-reporting generally hampered the quality assessment of the studies, and in 30/45 studies, the applicability of the study populations was of high or unclear concern.The summary sensitivity and specificity estimates for the 'Activity > background PET-CT positivity criterion were 77.4% (95% CI 65.3 to 86.1) and 90.1% (95% CI 85.3 to 93.5), respectively, but the accuracy estimates of these studies in ROC space showed a wide prediction region. This indicated high between-study heterogeneity and a relatively large 95% confidence region around the summary value of sensitivity and specificity, denoting a lack of precision. Sensitivity analyses suggested that the overall estimate of sensitivity was especially susceptible to selection bias; reference standard bias; clear definition of test positivity; and to a lesser extent, index test bias and commercial funding bias, with lower combined estimates of sensitivity observed for all the low 'Risk of bias' studies compared with the full analysis.The summary sensitivity and specificity estimates for the SUVmax ≥ 2.5 PET-CT positivity criterion were 81.3% (95% CI 70.2 to 88.9) and 79.4% (95% CI 70 to 86.5), respectively.In this group, the accuracy estimates of these studies in ROC space also showed a very wide prediction region. This indicated very high between-study heterogeneity, and there was a relatively large 95% confidence region around the summary value of sensitivity and specificity, denoting a clear lack of precision. Sensitivity analyses suggested that both overall accuracy estimates were marginally sensitive to flow and timing bias and commercial funding bias, which both lead to slightly lower estimates of sensitivity and specificity.Heterogeneity analyses showed that the accuracy estimates were significantly influenced by country of study origin, percentage of participants with adenocarcinoma, (¹⁸F)-2-fluoro-deoxy-D-glucose (FDG) dose, type of PET-CT scanner, and study size, but not by study design, consecutive recruitment, attenuation correction, year of publication, or tuberculosis incidence rate per 100,000 population.
AUTHORS' CONCLUSIONS
This review has shown that accuracy of PET-CT is insufficient to allow management based on PET-CT alone. The findings therefore support National Institute for Health and Care (formally 'clinical') Excellence (NICE) guidance on this topic, where PET-CT is used to guide clinicians in the next step: either a biopsy or where negative and nodes are small, directly to surgery. The apparent difference between the two main makes of PET-CT scanner is important and may influence the treatment decision in some circumstances. The differences in PET-CT accuracy estimates between scanner makes, NSCLC subtypes, FDG dose, and country of study origin, along with the general variability of results, suggest that all large centres should actively monitor their accuracy. This is so that they can make reliable decisions based on their own results and identify the populations in which PET-CT is of most use or potentially little value.
Topics: Carcinoma, Non-Small-Cell Lung; Cross-Sectional Studies; Humans; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Mediastinum; Multimodal Imaging; Positron-Emission Tomography; Prospective Studies; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 25393718
DOI: 10.1002/14651858.CD009519.pub2 -
PloS One 2014This systematic review and meta-analysis aimed to evaluate the overall survival, local recurrence, distant metastasis, and complications of mediastinal lymph node... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review and meta-analysis aimed to evaluate the overall survival, local recurrence, distant metastasis, and complications of mediastinal lymph node dissection (MLND) versus mediastinal lymph node sampling (MLNS) in stage I-IIIA non-small cell lung cancer (NSCLC) patients.
METHODS
A systematic search of published literature was conducted using the main databases (MEDLINE, PubMed, EMBASE, and Cochrane databases) to identify relevant randomized controlled trials that compared MLND vs. MLNS in NSCLC patients. Methodological quality of included randomized controlled trials was assessed according to the criteria from the Cochrane Handbook for Systematic Review of Interventions (Version 5.1.0). Meta-analysis was performed using The Cochrane Collaboration's Review Manager 5.3. The results of the meta-analysis were expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence interval (CI).
RESULTS
We included results reported from six randomized controlled trials, with a total of 1,791 patients included in the primary meta-analysis. Compared to MLNS in NSCLC patients, there was no statistically significant difference in MLND on overall survival (HR = 0.77, 95% CI 0.55 to 1.08; P = 0.13). In addition, the results indicated that local recurrence rate (RR = 0.93, 95% CI 0.68 to 1.28; P = 0.67), distant metastasis rate (RR = 0.88, 95% CI 0.74 to 1.04; P = 0.15), and total complications rate (RR = 1.10, 95% CI 0.67 to 1.79; P = 0.72) were similar, no significant difference found between the two groups.
CONCLUSIONS
Results for overall survival, local recurrence rate, and distant metastasis rate were similar between MLND and MLNS in early stage NSCLC patients. There was no evidence that MLND increased complications compared with MLNS. Whether or not MLND is superior to MLNS for stage II-IIIA remains to be determined.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Lymph Node Excision; Mediastinum; Neoplasm Staging
PubMed: 25296033
DOI: 10.1371/journal.pone.0109979 -
Surgical Oncology Sep 2014Adenocarcinoma of the gastroesophageal junction (GEJ) has a poor prognosis and survival rates significantly decreases if lymph node metastasis is present. An extensive... (Review)
Review
BACKGROUND
Adenocarcinoma of the gastroesophageal junction (GEJ) has a poor prognosis and survival rates significantly decreases if lymph node metastasis is present. An extensive lymphadenectomy may increase chances of cure, but may also lead to further postoperative morbidity and mortality. Therefore, the optimal treatment of cardia cancer remains controversial. A systematic review of English publications dealing with adenocarcinoma of the cardia was conducted to elucidate patterns of nodal spread and prognostic implications.
METHODS
A systematic literature search based on PRISMA guidelines identifying relevant studies describing lymph node metastasis and the associated prognosis. Lymph node stations were classified according to the Japanese Gastric Cancer Association guidelines.
RESULTS
The highest incidence of metastasis is seen in the nearest regional lymph nodes, station no. 1-3 and additionally in no. 7, 9 and 11. Correspondingly the best survival is seen when metastasis remain in the most locoregional nodes and survival equally tends to decrease as the metastasis become more distant. Furthermore, the presence of lymph node metastasis significantly correlates to the TNM-stage. Incidences of metastasis in mediastinal lymph nodes are associated with poor survival.
CONCLUSION
The best survival rates is seen when lymph node metastasis remains locoregional and survival rates decreases when distant lymph node metastasis is present. The dissection of locoregional lymph nodes offers significantly therapeutic benefit, but larger and prospective studies are needed to evaluate the effect of dissecting distant and mediastinal lymph nodes.
Topics: Adenocarcinoma; Cardia; Esophagogastric Junction; Humans; Lymph Nodes; Lymphatic Metastasis; Mediastinum; Neoplasm Staging; Prognosis; Stomach Neoplasms; Survival Rate
PubMed: 24953457
DOI: 10.1016/j.suronc.2014.06.001