ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer.

Accurate preoperative staging and restaging of mediastinal lymph nodes in patients with non-small cell lung cancer (NSCLC) is of paramount importance. It will guide choices of treatment and determine prognosis and outcome. Over the last years, different techniques have become available. They vary in accuracy and procedure-related morbidity. The Council of the ESTS initiated a workshop on preoperative mediastinal lymph node staging. This resulted in guidelines for primary staging and restaging. For primary staging, mediastinoscopy remains the gold standard for the superior mediastinal lymph nodes. Invasive procedures can be omitted in patients with peripheral tumors and negative mediastinal positron emission tomography (PET) images. However, in case of central tumors, PET hilar N1 disease, low fluorodeoxyglucose uptake of the primary tumor and LNs > or = 16 mm on CT scan, invasive staging remains indicated. PET positive mediastinal findings should always be cyto-histologically confirmed. Transbronchial needle aspiration (TBNA), ultrasound-guided bronchoscopy with fine needle aspiration (EBUS-FNA) and endoscopic esophageal ultrasound-guided fine needle aspiration (EUS-FNA) are new techniques that provide cyto-histological diagnosis and are minimally invasive. Their specificity is high but the negative predictive value is low. Because of this, if they yield negative results, an invasive surgical technique is indicated. However, if fine needle aspiration is positive, this result may be valid as proof for N2 or N3 disease. For restaging, invasive techniques providing cyto-histological information are advisable despite the encouraging results supported with the use of PET/CT imaging. Both endoscopic techniques and surgical procedures are available. If they yield a positive result, non-surgical treatment is indicated in most patients.     

ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer.

The European Society of Thoracic Surgeons (ESTS) organized a workshop dealing with lymph node staging in non-small cell lung cancer. The objective of this workshop was to develop guidelines for definitions and the surgical procedures of intraoperative lymph node staging, and the pathologic evaluation of resected lymph nodes in patients with non-small cell lung cancer (NSCLC). Relevant peer-reviewed publications on the subjects, the experience of the participants, and the opinion of the ESTS members contributing on line, were used to reach a consensus. Systematic nodal dissection is recommended in all cases to ensure complete resection. Lobe-specific systematic nodal dissection is acceptable for peripheral squamous T1 tumors, if hilar and interlobar nodes are negative on frozen section studies; it implies removal of, at least, three hilar and interlobar nodes and three mediastinal nodes from three stations in which the subcarinal is always included. Selected lymph node biopsies and sampling are justified to prove nodal involvement when resection is not possible. Pathologic evaluation includes all lymph nodes resected separately and those remaining in the lung specimen. Sections are done at the site of gross abnormalities. If macroscopic inspection does not detect any abnormal site, 2-mm slices of the nodes in the longitudinal plane are recommended. Routine search for micrometastases or isolated tumor cells in hematoxylin-eosin negative nodes would be desirable. Randomized controlled trials to evaluate adjuvant therapies for patients with these conditions are recommended. The adherence to these guidelines will standardize the intraoperative lymph node staging and pathologic evaluation, and improve pathologic staging, which will help decide on the best adjuvant therapy.     

Intraoperative radioguided sentinel lymph node biopsy in non-small cell lung cancer.

OBJECTIVES: The aim of this study was to determine the accuracy and the role of the sentinel lymph node (SLN) technique in patients with early non-small cell lung cancer (NSCLC). METHODS: This study was carried out on 29 consecutive patients (M/F = 24:5, mean age 65.9 +/- 7.1 years) with resectable NSCLC (Stage IA-IB). Intraoperative injection with a (99m)Tc-nanocolloid suspension was performed in the first ten patients; the following patients were injected under computed tomography scan guidance. A total dose of 37 MBq (1 ml) was administered in two to four divided aliquots (depending on the size), injected in the periphery of the tumour. Intraoperative radioactivity counting started a mean of 1 h (range 50-70 min) after the injection. The SLN was defined as the node with the highest count rate using a handheld gamma probe counter. Resection with mediastinal node dissection was performed and findings were correlated with histologic and immunohistochemistry (IHC) examination. RESULTS: Three of the 29 patients did not have NSCLC (two benign lesions, and one metastatic breast tumour) and were excluded. The SLN was identified in 25/26 (96.1%) patients (a total of 31 SLNs); 7/31 (22.5%) of the SLNs were positive for metastatic involvement after histologic and IHC examination. One inaccurately identified SLN was encountered (3.8%). CONCLUSIONS: These preliminary results demonstrate the feasibility of this procedure in identifying the first site of potential nodal metastases of NSCLC. The actual clinical impact of this procedure remains to be elucidated by further investigation in larger groups of patients.     

非小细胞肺癌淋巴结清扫方式临床研究

目的 比较非小细胞肺癌不同纵隔淋巴结清扫方式间的差异,为规范化开展肺癌淋巴结清扫临床研究提供依据.方法 在202例Ⅰa-Ⅲa期肺癌中进行前瞻性临床对照试验,比较常规清扫(RMLD)和全纵隔骨骼化清扫(SCLD)两种术式,分析手术经过和术后病理分期情况.结果 RMLD 107例,SCLD 95例.两组术前一般情况、临床分期及肺切除方式无明显差异,SCLD组平均扫除淋巴结组数显著高于RMLD组(8.9组对6.2组,P＜0.001),术后总体并发症(14.7%对14.0%,P=0.884)和病死率(2.1%对1.9%,P=0.904)无差异,但SCLD组分别有3例(3.2%)右侧乳糜胸和左侧喉返神经损伤发生.术后病理证实两组组织学类型及分期无明显差异,RNLD和SCLD组pN2分别占27.1%和24.2%(P=0.888),跳跃性纵隔转移率(RMLD 9.3%对SCLD 7.4%,P=0.613)以及纵隔多组转移率(RMLD 15.0%对SCLD 16.8%,P=0.714)亦无明显差异.分析纵隔各组淋巴结转移率发现上叶肺癌下纵隔转移率＜5%,而中、下叶肺癌上、下纵隔转移率均＞10%;cT1病例以及低度恶性肿瘤无一发生纵隔转移.结论 对非小细胞肺癌行常规纵隔清扫可达到与全纵隔骨骼化清扫同样的分期效果,后者手术风险并不高于常规清扫,但应避免右侧乳糜胸和左侧喉返神经损伤的发生;上叶肺癌仅需扫除上纵隔淋巴结而无需常规清扫下纵隔;早早期肺癌以及低度恶性肿瘤没有必要进行常规纵隔清扫.     

Sentinel lymph node biopsy for staging penile cancer

Eighteen sentinel lymph node biopsies were performed in 10 patients with invasive squamous carcinoma of the penis. Five of 15 biopsies associated with inguinal lymphadenopathy and 2 of 3 biopsies associated with palpably normal inguinal nodes were positive. Among 7 ipsilateral regional lymphadenectomies undertaken because of a positive biopsy, additional lymph node metastases were uncovered in only 1 instance. Among 5 patients with negative biopsies bilaterally, none had other superficial inguinal lymph node metastases and all but one have remained free of tumor (mean follow-up 26 months). These data support the possibility that the sentinel lymph node is often the first site of regional lymphatic metastasis in penile cancer.     

Sentinel node biopsy for staging lung cancer

The importance and value of accurate clinical and pathological staging of lung cancer is emphasized. The philosophy, techniques, and general results of the sentinel node technique for lymphatic mapping are reviewed. The experience with this technique in patients with non-small cell lung cancer is discussed and the future use of lymphatic mapping is pondered.     

Sentinel lymph node mapping in non-small cell lung cancer

Although identification of sentinel lymph nodes (SLN) with dye or radioisotope tracers has become a standard of care in both breast cancer and melanoma, it remains investigational in patients with lung cancer. SLN mapping has been performed in non-small cell lung cancer patients using isosulfan blue and radioisotope. The radioisotope method of SLN mapping appears to be more accurate than the dye technique in lung cancer patients. Several reports have demonstrated the feasibility of identifying the first site of potential nodal metastases of NSCLC. Furthermore, accurate sentinel node identification allows pathologists to focus on examinations with sensitive techniques to validate the SLN and to identify the presence of skip metastasis.     

FDG-PET imaging for lymph node staging and pathologic tumor response after neoadjuvant treatment of non-small cell lung cancer.

PURPOSE: A number of studies have demonstrated that 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is effective for staging of lung cancer. However, the efficacy of FDG-PET for staging lung cancer after neoadjuvant treatment is still controversial. This study compared FDG-PET and computed tomography (CT) for lung cancer staging, and evaluated the ability of the two methods to predict the pathologic response of the primary tumor to neoadjuvant treatment. PATIENTS AND METHODS: Twenty-two patients who underwent neoadjuvant treatment followed by surgery were investigated. Eighteen patients received chemoradiotherapy and four patients received chemotherapy only. One hundred and three lymph node stations in the 22 patients were evaluated by FDG-PET and CT. The pathologic responses of the tumors were compared by FDG-uptake and tumor size on CT for the 15 patients who underwent FDG-PET and CT both before and after neoadjuvant treatment. RESULTS: There was no significant difference in the ability of FDG-PET or CT to predict residual viable tumor. Although positive predictive value by FDG-PET (0.29) was lower than that by CT (0.64) (p=0.04) in the mediastinal lymph nodes, there were no statistically significant differences in the other results of lymph nodes by FDG-PET and CT. Both decrease in FDG-uptake and decrease in tumor size by CT after neoadjuvant treatment correlated significantly with pathologic response in the 15 patients (p=0.003 and 0.009, respectively). CONCLUSION: FDG-PET did not appear to offer any advantages over CT for lymph node staging or for predicting the pathologic response after neoadjuvant treatment of non-small cell lung cancer.     

Sentinel node biopsy for staging of small peripheral lung cancer

Is it possible to choose between limited lymph node sampling and systematic lymphadenectomy from the distribution of sentinel lymph nodes in patients with small lung cancer less than 2 cm in diameter? METHODS: Twenty-four patients with cN0M0 lung cancer less than 2 cm in diameter were enrolled. A radioisotope tracer (Tc-99 m tin colloid or phyphate) was injected in the vicinity of the tumor before surgery under computed tomography (CT) guidance. The radioactivity of each resected lymph node was measured separately with a hand-held gamma probe after complete tumor resection. Sentinel nodes were identified and the accuracy of sentinel node mapping was examined. RESULTS: Successful radionuclide migration occurred in 20 of the 24 patients (83.3%). There were 21 N0 patients and 3 N-positive patients. There was no false-negative case, so the sensitivity and the specificity was 100%. The lobar lymph nodes were identified as sentinel nodes more frequently than other lymph nodes. CONCLUSION: The sentinel node concept is valid in patients with small lung cancer less than 2 cm in diameter. We believe that, if sentinel nodes are identified, sentinel node mapping can allow the accurate intraoperative diagnosis of pathological N0 status in patients with small peripheral lung cancer.     

Current concepts in the mediastinal lymph node staging of nonsmall cell lung cancer

OBJECTIVE: To review the current concepts in the mediastinal staging of nonsmall cell lung cancer (NSCLC), evaluating traditional and modern staging modalities. SUMMARY BACKGROUND DATA: Staging of NSCLC includes the assessment of mediastinal lymph nodes. Traditionally, computed tomography (CT) and mediastinoscopy are used. Modern staging modalities include magnetic resonance imaging (MRI), positron emission tomography (PET), and endoscopic ultrasound with fine-needle aspiration (EUS-FNA) METHODS: Literature was searched with PubMed and SUMSearch for original, peer-reviewed, full-length articles. Studies were evaluated on inclusion criteria, sample size, and operating characteristics. Endpoints were accuracy, safety, and applicability of the staging methods. RESULTS: CT had moderate sensitivities and specificities. With few exceptions magnetic resonance imaging (MRI) offered no advantages when compared with CT, against higher costs. PET was significantly more accurate than CT. Mediastinoscopy and its variants were widely used as gold standard, although meta-analyses were absent. Percutaneous transthoracic needle biopsy (PTNB) and transbronchial needle biopsy (TBNA) were moderately sensitive and specific. EUS-FNA had high sensitivity and specificity, is a safe and fast procedure, and is cost-effective. EUS-FNA evaluates largely a nonoverlapping mediastinal area compared with mediastinoscopy. CONCLUSIONS: PET has the highest accuracy in the mediastinal staging of NSCLC, but is not generally used yet. EUS-FNA has the potential to perform mediastinal tissue sampling more accurate than TBNA, PTNB, and mediastinoscopy, with fewer complications and costs. Although promising, EUS-FNA is still experimental. Mediastinoscopy is still considered as gold standard for mediastinal staging of NSCLC.     

Intraoperative radioisotope sentinel lymph node mapping in non-small cell lung cancer

BACKGROUND: Lymph node metastases are the most significant prognostic factor in localized non-small cell lung cancer (NSCLC). Nodal micrometastases may not be detected. Identification of the first nodal drainage site (sentinel node) may improve detection of metastatic nodes. We performed intraoperative Technetium 99m sentinel lymph node (SN) mapping in patients with resectable NSCLC. METHODS: Fifty-two patients (31 men, 21 women) with resectable suspected NSCLC were enrolled. At thoracotomy, the primary tumor was injected with 2 mCi Tc-99. After dissection, scintographic readings of both the primary tumor and lymph nodes were obtained with a handheld gamma counter. Resection with mediastinal node dissection was performed and findings were correlated with histologic examination. RESULTS: Seven of the 52 patients did not have NSCLC (5 benign lesions, and 2 metastatic tumors) and were excluded. Forty-five patients had NSCLC completely resected. Mean time from injection of the radionucleide to identification of sentinel nodes was 63 minutes (range 23 to 170). Thirty-seven patients (82%) had a SN identified; 12 (32%) had metastatic disease. 35 of the 37 SNs (94%) were classified as true positive with no metastases found in other intrathoracic lymph nodes without concurrent SN involvement. Two inaccurately identified SNs were encountered (5%). SNs were mediastinal (N2) in 8 patients (22%). CONCLUSIONS: Intraoperative SN mapping with Tc-99 is an accurate way to identify the first site of potential nodal metastases of NSCLC. This method may improve the precision of pathologic staging and limit the need for mediastinal node dissection in selected patients.     

The current status of sentinel lymph node mapping in non-small cell lung cancer.

Sentinel lymph node (SLN) mapping has become a common procedure in the treatment of breast cancer and malignant melanoma. Its primary benefit is that it enables surgeons to avoid nontherapeutic lymph node dissection and the complications that follow. There are also several studies of the use of SLN mapping in the treatment of non-small cell lung cancer (NSCLC) reported in the English literature, and all present evidence for the existence of SLNs in NSCLC. Nevertheless, SLN mapping is not widely used in the treatment of NSCLC for several reasons: first, special precautions are required to minimize exposure when radioisotopes are used as tracers; second, it is difficult to detect the blue dyes used as tracers within anthoracotic thoracic lymph nodes; and third, major complications comparable to the arm edema seen in breast cancer or the lymphedema and nerve injury seen in melanoma are not seen with mediastinal lymph node dissection (MLND). To address these issues, new techniques are being developed by groups at several institutes, including our own. We believe that SLN mapping will enable surgeons to more precisely stage NSCLC, after which more sensitive techniques can be employed on a limited amount of tissue to detect occult micrometastatic disease with less cost and effort. SLN mapping can also be applied to video-assisted thoracic surgery (VATS) for NSCLC, enabling surgeons to avoid nontherapeutic and technically difficult MLND often necessary with traditional open surgery. For all of these reasons, we think that SLN mapping will be useful in the treatment of NSCLC, and that further development aimed at making SLN mapping a practical surgical procedure is warranted.