Systematic Lymph Node Sampling Research Articles

Investigation of mediastinal lymph node dissection in clinical stage IA pure-solid non-small cell lung cancer patients

ObjectiveTo explore the independent predictors of pathological mediastinal lymph node (pN2) metastasis in clinical stage IA (cIA) pure-solid non-small cell lung cancer (NSCLC) patients, and to find an appropriate method of mediastinal lymph node dissection.MethodsThis study retrospectively evaluated 533 cIA pure-solid NSCLC patients who underwent radical resection of lung cancer (lobectomy combined with systematic lymph node dissection) from January 2014 to December 2016. The relationship between clinicopathological characteristics and pN2 metastasis was analyzed, and the independent predictors of pN2 metastasis were determined by univariate and multivariate logistic regression analysis. We defined the new factor Y as composed of preoperative cT, CEA, and NSE.ResultsThere were 72 cases (13.5%) of pN2 metastasis in cIA pure-solid NSCLC patients. Preoperative clinical tumor diameter (cT), serum CEA level, serum NSE level, and pathological status of station 10 lymph nodes were independent predictors of pN2 metastasis. Patients with cT ≤ 21.5 mm, CEA ≤ 3.85 ng/mL, NSE ≤ 13.40 ng/mL and negative station 10 lymph node group showed lower rates of pN2 metastasis. The new factor Y was an independent predictor of pN2 metastasis. Only 3 (2.1%) of 143 patients in the Y low-risk group showed pN2 metastasis.ConclusionFor patients with low risk of pN2 metastasis, it might be feasible to take lobe-specific lymph node sampling or systematic lymph node sampling. As for those with high risk of pN2 metastasis, systematic lymph node dissection would be recommended.

Different nodal upstaging rates and prognoses for patients with clinical T1N0M0 lung adenocarcinoma classified according to the presence of solid components in the lung and mediastinal windows.

Little is known about the correlation between nodal upstaging and pulmonary nodules classified according to the presence of solid components in the lung and mediastinal windows. This study thus aimed to analyze the risk factors of nodal upstaging and prognosis based on different imaging features, clinical characteristics, and pathological results from patients with clinical stage T1N0M0 lung adenocarcinoma. A total of 340 patients between January 2016 and June 2017 were selected from the Affiliated Hospital of Qingdao University database. Imaging features, clinical characteristics, and pathological results were collected for survival and analysis of nodal upstaging risk factors. We used logistic regression models to identify important metastatic risk factors for nodal upstaging. Survival rates were calculated using Kaplan-Meier (KM) survival curves and compared with the log-rank test. Significant prognostic risk factors were identified using the Cox proportional hazards model. A total of 340 patients, with an average age of 64.89 (±8.775) years, were enrolled. Among them, nonnodal upstaging occurred both in 77 (22.6%) patients with pure ground-glass nodules (pGGNs) and in 30 (8.8%) patients with heterogenous ground-glass nodules (hGGNs). Compared to the 92 (27.1%) patients with real part-solid nodules (rPSNs), the 141 (41.5%) patients with solid nodules were significantly different in terms of in nodal upstaging (P<0.001). Moreover, preoperative carcinoembryonic antigen (CEA) level >3.4 µg/L [odds ratio (OR): 2.931; 95% confidence interval (CI): 1.511-5.688; P=0.001], imaging tumor size >18.3 mm (OR, 3.482; 95% CI: 1.609-7.535; P=0.002), and consolidation tumor ratio (CTR) >0.788 (OR 8.791; 95% CI: 3.570-21.651; P<0.001) were independent risk factors for nodal upstaging. The KM survival curve results showed that patients with pGGNs and those with hGGNs had a much better 5-year disease-free survival (DFS) and 5-year overall survival (OS) than did those with rPSNs and those with solid nodules (DFS: 98.7% vs. 100% vs. 81.4% vs. 73.7%, P<0.001; OS: 97.4% vs. 100% vs. 90.2% vs. 83.7%, P=0.003). In the multivariate Cox regression analysis of patients with rPSNs and solid nodules, tumor location and pathological lymph node grade were found to be independent risk factors for DFS and OS. Patients with pGGNs and those with hGGNs were more likely to be free of nodal upstaging and had better prognosis than did those with clinical stage IA rPSNs and solid nodules. The patients with pGGNs or hGGNs with preoperative CEA level <3.4 µg/L, imaging tumor size <18.3 mm, and CTR <0.788 can choose systematic lymph node sampling (SLNS) or decline lymph node dissection to avoid postoperative complications.

Identifying biomarkers associated with disease-free survival in stage I non–small cell lung cancer.

8543 Background: Patients with early stage, non-small cell lung cancer (NSCLC) with solitary pulmonary lesions ≤4 cm typically have favorable outcomes. However, disease recurrence impacts up to 30% of patients, leading to either additional surgical or systemic interventions. New methods to risk stratify patients based on clinical and molecular parameters may improve our ability to select cases that would benefit from more frequent surveillance or enrollment in clinical trials evaluating systemic therapy. Methods: We retrospectively analyzed data from 179 patients with early stage (T1a-2aN0M0) NSCLC from a single institution. All patients had anatomic resection, negative margins, and systematic nodal sampling. Clinical and demographic data were abstracted from patient charts and tumor samples were molecularly profiled using the Tempus xT solid tumor assay (DNA-seq of 595-648 genes at 500x coverage, whole exome-capture RNA-seq). Pathogenic alterations (single nucleotide variants and insertion/deletions) and RNA expression were examined. Bivariate Cox-proportional Hazards models were used to assess the association of individual clinical, demographic, and molecular variables with recurrence-free survival, defined as the time from surgery until recurrence or death. Results: Our dataset included 166 stage IA1-3 patients and 13 stage IB patients, of which 36 patients experienced a recurrence or death event after surgery. Clinical and DNA-seq data was available for all patients, and RNA expression data was available for 172 patients. Across all patients, the most common somatically mutated genes were TP53 (33% of tumors) and KRAS (16% of tumors), consistent with previous studies. Increasing log10-RNA expression for NTRK1 (HR: 5.95; 95% CI, 1.16-30.4; p = 0.027) and CD274 (PD-L1) (HR: 7.88; 95% CI, 1.61-38.6; p = 0.013) and decreasing log10-RNA expression for EGFR (HR: 0.24; 95% CI, 0.05-1.21; p = 0.071) and ERBB2 (Her2) (HR: 0.20; 95% CI, 0.04-0.97; p = 0.042) were associated with increased risk of recurrence or death. Conclusions: Increased expression of NTRK1 and CD274 (PD-L1) and decreased expression of EGFR and ERBB2 (Her2) were associated with a increased risk for recurrence following surgery. This may have mechanistic implications for heightened tumor aggressiveness and/or metastatic potential. Future work will expand our cohort and validate our findings in a broader set of early-stage NSCLC patients.

Utility of PET-CT in non-small cell lung cancer clinical stage IB-IIA according to AJCC 8th edition staging system: an alternative to invasive mediastinal staging?

ObjectiveMediastinal nodal staging in lung cancer is essential to determine treatment strategy and prognosis. There are controversies as to whether a mediastinal negative result in PET-CT may spare the invasive staging of the mediastinum. The main endpoint is to evaluate the negative predictive value (NPV) of PET-CT in non-small cell lung cancer (NSCLC) clinical stage IB-IIA without clinical nodal involvement. The secondary endpoint is to evaluate the prevalence of mediastinal and hilar nodal affection in this population.MethodsWe performed an observational descriptive study from January 2010 to January 2020, including 76 patients with clinical stage IB-IIA, who underwent pulmonary resection with systematic nodal sampling (pre-determined lymph node stations based on tumour location) for primary NSCLC. Clinically, nodal involvement was defined as any lymph node greater than 1 cm in the short axis on a CT or with metabolic uptake greater than 2.5 SUV on PET-CT. The prevalence of nodal metastases was recorded.ResultsFifty six patients had clinical stage IB and 20 had clinical stage IIA. Mean tumour size was 3.74 ± 0.5 cm. Lobectomy was the resection procedure most frequently performed. Of the 76 patients with clinical N0 by PET-CT who underwent surgical resection, 10 (13.1%) were upstaged to pN1 and none were upstaged to pN2. NPV of PET-CT for overall nodal metastasis was 87% (95% CI: 0.79–0.94). NPV of PET-CT for N2 metastasis was 100%.ConclusionPET-CT might be an alternative to invasive mediastinal staging in patients with NSCLC clinical stage IB-IIA who are surgical candidates. Further prospective multi-institutional studies are necessary to verify the external validity of our study.

Mediastinal staging for non-small cell lung cancer

The staging of mediastinal lymph nodes for lung cancer is crucial for planning treatments or reinterventions. In potentially curable patients the aim of mediastinal staging is to exclude the presence of malignancy in mediastinal lymph nodes with a high level of accuracy while also considering clinical factors and the balance of the benefits and risks of tissue sampling techniques. Mediastinal staging is based on computed tomography (CT) and positron emission tomography (PET) and can be sufficient when no mediastinal abnormalities are present and the probability of unforeseen N2 disease is low. In the case of bulky lymph nodes with a high probability of malignancy in PET-CT, tissue confirmation is not normally required. If mediastinal sampling is needed it can be achieved by endosonographic techniques, including endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) or a combination of the two. Positive results do not need further confirmation. In the case of negative results, surgical techniques still play a role in the selected cases discussed by multidisciplinary lung cancer committees. New mediastinal surgical techniques including video-assisted cervical mediastinoscopy (VACM), video-assisted mediastinoscopic lymphadenectomy (VAMLA), and transcervical extended mediastinal lymphadenectomy (TEMLA) have been shown to be useful in selected patients. Final pathological staging is based on lymph node removal during surgery and can be achieved by taking one of two approaches: lymph node sampling or systematic lymph node sampling. The accuracy of PET-CT and mediastinal endosonography is lower for mediastinal restaging than it is for surgical techniques; their false positive and false negative (FN) rate is high and so, they require histological confirmation. Here we explain and revise the results from the most recent studies and current international guidelines.

Standardizing lymph nodal sampling for Wilms tumor: A feasibility study with outcomes

BackgroundDespite being mandated by cooperative groups, omission of nodal sampling is the most frequent protocol deviation in surgery for Wilms tumor. The stations as well as the number of nodes that should be sampled are not clearly defined resulting in a marked variation in practices among surgeons. We propose a systematic method for nodal sampling intending to reduce interoperator variation. In this study, we have assessed the feasibility and yield of systematic lymph node sampling and also evaluated the factors influencing nodal metastasis. MethodsProspective evaluation of 113 Wilms tumor patients operated at a single tertiary cancer center between 2015 and 2019. All these patients underwent a systematic 5-station nodal sampling. ResultsMedian lymph node yield was 8 and 13.2% (15/113) patients harbored a histologically positive nodal disease. Of the patients with positive nodal disease, interaortocaval nodes had metastasis in 46.7% (n = 7). They represented isolated sites of nodal disease (skip metastases) in 28.6% (n = 4) of patients. Right-sided tumors had more frequent involvement of interaortocaval nodes and skip disease.Tumors with high-risk histology had 12.5 times more odds of harboring nodal disease as compared to low and intermediate-risk histology Wilms tumor. ConclusionsThe proposed method of systematic station wise sampling provides a template to guide surgeons in performing lymph node harvesting. Interaortocaval nodes sampling should be performed routinely as the incidence of disease at this station is sufficiently high and metastasis may skip hilar nodes. Study of diagnostic testLevel III evidence.

P47 A case of parenchymal nodular amyloidosis with Sjögren's syndrome mimicking a bronchogenic tumour

Abstract Background Amyloidosis is a disorder characterised by the misfolding of extracellular proteins. Patients with Sjögren’s syndrome frequently have a range of lung manifestations. Parenchymal nodular amyloidosis has been reported in association with Sjögren’s syndrome although occurrences are rare. Methods We present a 77 year old woman with a longstanding history of exertional breathlessness on a background of mild asthma since childhood, a cardiac pacemaker for atrial fibrillation and sick sinus syndrome. She has never smoked tobacco and has a good performance status. She presented with an episode of breathlessness and cough requiring hospital admission, receiving treatment for a lower respiratory tract infection. Results Chest X-rays had suggested two benign nodules in the right upper lobe which seemed to have progressed over the last ten years. Amongst her inpatient investigation, she underwent a CT-pulmonary angiogram which did not demonstrate a pulmonary embolism but found three lesions in the right upper lobe. The largest of the lesions measured 2.4cm in size and was suspicious for malignancy. A PET-CT scan showed two of these to be calcified lesions in the right upper lobe, and the other an irregular soft tissue density nodule with low-grade FDG uptake, suspicious of a primary bronchogenic tumour. Lung function showed mild airflow obstruction. Bronchoscopy and endobronchial ultrasound-guided biopsy did not yield a diagnosis. As surgery could be potentially curative, she underwent a right upper lobectomy and systematic nodal sampling. The histology on the lesions has shown abundant eosinophilic concretions with peripherally prominent foreign body giant cell reaction. This was congophilic and showed green birefringence. Further staining suggested AL amyloid. Histological appearances and the clinical picture seemed to represent parenchymal nodular amyloidosis. Further investigation revealed ANA was 1:640 speckled pattern and anti-Ro antibody positive. On further questioning, she reported sicca symptoms affecting eyes and mouth, fatigue and generalised arthralgia particularly affecting knees, ankles, wrist and shoulder. Schirmer’s test suggested severely dry eyes. A diagnosis of primary Sjögren’s was made and hydroxychloroquine was started. Conclusion Parenchymal nodular amyloidosis has been associated with Sjögren's syndrome but is a rare manifestation. However, there are other chronic inflammatory or haematological condition has been described. Parenchymal nodular amyloidosis is associated with multiple nodules, rarely a single nodule. Isolated pulmonary amyloidosis has four distinct patterns of presentation: diffuse alveolar septal, lymphatic, trachea-bronchial and nodule-parenchymal (typically found incidentally on routine imaging). These nodules remain stable over long periods of time. There is no curative treatment of nodular amyloid, but successful treatment has been documented with resection or laser therapy. In our patient, the presence of AL amyloidosis prompted us to investigate for an underlying cause and clinical features and immunological testing suggested primary Sjögren's and should be considered in the pulmonary manifestation of this condition. Disclosures K. Halai None. O. Savanovic-Abel None. T. Howell None.

Impact of Different Types of Lymphadenectomy Combined With Different Extents of Tumor Resection on Survival Outcomes of Stage I Non-small-cell Lung Cancer: A Large-Cohort Real-World Study.

Background: To investigate the prognostic impact of different types of lymphadenectomy with different extents of tumor resection on the outcomes of stage I non-small-cell lung cancer (NSCLC).Methods: Patients were classified into lobectomy and sublobectomy groups, and then each group was subdivided according to the types of lymphadenectomy. The end points of the study were overall survival (OS) and disease-free survival (DFS). Propensity score matched (PSM) comparative analysis and univariate and multivariate Cox regression analyses were performed.Result: A total of 1,336 patients were included in the current study. Lobectomy was associated with better OS and DFS. In the lobectomy group, lobectomy with bilateral mediastinal lymphadenectomy (BML) was associated with better OS than lobectomy with systematic nodal dissection (SND) or lobe-specific systematic node dissection (L-SND). Lobectomy with SND or L-SND was associated with better OS than lobectomy with systematic nodal sampling (SNS) or selected lymph node biopsy (SLNB). Additionally, lobectomy with BML or SND was associated with better DFS than lobectomy with L-SND or SNS or SLNB. After PSM, compared with lobectomy with SNS or SLNB, lobectomy with SND resulted in more favorable OS and DFS. There was no survival difference between different types of lymphadenectomy for patients who underwent sublobectomy. A multivariable analysis revealed independent associations of lobectomy with BML or SND with better OS and DFS compared with those of lobectomy with SNS or SLNB.Conclusion: This study reveals an association of lobectomy with more systematic and complete lymph node dissection, such as BML or SND, with better prognosis in stage I NSCLC patients.

AB016. LA01. Impact of lymph node dissection on thymic malignancy: The Korean Association for Research on the Thymus (KART) Database Study

: Macroscopic and microscopic complete resection is the most important goal of surgical treatment in thymic malignancy. Radical thymectomy of thymic tumor and surrounding thymic tissue is the best way to achieve complete resection. It has been established as the standard treatment for thymic malignancy. However, whether additional lymph node dissection (LND) is necessary during thymectomy remains controversial because actual incidence of lymph node metastasis has not been well known and the therapeutic role of LND in thymic malignancies has not been established yet. Considering that LND is an important surgical procedure for staging and treatment in patients with many other solid malignancies, the need to establish the role of LND in thymic malignancies has been increasing. In 2013, the International Thymic Malignancy Interest group (ITMIG) and the International Association for Study of Lung Cancer (IASLC) proposed a new lymph node map and separate N stage in the eighth edition of TNM stage classification system for thymic malignancies. Systematic lymph node sampling in thymoma and LND in thymic carcinoma were suggested by ITMIG. However, evidence supporting routine LND during thymectomy is insufficient. To address the issue of LND in thymic malignancy, in this collaborative effort, authors of this study collected data on 1,597 patients who underwent surgical resection for primary thymic malignancies between 2000 and 2013 from the Korean Association for Research on the Thymus (KART) Database Study. The objective of the present study was to verify prognostic implications of lymph node metastases and the role of LND in thymic malignancies by retrospectively reviewing multi-center database in a large scale.

P2.16-42 Standard Mediastinoscopy Versus Video-Assisted Mediastinoscopic Lymphadectomy in Clinical N1 Non-Small Cell Lung Cancer

A considerable number of patients with clinical N1 (cN1) non-small cell lung cancer (NSCLC) based on positron emission tomography–computed tomography (PET-CT) imaging have occult mediastinal nodal involvement (N2 disease). We aimed to compare the role of video-assisted mediastinoscopy lymphadenectomy(VAMLA) and standard mediastinoscopy in pre-resectional mediastinal staging in patients with cN1 disease. A total of 821 patients with potentially resectable NSCLC seen between January 2004 and November 2016 were included in the study. The preoperative mediastinal staging was accomplished by standard cervical mediastinoscopy or VAMLA in all patients except those with peripheral cT1N0 tumors. Resection via thoracotomy or video-assisted thoracoscopic surgery was performed in patients with no mediastinal lymph node metastasis. A systematic lymph node sampling or systematic lymph node dissection was performed during resectional surgery. Surgical-pathological results were compared with the pathological findings. Primary aim was to compare the sensitivities and accuracies to detect N2 by two methods. Out of 85 patients with cN1 on PET-CT, a mediastinal metastasis was disclosed in 29 patients (34.1%). Of 56 patients who underwent VAMLA 24(42.9%) were found to have N2/3 disease, whereas standard mediastinoscopy revealed N2/N3 disease in 7 patients(24.1%)(p=0.029) VAMLA and standard mediastinoscopy had both sensitivities of 85.7% to detect N2 disease(p=1). The NPVs were 87.5% and 85.7% by VAMLA and standard mediastinoscopy respectively(p=0.821). VAMLA is more accurate to detect mediastinal nodal disease in operable cN1 lung cancer, and could be used in patients with cN1 NSCLC patients since it discloses N2 disease in an important fraction of patients.

Pulmonary Laser Metastasectomy by 1318-nm Neodymium-Doped Yttrium-Aluminum Garnet Laser: A Retrospective Study About Laser Metastasectomy of the Lung.

The lungs are among the first organ affected by remote metastases from many primary tumors. The surgical resection of isolated pulmonary metastases represents an important and effective element of therapy. This is a retrospective study about our entire experience with pulmonary resection for metastatic cancer using 1318-nm neodymium-doped yttrium-aluminum garnet laser. In this single-institution study, we retrospectively analyzed a group of 209 patients previously treated for primary malignant solid tumors. We excluded 103 patients. The number and location of lesions in the lungs was determined using chest computed tomography and positron emission tomography-computed tomography. Disseminated malignancy was excluded. All pulmonary laser resections are performed via an anteroaxillary muscle-sparing thoracotomy. All lesions were routinely removed by laser with a small (5-10 mm) margin of the healthy lung. Patients received systematic lymph node sampling with intraoperative smear cytology of sampled lymph nodes. Mortality at 2 years from the first surgery is around 20% (10% annually). This value increases to 45% in the third year. The estimated median survival for patients who underwent the first surgery is reported to be approximately 42 months. Our results show that laser resection of lung metastases can achieve good result, in terms of radical resection and survival, as conventional surgical metastasectomy. The great advantage is the possibility of limiting the damage to the lung. Stapler resection of a high number of metastases would mutilate the lung.

What we know about surgical therapy in early-stage non-small-cell lung cancer: a guide for the medical oncologist.

Lung cancer remains the leading cause of death in cancer patients. The gold standard for the treatment of early-stage non-small-cell lung cancer is lobectomy with mediastinal lymph-node dissection or systematic lymph-node sampling. The evidence behind this recommendation is based on the sole randomized controlled trial conducted to date, done by the Lung Cancer Study Group and published in 1995, which found a superiority for lobectomy over sublobar resection with regard to local recurrence rate and improved survival. The population studied at that time were medically fit patients at low risk for surgery with a stage IA non-small-cell lung carcinoma, ie, a solitary tumor less than 3 cm in size. In practice, however, thoracic surgeons have continued to push the limit of a more conservative surgical resection in this patient population. Since then, several retrospective studies have attempted to identify the ideal population to benefit from sublobar resection without it affecting survival or local recurrence. Several variables have been studied, including tumor size, patient age, surgical approach, histological and radiological properties, and optimal surgical resection margin, as well as promising prognostic biomarkers. In this review, we summarize the data available in the literature regarding the surgical approach to patients with stage IA non-small-cell lung cancer studying all the aforementioned variables.

Systematic lymph node sampling at operation results in more node positive staging in NSCLC

It has been shown that the survival of patients with NSCLC is related to nodal involvement. Both BTS and SIGN guidelines recognise that simple nodal sampling is not adequate to accurately stage NSCLC and recommend at least systematic sampling of mediastinal nodes. In the West of Scotland all patients with node positive disease are considered for adjuvant chemotherapy. This requires accurate staging of lymph nodes.

178: Systematic lymph node sampling at operation results in more node positive staging in NSCLC

178: Systematic lymph node sampling at operation results in more node positive staging in NSCLC

Lobe-Specific Mediastinal Nodal Dissection Is Sufficient During Lobectomy by Video-Assisted Thoracic Surgery or Thoracotomy for Early-Stage Lung Cancer

Lobectomy with complete mediastinal lymphadenectomy is considered standard for patients with early-stage non-small cell lung cancer (NSCLC). However, the benefits of complete lymphadenectomy are unproven. There is evidence suggesting a predictable pattern of mediastinal nodal drainage. This study analyzed the frequency and pattern of mediastinal nodal disease and its impact on outcome in patients with early-stage NSCLC. Patients with clinical N0/N1 NSCLC staged with CT scans and PET scans were identified. Disease involvement of resected nodal stations was recorded. Patterns of recurrence in patients who underwent lobectomy with complete mediastinal systematic lymph node sampling (SLNS) were compared with those who underwent lobe-specific mediastinal SLNS. From July 2004 to April 2011, 370 patients were identified. Complete SLNS was performed in 282 patients. Fifteen patients (5.3%) in the group with complete SLNS were found to have N2 disease after pathologic evaluation. Patients with left-sided tumors were more likely to have pathologic N2 disease than were patients with right-sided tumors (P = .03). Only one patient (0.36%) had positive N2 disease in the distal mediastinum while skipping lobe-specific mediastinal nodes. In addition, patients with complete SLNS had a rate of recurrence similar to that of the group that had lobe-specific mediastinal evaluation (20.6% vs 18.2%, P = .68). Mediastinal N2 metastases follow predictable lobe-specific patterns in patients with negative preoperative CT scans and PET scans. Lobe-specific N2 nodal evaluation results in a recurrence rate similar to that of complete mediastinal evaluation. Lobe-specific mediastinal nodal evaluation appears acceptable in patients with early-stage NSCLC.

S35 A randomised controlled trial comparing combined EBUS/EUS followed by surgical staging versus surgical staging alone in non-small cell lung cancer: the ASTER study

BackgroundFor many years the standard approach to staging of the mediastinum in non-small cell lung cancer (NSCLC) has been surgical using cervical mediastinoscopy, left anterior mediastinotomy or video assisted thoracoscopic...

The value of mediastinal staging with endobronchial ultrasound-guided transbronchial needle aspiration in patients with lung cancer☆

To evaluate the diagnostic yield, the learning curve and the safety of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) in mediastinal staging of patients with lung cancer. Mediastinal staging was performed with EBUS-TBNA according to the Danish national guidelines in patients fulfilling one or more of the following criteria: (1) central tumour; (2) enlarged (>10 mm) mediastinal lymph nodes on computed tomography; or (3) positron emission tomography (PET)-positive mediastinal lymph nodes. The study period began in January 2006 when EBUS-TBNA was introduced in the department and ended in December 2007. All records were reviewed retrospectively. None of the four examiners had any previous experience with EBUS-TBNA or ultrasound when the study began. All examinations were performed under general anaesthesia. Patients without useful cytological material from the EBUS-TBNA were subjected to a supplementary standard cervical mediastinoscopy if the mediastinal lymph nodes were found to be enlarged (>10 mm), PET positive or if the examiner was insecure of the result of the EBUS-TBNA. Patients with mediastinal lymph node involvement, detected by EBUS-TBNA or standard cervical mediastinoscopy, were referred to oncological treatment, while those without mediastinal lymph node involvement underwent--if they were otherwise eligible for surgery--resection and systematic lymph node sampling either by thoracotomy or by video-assisted thoracoscopy. Final mediastinal staging was defined as positive if mediastinal lymph node involvement was detected by EBUS-TBNA, standard cervical mediastinoscopy or surgery, or defined as negative otherwise. A total of 157 patients were included in the study. N2/N3 disease was found in 67 patients (42.6%). EBUS-TBNA missed the mediastinal spread in 10 patients. Five of the ten patients had lymph node metastases in station 5, 6 or 8--out of reach of EBUS-TBNA or standard cervical mediastinoscopy. EBUS-TBNA had a sensitivity of 0.85 (0.74-0.93) and a negative predictive value of 0.90 (0.82-0.95). No complications occurred from EBUS-TBNA. The number of supplementary standard cervical mediastinoscopies decreased significantly in the study period. The results of this study suggest that staging of the mediastinum with EBUS-TBNA is safe and easy to learn--even without previous experience with ultrasound. The diagnostic yield of EBUS-TBNA is in accordance with the yield of standard cervical mediastinoscopy reported in the literature. We do not find any indications in the present study of the recommended necessity for mediastinoscopy in all EBUS-TBNA-negative patients.

Endoscopic Ultrasound Reduces Surgical Mediastinal Staging in Lung Cancer

Assessment of mediastinal lymph nodes is recommended in patients with non-small cell lung cancer without distant metastases. Linear transesophageal endoscopic ultrasound with real-time guided fine-needle aspiration (EUS-FNA) is a promising, nonsurgical tool for mediastinal staging. We conducted a randomized controlled trial comparing surgical staging with EUS-FNA. Patients with proven or suspected non-small cell lung cancer in whom mediastinal exploration was required were randomly assigned to undergo EUS-FNA or the appropriate surgical staging procedure. When EUS-FNA did not show malignant lymph node invasion, a confirmatory surgical staging procedure was done. A negative surgical staging procedure was followed by thoracotomy with systematic lymph node sampling. The primary endpoint was the rate of surgical staging interventions. The secondary endpoints were test performance of EUS-FNA and surgical staging, morbidity, and length of hospital stay, considering surgical staging was performed as an in-patient procedure. A total of 40 patients were randomized: 19 to EUS-FNA, and 21 to surgical mediastinal staging. Patient and tumor characteristics were well balanced between both groups. For patients allocated to EUS-FNA, surgical staging was needed in 32% (P < 0.001). The sensitivity to detect malignant lymph node invasion was 93% (95% confidence interval, 66-99%) for EUS-FNA and 73% (95% confidence interval, 39-93%) for surgical staging (P = 0.29). Complication rate was 0% for EUS-FNA and 5% for surgical staging (P = 1.0). The median hospital stay was significantly shorter for EUS-FNA than for surgical staging (0 vs. 2 nights; P < 0.001). EUS-FNA reduces the need for surgical staging procedures in patients with (suspected) lung cancer in whom a mediastinal exploration is needed.

Clinical and Surgical Staging of Non-Small Cell Lung Cancer

The necessity for a compulsive attitude toward preoperative assessment of lung cancer is to be emphasized, since rational treatment and prognosis depend largely on the stage of disease at the time of diagnosis. In the preoperative setting, the techniques used should be sequential, logical, and help to identify patients suitable for treatment with curative intent. With regard to the primary tumor (T status), the accuracy of CT or MRI to predict the need for extended resections is limited. Similarly, all noninvasive methods to determine the nodal status (N) are valuable, but mediastinoscopy has a greater sensitivity and specificity than either CT or MRI. The role of routine organ screening for the detection of distant occult metastasis in the asymptomatic patient is still controversial. Ultimately, the prognosis of the resected patient with lung cancer is based on complete intraoperative staging, which can be done by either systematic node sampling or complete lymphadenectomy. At present, neither of these techniques has been shown to improve the quality of staging or survival.