Role of ICG-<Superscript>99m</Superscript>Tc-nanocolloid for sentinel lymph node detection in cervical cancer: a pilot study

Purpose

Sentinel lymph node biopsy (SLNB) can be used for nodal staging in early cervical cancer. For this purpose, the tracers most commonly used are radiotracers based on technetium. For the last decade, indocyanine green (ICG) has been used as a tracer for SLNB in other malignancies with excellent results and, more recently, a combination of ICG and a radiotracer has been shown to have the advantages of both tracers. The aim of this study was to evaluate the role of ICG-^99mTc-nanocolloid in SLN detection in patients with cervical cancer.

Methods

This prospective study included 16 patients with cervical cancer. The hybrid tracer was injected the day (19–21 h) before surgery for planar and SPECT/CT lymphoscintigraphy. Blue dye was administered periorificially in 14 patients. SLNs were removed according to their distribution on lymphoscintigraphy and when radioactive, fluorescent and/or stained with blue dye. Nodal specimens were pathologically analysed for metastases including by immunochemistry.

Results

Lymphoscintigraphy and SPECT/CT showed drainage in all patients. A total of 69 SLNs were removed, of which 66 were detected by their radioactivity signal and 67 by their fluorescence signal. Blue dye identified only 35 SLNs in 12 of the 14 patients (85.7%). All patients showed bilateral pelvic drainage. Micrometastases were diagnosed in two patients, and were the only lymphatic nodes involved.

Conclusions

SLNB with ICG-^99mTc-nanocolloid is feasible and safe in patients with early cervical cancer. This hybrid tracer provided bilateral SLN detection in all patients and a higher detection rate than blue dye, so it could become an alternative to the combined technique.

     

The best of both worlds: a hybrid approach for optimal pre- and intraoperative identification of sentinel lymph nodes

Purpose

Hybrid image-guided surgery technologies such as combined radio- and fluorescence-guidance are increasingly gaining interest, but their added value still needs to be proven. In order to evaluate if and how fluorescence-guidance can help realize improvements beyond the current state-of-the-art in sentinel node (SN) biopsy procedures, use of the hybrid tracer indocyanine green (ICG)-^99mTc-nancolloid was evaluated in a large cohort of patients.

Patients and methods

A prospective trial was conducted (n?=?501 procedures) in a heterogeneous cohort of 495 patients with different malignancies (skin malignancies, oral cavity cancer, penile cancer, prostate cancer and vulva cancer). After injection of ICG-^99mTc-nanocolloid, SNs were preoperatively identified based on lymphoscintigraphy and SPECT/CT. Intraoperatively, SNs were pursued via gamma tracing, visual identification (blue dye) and/or near-infrared fluorescence imaging during either open surgical procedures (head and neck, penile, vulvar cancer and melanoma) or robot assisted laparoscopic surgery (prostate cancer). As the patients acted as their own control, use of hybrid guidance could be compared to conventional radioguidance and the use of blue dye (n?=?300). This was based on reported surgical complications, overall survival, LN recurrence free survival, and false negative rates (FNR).

Results

A total of 1,327 SN-related hotspots were identified on 501 preoperative SPECT/CT scans. Intraoperatively, a total number of 1,643 SNs were identified based on the combination of gamma-tracing (>98%) and fluorescence-guidance (>95%). In patients wherein blue dye was used (n?=?300) fluorescence-based SN detection was superior over visual blue dye-based detection (22–78%). No adverse effects related to the use of the hybrid tracer or the fluorescence-guidance procedure were found and outcome values were not negatively influenced.

Conclusion

With ICG-^99mTc-nanocolloid, the SN biopsy procedure has become more accurate and independent of the use of blue dye. With that, the procedure has evolved to be universal for different malignancies and anatomical locations.

     

SPECT/CT sentinel lymph node identification in papillary thyroid cancer: lymphatic staging and surgical management improvement

Purpose

Lymphadenectomy in papillary thyroid carcinoma (PTC) continues to be controversial. A better staging method is needed to provide adequate individual surgical treatment. SPECT/CT lymphoscintigraphy and sentinel lymph node (SLN) biopsy may improve lymphatic staging and surgical treatment. Our main objectives were to describe the lymphatic drainage of PTC using lymphoscintigraphy, to evaluate the lymphatic spread (comparing SLN and lymphadenectomy results) and to analyse the impact of SLN identification in surgery.

Methods

We prospectively studied 24 consecutive patients with PTC (19 women; mean age 52.7 years, range 22–81 years). The day before surgery, lymphoscintigraphy with ultrasound-guided intratumoral injection (^99mTc-nanocolloid, 148 MBq) was performed, obtaining planar and SPECT/CT images. All patients underwent total thyroidectomy, SLN biopsy (hand-held gamma probe) with perioperative analysis, central compartment node dissection, or laterocervical lymphadenectomy if perioperative stage N1b or positive SLNs in this lymphatic basin.

Results

Lymphoscintigraphy revealed at least one SLN in 19 of 24 patients (79 %) on planar and SPECT/CT images, and in 23 of 24 patients (96 %) during surgery using a hand-held gamma probe. Lymph node metastases were detected with classical perioperative techniques (ultrasound guidance and surgical inspection) in 3 of 24 patients, by perioperative SLN analysis in 10 of 23, and by definitive histology in 13 of 24. The false-negative (FN) ratio for SLN was 7.7 % (one patient with bulky lymph nodes). The FN ratio for perioperative frozen sections was 15.4 % (two patients, one with micrometastases, the other with bilateral SLN). Lymphatic drainage was only to the central compartment in 6 of 24 patients (3 of the 6 with positive SLNs for metastases), only to the laterocervical basin in 5 of 24 patients (all unilateral, 2 of 5 positive SLNs) and to the central and laterocervical compartments in 12 of 24 patients (6 of 12 and 3 of 12 positive SLNs, respectively).

Conclusion

Lymphoscintigraphy reveals the lymph node drainage in a high proportion of patients. It detects laterocervical drainage in a significant percentage of patients, allowing the detection of occult lymph node metastases and improving the surgical management in PTC.     

Sentinel lymph node biopsy in pregnant patients with breast cancer

Purpose

Sentinel lymph node biopsy (SLNB) is currently not recommended in pregnant patients with breast cancer due to radiation concerns.

Methods

Twelve pregnant patients with breast cancer received low-dose (10 MBq on average) lymphoscintigraphy using ^99mTc human serum albumin nanocolloids.

Results

The sentinel lymph node (SLN) was identified in all patients. Of the 12 patients, 10 had pathologically negative SLN. One patient had micrometastasis in one of four SLN. One patient had metastasis in the SLN and underwent axillary clearance. From the 12 pregnancies, 11 healthy babies were born with no malformations and normal weight. One baby, whose mother underwent lymphatic mapping during the 26th week of gestation, was operated on at the age of 3 months for a ventricular septal defect and at 43 months was in good health. This malformation was suspected at the morphological US examination during week 21, well before lymphoscintigraphy, and was confirmed a posteriori by a different observer based on videotaped material. No overt axillary recurrence appeared in the patients with negative SLNs after a median follow-up of 32 months.

Conclusion

Our experience supports the safety of SLNB in pregnant patients with breast cancer, when performed with a low-dose lymphoscintigraphic technique.     

Predicting sentinel lymph node metastasis in breast cancer with lymphoscintigraphy

Objective

Lymphoscintigraphy is an effective method for detecting sentinel lymph nodes (SLNs). However, the rate and degree of SLN detection is not uniform. We quantified SLNs detected with lymphoscintigraphy, and investigated correlations with factors that may influence detection. We then attempted to predict SLN metastasis from lymph node counts, comparing the predictions to subsequent biopsy results.

Methods

We assessed lymph node counts in 100 breast cancer patients in whom a single SLN was detected with a fixed lymphoscintigraphy procedure. We examined correlations between the counts and factors known to influence lymphoscintigraphic SLN detection (age, body mass index, tumor size, and presence or absence of metastasis), and determined reference values (lymph node counts of 10.0, 19.4 and 53.0) which were used to predict SLN metastasis in 100 subsequent patients. The predictions were then compared with the SLN biopsy findings.

Results

SLN counts correlated strongly with the presence or absence of metastasis, with metastasis-positive lymph nodes showing significantly lower counts than negative nodes (p < 0.001). Prediction of SLN metastasis achieved a 100% positive predictive value at a reference value of 10.0, and a 100% negative predictive value at a reference value of 53.0. At a reference value of 19.4, the sensitivity, specificity, and diagnostic accuracy were 77.8, 73.2, and 74.0%, respectively.

Conclusions

The SLN counts detected with lymphoscintigraphy were significantly lower in metastasis-positive lymph nodes than in metastasis-negative lymph nodes. This suggests that prediction of SLN metastasis in breast cancer is possible using lymphoscintigraphy.     

Multimodal fusion imaging ensemble for targeted sentinel lymph node management: initial results of an innovative promising approach for anatomically difficult lymphatic drainage in different tumour entities

Purpose There are situations where exact identification and localisation of sentinel lymph nodes (SLNs) are very difficult using lymphoscintigraphy, a hand-held gamma probe and vital dye, either a priori or a posteriori. We developed a new method using a simultaneous injection of two lymphotropic agents for exact topographical tomographic localisation and biopsy of draining SLNs. The purpose of this prospective pilot study was to investigate the feasibility and efficacy of this method ensemble. Methods Fourteen patients with different tumour entities were enrolled. A mixture of ^99mTc-nanocolloid and a dissolved superparamagnetic iron oxide was injected interstitially. Dynamic, sequential static lymphoscintigraphy and SPECT served as pathfinders. MR imaging was performed 2 h after injection. SPECT, contrast MRI and, if necessary, CT scan data sets were fused and evaluated with special regard to the topographical location of SLNs. The day after injection, nine patients underwent SLN biopsy and, in the presence of SLN metastasis, an elective lymph node dissection. Results Twenty-five SLNs were localised in the 14 patients examined. A 100% fusion correlation was achieved in all patients. The anatomical sites of SLNs detected during surgery showed 100% agreement with those localised on the multimodal fusion images. SLNs could be excised in 11/14 patients, six of whom had nodal metastasis. Conclusion Our novel approach of multimodal fusion imaging for targeted SLN management in primary tumours with lymphatic drainage to anatomically difficult regions enables SLN biopsy even in patients with lymphatic drainage to obscure regions. Currently, we are testing its validity in larger patient groups and other tumour entities.     

Intraoperative 3-D imaging improves sentinel lymph node biopsy in oral cancer

Purpose

The aim of this study was to prospectively evaluate the feasibility and potential advantages of freehand single-photon emission computed tomography (fhSPECT) compared with conventional intraoperative localization techniques for sentinel lymph node biopsy (SLNB) in oral cancer.

Methods

Between November 2012 and February 2014, 23 consecutive patients with clinical T1/T2 oral squamous cell carcinoma and a cN0 neck were recruited. All patients underwent SLNB followed by elective neck dissection (END). All patients received preoperative lymphoscintigraphy. To detect the SLNs intraoperatively, fhSPECT with a combination of conventional acoustic SLN localization and 3-D visual navigation was used.

Results

All but one of the SLNs detected by preoperative imaging were successfully mapped intraoperatively by fhSPECT (detection rate 98 %), including those in six patients with a tumour in the floor of the mouth. A histopathology analysis revealed positive SLNs in 22 % of patients. No further metastases were found in LNs resected during END. SLNB correctly predicted the final LN stage in all patients (accuracy 100 %). Additional radioactive LNs, which were not present on preoperative lymphoscintigraphy, were observed in three patients.

Conclusion

FhSPECT is a feasible technology that allows the accurate identification of SLNs in oral cancer. FhSPECT overcomes the shine-through phenomenon, one of the most important limitations of SLNB, thereby confirming the importance of SLNB in patients with cN0 oral cancer.     

Contribution of SLN investigation with <Superscript>99m</Superscript>Tc-nanocolloid in clinical staging of thyroid cancer: technical feasibility

Purpose It is a matter of controversy whether prophylactic lymph node dissection improves prognosis and survival in papillary thyroid carcinoma (PTC) patients without suspicion of lymph node metastases either clinically or on ultrasonography. It is possible that in such patients the use of lymphatic mapping and sentinel lymph node (SLN) biopsy, as are employed for other tumours, will be of assistance. The aim of this study was to evaluate the feasibility of preoperative ^99mTc-nanocolloid lymphoscintigraphy and an intra-operative SLN procedure in the management of PTC patients. Methods Twenty-five consecutive patients were entered in the study between April 2005 and October 2005. All had a preoperative diagnosis of malignancy obtained by fine-needle aspiration cytology (FNAC), without clinical or ultrasonographic evidence of loco-regional lymph node involvement. Patients underwent preoperative lymphoscintigraphy after the injection of ^99mTc-nanocolloid [median 6 MBq (range 4–9 MBq) in 0.1–0.2 ml saline injected intratumorally under ultrasound guidance] and an intra-operative SLN procedure using a hand-held gamma probe. Surgery was performed by the same surgeon in all patients. Results Preoperative lymphoscintigraphy identified at least one SLN in all patients. During surgery, using the gamma probe, the surgeon was able to find at least one SLN in all cases. A good correlation was found between preoperative imaging and probe results. Metastasis was found in at least one SLN in 12 (48%) patients. In seven (28%) patients the involved SLN was the most radioactive SLN, while in five (20%) patients a less radioactive SLN was involved by malignancy. Ten of these 12 patients had only micrometastases (<2 mm). Micrometastases were found in the most radioactive SLN in six cases and in less radioactive SLNs in four cases, while in two patients more lymph nodes visualised at lymphoscintigraphy ipsilateral to the primary tumour were sites of metastasis. Conclusion The rate of nodal involvement was very high in our series: in 48% of patients at least one metastatic lymph node was found. From a technical point of view the intra-operative SLN procedure in PTC patients was easy to perform, without major intra-operative complications. Our promising preliminary experience needs to be confirmed in larger series of patients series with longer follow-up.     

Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern?

Purpose

To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only.

Methods

Patients were included prospectively at four centres in The Netherlands. Lymphatic flow was studied using planar lymphoscintigraphy and SPECT/CT until 4?h after administration of ^99mTc-nanocolloid in the largest tumour. Subsequently, the smaller tumour(s) was injected intratumorally followed by the same imaging sequence. Sentinel nodes were intraoperatively localized using a gamma ray detection probe and vital blue dye.

Results

Included in the study were 50 patients. Additional lymphatic drainage was depicted after the second and/or third injection in 32 patients (64?%). Comparison of planar images and SPECT/CT images after consecutive injections enabled visualization of the number and location of additional sentinel nodes (32 axillary, 11 internal mammary chain, 2 intramammary, and 1 interpectoral. A sentinel node contained metastases in 17 patients (34?%). In five patients with a tumour-positive node in the axilla that was visualized after the first injection, an additional involved axillary node was found after the second injection. In two patients, isolated tumour cells were found in sentinel nodes that were only visualized after the second injection, whilst the sentinel nodes identified after the first injection were tumour-negative.

Conclusion

Lymphoscintigraphy and SPECT/CT after consecutive intratumoral injections of tracer enable lymphatic mapping of each tumour separately in patients with multiple malignancies within one breast. The high incidence of additional sentinel nodes draining from tumours other than the largest one suggests that separate tumour-related tracer injections may be a more accurate approach to mapping and sampling of sentinel nodes in patients with multicentric or multifocal breast cancer.     

First demonstration of 3-D lymphatic mapping in breast cancer using freehand SPECT

Purpose

Freehand SPECT is a 3-D tomographic imaging modality based on data acquisition with a hand-held detector that is moved freely, in contrast to conventional, fixed gamma camera systems. In this pilot study, the feasibility of freehand SPECT for 3-D lymphatic mapping in breast cancer was evaluated.

Methods

A total of 85 patients (age: 29–88 years) with an initial diagnosis of invasive breast cancer and no clinical evidence of nodal involvement prospectively underwent sentinel lymph node (SLN) biopsy. Preoperative lymphatic mapping (35–87 MBq ^99mTc-Nanocoll) included tomographic imaging with a SPECT/CT device (Siemens Symbia T6) serving as reference. Initially, the freehand SPECT approach was assessed in a pilot study consisting of 50 patients. The quality of each freehand SPECT acquisition was assessed and ranked as good, intermediate or poor. In another series comprising a further 35 patients (validation study), a guidance system for the acquisition was implemented based on the results of the pilot study, ensuring acquisitions with good quality. For 3-D tomographic image reconstruction, ad hoc models and iterative reconstruction algorithms were used in all 85 patients. To allow for adequate comparison, SPECT/CT data and freehand SPECT data were registered within the same coordinate system.

Results

In the pilot study, freehand SPECT enabled mapping of 24 of 83 SLNs in 20 of 44 patients (3 dropouts, 3 patients without SLN either in SPECT/CT or in freehand SPECT). Using SPECT/CT as reference, the accuracy of freehand SPECT was 77.8% (7/9 nodes) in scans with good quality, while for intermediate and poor quality scans, the accuracy was reduced to 34.3 and 12.8%, respectively. In the validation study, quality feedback improved the results significantly and freehand SPECT enabled the mapping of at least one SLN in 87.5% of the patients (28/32 ? 3 dropouts). Compared to the reference method, freehand SPECT showed a sensitivity of 83.3% (35/42 nodes). False-negative findings were related to insufficient scanning time, insufficient coverage of the axillary region, close proximity of the SLN to the injection site and low tracer uptake in the SLNs.

Conclusion

In this preliminary study, we could demonstrate that 3-D localization of SLNs is feasible using freehand SPECT technology. Prerequisites for acquisition of a good scan quality, most likely allowing precise SLN mapping, have been defined. This approach has high potential to allow image-guided biopsy and further standardization of SLN dissection, thus bringing 3-D nuclear imaging into the operating room.     

The added value of SPECT-CT for the identification of sentinel lymph nodes in early stage oral cancer

Purpose

To assess the role of single-photon emission computed tomography with computed tomography (SPECT-CT) for the identification of sentinel lymph nodes (SLNs) in patients with early stage (T1–T2) oral cancer and a clinically negative neck (cN0).

Methods

In addition to planar lymphoscintigraphy, SPECT-CT was performed in 66 consecutive patients with early stage oral cancer and a clinically negative neck. The addition of SPECT-CT to planar images was retrospectively analyzed for the number of additional SLNs, more precise localization of SLNs, and importance of anatomical information by a team consisting of a nuclear physician, surgeon, and investigator.

Results

Identification rate for both imaging modalities combined was 98% (65/66). SPECT-CT identified 15 additional SLNs in 14 patients (22%). In 2/15 (13%) of these additional SLNs, the only metastasis was found, resulting in an upstaging rate of 3% (2/65). In 20% of the patients with at least one positive SLN, the only positive SLN was detected due to the addition of SPECT-CT. SPECT-CT was considered to add important anatomical information in two patients (3%). In 5/65 (8%) of the patients initially scored SLNs on planar lymphoscintigrams were scored as non-SLNs when SPECT-CT was added. There were four false-negative SLN biopsy procedures in this cohort.

Conclusions

The addition of SPECT-CT to planar lymphoscintigraphy is recommended for the identification of more (positive) SLNs and better topographical orientation for surgery in sentinel lymph node biopsy for early stage oral cancer.

     

Fusion of freehand SPECT and ultrasound: First experience in preoperative localization of sentinel lymph nodes

Purpose

Radioguided sentinel lymph node biopsy (SLNB) is the standard of care in breast cancer and melanoma. Additional preoperative Single-photon emission computed tomography (SPECT/CT) for improved anatomical co-registration of the SLNs causes additional radiation exposure and is time-consuming and expensive. The aim of this prospective study was to evaluate a novel approach involving real-time fusion of freehand SPECT (fhSPECT) and ultrasound (US) for anatomical co-registration of SLNs.

Methods

From February 2015 to February 2016, 153 patients were included in this prospective study. All patients underwent lymphoscintigraphy according to practical guidelines and 151 (118 cases of breast cancer, 30 cutaneous malignancies, and three cases of vulvar cancer) of the 153 patients were additionally investigated with fhSPECT-US. FhSPECT connected to a hand-held gamma detector generates three-dimensional images of the radioactivity distribution in the scanned area. For co-registration and real-time fusion of fhSPECT and subsequently performed US, an infrared stereo tracking system was used.

Results

In all patients an SLN was found on lymphoscintigraphy, and the fhSPECT detected corresponding hotspots in all but one patient. In 72 % of patients and 73 % of lymph node basins, real-time anatomical co-registration with US was feasible. The rate of success in achieving good co-registration increased from 60 to 75 % after training by a radiologist specialized in breast imaging. A higher co-registration rate (78 %) was observed in patients with only one SLN than in those with two SLNs (68 %) or three or more SLNs (0 %).

Conclusions

Real-time fusion of fhSPECT and US for preoperative anatomical co-registration of SLNs is feasible. However, before this approach can completely replace preoperative lymphatic imaging, further technical developments are needed.

     

The Clinical Value of Hybrid Sentinel Lymphoscintigraphy to Predict Metastatic Sentinel Lymph Nodes in Breast Cancer

Purpose

Hybrid imaging techniques can provide functional and anatomical information about sentinel lymph nodes in breast cancer. Our aim in this study was to evaluate which imaging parameters on hybrid sentinel lymphoscintigraphy predicted metastatic involvement of sentinel lymph nodes (SLNs) in patients with breast cancer.

Methods

Among 56 patients who underwent conventional sentinel lymphoscintigraphy, 45 patients (age, 53.1 ± 9.5 years) underwent hybrid sentinel lymphoscintigraphy using a single-photon emission computed tomography (SPECT)/computed tomography (CT) gamma camera. On hybrid SPECT/CT images, we compared the shape and size (long-to-short axis [L/S] ratio) of the SLN, and SLN/periareolar injection site (S/P) count ratio between metastatic and non-metastatic SLNs. Metastatic involvement of sentinel lymph nodes was confirmed by pathological biopsy.

Results

Pathological biopsy revealed that 21 patients (46.7 %) had metastatic SLNs, while 24 (53.3 %) had non-metastatic SLNs. In the 21 patients with metastatic SLNs, the SLN was mostly round (57.1 %) or had an eccentric cortical rim (38.1 %). Of 24 patients with non-metastatic SLNs, 13 patients (54.1 %) had an SLN with a C-shape rim or eccentric cortex. L/S ratio was 2.04 for metastatic SLNs and 2.38 for non-metastatic SLNs. Seven (33 %) patients had T1 primary tumors and 14 (66 %) had T2 primary tumors in the metastatic SLN group. In contrast, 18 (75 %) patients had T1 primary tumors and six (25 %) had T2 tumors in the non-metastatic SLN group. S/P count ratio was significantly lower in the metastatic SLN group than the non-metastatic SLN group for those patients with a T1 primary tumor (p = 0.007).

Conclusions

Hybrid SPECT/CT offers the physiologic data of SPECT together with the anatomic data of CT in a single image. This hybrid imaging improved the anatomic localization of SLNs in breast cancer patients and predicted the metastatic involvement of SLNs in the subgroup of breast cancer patients with T1 primary tumors.     

Multimodal hybrid imaging agents for sentinel node mapping as a means to (re)connect nuclear medicine to advances made in robot-assisted surgery

Purpose

Radical prostatectomy and complementary extended pelvic lymph node dissection (ePLND) of sentinel lymph nodes (SNs) and non-sentinel lymph nodes (LNs) at risk of containing metastases are increasingly being performed using high-tech robot-assisted approaches. Although this technological evolution has clear advantages, the physical nature of robotic systems limits the integrated use of routine radioguided surgery technologies. Hence, engineering effort in robotics are focused on the integration of fluorescence guidance technologies. Using the hybrid SN tracer indocyanine green-^99mTc-nanocolloid (radioactive and fluorescent), for the first time in combination with a robot-integrated laparoscope, we investigated whether the robot-assisted approach affects the accuracy of fluorescence detection of SNs identified preoperatively using nuclear medicine.

Methods

The study included 55 patients (Briganti nomogram-based risk >5 % on LN metastases) scheduled for robot-assisted radical prostatectomy, SN biopsy and ePLND. Following indocyanine green-^99mTc-nanocolloid injection, preoperative nuclear imaging (lymphoscintigraphy and SPECT/CT) was used to locate the SN(s). The fluorescence laparoscope was used intraoperatively to identify the SN(s) with standard fluorescence settings (in 50 patients) and with customized settings (in 5 patients). The number and location of the SNs, the radioactive, fluorescence (both in vivo and ex vivo) and tumour status of the resected SNs/LNs, and postoperative complications were recorded and analysed.

Results

Combined, preoperative lymphoscintigraphy and SPECT/CT imaging identified 212 SNs (median 4 per patient). Intraoperative fluorescence imaging using standard fluorescence settings visualized 80.4 % (148/184 SNs; 50 patients; ex vivo 97.8 %). This increased to 85.7 % (12/14 SNs; 5 patients; ex vivo 100 %) with customized fluorescence settings. SPECT/CT images provided guidance towards the residual SNs. Ex vivo all removed SNs were radioactive. SNs were tumour-positive in 25.4 % of patients (14/55; false-negative rate 7 %, 1/14 patients). In ten patients, the SN was the only tumour-positive LN. Surgical complications were minimal.

Conclusion

Directly linking 3D preoperative nuclear imaging information on SNs to a robot-integrated fluorescence laparoscope improved the surgeon’s use of the technology and did not influence the sensitivity or morbidity of the procedure. To our surprise, however, the detection rates with the current fluorescence camera did not improve.

     

Freehand SPECT for image-guided sentinel lymph node biopsy in breast cancer

Purpose

Sentinel lymph node biopsy (SLNB) is standard of care in early-stage breast cancer. Freehand SPECT (FhSPECT) is a system generating 3-D images for intraoperative visual detection of radioactivity in the body. The aim of our study was to evaluate the sensitivity of this technology for sentinel lymph node (SLN) detection and SLNB guidance.

Methods

In 40 patients, FhSPECT was additionally used after planar imaging and probe localization for SLNB. The number of SLNs detected was compared with the number detected by planar scintigraphy (reference method) and the conventional acoustic gamma probe (standard alternative). The sensitivity of FhSPECT was compared with that of the conventional gamma probe (McNemar’s test).

Results

FhSPECT mapped the SLNs in 92.3 % of the basins (36/39) intraoperatively in identical positions to those seen on planar scintigrams. The conventional gamma probe correctly detected the SLNs in 35 of 39 basins (89.7 %). After SLNB, remaining radioactivity was detected by FhSPECT in nine patients, resulting in additional resection of SLNs in four patients.

Conclusion

FhSPECT is a highly sensitive modality for intraoperative detection of SLNs, resulting in the identification of a higher number of SLNs than conventional gamma probe detection.     

Fluorescence guided surgery and tracer-dose,fact or fiction?

Introduction

Fluorescence guidance is an upcoming methodology to improve surgical accuracy. Challenging herein is the identification of the minimum dose at which the tracer can be detected with a clinical-grade fluorescence camera. Using a hybrid tracer such as indocyanine green (ICG)-^99mTc-nanocolloid, it has become possible to determine the accumulation of tracer and correlate this to intraoperative fluorescence-based identification rates. In the current study, we determined the lower detection limit of tracer at which intraoperative fluorescence guidance was still feasible.

Methods

Size exclusion chromatography (SEC) provided a laboratory set-up to analyze the chemical content and to simulate the migratory behavior of ICG-nanocolloid in tissue. Tracer accumulation and intraoperative fluorescence detection findings were derived from a retrospective analysis of 20 head-and-neck melanoma patients, 40 penile and 20 prostate cancer patients scheduled for sentinel node (SN) biopsy using ICG-^99mTc-nanocolloid. In these patients, following tracer injection, single photon emission computed tomography fused with computed tomography (SPECT/CT) was used to identify the SN(s). The percentage injected dose (% ID), the amount of ICG (in nmol), and the concentration of ICG in the SNs (in μM) was assessed for SNs detected on SPECT/CT and correlated with the intraoperative fluorescence imaging findings.

Results

SEC determined that in the hybrid tracer formulation, 41 % (standard deviation: 12 %) of ICG was present in nanocolloid-bound form. In the SNs detected using fluorescence guidance a median of 0.88 % ID was present, compared to a median of 0.25 % ID in the non-fluorescent SNs (p-value?<?0.001). The % ID values could be correlated to the amount ICG in a SN (range: 0.003–10.8 nmol) and the concentration of ICG in a SN (range: 0.006–64.6 μM).

Discussion

The ability to provide intraoperative fluorescence guidance is dependent on the amount and concentration of the fluorescent dye accumulated in the lesion(s) of interest. Our findings indicate that intraoperative fluorescence detection with ICG is possible above a μM concentration.

     

Usefulness of sentinel lymph node detection in early stages of cervical cancer

Purpose Sentinel lymph node (SLN) mapping in combination with surgical biopsy is an emerging technique for use in the early stages of cervical cancer. The purpose of this study was to evaluate the technique in a series of 40 consecutive women with early stage cervical cancer.Methods Forty patients with early stage cervical cancer [FIGO stage IA2 (2), IB1 (34), IB2 (1) or IIA (3)] were referred for radical hysterectomy with pelvic lymphadenectomy. Patients were submitted to preoperative lymphoscintigraphy (four ^99mTc-nanocolloid injections around the tumour) and intraoperative SLN detection. Hand-held or laparoscopic gamma probes were used to locate SLNs during surgery.Results The mean number of SLNs was 2.5 per patient (interiliac 49%, external iliac 19%). Of the total of 99 SLNs, six, in four women, showed metastases (all 68 non-SLNs removed were negative). In the other 36 patients, all the removed lymph nodes (sentinel and non-sentinel) were negative (0% false negative rate). During the follow-up (median 25 months), only two patients presented distant metastases: one died 6 months after surgery (two of three SLNs positive, both hot and blue), while the second patient is alive 4 years after surgery (lung metastasis, no isotope drainage, negative blue SLN). The survival rate was 95% and disease-free survival, 97%.Conclusion SLN surgical biopsy based on lymphoscintigraphy and blue dye is a feasible and useful technique to avoid lymph node dissection in the early stages of cervical cancer. It has a high negative predictive value, can be incorporated into clinical routine (laparoscopy or open surgery) and is close to achieving validation in this setting.     

How long the lymphoscintigraphy imaging should be continued for sentinel lymph node mapping?

Objective  We assessed the need for delayed lymphoscintigraphy imaging for sentinel lymph node (SLN) biopsy in stage I and II breast cancer patients using intradermal injection of ^99mTc-antimony sulfide colloid. Method  Seventy-five patients with early-stage breast cancer were included in our study. Periareolar intradermal injections of 0.5 mCi/0.2 mL ^99mTc-antimony sulfide colloid was used for the patients without previous excisional biopsy (45 patients). Two intradermal injection of 0.5 mCi/0.2 mL ^99mTc-antimony sulfide colloid was used on each side of the dermal incision in patients with the history of excisional biopsy (30 patients). Anterior and lateral static images were taken at 2 min. If SLN was not visualized, delayed imaging at 5, 10, 30, 60, 90, 150, and 180 min was done (till the visualization of the SLN or 180 min). SLN was performed by the combination of gamma probe and blue dye during surgery. Results  Sentinel lymph node detection rate was 96% (72/75). SLNs were detected on the immediate (2 min) images in 55 (73.33%) patients. In the remaining patients, the SLNs were detected first on the 5-, 10-, and 30-min images in 10 (13/33%), 5 (6.66%), and 2 (2.66%) patients, respectively. In three patients (4%), SLN was not detected by lymphoscintigraphy even on 180-min images. During surgery, SLN was not detected in these three patients either. Conclusion  Considering the rapid flow of ^99mTc-antimony sulfide colloid in our study, lymphoscintigraphy imaging can be completed in the nuclear medicine department without any delay in sending the patient back to the surgery department. Thirty minutes after radiotracer injection seems to be the optimal time for lymphoscintigraphy and delayed imaging beyond 30 min would not be necessary.     

Is the identification of in-transit sentinel lymph nodes in malignant melanoma patients really necessary?

The sentinel lymph node (SLN) is the first node in a nodal basin to receive the direct lymphatic flow from a malignant melanoma. However, in some patients, lymphoscintigraphic study reveals the presence of lymphatic nodes in the area between the primary melanoma and the regional basin. These nodes are called in-transit nodes or interval nodes and, by definition, are also SLNs. The purpose of this study was to determine the incidence and location of in-transit SLNs in patients with malignant melanoma and to assess whether it is really necessary to harvest them. The evaluation involved 600 consecutive malignant melanoma patients. Lymphoscintigraphy was performed on the day before surgery following intradermal injection of 74–111 MBq of ^99mTc-nanocolloid in four doses around the primary melanoma or the biopsy scar. Dynamic and static images were obtained and revealed SLNs in 599 out of 600 patients. The SLN was intraoperatively identified with the aid of patent blue dye and a hand-held gamma probe. Lymphoscintigraphy showed in-transit SLNs in 59/599 patients (9.8%). During surgery, all these in-transit SLNs were harvested, with those in the popliteal and epitrochlear regions being the most difficult to identify and excise. Metastatic cell deposits were subsequently identified in ten (16.9%) of these in-transit SLNs. In conclusion, lymphoscintigraphy has a key role in the identification of in-transit SLNs. Although the incidence of these nodes is relatively low in malignant melanoma patients, such SLNs present metastatic deposits in a significant percentage of cases and therefore the identification of in-transit SLNs in these patients is really necessary.     

Practice variation in defining sentinel lymph nodes on lymphoscintigrams in oral cancer patients

Purpose

Lymphoscintigraphic imaging and adequate interpretation of the lymphatic drainage pattern is an essential step in the sentinel lymph node biopsy (SLNB) procedure. In oral cancer, identification of the sentinel lymph node (SLN) can be challenging. In this study, interobserver variability in defining SLNs on lymphoscintigrams was evaluated in patients with T1–T2 stage N0 oral cancer.

Methods

Sixteen observers (head and neck surgeons, nuclear medicine physicians or teams of both) from various institutes were asked which criteria they use to consider a hot focus on the lymphoscintigram as SLN. Lymphoscintigrams of 9 patients with 47 hot foci (3–9 per patient) were assessed, using a scale of ‘yes/equivocal/no’. Bilateral drainage was seen in four of nine cases. In three cases additional late single photon emission computed tomography (SPECT)/CT scanning was performed. Interobserver variability was evaluated by kappa (к) analysis, using linear weighted pairwise comparison of the observers. Conservative (equivocal analysed as no) and sensitive (equivocal analysed as yes) assessment strategies were investigated using pairwise kappa analysis.

Results

Various definitions of SLN on lymphoscintigrams were given. Interobserver variability of all cases using a 3-point scale showed fair agreement (71 %, к_w?=?0.29). The conservative and sensitive analyses both showed moderate agreement: conservative approach к?=?0.44 (in 80 % of the hot foci the observers agreed) and sensitive approach к?=?0.42 (81 %) respectively. Multidisciplinary involvement in image interpretation and higher levels of observer experience appeared to increase agreement.

Conclusion

Among 16 observers, there is practice variation in defining SLNs on lymphoscintigrams in oral cancer patients. Interobserver variability of lymphoscintigraphic interpretation shows moderate agreement. In order to achieve better agreement in defining SLNs on lymphoscintigrams specific guidelines are warranted.