Lymphatic mapping and sentinel lymph node biopsy

Malignant melanoma--cancer of the pigment cells--has the highest mortality rate of all skin cancers. With early detection and treatment, however, malignant melanoma is highly curable. Recently, diagnostic modalities for nodal involvement have been perfected, reducing the morbidity of elective lymph node dissections and rendering them unnecessary in many cases. Total lymphadenectomy procedures are being replaced by intraoperative lymphatic mapping and sentinel lymph node biopsy using gamma detector probes. This article reviews lymphatic drainage from the primary site to possible lymph node basins and selective lymph node dissection using lymphoscintigraphy and intraoperative mapping as guides. This article also includes a case study, beginning with a diagnosis of malignant melanoma and following a successful postoperative course.     

99mTc标记硫胶体淋巴显像探测皮肤恶性黑色素瘤前哨淋巴结的价值

目的：探讨99mTc 标记硫胶体（99mTc-SC）淋巴显像探测皮肤恶性黑色素瘤前哨淋巴结（SLN）的临床应用价值和影响因素。方法选取99例Ⅰ、Ⅱ期皮肤恶性黑色素瘤患者,术前4-6 h在肿瘤病灶周围皮下注射显像剂99mTc-SC,行早期局部及延迟全身显像,结合显像进行体表定位。随后行前哨淋巴结活检术（SLNB）,对初诊患者加行原发病灶切除术,对SLN及原发病灶行详细病理检查。结果99mTc-SC的SLN总检出率为90.9%（90/99）,检出率与原发灶部位有关（P＜0.001）;区间淋巴结检出率为7.1%（7/99）;SLN转移阳性率为28.9%（26/90）,与肿瘤的病理组织学特点（Breslow厚度、Clark分级）呈正相关;假阴性率为3.7%（1/27）,灵敏度为96.3%（26/27）,特异度为98.4%（63/64）。结论99mTc-SC显像可准确显示SLN部位及淋巴引流情况,减少药物标记时间,进一步提高区域淋巴结检出,为恶性黑色素瘤区域淋巴结的诊治决策提供重要的临床依据。     

Role of sentinel lymph node dissection in breast cancer

The sentinel node concept is valid for penile cancer, melanoma, breast cancer and is probably also applicable to other solid malignancies. Sentinel nodes are the one or two initial nodes in the regional nodal drainage basin encountered by the lymphatic effluent from a tumour, which can be identified with an injection of vital dye or other lymphogogue. Sentinel lymph node dissection (SLND), a minimally invasive procedure with negligible morbidity, has therefore been utilized as an alternative to complete axillary lymph node dissection (ALND) for staging breast cancer. Examination of sentinel nodes provides a focused histopathological assessment of tissue most likely to harbour metastases, providing enhanced staging accuracy with a low false-negative rate. Tumour-free sentinel nodes are predictive of a tumour-free axilla, thereby allowing for the possibility of SLND without ALND and sparing patients the morbidity of ALND. Most of the experience from SLND has been obtained for axillary sentinel nodes. However, sentinel nodes have been identified in nonaxillary sites, such as the internal mammary nodes, but data on SLND for these regions is scarce. The ultimate role of SLND in breast cancer, which may be to identify sentinel-node-negative patients or even those with sentinel node metastases who can safely avoid ALND without sacrificing regional control and possibly gain a therapeutic benefit, cannot be defined before we have the results of large trials that are currently in progress.     

Sentinel-Lymphknoten bei oralen und oropharyngealen epithelialen Tumoren

Carcinomatous metastases in regional lymph nodes worsen substantially the prognosis of patients with oral cavity and oropharyngeal cancer. Due to the high probability of occult metastasis (about 30%), during surgical resection of the primary tumor usually also elective dissection of lymph nodes is performed. Opinions on the extent of the elective neck dissection still differ, whereas selective dissection increasingly gains in importance. The aim of selective dissections, based on the predictability of formation of metastases, is the identification and exstirpation of the sentinel lymph node. In this prospective study the applicability of the concept of the sentinel lymph node in patients with oral cavity and oropharyngeal cancer was analysed. 12 patients with oral cavity and orophangeal cancer, staging T1-T3, all N0 (examined by palpation and sonography) were included. The localization of the sentinel(s) was determined preoperatively by radioisotope (Tc Nanocolloid). Sentinel(s) were identified first with a gamma probe (Neoprobe 2000); we then injected methylene blue into the peritumoral area for easier detection of the sentinel(s). The sentinels were removed and sent for frozen section examination. Regardless of the findings of the frozen section examination modified dissection was carried out. Later we compared frozen sections with paraffin microtome sections of sentinel(s) and of other exstirpated neck lymph nodes. We could identify the sentinel lymph node in all patients, in 6/12 patients we found several sentinels. If sentinels were not affected by tumor cells, there were no metastases in the downstream neck lymph nodes either. If in the sentinel lymph nodes no metastases can be determined, eliminating the environment alone could be sufficient. However, this assumption requires verification in a larger patient group.     

Sentinel node mapping and biopsy in thyroid cancer: a surgical perspective.

The clinical role of sentinel node biopsy (SNB) in thyroid cancer remains an open matter in literature. The main reason of this fact is that nodal disease is considered a non-relevant prognostic factor by some authors in differentiated thyroid cancer (DTC). Aim of this study was to investigate the efficacy of radiocolloid lymphoscintigraphy and of hand held gamma probe procedure for SNB in patients with DTC and its potential clinical role. Forty-one consecutive pts with a small thyroid nodule highly suspected for malignancy at fine-needle aspiration cytology (FNAC) and without clinical and ultrasonographic (US) evidence of lymph node involvement entered the study. All patients underwent lymphoscintigraphy 3 hours before intervention using a 99mTc-nanocolloid solution. One single intratumoral injection of 4-9 MBq in 0.1-02 ml normal saline was obtained under US-guidance followed by a dynamic lymphoscintigraphy. After total thyroidectomy central and lateral compartments of the neck were scanned with a hand held gamma probe. The hottest node and any lymph node with a count rate of more than 10% of the hottest node were removed. SLNs were sent to frozen section analysis and a surgical enlargement of corresponding compartment was performed when at least one SLN was positive at histology. Preoperative lymphoscintigraphy was able to identify one node in six cases, two nodes in five cases, three nodes in 14 cases, four or more nodes in 16 cases. A papillary thyroid carcinoma (PTC) was diagnosed in 39 cases, a mixed papillary-medullary carcinoma in one case and a micro-follicular adenoma in one case. In 21/40 patients (pts) positive lymph nodes were found: in 16/21 patient one node showed micrometastasis only, in 5/21 patients more nodes were metastatic. In particular in 11 cases the first hottest node was involved (true SLN), in 10 cases a second or third hot lymph node was involved. In our preliminary experience lymphoscintigraphy with 99mTc-nanocolloid resulted highly sensitive: in fact at least one lymph node was visualized in all cases and the surgeon was able to detect by means of hand held probe during intervention al least one hot SLN in all cases. In 21/40 pts (more than 50% of cases) metastatic lymph nodes were found despite preoperative clinical and US examination negative for lymph node involvement. In prospective SLN technique might be proposed as a relevant tool in lymphoadenectomy decision in DTC patients with a small tumor.     

Sentinel node biopsy in breast cancer--a minimally invasive procedure for staging of the axilla

Clinical examinations and imaging methods are not sufficiently reliable for an exact staging of axillary nodes in breast cancer. The sentinel node biopsy concept is a minimally invasive procedure to locate and remove the first and important nodes responsible for draining a tumor. Histologic examinations using immunohistochemical methods permit more accurate staging than hematoxylin and eosin staining alone. Between 4/1997 and 9/1998 a total of 62 patients with 65 breast cancers underwent surgery. The sentinel node procedure with radio tracers and/or blue dye was performed in patients with clinically negative or unclear positive findings in the axilla, with a primary tumor size less than 5 cm; 11 patients had received preoperative chemotherapy. The sentinel node biopsy was followed by axillary dissection in 44 cases. In 58 (89%) cases we found one or more (on an average 1.4) sentinel nodes with radio tracers (in 73%) and/or the blue dye method (in 85%). Axillary nodal status was correctly predicted in 43 of 44 (97.7%) cases; only in one patient was the sentinel node false negative. After preoperative chemotherapy sentinel nodes were found in 9 cases; all of these were predictive. Micrometastases were found in two patients only after cytokeratine staining. Our results concur with the experience of other study groups in regard of sentinel node biopsy. The sentinel node concept is a fascinating method; its importance in breast cancer treatment appears to be comparable with introduction of breast saving surgery in the 1980's.     

美蓝染色法乳腺癌前哨淋巴结活检100例临床应用研究

目的探讨乳腺癌前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）的应用价值。方法以100例可手术乳腺癌患者作为研究对象,临床体检腋窝淋巴结（ALN）阴性,均单独采用美蓝作为前哨淋巴结（sentinel lymph node,SLN）示踪剂。结果全部行乳腺癌改良根治术,行SLN和ALN活检,灵敏度为97．44％,准确率为92．71％,假阴性率为10．26％,假阳性率7．69％。SLNB与ALN转移检测比较效果相一致,准确率高,统计无差异性。结论应用美蓝进行SLN的认定有利于简化乳腺癌手术方式,提高患者术后生活质量。     

Role of High-Resolution Ultrasound and PET/CT Imaging for Preoperative Characterization of Sentinel Lymph Nodes in Cutaneous Melanoma

The purpose of our study was the comparison of high-resolution ultrasound (HRUS) and positron emission tomography combined with computerised tomography (PET/CT) in the preoperative characterization and identification of subclinical nodal metastases focusing on sentinel lymph nodes (SLN) in melanoma patients. Patients with cutaneous melanoma (CM) who received sentinel lymph node biopsy at the Department of Dermatology and Allergy, University of Bonn, between January 2009 and January 2011 had been evaluated with a retrospective computer-aided search concerning preoperative staging procedures. A combination of PET/CT and HRUS had been performed preoperatively in 20 of 123 patients. A total of 59 SLNs had been removed in those 20 patients followed by histopathologic examination. HRUS correctly identified two of 17 positive SLNs whereas PET/CT imaging identified none. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HRUS were 11.8 % (95 % confidence interval [CI] = 3.3–34.3), 100 % (95 % CI = 91.6–100.0), 100.0 % (95 % CI = 34.2–100.0), and 73.7 % (95 % CI = 61.0–83.3), respectively. On the basis of this limited study cohort, HRUS had a better value than PET/CT in preoperative identification of positive SLNs, suggesting a possible diagnostic superiority of HRUS in general characterization of peripheral nodal disease in CM.     

When will selective lymphadenectomy become standard of care in melanoma?

In 2006 Meiron Thomas, writing in the British Journal of Surgery, made the following statement about the value of sentinel lymph node biopsy (SLNB) as a staging procedure in cutaneous malignant melanoma (1): "Perhaps a more important concern for those hoping to gain reassurance from accurate nodal staging relates to positive SN(S) that are prognostically inaccurate, information that can be devastating for the patient, leading to unnecessary lymphadenectomy and possibly unnecessary adjuvant therapy". In September 2011 Meyrick Ross and Gershenwald, writing in the Journal of Surgical Oncology, made the following statement about the management of patients with cutaneous malignant melanoma (2): "Sentinel node biopsy has become an important component of the initial management of many of these patients for accurate staging of regional lymph nodes, as well as enhanced regional disease control and improved survival in the patients with microscopically involved nodes." These two extremes have polarized the debate about the proper management of patients with malignant melanoma and have lead to widespread confusion and dismay amongst practicing clinicians, GP's and patient groups. In fact both statements are inaccurate, misleading and result from a false reading of the literature and in the case of Ross and Gershenwald a false interpretation of their own data (3). The following article explains why.     

超声造影检测前哨淋巴结的实验研究

目的在肿瘤周围皮下注射超声造影剂,观察是否能够探测淋巴管和前哨淋巴结,是否能够探测前哨淋巴结内的转移灶。方法用普通超声、彩色多普勒和反向灰阶二次谐波超声对6头猪,17个黑色素瘤进行了研究。在肿瘤周边皮下注射超声造影剂Sonazoid(总量1ml)。淋巴超声造影后,进行99mTC硫化物胶体皮下注射,然后皮下注射。由两位医生来判断超声造影时是否前哨淋巴结有转移。结果超声造影发现28个前哨淋巴结,而淋巴系闪烁造影检出27个热点(Hotspots),可能为前哨淋巴结(2例假阳性)。蓝色染料注射后的手术切除检出31个前哨淋巴结。超声探测前哨淋巴结无假阳性。淋巴系闪烁造影漏诊6个前哨淋巴结;这其中5个前哨淋巴结,皮下注射超声造影剂后都能清晰显示。皮下超声造影探测前哨淋巴结的准确性为90%(28/31),而淋巴系闪烁造影为81%(p=0.29)。皮下注射超声造影剂在20个发生转移的前哨淋巴结中,成功检出19个;在8个无转移的前哨淋巴结中,成功检出5个,准确性86%(k=0.62)。结论皮下注射超声造影剂后都能显示前哨淋巴结,并可显示前哨淋巴结内的转移灶。皮下超声造影比淋巴系闪烁造影更有效。     

Radio-guided sentinel node mapping in patients with superficial esophageal carcinoma: feasibility study.

The aim of this study was to assess whether the sentinel node concept could be applicable to clinically early carcinoma of the esophagus. We studied ten consecutive cT1N0 patients who underwent radical esophagectomy with regional lymph node dissection. On the day before surgery, 99m-Tc tin colloid was injected endoscopically around the primary tumor. Lymphoscintigraphy was also performed about three hours after injection. Immediately after surgery, the radioactivity of all dissected lymph nodes was measured with a hand-held gamma probe. The radioactivity and the metastatic status assessed by routine histopathologic examination were compared. A total of six patients had hot spots detected by lymphoscintigraphy, of which the detection rate was 60% (6 of 10). The ex vivo hot node detection rate was 90% (9 of 10). Three patients were found to have metastatic nodes. In one patient, sentinel node mapping failed to identify any hot spot or hot node. In the other two patients, the metastatic nodes did not correspond to hot nodes. The accuracy of hot node status was 77.8% (7 of 9), and the false-negative rate was 100% (2 of 2). The present study showed that radio-guided sentinel node detection is insufficiently reliable at present due to the high false-negative rate and low accuracy.     

The role of sentinel node biopsy in patients with cutaneous melanoma

The role of sentinel lymph node biopsy (SLNB) as a prognostic indicator in melanoma patients has been controversial in the fields of surgical oncology and dermatology for decades. This minimally invasive surgical technique was introduced in 1990 for diagnosing melanoma lymphatic metastases and has been deemed the standard of surgical care of cutaneous malignant melanoma by the World Health Organization and the Sunbelt Melanoma Clinical Trial. Its usefulness as a prognostic indicator of metastases led to expanded applications for breast, colon, gastric, esophageal, head and neck, thyroid, and lung cancers. This article first provides an overview of cutaneous melanoma and staging methods and treatment modalities. A brief study of the lymphatic system and the SLNB procedure are reviewed, followed by a discussion of its usefulness in patients who have melanoma, including risks and benefits. This article also discusses nursing considerations for patients undergoing the procedure, and patient education tips. Lastly, future indications for SLNB and new prognostic indicators for melanoma are discussed.     

乳腺癌前哨淋巴结活检在新辅助化疗后的应用价值

目的通过对比术前未接受化疗和术前接受新辅助化疗两组乳腺癌患者前哨淋巴结活检的结果,探讨对术前接受新辅助化疗后降期的患者以核素法行前哨淋巴结活检的临床价值。方法以本院2006年4月~2009年3月期间收治的99例乳腺癌患者作为研究对象。术前未行化疗组60例,临床分期为T1~2N0M0,直接行前哨淋巴结活检。术前新辅助化疗组39例,临床分期T2~3N0M0,患者术前先给予3~4个疗程的新辅助化疗,降期为T1~2N0M0后再行前哨淋巴结活检。所有患者术前均经乳晕下4点平均注射99m锝标记的非过滤硫胶体,术中用γ探针探测腋窝具有放射活性的前哨淋巴结并切除,然后常规清扫腋窝Ⅰ、Ⅱ组淋巴结。术后对前哨淋巴结活检和腋窝淋巴结清扫的病理结果进行比较分析。结果A组成功率、假阴性率、灵敏度、特异度、准确性、阳性预测值和阴性预测值分别为98.3%、3.3%、96.7%、100%、98.3%、100%和96.7%。B组分别为100%、10%、90%、100%、94.9%、100%和90.5%。两组比较假阴性率、准确性均无统计学差异。(P均>0.05)。结论对新辅助化疗后降期的局部进展期乳腺癌患者,以核素法行前哨淋巴结活检仍能够获得较高的成功率,同早期乳腺癌患者相比假阴性率没有统计学差异。     

哨兵淋巴结活检预测结肠癌淋巴结转移的价值

目的探讨哨兵淋巴结活检(SLNB)预测结肠癌患者淋巴结转移状态的重要性和可行性。方法使用亚甲蓝对42例结肠癌患者进行SLNB,随后行标准的结肠癌根治术。哨兵淋巴结阴性患者进行连续切片病理检测。结果SL-NB成功率为80.95%,敏感度为97.06%,特异度为100%,预测淋巴结转移状态率为95.45%,假阴性率为4.55%。结论利用亚甲蓝淋巴定位方法进行的SLNB可以准确预测淋巴结转移状态,SLN连续切片、HE染色检测有助于提高SLNB的敏感性。     

Gastric lymphatic basin dissection for sentinel node biopsy using hybrid natural orifice transluminal endoscopic surgery (NOTES)

Abstract

The aim of the present study was to describe a method of gastric lymphatic basin dissection for sentinel node biopsy using natural orifice transluminal endoscopic surgery with laparoscopic assistance (hybrid NOTES) in a porcine model. Lymph node dissection was performed in three healthy female domestic farm pigs (each around 40 kg) between October, 2007, and December, 2007. The pigs were administered a general anesthetic and laparoscopy-guided transvaginal colpotomy was performed. A two-channel endoscope was then inserted through the incision into the peritoneal cavity via the transvaginal route. An endoscope was inserted simultaneously into the mouth and indocyanine green solution was injected into the submucosal layer of the gastric wall at four sites. Dyed omentum and lymphatics were dissected using a laparoscopic dissector and the grasping forceps of a transvaginal endoscope. Lymphatics and omentum (mean 13.3 cm, range 8–20 cm) were removed transvaginally. The mean number of detected and resected sentinel nodes was 2.6 (range 1–4, diameter 2～12 mm). Sentinel lymphatic basin dissection was performed successfully and without intraoperative complications in all three cases. Hybrid NOTES is technically feasible, and this procedure may represent an alternative to laparoscopic sentinel lymph node dissection of the stomach.     

Imaging of the lymphatic system: new horizons

The lymphatic system is a complex network of lymph vessels, lymphatic organs and lymph nodes. Traditionally, imaging of the lymphatic system has been based on conventional imaging methods like computed tomography (CT) and magnetic resonance imaging (MRI), whereby enlargement of lymph nodes is considered the primary diagnostic criterion for disease. This is particularly true in oncology, where nodal enlargement can be indicative of nodal metastases or lymphoma. CT and MRI on their own are, however, anatomical imaging methods. Newer imaging methods such as positron emission tomography (PET), dynamic contrast‐enhanced MRI (DCE‐MRI) and color Doppler ultrasound (CDUS) provide a functional assessment of node status. None of these techniques is capable of detecting flow within the lymphatics and, thus, several intra‐lymphatic imaging methods have been developed. Direct lymphangiography is an all‐but‐extinct method of visualizing the lymphatic drainage from an extremity using oil‐based iodine contrast agents. More recently, interstitially injected intra‐lymphatic imaging, such as lymphoscintigraphy, has been used for lymphedema assessment and sentinel node detection. Nevertheless, radionuclide‐based imaging has the disadvantage of poor resolution. This has lead to the development of novel systemic and interstitial imaging techniques which are minimally invasive and have the potential to provide both structural and functional information; this is a particular advantage for cancer imaging, where anatomical depiction alone often provides insufficient information. At present the respective role each modality plays remains to be determined. Indeed, multi‐modal imaging may be more appropriate for certain lymphatic disorders. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve diagnostic accuracy. Published in 2006 by John Wiley & Sons, Ltd.     

The predicted probability of having positive non-sentinel lymph nodes in patients who received neoadjuvant chemotherapy for large operable breast cancer

The accuracy of the nomogram in women with positive sentinel nodes following neoadjuvant chemotherapy (NCT) is unknown. The aim of this study was to evaluate the accuracy of the nomogram in patients receiving NCT. Between December 1999 and December 2005, we identified 233 patients who had a positive sentinel lymph node biopsy (SLNB) and complete axillary lymph node dissection at Magee-Womens Hospital of University of Pittsburgh Medical Center. Thirty-two patients (14%) had presented with clinically N0 breast cancer (BC) for which NCT was administered. The computerised BC nomogram was used to calculate the probability of non-sentinel node metastases utilising tumour size before NCT and after NCT for the same patient. The discrimination of the nomogram was assessed by calculating the area under (AUC) the receiver operating characteristic curve (ROC). The median patient age was 51.5 (range: 39-66) years in the NCT group of patients. Twelve patients (37%) had positive axillary non-sentinel lymph nodes (NSLNs). The nomogram was first validated in our institution for 201 patients without NCT and the predicted accuracy of the nomogram by the AUC was 0.73. The area under the ROC was identical regardless of whether pre- or posttreatment tumour size was used to determine predicted probability of NSLN metastases (0.66). The predictive accuracy of the nomogram was found to have less power for patients receiving NCT (0.66) than the non-NCT group of patients.