EUROPEAN UROLOGY 65 (2014) 1169–1170
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Editorial Referring to the article published on pp. 1162–1168 of this issue
Fluorescence Guidance During Radical Prostatectomy Fijs W.B. van Leeuwen a,b,*, Stephan Hruby c a
Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands;
b
Department of
c
Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; University Clinic of Urology and Andrology Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria
With the availability of surgical guidance technologies, the quest for prostate cancer–related tumor-draining lymph nodes is increasingly gaining interest [1]. These lymph nodes are located deep in the pelvic area and are excised during a (robot-assisted) laparoscopic procedure. Despite the attempts to reduce postoperative complications, using either a sentinel node (SN) or a lymphangiography approach, (extended) nodal dissection followed by pathologic examination of the tissue samples is still considered the gold standard to assess metastatic spread within the lymphatic system. In a laparoscopic setting, the surgeon’s senses are limited to acoustic or visual detection. Preoperative imaging with lymphoscintigraphy (and single-photon emission tomography/computed tomography) followed by acoustic tracing of nodes that have accumulated a radiocolloid has long been the standard [2]. However, the potential to identify nodes visually has stimulated a push toward the off-label use of the near-infrared (NIR) fluorescent dye indocyanine green (ICG). ICG has been used as a free chemical entity or as the hybrid tracer ICG-technetium (99mTc) nanocolloid. Neither of these compounds has an affinity for tumor tissue. Equally important to realize is the fact that the tissue penetration of NIR fluorescent signals lies below 1 cm [1], a photophysical limitation that may prevent the identification of (distant) aberrant drainage profiles. The small size of free ICG means that it flows freely through the lymphatic system and is therefore suited for real-time lymphangiography. This approach enables accurate identification of both lymph nodes and draining lymphatic vessels [3]. Because ICG is in origin an angiographic imaging agent, shunting during intraoperative tracer administration may yield background signals in the form of fluorescent blood vessels. The much larger
ICG-99mTc-nanocolloid particles are retained in the SNs— accompanied by the occasional overflow in second echelon nodes—and complement the standard radioguided approach with intraoperative fluorescence guidance toward these exact nodes [4]. The low dose used here in combination with the 3 h between tracer administration and surgery limit the chance of background signals. Next to the particle type, the injection technique may also influence the procedure. To allow the tracer to follow individual lymphatic paths, tracer administration is commonly performed prior to surgery and in the peripheral zone or the region most likely to contain tumor [2–4]. Manny et al., however, suggest that after initial dissection, ICG can be injected percutaneously in the prostate [5]. As a prerequisite for this random injection procedure, the authors assume that ICG diffuses freely through the prostate. Although it is known from pathologic studies that intraprostatic diffusion of the larger ICG-99mTc-nanocolloid particles is somewhat limited [6], the diffusion of ICG is still under investigation. Such diffusion data are required before statements can be made about the value of alternative injection procedures. In addition, prior dissection of the prostate or periprostatic space may alter the natural lymphatic drainage pattern, generating an unwanted bias. Until proven otherwise, we believe it is still mandatory to perform injections before any dissection has taken place and to place the tracer deposits in the peripheral zone of the prostate or in and around the tumor. Laparoscopic NIR camera systems are available commercially from three major vendors: Intuitive Surgical, KARL STORZ Endoscope, and Olympus. All three systems were designed for angiography with ICG (only U.S. Food and Drug Administration–approved use), and, as far as we know, only the first two have been used for lymphatic imaging in relation
DOI of original article: http://dx.doi.org/10.1016/j.eururo.2013.11.017. * Corresponding author. Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands. E-mail address: [email protected] (Fijs W.B. van Leeuwen). 0302-2838/$ – see back matter # 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.eururo.2013.12.050
1170
EUROPEAN UROLOGY 65 (2014) 1169–1170
to prostate cancer. While the Firefly of Intuitive Surgical is an integral part of the da Vinci Si system, the image HUB 1 HD camera of KARL STORZ Endoscope has been used as an add-on during robotic procedures and as the sole endoscope during laparoscopic procedures. Both approaches were successfully applied during radical prostatectomy [3,4]. In this issue Manny et al. report the first use of the Firefly system for lymphangiography of the prostate [5]. The Firefly system, however, was previously already used for lymphangiography procedures in gynecologic cancers [7]. The fact that tumor-bearing lymph nodes have been reported outside the extended nodal dissection field used for prostate cancer [4,8] and that laparoscopic NIR fluorescence imaging is now available offers an accessible opportunity to improve on nodal dissection during robotic surgery. The concept here is that fully integrated fluorescence-aided nodal identification provides a rapid and easy-to-use technique to introduce the concept of specific lymph node detection in conjunction with extended nodal dissection.
[2] Janetschek G. Radioisotope-guided lymph node dissection for pros-
Conflicts of interest: The authors have nothing to disclose.
[7] Rossi EC, Ivanova A, Boggess JF. Robotically assisted fluorescence-
tate cancer: potential and limitations. Eur Urol 2008;53:16–8, discussion 18–20. [3] Jeschke S, Lusuardi L, Myatt A, Hruby S, Pirich C, Janetschek G. Visualisation of the lymph node pathway in real time by laparoscopic radioisotope- and fluorescence-guided sentinel lymph node dissection in prostate cancer staging. Urology 2012;80: 1080–6. [4] van der Poel HG, Buckle T, Brouwer OR, Valde´s Olmos RA, van Leeuwen FWB. Intraoperative laparoscopic fluorescence guidance to the sentinel lymph node in prostate cancer patients: clinical proof of concept of an integrated functional imaging approach using a multimodal tracer. Eur Urol 2011;60:826–33. [5] Manny TB, Patel M, Hemal AK. Fluorescence-enhanced robotic radical prostatectomy using real-time lymphangiography and tissue marking with percutaneous injection of unconjugated indocyanine green: the initial clinical experience in 50 patients. Eur Urol 2014; 65:1162–8. [6] Buckle T, Brouwer OR, Valde´s Olmos RA, van der Poel HG, van Leeuwen FWB. Relationship between intraprostatic tracer deposits and sentinel lymph node mapping in prostate cancer patients. J Nucl Med 2012;53:1026–33. guided lymph node mapping with ICG for gynecologic malignan-
References
cies: a feasibility study. Gynecol Oncol 2012;124:78–82. [8] Joniau S, Van den Bergh L, Lerut E, et al. Mapping of pelvic lymph
[1] van den Berg NS, Valde´s-Olmos RA, van der Poel HG, van Leeuwen FWB. Sentinel lymph node biopsy for prostate cancer: a hybrid approach. J Nucl Med 2013;54:493–6.
node metastases in prostate cancer. Eur Urol 2013;63:450–8.
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Editorial Referring to the article published on pp. 1162–1168 of this issue
Fluorescence Guidance During Radical Prostatectomy Fijs W.B. van Leeuwen a,b,*, Stephan Hruby c a
Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands;
b
Department of
c
Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; University Clinic of Urology and Andrology Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria
With the availability of surgical guidance technologies, the quest for prostate cancer–related tumor-draining lymph nodes is increasingly gaining interest [1]. These lymph nodes are located deep in the pelvic area and are excised during a (robot-assisted) laparoscopic procedure. Despite the attempts to reduce postoperative complications, using either a sentinel node (SN) or a lymphangiography approach, (extended) nodal dissection followed by pathologic examination of the tissue samples is still considered the gold standard to assess metastatic spread within the lymphatic system. In a laparoscopic setting, the surgeon’s senses are limited to acoustic or visual detection. Preoperative imaging with lymphoscintigraphy (and single-photon emission tomography/computed tomography) followed by acoustic tracing of nodes that have accumulated a radiocolloid has long been the standard [2]. However, the potential to identify nodes visually has stimulated a push toward the off-label use of the near-infrared (NIR) fluorescent dye indocyanine green (ICG). ICG has been used as a free chemical entity or as the hybrid tracer ICG-technetium (99mTc) nanocolloid. Neither of these compounds has an affinity for tumor tissue. Equally important to realize is the fact that the tissue penetration of NIR fluorescent signals lies below 1 cm [1], a photophysical limitation that may prevent the identification of (distant) aberrant drainage profiles. The small size of free ICG means that it flows freely through the lymphatic system and is therefore suited for real-time lymphangiography. This approach enables accurate identification of both lymph nodes and draining lymphatic vessels [3]. Because ICG is in origin an angiographic imaging agent, shunting during intraoperative tracer administration may yield background signals in the form of fluorescent blood vessels. The much larger
ICG-99mTc-nanocolloid particles are retained in the SNs— accompanied by the occasional overflow in second echelon nodes—and complement the standard radioguided approach with intraoperative fluorescence guidance toward these exact nodes [4]. The low dose used here in combination with the 3 h between tracer administration and surgery limit the chance of background signals. Next to the particle type, the injection technique may also influence the procedure. To allow the tracer to follow individual lymphatic paths, tracer administration is commonly performed prior to surgery and in the peripheral zone or the region most likely to contain tumor [2–4]. Manny et al., however, suggest that after initial dissection, ICG can be injected percutaneously in the prostate [5]. As a prerequisite for this random injection procedure, the authors assume that ICG diffuses freely through the prostate. Although it is known from pathologic studies that intraprostatic diffusion of the larger ICG-99mTc-nanocolloid particles is somewhat limited [6], the diffusion of ICG is still under investigation. Such diffusion data are required before statements can be made about the value of alternative injection procedures. In addition, prior dissection of the prostate or periprostatic space may alter the natural lymphatic drainage pattern, generating an unwanted bias. Until proven otherwise, we believe it is still mandatory to perform injections before any dissection has taken place and to place the tracer deposits in the peripheral zone of the prostate or in and around the tumor. Laparoscopic NIR camera systems are available commercially from three major vendors: Intuitive Surgical, KARL STORZ Endoscope, and Olympus. All three systems were designed for angiography with ICG (only U.S. Food and Drug Administration–approved use), and, as far as we know, only the first two have been used for lymphatic imaging in relation
DOI of original article: http://dx.doi.org/10.1016/j.eururo.2013.11.017. * Corresponding author. Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands. E-mail address: [email protected] (Fijs W.B. van Leeuwen). 0302-2838/$ – see back matter # 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.eururo.2013.12.050
1170
EUROPEAN UROLOGY 65 (2014) 1169–1170
to prostate cancer. While the Firefly of Intuitive Surgical is an integral part of the da Vinci Si system, the image HUB 1 HD camera of KARL STORZ Endoscope has been used as an add-on during robotic procedures and as the sole endoscope during laparoscopic procedures. Both approaches were successfully applied during radical prostatectomy [3,4]. In this issue Manny et al. report the first use of the Firefly system for lymphangiography of the prostate [5]. The Firefly system, however, was previously already used for lymphangiography procedures in gynecologic cancers [7]. The fact that tumor-bearing lymph nodes have been reported outside the extended nodal dissection field used for prostate cancer [4,8] and that laparoscopic NIR fluorescence imaging is now available offers an accessible opportunity to improve on nodal dissection during robotic surgery. The concept here is that fully integrated fluorescence-aided nodal identification provides a rapid and easy-to-use technique to introduce the concept of specific lymph node detection in conjunction with extended nodal dissection.
[2] Janetschek G. Radioisotope-guided lymph node dissection for pros-
Conflicts of interest: The authors have nothing to disclose.
[7] Rossi EC, Ivanova A, Boggess JF. Robotically assisted fluorescence-
tate cancer: potential and limitations. Eur Urol 2008;53:16–8, discussion 18–20. [3] Jeschke S, Lusuardi L, Myatt A, Hruby S, Pirich C, Janetschek G. Visualisation of the lymph node pathway in real time by laparoscopic radioisotope- and fluorescence-guided sentinel lymph node dissection in prostate cancer staging. Urology 2012;80: 1080–6. [4] van der Poel HG, Buckle T, Brouwer OR, Valde´s Olmos RA, van Leeuwen FWB. Intraoperative laparoscopic fluorescence guidance to the sentinel lymph node in prostate cancer patients: clinical proof of concept of an integrated functional imaging approach using a multimodal tracer. Eur Urol 2011;60:826–33. [5] Manny TB, Patel M, Hemal AK. Fluorescence-enhanced robotic radical prostatectomy using real-time lymphangiography and tissue marking with percutaneous injection of unconjugated indocyanine green: the initial clinical experience in 50 patients. Eur Urol 2014; 65:1162–8. [6] Buckle T, Brouwer OR, Valde´s Olmos RA, van der Poel HG, van Leeuwen FWB. Relationship between intraprostatic tracer deposits and sentinel lymph node mapping in prostate cancer patients. J Nucl Med 2012;53:1026–33. guided lymph node mapping with ICG for gynecologic malignan-
References
cies: a feasibility study. Gynecol Oncol 2012;124:78–82. [8] Joniau S, Van den Bergh L, Lerut E, et al. Mapping of pelvic lymph
[1] van den Berg NS, Valde´s-Olmos RA, van der Poel HG, van Leeuwen FWB. Sentinel lymph node biopsy for prostate cancer: a hybrid approach. J Nucl Med 2013;54:493–6.
node metastases in prostate cancer. Eur Urol 2013;63:450–8.
