F.W.B. van Leeuwen

Multimodal surgical guidance towards the sentinel node in vulvar cancer

INTRODUCTIONnConventional sentinel node (SN) mapping is performed by injecting a radiocolloid followed by lymphoscintigraphy (and SPECT/CT imaging). An extra intraoperative injection with blue dye can then allow for optical identification of the SN. In order to improve the current clinical standard, the hybrid tracer indocyanine green (ICG)-(99m)Tc-nanocolloid was introduced, a tracer that is both radioactive and fluorescent. This feasibility study aimed to evaluate the value of a multimodal-based SN biopsy in vulvar cancer.nnnMATERIALS AND METHODSnFifteen patients with vulvar cancer (29 groins) scheduled for SN biopsy were peritumorally injected with ICG-(99m)Tc-nanocolloid followed by lymphoscintigraphy and SPECT/CT imaging to identify the SNs. In thirteen patients, shortly before the start of the operation, blue dye was intradermally injected around the lesion. SNs were harvested using a combination of radiotracing, fluorescence imaging, and optical blue dye detection. A portable gamma camera was used before and after SN excision to confirm excision of the preoperatively defined SNs.nnnRESULTSnPreoperative lymphoscintigraphy and SPECT/CT imaging visualized drainage to 39 SNs in 28 groins. During the operation, 98% (ex vivo 100%) of the SNs were radioactive. With fluorescence imaging 96% of the SNs (ex vivo 100%) could be visualized. Only 65% of the SNs had stained blue at the time of excision.nnnCONCLUSIONnICG-(99m)Tc-nanocolloid can be used for preoperative SN identification and enables multimodal (radioactive and fluorescent) surgical guidance in patients with vulvar cancer. The addition of fluorescence-based optical guidance offers more effective SN visualization compared to blue dye.

Hybrid radioguided occult lesion localization (hybrid ROLL) of 18F-FDG-avid lesions using the hybrid tracer indocyanine green-99mTc-nanocolloid

PURPOSEnTo assess if combined fluorescence- and radio-guided occult lesion localization (hybrid ROLL) is feasible in patients scheduled for surgical resection of non-palpable (18)F-FDG-avid lesions on PET/CT.nnnMETHODSnFour patients with (18)F-FDG-avid lesions on follow-up PET/CT that were not palpable during physical examination but were suspected to harbor metastasis were enrolled. Guided by ultrasound, the hybrid tracer indocyanine green (ICG)-(99m)Tc-nanocolloid was injected centrally in the target lesion. SPECT/CT imaging was used to confirm tracer deposition. Intraoperatively, lesions were localized using a hand-held gamma ray detection probe, a portable gamma camera, and a fluorescence camera. After excision, the gamma camera was used to check the wound bed for residual activity.nnnRESULTSnA total of six (18)F-FDG-avid lymph nodes were identified and scheduled for hybrid ROLL. Comparison of the PET/CT images with the acquired SPECT/CT after hybrid tracer injection confirmed accurate tracer deposition. No side effects were observed. Combined radio- and fluorescence-guidance enabled localization and excision of the target lesion in all patients. Five of the six excised lesions proved tumor-positive at histopathology.nnnCONCLUSIONnThe hybrid ROLL approach appears to be feasible and can facilitate the intraoperative localization and excision of non-palpable lesions suspected to harbor tumor metastases. In addition to the initial radioguided detection, the fluorescence component of the hybrid tracer enables high-resolution intraoperative visualization of the target lesion. The procedure needs further evaluation in a larger cohort and wider range of malignancies to substantiate these preliminary findings.

Multimodal imaging in radioguided surgery

Radioguided surgery (RGS) utilizes radiolabeled tracers that accumulate in the lesion of interest following local or systemic administration. RGS is an expanding surgical guidance technology, but unfortunately most currently available radiotracers are unable to provide intraoperative optical information regarding the location of the lesion. In 2011, a new hybrid tracer (both radioactive and fluorescent) was introduced for sentinel lymph node detection. This hybrid tracer (indocyanine green-99mTc-nanocolloid) has helped to generate a new hybrid surgical guidance concept, thereby expanding the traditional RGS-based approach. Based on its radioactive signature a hybrid tracer is able to preserve the “traditional” role for RGS. Furthermore, as an additional tool in the operating room, a hybrid tracer provides optical information via fluorescence guidance. This review discusses the most common RGS approaches. Different clinically used radioactive tracers and their potential hybrid derivatives are also discussed. Furthermore, the various imaging devices designed for radioactivity-based detection are reviewed in the context of generating hybrid-imaging modalities.

Sentinel node biopsy and lymphatic mapping in penile and prostate cancer

BackgroundNodal metastases are linked to poor outcome in men with penile or prostate cancer. Early detection and resection are important for staging and for the prognosis. However, lymphadenectomy is associated with morbidity and may miss metastases when performed solely on the basis of anatomical templates.MethodsIn this article we describe the technique and benefits of sentinel node biopsy (SNB) and provide a review of the literature.ResultsDynamic sentinel node techniques using both radioactive and optical (hybrid) tracers have been proven effective in penile cancer. For prostate cancer, SNB added to extended nodal dissection may further tailor dissection to the highly variable lymphatic drainage patterns in the pelvis. The sensitivity of SNB was found to be superior to conventional imaging methods; however, false-negative SNB procedures can occur and axa0complementary extensive lymphadenectomy is required to remove additional positive nodes that were not detected in the SNB template.ConclusionSNB is axa0standard method for early detection of nodal metastases in penile cancer and provides superior diagnostic accuracy to conventional imaging modalities in prostate cancer.ZusammenfassungHintergrundEine lymphogene Metastasierung stellt einen ungünstigen prognostischen Faktor beim Penis- und Prostatakarzinom dar. Daher ist die frühe Erkennung und Resektion nicht nur zum korrekten Staging notwendig, sondern könnte auch für die Patienten von prognostischer Bedeutung sein. Die Lymphadenektomie ist jedoch mit einer gewissen Morbidität vergesellschaftet und birgt auch das Risiko, dass Lymphknotenmetastasen übersehen werden, vor allem, wenn sie sich nur an anatomischen Template-Feldern orientiert.MethodikEs erfolgt die Beschreibung der Technik und der Vorteile der Wächterlymphknotenresektion („sentinel node biopsy“, SNB) sowie eine Literaturübersicht.ErgebnisseDie Technik der dynamischen SNB, die radioaktive oder optische Tracer verwendet, ist beim Peniskarzinom etabliert. Beim Prostatakarzinom und dem hochgradig variablen Lymphabfluss im kleinen Becken könnte die SNB in Kombination mit einer ausgedehnten pelvinen Lymphknotendissektion von zusätzlichem Nutzen sein. Die Sensitivität der SNB ist der konventionellen Bildgebung überlegen, wobei jedoch auch hier falsch-negative Ergebnisse beobachtet werden, sodass bei diesen Patienten noch eine ergänzende ausgedehnte pelvine Lymphknotendissektion benötigt wird.SchlussfolgerungDie SNB ist eine Standardmethode zum frühen Erkennen von Lymphknotenmetastasen beim Peniskarzinom und ermöglicht eine erhöhte diagnostische Sicherheit im Vergleich zur konventionellen Bildgebung beim Prostatakarzinom.

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

PurposeHybrid 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 methodsA prospective trial was conducted (nu2009=u2009501 procedures) in axa0heterogeneous 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). Asxa0the patients acted as their own control, use of hybrid guidance could bexa0compared to conventional radioguidance and the use of blue dye (nu2009=u2009300). This was based on reported surgical complications, overall survival, LN recurrence free survival, and false negative rates (FNR).ResultsA 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 (nu2009=u2009300) 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.ConclusionWith 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.

A prediction model relating the extent of intraoperative fascia preservation to erectile dysfunction after nerve-sparing robot-assisted radical prostatectomy

Robot-assisted radical prostatectomy (RARP) is performed in patients with prostate cancer. Unfortunately, 10–46% of patients may still suffer from limited erectile function (EF) after RARP. This study aimed to develop a prediction model based on the extent of fascia preservation (FP) and postoperative EF after RARP. A previously developed FP score quantizing the extent and regions of nerve-preservation was determined in a cohort of 1241 patients who underwent RARP. The predictive value of the FP score for post-prostatectomy EF (following the international index erectile function (IIEF) score, EF domain) was analyzed. To increase the predictive value of the scoring system, the FP regions were related to postoperative EF, nerve distribution and co-morbidity factors. Finally, a prediction model for EF was developed based on the studied cohort. When corrected for the preoperative IIEF-EF, the FP score was shown to be a significant denominator for IIEF (pu2009=u20092.5xa0×xa010−u200915) with an R2 of 35%. Variable selection performed using the Akaike information criterion led to a final prediction model for postoperative IIEF after nerve-preservation based on the FP score. Furthermore, patient’s age, preoperative IIEF score, CCIS and use of clips for nerve sparing were significantly associated with postoperative IIEF-EF. More anterior fascia preservation was correlated with better EF outcome and age was a strong independent predictor of EF outcome. In older men, the relative benefit of more extensive fascia preservation was at least similar to younger men, despite a lower baseline IIEF-EF score. Quantitative nerve-sparing FP scoring could be related to the postoperative IIEF-EF and integrated into a multivariate prediction model, which includes with age, use of surgical clips, the Charlson Comorbidity Index Score (CCIS), and preoperative IIEF-EF. When further validated the prediction model could provide patients and care-givers a qualitative estimation of EF outcome after RARP.