Sentinel node biopsy for oral and laryngopharyngeal squamous cell carcinoma: a retrospective study of 177 patients in Japan

Objective

Sentinel node (SN) biopsy in the head and neck region has not been widely used in Japan, except at a few facilities. However, almost all these facilities perform preoperative localization and intraoperative diagnosis by frozen section analysis of SN to select patients who must undergo neck dissection in a one-stage procedure. The objective of this study was to determine the actual status of SN biopsy at those facilities in Japan that have actively conducted this procedure, and to elucidate the usefulness and drawbacks of this technique in head and neck cancer.

Methods

We retrospectively reviewed 177 patients who had undergone SN biopsy at 7 facilities. The underlying pathology was laryngeal or hypopharyngeal cancer in 20 patients from one hospital, while the remaining 157 patients had oral cancer. Preoperative localization of SN was determined using conventional lymphoscintigraphy with or without single photon emission computed tomography with CT (SPECT-CT). Intraoperative localization and diagnosis of SN were performed by gamma probe and frozen section analysis.

Results

Conventional lymphoscintigraphy detected a mean of 2.6 SNs per patient in 137 patients with oral cancer, compared to 2.7 in 71 patients using SPECT-CT and 2.9 in 154 patients using the gamma probe. No significant differences were apparent between techniques. Forty of the 520 SNs (7.7%; 33 in oral cancer and 7 in laryngeal or hypopharyngeal cancer) were pathologically positive in the final diagnosis. Of these, 3 were not processed for frozen sectioning and were diagnosed only with hematoxylin and eosin staining. Among the others, 32 (86.5%) were diagnosed intraoperatively as showing metastasis. In terms of the false-negative rate, 144 patients were determined by SN biopsy to have no positive SNs. Of these, 2 patients had non-SN metastases found in their dissected neck and 8 patients without neck dissection showed late nodal recurrence. The false-negative rate was thus 6.9%.

Conclusion

Frozen section analysis, particularly multislice sectioning, offers a relatively reliable intraoperative diagnostic method. We were able to perform immediate neck dissection based on the results of multislice sectioning as a single-stage procedure.     

Impact of sentinel lymph node biopsy in patients with Merkel cell carcinoma: results of a prospective study and review of the literature

Purpose Merkel cell carcinoma (MCC) is the most aggressive of the cutaneous malignancies, showing a propensity to spread to regional lymph nodes (LNs). The aim of this prospective study was to examine the feasibility and clinical impact of sentinel lymph node biopsy (SLNB) in this cutaneous malignancy. Methods The study population comprised 23 patients with stage I MCC (median age 70 years, range 50–85 years). Lymphoscintigraphic mapping with ^{99 m}Tc-nanocolloid was performed in all patients. Sentinel lymph nodes (SLNs) were identified, excised and analysed in serial sections by conventional histopathology and cytokeratin-20 immunohistochemistry. Results Metastatic disease was determined in the SLNs of 11 patients (47.8%). Elective lymph node dissection (ELND) was performed in eight of these 11 patients, four of whom had additional positive LNs. During follow-up (median 36.1 months, range 3–79 months), seven of the 23 patients (30%) relapsed: four had a local recurrence and three, in-transit metastases. Recurrence developed in two SLN-negative patients with local LN metastases and in one SLN-positive patient with distant metastases. This patient died, representing the only tumour-related death in our sample. Median survival was 49.1 and 35.5 months for SLN-negative and SLN-positive patients, respectively. This difference was not statistically significant (p=0.3452). Conclusion SLNB allows for exact nodal staging in patients with MCC. Whether additional ELND is of further benefit remains unclear.     

淋巴显像技术在口腔鳞癌哨位淋巴结活检中的应用

目的:评价淋巴显像技术在口腔鳞癌哨位淋巴结活检中的价值。方法:应用颈淋巴显像技术结合蓝染法及SPECT/CT同机融合技术,对21例临床NO(cNO)口腔鳞癌患者的哨位淋巴结(sentinel lymph node,SLN)进行研究。结果:全组患者SLN检出率为100％,21例中有7例SLN活检阳性,颈清术后标本同样证实有颈淋巴结转移,无假阴性结果,SLN活检对全组病例颈淋巴结转移状况预测的准确性为100％。结论:颈淋巴显像技术结合蓝染法及SPECT/CT同机融合技术能有效地对口腔鳞癌SLN进行定位,从而准确预测颈淋巴结转移状况。     

探测前哨淋巴结在乳腺癌、早期宫颈癌和头颈鳞癌中的应用

目的评价核素淋巴显像和γ探针定位在乳腺癌、宫颈癌和头颈鳞癌中确定前哨淋巴结(SLN)的应用价值。方法女性乳腺癌116例,体检腋窝未扪及肿块。应用99Tcm-DX37~74MBq(1~2mCi)经皮下注射,或术中注射专利兰1ml,术中用γ探针定位并行前哨淋巴结活检,与手术、病理对照。宫颈癌27例,体检盆腔未扪及肿块。应用99Tcm-DX74MBq(2mCi)在宫颈肿瘤周围2°或10°处或99Tcm-SC74MBq(2mCi)阴道镜直视下四点注射,行核素淋巴显像后,手术后的标本用γ探针行体外定位,并与病理的结果加以对照。N0头颈鳞癌10例,99Tcm-DX74MBq(2mCi)肿瘤周围成分下注射,术中用γ探针定位并行前哨淋巴结活检,与手术、病理对照。结果116例乳腺癌中活检SLN108例,灵敏度为92.6%(22/27例),特异性100%(81/81例)。27例宫颈癌中SLN的灵敏度为100%(6/6例),特异性100%(21/21例)。10例N0头颈鳞癌中SLN转移3例,NSLN转移1例。结论核素淋巴显像和γ探针定位应用于乳腺癌、宫颈癌和N0头颈鳞癌是切实可行和可能的,这是一种简便、安全、易被病人接受的探测前哨淋巴结的检查方法,对预测腋窝淋巴结、盆腔淋巴结等转移有很大的临床实用价值。     

Sentinel Lymph Node Biopsy for Melanoma: How Many Radioactive Nodes Should be Removed?

Background: Sentinel lymph node (SLN) biopsy has become a standard method of staging patients with cutaneous melanoma. Sentinel lymph node biopsy usually is performed by intradermal injection of a vital blue dye (isosulfan blue) plus radioactive colloid (technetium sulfur colloid) around the site of the tumor. Intraoperative gamma probe detection has been shown to improve the rate of SLN identification compared to the use of blue dye alone. However, multiple sentinel nodes often are detected using the gamma probe. It is not clear whether these additional lymph nodes represent true sentinel nodes, or second-echelon lymph nodes that have received radiocolloid particles that have passed through the true sentinel node. This analysis was performed to determine the frequency with which these less radioactive lymph nodes contain metastatic disease when the most radioactive, or hottest, node does not.Materials and Methods: In the Sunbelt Melanoma Trial, 1184 patients with cutaneous melanoma of Breslow thickness 1.0 mm or more had sentinel lymph nodes identified. Sentinel lymph node biopsy was performed by injection of technetium sulfur colloid plus isosulfan blue dye in 99% of cases. Intraoperative determination of the degree of radioactivity of sentinel nodes (ex vivo) was measured, as well as the degree of blue dye staining.Results:Sentinel nodes were identified in 1373 nodal basins in 1184 patients. A total of 288 of 1184 patients (24.3%) were found to have sentinel node metastases detected by histology or immunohistochemistry. Nodal metastases were detected in 306 nodal basins in these 288 patients. There were 175 nodal basins from 170 patients in which at least one positive sentinel node was found and more than one sentinel node was harvested. Blue dye staining was found in 86.3% of the histologically positive sentinel nodes and 66.4% of the negative sentinel nodes. In 40 of 306 positive nodal basins (13.1%), the most radioactive sentinel node was negative for tumor when another, less radioactive, sentinel node was positive for tumor. In 20 of 40 cases inding a positive sentinel node other than the hottest node.Conclusions: If only the most radioactive sentinel node in each basin had been removed, 13.1% of the nodal basins with positive sentinel nodes would have been missed. It is recommended that all blue lymph nodes and all nodes that measure 10% or higher of the ex vivo radioactive count of the hottest sentinel node should be harvested for optimal detection of nodal metastases.Preliminary findings presented at the annual meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Change in clinical management of sentinel lymph node location in early stage cervical cancer: the role of SPECT/CT

Objective

The aim of this study was to investigate the feasibility of the sentinel lymph node (SLN) identification with SPECT/CT lymphoscintigraphy imaging in the early stage invasive cervical cancer in patients undergoing radical hysterectomy and pelvic lymphadenectomy.

Methods

Between March 2007 and June 2009, a prospective consecutive study was designed for SLN mapping. Twenty-two patients with cervical cancer FIGO stage IB1 (n = 20) or stage IIA1 (n = 2) underwent SLN identification with preoperative SPECT/CT and planar images (technetium-99 m colloid albumin injection around the tumor) and posterior intraoperative detection with both blue dye and a handheld or laparoscopic gamma probe. Complete pelvic lymphadenectomy was performed in all cases by open (n = 2) or laparoscopic (n = 20) surgery.

Results

In the present series, a total of 35 SLN were detected with planar images and 40 SLN were identified and well located by SPECT/CT lymphoscintigraphy (median 2.0 nodes per patient). In 5/22 patients (22.7%) SPECT/CT procedure improves the number of localized SLN. Intraoperatively, 57 SLNs were identified, with a median of 3 SLNs per patient by gamma probe (a total of 53 hot nodes) and a median of 2 nodes per patient after blue dye injection (a total of 42 blue nodes). Microscopic nodal metastases (eight nodes, corresponding to four patients) were confirmed in 18.18% of cases; all these lymph nodes were previously detected as SLN. The remaining 450 nodes, including SLNs, following complete pelvic lymphadenectomy, were histologically negative.

Conclusions

Sentinel lymph node detection is improved by SPECT/CT imaging because of the increased number of SLN detected and the better tridimensional anatomic location, allowing easier intra-operative detection with gamma probe and showing, in this series, a 100% negative predictive value.     

Value of sentinel node mapping in cancer of the cervix

Objectives

To compare the relative value of two methods of detection for the sentinel lymphatic nodes (SLNs): colorimetric with Isosulfan blue (ISB) and radio-isotopic with Technetium-99 (Tc99), and to evaluate the concept of the SLN mapping applied to cervical cancer.

Methods

From October 2000 to December 2006, radical surgery was planned in 211 patients who presented early-stage cancer of the cervix. Both ISB and Tc99 were used to detect the SLNs. In all cases, we proceeded with laparoscopy for the identification and removal of the SLNs, followed by a complete pelvic lymphadenectomy with or without para-aortic node sampling. The SLNs were sent for frozen section (1 level) and were ultra-staged (6 levels) for final pathology. Detection rate, sensitivity and negative predictive value (NPV) were calculated.

Results

Among the 211 patients, ISB (n = 152) identified at least 1 SLN in 92.8% of the cases. With Tc99 (n = 166), the detection rate of SLN increased to 96.9%. When both techniques were used together (n = 107), Tc99 was significantly better than ISB by 7.8% (p = 0.0094) and at least 1 SLN (hot and/or blue) was found in 99.1% of the cases. In 16.7% of patients, a SLN was located in aberrant sites, including 3.8% in the para-aortic area. Thirty-three out of the 211 patients (15.6%) had lymph node metastases. When considering only the 181 patients with bilateral SLNs identified, the NPV of SLN is 100% after ultra staging on final pathology and 94.2% on frozen section (FS).

Conclusion

Sentinel node mapping is feasible using laparoscopy. The radio-isotopic technique adds significantly to the rate of detection. The main benefits of SLN mapping in cervical cancer are the detection of micro-metastases on ultra staging which might be missed on routine pathological evaluation, and identification of aberrant drainage sites. However, the current frozen section techniques lack sensitivity to identify very small metastases and need refinement. SLN mapping should become the standard of care in the modern management of cervical cancer and complete pelvic lymphadenectomy could be avoided when bilateral SLNs are detected in patients with lesions less than 2 cm.     

Sentinel lymph node biopsy in penile carcinoma

Sentinel lymph node (SLN) biopsy is a fairly new technique that is becoming the standard of care for regional lymph node staging of many solid tumors. This technique is based on the hypothesis of stepwise distribution of malignant cells in the lymphatic system. The absence of tumor cells in the first lymph node(s) in the lymphatic drainage of a tumor would indicate the absence of further spread in the regional lymph node basin(s). Therefore, this first lymph node is the guardian (sentinel) of the regional lymph node basin. To localize the sentinel node preoperatively, lymphoscintigraphy is usually performed after intradermal peritumoral injections of colloid particles labeled with technetium-99m. The tracer is transported through the lymphatic channels to the first draining nodes in the groins and is visible on the lymphoscintigram as hot spots. The main advantage of SLN biopsy in penile cancer is to decrease the treatment-related morbidity without compromising the survival benefit for the patient. Recent figures indicate a false-negative rate of 7%, with a complication rate of less than 5% for SLN biopsy. In conclusion, sentinel node biopsy of patients with penile cancer has evolved into a highly reliable procedure enabling the detection of lymph node invasion at the earliest possible time with minimal morbidity. With this technology at hand, which minimizes the treatment-related morbidity, there is hardly any place for standard lymphadenectomy in penile cancer patients.     

Size Control of 99mTc-tin Colloid Using PVP and Buffer Solution for Sentinel Lymph Node Detection

Colloidal particle size is an important characteristic that allows mapping sentinel nodes in lymphoscintigraphy. This investigation aimed to introduce different ways of making a ^99mTc-tin colloid with a size of tens of nanometers. All agents, tin fluoride, sodium fluoride, poloxamer-188, and polyvinylpyrrolidone (PVP), were mixed and labeled with ^99mTc. Either phosphate or sodium bicarbonate buffers were used to adjust the pH levels. When the buffers were added, the size of the colloids increased. However, as the PVP continued to increase, the size of the colloids was controlled to within tens of nanometers. In all samples, phosphate buffer added PVP (30 mg) stabilized tin colloid (^99mTc-PPTC-30) and sodium bicarbonate solution added PVP (50 mg) stabilized tin colloid (^99mTc-BPTC-50) were chosen for in vitro and in vivo studies. ^99mTc-BPTC-50 (<20 nm) was primarily located in bone marrow and was then secreted through the kidneys, and ^99mTc-PPTC-30 (>100 nm) mainly accumulated in the liver. When a rabbit was given a toe injection, the node uptake of ^99mTc-PPTC-30 decreased over time, while ^99mTc-BPTC-50 increased. Therefore, ^99mTc-BPTC-50 could be a good candidate radiopharmaceutical for sentinel node detection. The significance of this study is that nano-sized tin colloid can be made very easily and quickly by PVP.

Graphical Abstract

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