Sentinel node detection by lymphoscintigraphy and sentinel lymph node biopsy in vulvar melanoma

Purpose

Vulvar melanoma is a rare malignant tumour. Its surgical excision is the mainstay of treatment whilst the surgical management of regional lymph nodes remains controversial; on the contrary elective inguinofemoral lymphadenectomy causes considerable morbidity. Lymphoscintigraphy (LS) and sentinel lymph node biopsy (SLNB) are accurate staging procedures of lymph node status in breast cancer and cutaneous melanoma patients. In this retrospective paper we report our experience of LS and SLNB in vulvar melanoma patients.

Methods

Twenty-two consecutive patients with a diagnosis of vulvar melanoma were treated at our institute: patients with clinically positive groin nodes or with previous surgery on the primary tumour were excluded. Twelve were selected for our analysis. All patients underwent sentinel lymph node localization with LS the day before surgery and the surgical procedure of SLNB associated with radical surgery.

Results

Six patients had metastatic SLNB and in five of six (83.3%) it was the only positive node. In the other six patients SLNB was negative for metastatic disease. No skip metastases were observed. In SLNB negative patients the mean Breslow thickness was 2.06 mm (range: 0.60–7.10) and only one patient showed a high Breslow thickness (patient 8). In SLNB positive patients the mean Breslow thickness was 4.33 mm (1.8–6.0).

Conclusion

Our data indicate that, even in vulvar melanoma, the sentinel lymph node pathological status predicts the pathological status of the remaining groin nodes and suggests that elective groin dissection can be spared in cases of a negative SLNB. Breslow thickness (<1 mm) was not predictive of negative nodes.     

Fusion lymphoscintigraphy with a 24-hour Tc-99m MDP bone scan for sentinel lymph node detection and imaging

A 62-year-old woman with right breast carcinoma who had a breast biopsy 3 weeks earlier was referred for a whole-body Tc-99m MDP bone scan to identify possible osseous metastases. Twenty-four hours later, she underwent lymphoscintigraphy using four peritumoral injections of 250 microCi filtered Tc-99m sulfur colloid of 0.22 microm each. The lymphoscintigraphic images showed good delineation of three right axillary lymph nodes in relation to the rib cage. Performing a bone scan just before lymphoscintigraphy for sentinel node detection may help the surgeon to identify sentinel lymph nodes. This is more anatomically precise than using a flood source to delineate body contour. A Tc-99m MDP bone scan followed by lymphoscintigraphy should be considered in patients with breast carcinoma who will have both bone imaging and lymphoscintigraphy.     

Identification of sentinel lymph node in stage I-II breast cancer with lymphoscintigraphy and surgical gamma probe: comparison of Tc-99m MIBI and Tc-99m sulfur colloid

AIM: To evaluate the efficacy of the surgical gamma probe (SGP) after peritumoral injection of Tc-99m MIBI and filtered Tc-99m sulfur colloid (SC) in sentinel lymph node (SLN) detection in stage I and II breast cancer for deciding on the need for axillary dissection. MATERIALS AND METHODS: Thirty patients with stage I-II breast cancer had peritumoral injection of Tc-99m MIBI (74 MBq/0.2 mL [2 mCi/0.2 mL] at 4 different locations) and 42 different patients had peritumoral injection of filtered Tc-99m sulfur colloid (50 MBq/0.2 mL [1.3 mCi/0.2 mL] at 4 different locations). Anterior, lateral, and anterolateral spot images were acquired at 10, 30, 45, 60, and 120 minutes and 24 hours are injection in 5 patients. During surgery, counts were obtained from the injection site, affected breast tissue, internal mammary, axillary, and supraclavicular regions and the contralateral side using the gamma probe. Peritumoral blue dye was also injected during surgery. The first lymph nodes with counts at least twice the background tissue and/or with blue dye uptake were surgically isolated. Modified radical mastectomy and axillary dissection were performed. RESULTS: Histopathologic evaluation was made on SLN and other excised tissues. In the Tc-99m sulfur colloid group, lymphatic drainage and lymph nodes were demonstrated with lymphoscintigraphy in 31 of 42 patients. SLN was detected by SGP in 35 of 42 patients. In the Tc-99m MIBI group, lymphatic drainage and lymph nodes were visualized with lymphoscintigraphy in 23 of 30 patients. SLN was detected in 25 of 30 patients with SGP in this group. CONCLUSION: In patients with stage I-II breast cancer, SLN could be successfully demonstrated with lymphoscintigraphy and SGP by the peritumoral injection of filtered Tc-99m sulfur colloid and Tc-99m MIBI.     

Phytate technetium-99m versus dextran 500 technetium-99m in the sentinel lymph node biopsy

PURPOSE: To study which of the two most used radiopharmaceutical drugs for the sentinel lymph node (SLN) biopsy procedure (dextran 500 99mTc and phytate 99mTc) best defines the SLN and migrates less to other lymph nodes. MATERIAL AND METHODS: Thirty-two rats, separated into two groups, underwent lymphoscintigraphy examination with either dextran or phytate followed by sentinel (popliteal), lumbar, and inguinal lymph node biopsy. Radiation was detected with a gamma probe. RESULTS: The statistical study indicated count rates significantly higher in the SLN than in the other basins for both the dextran (P<0.01) and phytate groups (P<0.001). There was no statistically significant difference concerning SLN absorption in either group (P=0.2981). In the dextran group, migration occurred to 1.5 lymphatic basins with counting higher than 10% of that found in the SLN versus 0.8 in the phytate group (P=0.0023). Migration was thus higher in the dextran group (P=0.0207). CONCLUSION: There was no statistically significant difference between dextran and phytate in the SLN identification, but the phytate migrated to fewer lymphatic basins beyond the SLN and with less intensity.     

Use of lymphoscintigraphy with SPECT/CT for sentinel node localization in a case of vaginal melanoma

A 45-year-old woman with vaginal melanoma underwent Tc-99m sulfur colloid (filtered) lymphoscintigraphy with the acquisition of planar and SPECT/CT images for localization of a sentinel node before surgery. The study identified both inguinal and perirectal sentinel nodes, which proved beneficial in mapping potential anatomic spread of disease for staging and therapy planning. These results provide evidence for the use of routine SPECT/CT imaging for pelvic lymphoscintigraphic studies or as an adjunct tool for localizing sentinel nodes in cases that would not be demonstrated with planar imaging alone.     

A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran.

We report the synthesis and preliminary biologic testing of a synthetic macromolecule, (99m)Tc-diethylenetriaminepentaacetic acid (DTPA)--mannosyl-dextran, for sentinel node detection. METHODS: Synthesis started with a 2-step process that attaches a high density of amino-terminated leashes to a dextran backbone. Allyl-bromide was reacted with pharmaceutical-grade dextran to yield allyl-dextran. After diafiltration with water, filtration, and lyophilization, the product was reacted with aminoethanethiol and ammonium persulfate. The resulting amino-conjugated dextran was dialyzed, filtered, and lyophilized. The mixed anhydride method was used to attach DTPA; after dialysis, filtration, and lyophilization, 2-imino-2-methoxyethyl-1-D-mannose was used to attach the receptor substrate. The molecular diameter was measured by dynamic light scattering. Amino, mannose, and DTPA densities were measured by trinitrobenzene sulfonate assay, sulfuric acid/phenol assay, and inductively coupled plasma spectroscopy of gadolinium-DTPA-mannosyl-dextran, respectively. Receptor affinity was measured by Scatchard assay of rabbit liver. Axillary, popliteal, and iliac lymph nodes and each injection site were assayed for radioactivity at 1 and 3 h after injection of approximately 3.7 MBq (0.050 mL) (99m)Tc-DTPA-mannosyl-dextran (0.22 nmol) or filtered (99m)Tc-sulfur colloid into the foot pads. Four animals were studied at each time point. RESULTS: DTPA-mannosyl-dextran had a molecular weight of 35,800 g/mol and a molecular diameter of 7.1 nm. The final amine, mannose, and DTPA densities were 23, 55, and 8 mol per dextran. Labeling yields were in excess of 98% and stable for 6 h. Specific activities of 74 x 10(6) GBq/mol were achieved. The equilibrium dissociation constant for binding to the mannose-terminated glycoprotein receptor was 0.12 +/- 0.07 nmol/L. The popliteal extraction at both 1 h and 3 h was significantly (P < 0.05) higher for (99m)Tc-DTPA-mannosyl-dextran (90.1% +/- 10.7% and 97.7% +/- 2.0%, respectively) than for filtered (99m)Tc-sulfur colloid (78.8 +/- 6.5 and 67.4% +/- 26.8%, respectively). (99m)Tc-DTPA-mannosyl-dextran exhibited significantly faster injection site clearance than did filtered (99m)Tc-sulfur colloid. The (99m)Tc-DTPA-mannosyl-dextran percentage injected dose (%ID) for the front and rear paws was 52.6 +/- 10.5 and 52.3 +/- 8.0 at 1 h and 45.7 +/- 8.5 and 43.6 +/- 8.2 at 3 h after administration. The filtered (99m)Tc-sulfur colloid %ID for the front and rear paws was 70.4 +/- 11.0 and 66.3 +/- 15.1 at 1 h and 55.5 +/- 7.8 and 66.9 +/- 8.5 at 3 h. Lymph node accumulation of each agent at either 1 or 3 h was not significantly different. CONCLUSION: (99m)Tc-DTPA-mannosyl-dextran is a receptor-based sentinel node radiotracer that exhibits the desired properties of rapid injection site clearance and low distal node accumulation. This molecule is the first member of a new class of diagnostic agents based on a macromolecular backbone with a high density of sites for the attachment of substrates and imaging reporters.     

467例乳腺癌患者^99Tc^m-利妥昔单抗前哨淋巴结显像结果分析

目的探讨应用前哨淋巴结（SLN）显像剂^99Tc^m-利妥昔单克隆抗体（简称利妥昔单抗,美罗华）进行乳腺癌SLN活组织检查（SLNB）的可行性与可靠性,以及不同因素对SLN显像及SLNB的影响。方法467例乳腺癌患者在超声引导下于乳腺肿块周围及肿块表面皮下注射^99Tc^m-利妥昔单抗后行SLN显像。术中凭显像结果行腋窝区SLNB,将切取的SLN行常规HE染色及免疫组织化学检查。结果SLN显像成功率99．14％（463／467）,共显示SLN837枚,人均1．79枚（837／467）,分布于腋窝区、内乳区、乳腺组织内及锁骨下区。腋窝区SLNB成功率99．57％（465／467）,手术共探测到SLN1182枚,人均2．53枚。病理检查发现腋窝SLN有转移者131例,转移SLN194枚。其中1例单纯由免疫组织化学法发现微小转移灶。患者年龄、显像时间、病理类型、临床分期、显像前是否行乳腺肿块手术切取活组织检查对SLN显影率、SLNB成功率及SLN转移率均无影响。不同病理类型及临床分期的患者其SLN转移率的差异有统计学意义（χ^2=14．134,29．184,P均〈0．05）。结论应用^99Tc^m-利妥昔单抗行乳腺癌SLN显像及SLNB成功率较高,具有较好的临床应用前景。     

Use of (99m)Tc-labeled liposomes encapsulating blue dye for identification of the sentinel lymph node.

Colloidal radiopharmaceuticals are commonly used in combination with blue dye for localization of the sentinel node. Liposomes are colloidal particles composed of spontaneously forming lipid spheres that can carry a wide variety of diagnostic and therapeutic agents. Conventional liposomes are poorly retained in lymph nodes (<2% of the subcutaneously injected dose). We have previously described a system for increasing the retention of liposomes in the lymph nodes by approximately 7-fold. This system is comprised of subcutaneously injected biotin-coated liposomes, followed by an adjacent injection of avidin. When the avidin moves into the lymphatic vessels, it causes aggregation of the biotin-coated liposomes that are also in the process of migrating through the lymphatic vessels. These aggregated liposomes become entrapped in the next encountered lymph node. In this study, we use this novel lymph node delivery system with liposomes that encapsulate blue dye, resulting in intense blue staining of the sentinel node. These liposomes can also be labeled with (99m)Tc, permitting scintigraphic imaging and radioguided probe localization of the sentinel node. METHODS: Liposomes coated with biotin and coencapsulating blue dye and glutathione were labeled with (99m)Tc using hexamethylpropyleneamine oxime. Rabbits were subcutaneously administered 0.3 mL (99m)Tc-biotin-liposomes containing blue dye in both hind feet, followed by a subcutaneous injection (0.3 mL) of 5 mg avidin in only one hind foot (experimental). The other hind foot served as a control. RESULTS: Labeling efficiencies (mean +/- SEM) for liposomes encapsulating blue dye were 92.1% +/- 1.9%. Necropsy at 24 h revealed that the popliteal node on the experimental leg receiving the avidin was intensely blue stained compared with virtually no blue coloration of the control node. Tissue counts of these nodes were 12.2 +/- 1.5 percentage injected dose (%ID) in the experimental node compared with 1.2 +/- 0.1 %ID in the control nodes (P<0.0001). CONCLUSION: Biotin-liposomes encapsulating blue dye can be successfully labeled with (99m)Tc, providing a convenient option for the visualization and radiolocalization of the sentinel node. This biotin-liposome/avidin system may also have potential for the delivery of therapeutic drugs and radiopharmaceuticals to lymph nodes.     

Cost-effectiveness of preoperative SPECT/CT combined with lymphoscintigraphy vs. lymphoscintigraphy for sentinel lymph node excision in patients with cutaneous malignant melanoma

Purpose

Malignant melanoma has become a major growing interdisciplinary problem in public health worldwide. Sentinel lymph node excision (SLNE) in conjunction with preoperative SPECT/CT is considered the most sensitive and specific staging test for the detection of micrometastatic melanoma in regional lymph nodes. Among patients with clinically lymph node-negative melanoma, the use of SPECT/CT-aided SLNE compared with SLNE alone has been found to be associated with a higher frequency of metastatic involvement and a higher rate of disease-free survival. The aim of this study was to analyse the cost-effectiveness of SLNE with preoperative SPECT/CT for detecting sentinel lymph nodes versus that of standard SLNE with preoperative lymphoscintigraphy from a single-institution database.

Methods

Cost-effectiveness analysis of two surgical approaches for SLNE for malignant melanoma at the University Hospital Essen, Skin Cancer Center in Essen, Germany. Between March 2003 and April 2011 464 patients eligible for SLNE were identified . Of these patients, 403 with clinically negative lymph nodes who underwent SLNE with or without preoperative SPECT/CT qualified for subsequent analysis.

Results

Between March 2003 and October 2008, 254 patients were operated upon with the standard technique. From November 2008, 149 patients underwent the SPECT/CT technique. Cost analysis showed a mean cost saving of € 710.50 when SPECT/CT was added to preoperative imaging. This was achieved by a reduction in operative time (median, Q1;Q3, 40 min, 40;50 min, vs. 45 min, 35;60 min; p?=?0.002), hospital stay duration (5 days, 3;8 days, vs. 8 days, 4.5;14.5 days; p?<?0.001) and more frequent use of local anaesthesia (90.6 % vs. 70.5 %; p?<?0.001). The median cost of SLNE using SPECT/CT was € 1,619.7 (Q1;Q3 € 1,317.0;2,603.4) and of SLNE without SPECT/CT was € 2,330.2 (€ 1,468.3;4,058.1; p?<?0.001), a cost saving of 30.5 %.

Conclusion

In patients with cutaneous melanoma, the use of preoperative SPECT/CT-aided SLNE compared with standard SLNE was associated not only with higher detection of metastatic involvement but also with a significant cost reduction.     

(99m)Tc]MAG(3)-mannosyl-dextran: a receptor-binding radiopharmaceutical for sentinel node detection

Technetium-99m-labeled benzoyl-mercaptoacetylglycylglycyl-glycine-mannosyl-dextran ([(99m)Tc]MAG(3)-mannosyl-dextran) is a receptor-binding radiotracer that binds to mannose-binding protein, a receptor expressed by recticuloendothelial tissue. This agent is composed of a 10.5-kilodalton molecule of dextran and multiple units of mannose, and benzoyl-mercaptoacetylglycylglycyl-glycine (BzMAG(3)). The tetraflorophenol-activated ester of BzMAG(3) and the imidate of thiomannose were used to covalently attach BzMAG(3) and mannose to an amino-terminated conjugate of dextran. This yielded a 19-kilodalton macromolecule consisting of 3 BzMAG(3) and 21 mannose units per dextran. Dynamic light scattering was used to measure a mean diameter of 5.5 nanometers for BzMAG(3)-mannosyl-dextran and 0.28 microns for filtered Tc-99m sulfur colloid. A preliminary sentinel node detection study employing right fore and hind footpad injections of [(99m)Tc]MAG(3)-mannosyl-dextran and left fore and hind footpad injections of filtered Tc-99m sulfur colloid demonstrated greater sentinel lymph node uptake by the receptor-binding agent.     

Dose-dependent biodistribution of [(99m)Tc]DTPA-mannosyl-dextran for breast cancer sentinel lymph node mapping

[^99mTc]DTPA-mannosyl-dextran is a receptor-binding radiopharmaceutical specifically designed for sentinel lymph node mapping. The purpose of this study was to test the biodistribution and safety of [^99mTc]DTPA-mannosyl-Dextran at different molar doses. Twenty-four female breast cancer patients participated in this study. Four groups of 6 patients received an injection of 0.2, 1.0, or 5.0 nmol of [^99mTc]DTPA-mannosyl-Dextran or filtered [^99mTc]sulfur colloid. The injection site clearance was monitored by dynamic imaging for three hours. Whole body scans were acquired at 2.5 and 12, and lymph nodes were assayed for radioactivity after gamma-guided sentinel lymph node biopsy. Injection site clearance of [^99mTc]DTPA-mannosyl-Dextran was not statistically different in a dose-dependent manner. Dose-dependent sentinel node uptake was observed (p = 0.03). There were no clinically significant alterations in laboratory parameters among all dose levels at 4 h or 24 h post injection compared to preoperative levels. Radiation absorbed doses did not differ among the three dose levels, but were lower than filtered [^99mTc]sulfur colloid.     

Optimization of lymphoscintigraphy in sentinel node biopsy in the staging of malignant melanoma

PURPOSE: To optimize the lymphoscintigraphic procedure in the staging of malignant cutaneous melanoma. MATERIAL AND METHODS: Fifty-five patients (21 men and 34 women) were enrolled. Breslow thickness of the lesions ranged 0.75-1 mm (Clark III-IV) to 1-4 mm. Lymphoscintigraphy was performed with a large-view gamma camera equipped with a low-energy general purpose collimator, two weeks after melanoma excision. A single perilesional dose of 30-50 MBq nanocoll-Tc99m (volume 0.2-0.3 mL) was injected 18 hours before surgery (6 hours in head localizations). After injection a gentle local massage was applied. A planar static scintigraphy (matrix 512 x 512, pre-set time 5 min) in anterior and/or oblique view(s) was obtained 5-10 min after radiotracer injection. The skin projection of the first node was stained with an external radioactive marker. Fifteen minutes before surgery a blue-vital dye was injected around the lesion. A radioguided biopsy of the sentinel node was performed. RESULTS: The site of the sentinel node was typical in 80% of patients. Two or three nodes were identified in 20% of patients. An unexpected node site was detected in 9% of patients. The total rate of micrometastasis to the sentinel node was 14.7% but significant differences were observed relative to the melanoma thickness. CONCLUSIONS: Preoperative scintigraphy increases the accuracy of sentinel node identification in unusual lymphatic drainage pathways, in unexpected sites and in fast lymphatic drainage. Radioguided biopsy reduces surgical time, requires only local anesthesia and permits shorter hospitalization.     

Successful internal mammary visualization with periareolar injections of Tc-99m antimony sulfur colloid in sentinel node breast lymphoscintigraphy

PURPOSE: The subareolar and periareolar injection techniques result in higher detection rates and do not require tumor localization in impalpable lesions when compared with the peritumoral technique. One of the main criticisms, however, is the widely reported inability to detect internal mammary nodes. This contrasts with our clinical experience using Tc-99m antimony sulfur colloid, in which internal mammary nodes are commonly seen. METHODS: A retrospective analysis of 241 patients over 38 months was performed to investigate the ability of our periareolar injection technique to detect internal mammary lymph node drainage in breast cancer sentinel node lymphoscintigraphy. Four injections of 5 to 10 MBq (0.14-0.27 mCi) Tc-99m antimony sulfur colloid were administered on the day of surgery followed by massage and imaging. The radioisotope was suspended in 0.1 mL with a 0.5-mL air lock. Each injection was performed over 2 seconds with a 25-gauge needle at a depth of 1.1 to 1.3 cm. Patients whose records could not be retrieved or who underwent an injection technique apart from periareolar or peritumoral were removed from the analysis. RESULTS: One hundred thirty-three patients underwent the periareolar technique, 72 patients underwent the peritumoral technique, and 36 patients were excluded from the analysis. Internal mammary drainage was seen in 24 of 133 (18.0%) patients, of which 12 (9%) were seen only in the internal mammary chain. This is much higher than previous studies quoting 0.0% to 4.3% and is similar to previously reported rates using the peritumoral technique. CONCLUSIONS: Our periareolar injection technique using Tc-99m antimony sulfur colloid is able to detect internal mammary lymph nodes in at least 18.0% of patients.