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.     

Increasing age does not affect efficacy of sentinel lymph node biopsy using smaller-sized technetium-99m tin colloids for breast cancer patients

BACKGROUND: Increasing age of breast cancer patients was reported to cause not only failure of sentinel lymph node (SLN) identification but also false negative results. METHODS: A retrospective review was conducted of breast cancer patients who underwent sentinel lymph node biopsy (SLNB) using small-sized technetium-99m-labeled tin colloid (particle size: 200-400 nm in diameter). A comparison between 82 patients who were less than 60 years and 40 patients who were > or =60 years of age was performed to evaluate the efficacy of SLNB using the small-sized tin colloid in older patients. RESULTS: One hundred twenty-two clinically node-negative breast cancer patients underwent SLNB. Apart from age, there were no statistically significant differences between the younger patients and the older patients in terms of the clinicopathologic characteristics. Successful mapping rates, false negative rates, and accuracy were comparable between the 2 groups. CONCLUSIONS: SLNB using the small-sized tin colloid was not affected by increasing age.     

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.     

Intraoperative injection of technetium-99m sulfur colloid is effective in the detection of sentinel lymph nodes in breast cancer

BACKGROUND: Our objective was to determine if intraoperative injection of technetium-99m-labeled sulfur colloid is as effective as preoperative injection in the detection of sentinel lymph nodes (SLNs). METHODS: Two hundred consecutive patients with breast cancer underwent SLN biopsy examination. Radiocolloid was injected in the preoperative area (group A) or immediately after induction of anesthesia in the operating room (group B). RESULTS: The SLN detection rate was similar for groups A (96%) and B (100%; P = .2). Radioactive SLNs were detected in 95% of patients in group A and in 97% of patients in group B (P = .1). The mean number of SLNs harvested was 1.6 and 2.1 for groups A and B, respectively. There was no significant difference in positive SLNs between groups (P = .11). CONCLUSIONS: Intraoperative injection of sulfur colloid is highly effective in the detection of SLNs, avoiding patient discomfort and surgical schedule delays.     

Lymphatic mapping and sentinel node biopsy using 99mTc tin colloid in gastric cancer

OBJECTIVE: The aim of this study was to determine the feasibility of sentinel lymph node (SLN) biopsy in patients with gastric cancer for the assessment of regional lymph node status. SUMMARY BACKGROUND DATA: SLN is the first draining node from the primary lesion, and it is the first site of lymph node metastasis in malignancy. SLN mapping and biopsy are of great significance in the determination of the extent of lymphadenectomy, allowing patients with gastric cancer to have a better quality of life without jeopardizing survival. METHODS: The SLN biopsy was performed in 46 consecutive patients having gastric cancer with a preoperative imaging stage of T1/T2, N0, or M0. Three hours prior to each operation, Tc tin colloid (2.0 mL, 1.0 mCi) was endoscopically injected into the gastric submucosa around the primary tumor. Subsequently, serial lymphoscintigraphy was performed using a dual-head gamma camera. After the SLN biopsy had been performed using a gamma probe, all patients underwent radical gastrectomy (D2 or D2+alpha). The SLN was cut and immediately frozen-sectioned. A paraffin block was then produced for permanent hematoxylin-eosin staining and immunohistochemistry (IHC). RESULTS: SLNs were successfully identified in 43 of 46 patients (success rate, 93.5%). On average, 2 (range, 1-8) SLNs were identified per patient. The positive predictive value, negative predictive value, sensitivity, and specificity of SLN biopsy were 100% (11 of 11), 93.8% (30 of 32), 84.6% (11 of 13), and 100% (30 of 30), respectively. SLNs were located at the level I lymph nodes in 38 (88.4%), the level I+II nodes in 2 (4.7%), and the level II nodes in 3 (7.0%). No micrometastases of SLNs was found on IHC for cytokeratin. CONCLUSIONS: SLN biopsy using a radioisotope in patients with gastric cancer is a technically feasible and accurate technique, and it is a minimally invasive approach in the assessment of patient nodal status.     

Subareolar injection of radioactive colloid for sentinel lymph node identification in breast cancer patients

Sentinel lymph node biopsy (SLNB) is becoming the standard for staging the axilla in breast cancer patients in many institutions. The best method of injection is still questionable. The purpose of this study was to compare the results of SLNB using the peritumoral or the subareolar injection site. Between December 1997 and March 2000, we performed 100 SLNBs. Technecium-labeled colloidal human serum albumin was injected peritumorally (Group A, 31 patients; Group B, 31 patients) or subareolarly (Group C, 38 patients). Patent blue dye was given periareolarly (Group A) or peritumorally (Groups B and C). Preoperative lymphoscintigraphy was performed in all patients. SLNB was successful in 94 patients (94%). The identification rate improved from 80 per cent (first 25 patients) to 99 per cent (last 75). The subareolar injection of the colloid did not adversely influence the results of SLNB compared with the peritumoral injection (identification rate, 100% vs 97%; false negative rate, 6% vs 14%). The subareolar injection of colloid is a simple and at least as accurate technique as the peritumoral one. This technique can also improve the identification rate of SLNB for breast cancer 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.     

Particle size of tin and phytate colloid in sentinel node identification

BACKGROUND: Sentinel node navigation surgery (SNNS) has recently been introduced for various types of carcinoma. Numerous radioisotopes are used as tracers for SNNS. However, few reports have examined particle sizes of isotope colloids used in SNNS. MATERIALS AND METHODS: Tin and phytate colloids were used in the present study. Isotonic sodium chloride and tin solutions were mixed ratios of 1:4, 1:2, 1:1, 2:1, and 4:1. Calcium solution and Tc-phytate were mixed at ratios of 1:4, 1:2, 1:1, 2:1 and 4:1. Particle size was measured using a Coulter Model N4SD Sub-micron Particle Analyzer. RESULTS: When isotonic sodium chloride and tin solutions were mixed at ratios of 1:4, 1:2, 1:1, 2:1, and 4:1, particle size was 47 +/- 9, 96 +/- 10, 712 +/- 83, 925 +/- 66 and 1079 +/- 132 nm, respectively. As the ratio of tin solution decreased, colloid particle size increased. Particle size of phytate colloid varied from 174 +/- 39 nm to 1222 +/- 283 nm, according to calcium concentration. Phytate colloid particle size became larger as the ratio of phytate solution decreased. CONCLUSIONS: We ascertained that the particle size of tin and phytate colloids is controllable by manipulating the conditions under which the colloids form. These results will offer useful information when SNNS is performed.     

Concordance of peritumoral technetium 99m colloid and subareolar blue dye injection in breast cancer sentinel lymph node biopsy

INTRODUCTION: Sentinel lymph node (SLN) mapping has emerged as a less invasive method for axillary lymph node staging in patients with breast cancer. Blue dye and radioisotopes are commonly used agents to localize SLNs, but the optimal site for the injection of these agents continues to be debated. In this study, we evaluated whether subareolar injection of blue dye led to the identification of the same SLNs as peritumoral injection of technetium colloid. METHODS: From March 2003 to August 2006, 124 patients with invasive breast cancer, diagnosed by core needle biopsy, were included in this study. Demographic and clinical data were abstracted from medical records. Approximately 1 h prior to surgery, all patients had peritumoral injection of 37 Mbq of Tc-99m-sulfur colloid. In the operating room, 3 to 5 mL of 1% lymphazurin was injected into the subareolar area. SLNs were categorized as radio-labeled-only, blue-only, or radio-labeled + blue. Data were analyzed with 95% exact confidence intervals, Spearman rank coefficient and kappa coefficient. RESULTS: The mean number of SLNs identified was 1.9 (range 1-5). With the combination of two methods 122 out of 124 patients (98.4%) had successful identification of SLNs. One hundred fifteen patients (92.7%) had SLNs that were blue and 121 patients (97.6%) had radio-labeled SLNs. One hundred fourteen patients had at least one SLN that was both blue and radio-labeled, yielding a concordance rate of 91.9% (95% CI, 0.88-0.98). Metastatic disease was identified in SLNs of 28 patients. All lymph nodes with evidence of metastasis were both blue and radio-labeled. CONCLUSIONS: Our study showed a high degree of concordance between subareolar blue dye and peritumoral radiocolloid in identification of SLNs. These results further support that the breast parenchyma and subareolar plexus drain to similar SLNs within the axilla. These two techniques can complement each other in localizing SLNs with a high success rate.     

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.     

Developing intrathoracic sentinel lymph node mapping with near-infrared fluorescent imaging in non-small cell lung cancer

With poor survival and high recurrence rates, early-stage lung cancer currently appears to be understaged or undertreated, or both. Although sentinel lymph node biopsy is standard for patients with breast cancer and melanoma, its success has been unreliable in non-small cell lung cancer. Sentinel lymph node biopsy might aid in the identification of lymph nodes at the greatest risk of metastasis and allow for more detailed analysis to select for patients who might benefit from adjuvant therapy. The early results in our recent clinical trial of patients with early-stage lung cancer have suggested that near-infrared imaging might offer a platform for reliable sentinel lymph node identification in these patients.     

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.     

A novel method for sentinel lymph node mapping using magnetite in patients with non-small cell lung cancer

OBJECTIVE: The detection rate of sentinel lymph nodes in patients with non-small cell lung cancer using isosulfan blue dye is too low for clinical use. Although exposure to radioactivity is reportedly minimal, special procedures are nonetheless required when a radioactive isotope is used as a tracer. Therefore, to eliminate the need for a radioactive tracer and to obtain a better detection rate than is obtained with isosulfan blue dye, we have developed a novel method that employs magnetite as the tracer. The aim of the present study was to test the feasibility of this technique. METHODS: The tracer employed was ferumoxides, a colloidal superparamagnetic iron oxide of nonstoichiometric magnetite. Thirty-eight non-small cell lung cancer patients participated in the study; each received 5 mL of ferumoxides, injected around the tumor intraoperatively. Fifteen minutes after injection, lung resection and lymph node dissection were carried out. The magnetic force within the lymph nodes was measured using a highly sensitive handheld magnetometer ex vivo. All lymph nodes were also subjected to conventional histological analysis. RESULTS: The rate of detection of sentinel lymph nodes was 81.6% (31/38). The accuracy, sensitivity, and false-negative rates were 96.8% (30/31), 85.7% (6/7), and 14.3% (1/7), respectively. CONCLUSION: Intraoperative sentinel lymph node mapping using ferumoxides and a highly sensitive magnetometer is a safe, accurate, and sensitive way to detect sentinel lymph nodes in non-small cell lung cancer patients.     

Subareolar injection of99mTc facilitates sentinel lymph node identification

BACKGROUND: Sentinel lymph node (SLN) biopsy with the standard intraparenchymal injection has been accepted as an alternative to routine axillary dissection for patients with breast cancer. However, the identification and false-negative rates with this method can vary widely from surgeon to surgeon. The subareolar location contains a rich lymphatic network and represents a potential site of injection for SLN identification. METHODS: Between August 1, 1999, and December 31, 2000, we performed 159 SLN biopsy procedures on 158 patients with breast cancer. For each patient, 99mTc-labeled sulfur colloid was injected into the subareolar location, and 1% isosulfan blue dye was given as an intraparenchymal injection. RESULTS: In every case, at least one radioactive SLN was identified with the subareolar injection of technetium; a blue SLN was found in 97% of the cases. The blue SLN was also radioactive in 98% of the cases, indicating that the blue dye injected around the tumor and the technetium injected into the subareolar location drained to the same SLN. CONCLUSIONS: Subareolar injection of technetium can improve SLN identification rates for breast cancer. The simplicity and accuracy of this technique may also reduce the variable results reported with the standard intraparenchymal method.     

Sentinel lymph node identification for patients with breast cancer using large-size radiotracer particles: technetium-99m-labeled tin colloids produced excellent results

Sentinel lymph node (SLN) biopsies using radioactive tracers have been reported to detect the metastatic status of the axillary lymph nodes in breast cancer patients. However, the optimal radioactive tracer particle sizes remain to be determined. In this study, identification of SLNs with large radiolabeled tin colloid particles was evaluated. Seventy-five patients with T1-2, N0 breast cancer were enrolled. Two hours prior to surgery, 1 to 2.5 mL technetium-99m–labeled tin colloid particles were injected around the tumor under ultrasonographic guidance. Immediately before the operation, dye fluids were also injected around the tumor to increase the interstitial pressure. After axillary dissection, lymph nodes with ×100 or more uptake of radioactivity than the mean of the other lymph nodes are considered to be SLN. All lymph nodes from the axillary dissections were pathologically investigated, and the characteristics of SLNs were evaluated. SLNs were clearly identified in 74 of 75 patients (98.7%). Of 37 patients without SLN metastasis, pathological investigation revealed no further involvement of the remaining non-SLNs. The SLNs tended to be larger in size, and more than 50% were located in the lower medial site of the axilla. This is the first study to show that SLNs could successfully be identified with radiolabeled tin colloid particles. When SLNs were negative for metastases, non-SLNs were always negative.