Abstract Background Integration of molecular imaging and in particular intraoperative image guidance is expected to improve the surgical accuracy of laparoscopic lymph node (LN) dissection. Objective ...To show the applicability of combining preoperative, intraoperative, and postoperative sentinel node imaging using an integrated diagnostic approach based on an imaging agent that is both radioactive and fluorescent. Design, setting, and participants Before surgery, multimodal indocyanine green (ICG)-99m Tc-NanoColl was injected into the prostate. Subsequent lymphoscintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging of pelvic nodes was performed to determine the location of the sentinel lymph nodes (SLNs) preoperatively. During the surgical procedure a fluorescence laparoscope, optimized for detection in the near infrared range, was used to visualize the nodes identified on SPECT/CT. Eleven patients scheduled for robot-assisted laparoscopic prostatectomy (RALP) with an increased risk of nodal metastasis, based on Memorial Sloan-Kettering Cancer Center/Kattan nomogram estimation, participated in a pilot assessment (N09IGF). Surgical procedure Patients underwent RALP with LN dissection for prostate cancer. Measurements Radioactive and fluorescent signals were monitored using different modalities, and the correlation between the two types of signals was studied. The location of preoperatively detected SLNs was documented. Results and limitations Preoperatively, SLNs were identified by SPECT/CT, and the multimodal nature of the imaging agent also enabled intraoperative detection via fluorescence imaging. Fluorescence particularly improved surgical guidance in areas with a high radioactive background signal such as the injection site. Ex vivo analysis revealed a strong correlation between the radioactive and fluorescent content in the excised LNs. Fluorescence detection is limited by the severe tissue attenuation of the signal. Therefore, radio guidance to the areas of interest is still desirable. Conclusions Initial data indicate that multimodal ICG-99m Tc-NanoColloid, in combination with a laparoscopic fluorescence laparoscope, can be used to facilitate and optimize dissection of SLNs during RALP procedures.
Purpose
The accurate harvesting of a sentinel node in breast cancer includes a sequence of procedures with components from different medical specialities, including nuclear medicine, radiology, ...surgical oncology and pathology. The aim of this document is to provide general information about sentinel lymph node detection in breast cancer patients.
Methods
The Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the European Association of Nuclear Medicine (EANM) have written and approved these guidelines to promote the use of nuclear medicine procedures with high quality. The final result has been discussed by distinguished experts from the EANM Oncology Committee, the SNMMI and the European Society of Surgical Oncology (ESSO).
Conclusion
The present guidelines for nuclear medicine practitioners offer assistance in optimizing the diagnostic information from the SLN procedure. These guidelines describe protocols currently used routinely, but do not include all existing procedures. They should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary.
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)-
99m
Tc-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-
99m
Tc-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.
Purpose The management of regional nodes of penile squamous cell carcinoma has changed with time due to improved knowledge about diagnosis and treatment. To determine whether changes in the treatment ...of regional nodes have improved survival, we compared contemporary 5-year cancer specific survival of patients with squamous cell carcinoma of the penis with that of patients in previous cohorts. Materials and Methods In an observational cohort study of 1,000 patients treated during 56 years 944 were eligible for analysis. Tumors were staged according to the 2009 TNM classification, and patients were divided into 4 cohorts of 1956 to 1987, 1988 to 1993, 1994 to 2000 and 2001 to 2012, reflecting changes in clinical practice regarding regional nodes. Kaplan-Meier survival curves with the log rank test and Cox proportional hazards modeling were used to examine trends in 5-year cancer specific survival. Results The 5-year cancer specific survival of patients with cN0 disease treated between 2001 and 2012 was 92% compared to 89% (1994 to 2000), 78% (1988 to 1993) and 85% (1956 to 1987). The 5-year cancer specific survival improved significantly since 1994, the year dynamic sentinel node biopsy was introduced, at 91% (1994 to 2012) vs 82% (1956 to 1993) (p = 0.021). This conclusion still holds after adjustment for pathological T stage and grade of differentiation (HR 2.46, p = 0.01). Extranodal extension, number of tumor positive nodes and pelvic involvement in node positive (pN+) cases were associated with worse 5-year cancer specific survival. Conclusions Despite less surgery being performed on regional nodes, 5-year cancer specific survival has improved in patients with cN0 disease. The number of tumor positive nodes, extranodal extension and pelvic involvement were highly associated with worse cancer specific survival in patients with pN+ disease. In this group other treatment strategies are needed as no improvement was observed.
Sentinel node biopsy is used to evaluate the nodal status of patients with clinically node-negative penile carcinoma. Its use is not widespread, and the majority of patients with clinically ...node-negative disease undergo an elective inguinal lymph node dissection. Reservations about the use of sentinel node biopsy include the fact that most current results come from one institution and the supposedly long learning curve associated with the procedure. The purpose of this study was to address these issues by analyzing results from two centers and by evaluating the learning curve.
All patients undergoing sentinel node biopsy for penile carcinoma at two centers were included. The sentinel node identification rate, false-negative rate, and morbidity of the procedure were calculated.
from the first 30 procedures were assessed for a potential learning curve. Results A total of 323 patients with penile squamous cell carcinoma, which included 611 clinically node-negative groins, were scheduled for sentinel node biopsy. A sentinel node was found in 572 of the 592 groins (97%) that proceeded to sentinel node biopsy. In 79 groins, a sentinel node was positive for tumor. Six inguinal node recurrences occurred after a negative sentinel node procedure, all within 15 months after sentinel node biopsy. The combined false-negative rate was 7%. Complications occurred in 4.7% of explored groins. None of the false-negative procedures occurred in the initial 30 procedures.
Sentinel node biopsy is a suitable procedure to stage clinically node-negative penile cancer, and it has a low complication rate. No learning curve was demonstrated in this study.
Abstract Background Sentinel node (SN) biopsy in penile cancer is typically performed using a combination of radiocolloid and blue dye. Recently, the hybrid radioactive and fluorescent tracer ...indocyanine green (ICG)-99m Tc-nanocolloid was developed to combine the beneficial properties of both radio-guidance and fluorescence imaging. Objective To explore the added value of SN biopsy using ICG-99m Tc-nanocolloid in patients with penile carcinoma. Design, setting, and participants Sixty-five patients with penile squamous cell carcinoma were prospectively included (January 2011 to December 2012). Preoperative SN mapping was performed using lymphoscintigraphy and single-proton emission computed tomography supplemented with computed tomography (SPECT/CT) after peritumoural injection of ICG-99m Tc-nanocolloid. During surgery, SNs were initially approached using a gamma probe, followed by patent blue dye and/or fluorescence imaging. A portable gamma camera was used to confirm excision of all SNs. Surgical procedure Patients underwent SN biopsy of the cN0 groin and treatment of the primary tumour. Outcome measurements and statistical analysis The number and location of preoperatively identified SNs were documented. Intraoperative SN identification rates using radio- and/or fluorescence guidance were assessed and compared with blue dye. Statistical evaluation was performed using a two-sample test for equality of proportions with continuity correction. Results and limitations Preoperative imaging after injection of ICG-99m Tc-nanocolloid enabled SN identification in all patients (a total of 183 SNs dispersed over 119 groins). Intraoperatively, all SNs identified by preoperative SN mapping were localised using combined radio-, fluorescence-, and blue dye guidance. Fluorescence imaging enabled visualisation of 96.8% of SNs, while only 55.7% was stained by blue dye ( p < 0.0001). The tissue penetration of the fluorescent signal, and the rapid flow of blue dye limited the detection sensitivity. A tumour-positive SN was found in seven patients. Conclusions ICG-99m Tc-nanocolloid allows for both preoperative SN mapping and combined radio- and fluorescence-guided SN biopsy in penile carcinoma patients and significantly improves optical SN detection compared with blue dye.
Abstract Context Extended pelvic lymph node dissection (ePLND) is the gold standard for detecting lymph node (LN) metastases in prostate cancer (PCa). The benefit of sentinel node biopsy (SNB), which ...is the first draining LN as assessed by imaging of locally injected tracers, remains controversial. Objective To assess the diagnostic accuracy of SNB in PCa. Evidence acquisition A systematic literature search of Medline, Embase, and the Cochrane Library (1999–2016) was undertaken using PRISMA guidelines. All studies of SNB in men with PCa using PLND as reference standard were included. The primary outcomes were the nondiagnostic rate (NDR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and false positive (FP) and false negative (FN) rates. Relevant sensitivity analyses based on SN definitions, ePLND as reference standard, and disease risk were undertaken, including a risk of bias (RoB) assessment. Evidence synthesis Of 373 articles identified, 21 studies recruiting a total of 2509 patients were eligible for inclusion. Median cumulative percentage (interquartile range) results were 4.1% (1.5–10.7%) for NDR, 95.2% (81.8–100%) for sensitivity, 100% (95.0–100%) for specificity, 100% (87.0–100%) for PPV, 98.0% (94.3–100%) for NPV, 0% (0–5.0%) for the FP rate, and 4.8% (0–18.2%) for the FN rate. The findings did not change significantly on sensitivity analyses. Most studies (17/22) had low RoB for index test and reference standard domains. Conclusions SNB appears to have diagnostic accuracy comparable to ePLND, with high sensitivity, specificity, PPV and NPV, and a low FN rate. With a low FP rate (rate of detecting positive nodes outside the ePLND template), SNB may not have any additional diagnostic value over and above ePLND, although SNB appears to increase nodal yield by increasing the number of affected nodes when combined with ePLND. Thus, in high-risk disease it may be prudent to combine ePLND with SNB. Patient summary This literature review showed a high diagnostic accuracy for sentinel node biopsy in detecting positive lymph nodes in prostate cancer, but further studies are needed to explore the effect of sentinel node biopsy on complications and oncologic outcome.
Abstract Background Knowledge regarding the lymphatic drainage pattern of penile cancer is the basis for the extent of inguinal lymph node dissection for this disease. Objective To prospectively ...analyze the lymphatic drainage pattern of penile carcinoma using SPECT-CT and evaluate the implications for the extent of inguinal lymph node dissection. Design, Setting, and Participants The lymphatic drainage patterns of 50 patients scheduled for dynamic sentinel node biopsy were analyzed using a hybrid SPECT-CT scanner. Measurements A total of 86 clinically node-negative (cN0) inguinal and pelvic regions was evaluated. The sentinel and higher-tier nodes on SPECT-CT were divided into different zones in the groin and pelvic region. The groin was divided according to Daseler's five zones, four zones obtained by drawing a vertical and horizontal line over the saphenofemoral junction and one zone directly overlying this junction. The nodes in the pelvic region were classified into three zones: the external iliac/obturator zone, the common iliac zone, and the paraaortal zone. Results and Limitations Lymphatic drainage was visualised in 82 of the 86 cN0 groins (95.3%). A total of 115 sentinel nodes and 182 higher-tier nodes was found. All sentinel nodes were located in superior and central inguinal zones. The higher-tier nodes were located in the groin and pelvic region. No lymphatic drainage was seen to the inferior two regions of the groin. A potential limitation of the study is that the unilateral lymphatic drainage seen in some patients could be normal, but it could also be caused by blockage of lymphatic drainage due to a grossly involved metastatic lymph node. Another possible limitation is that this study relies on the quality and accuracy of lymphoscintigraphy and the subsequent sentinel node procedure. Conclusions All sentinel and higher-tier nodes were located in the superior and central inguinal zones and the pelvic region. No lymphatic drainage to the inferior inguinal zones was seen. This suggests that the extent of inguinal node dissection in cN0 patients could be reduced to removal of the superior and central inguinal zones. This may decrease the extensive morbidity associated with this procedure.
Letter to the editor‐in‐chief of Head and Neck Rubello, Domenico; Tartaglione, Girolamo; Valdes Olmos, Renato ...
Head & neck,
December 2019, 2019-12-00, 20191201, Volume:
41, Issue:
12
Journal Article
Abstract Background The hybrid tracer was introduced to complement intraoperative radiotracing towards the sentinel nodes (SNs) with fluorescence guidance. Objective Improve in vivo ...fluorescence-based SN identification for prostate cancer by optimising hybrid tracer preparation, injection technique, and fluorescence imaging hardware. Design, setting, and participants Forty patients with a Briganti nomogram–based risk >10% of lymph node (LN) metastases were included. After intraprostatic tracer injection, SN mapping was performed (lymphoscintigraphy and single-photon emission computed tomography with computed tomography (SPECT-CT)). In groups 1 and 2, SNs were pursued intraoperatively using a laparoscopic gamma probe followed by fluorescence imaging (FI). In group 3, SNs were initially located via FI. Compared with group 1, in groups 2 and 3, a new tracer formulation was introduced that had a reduced total injected volume (2.0 ml vs 3.2 ml) but increased particle concentration. For groups 1 and 2, the Tricam SLII with D-Light C laparoscopic FI (LFI) system was used. In group 3, the LFI system was upgraded to an Image 1 HUB HD with D-Light P system. Intervention Hybrid tracer-based SN biopsy, extended pelvic lymph node dissection, and robot-assisted radical prostatectomy. Outcome measurements and statistical analysis Number and location of the preoperatively identified SNs, in vivo fluorescence-based SN identification rate, tumour status of SNs and LNs, postoperative complications, and biochemical recurrence (BCR). Results and limitations Mean fluorescence-based SN identification improved from 63.7% (group 1) to 85.2% and 93.5% for groups 2 and 3, respectively ( p = 0.012). No differences in postoperative complications were found. BCR occurred in three pN0 patients. Conclusions Stepwise optimisation of the hybrid tracer formulation and the LFI system led to a significant improvement in fluorescence-assisted SN identification. Preoperative SPECT-CT remained essential for guiding intraoperative SN localisation. Patient summary Intraoperative fluorescence-based SN visualisation can be improved by enhancing the hybrid tracer formulation and laparoscopic fluorescence imaging system.