Sentinel node approach in prostate cancer | Revista Española de Medicina Nuclear e Imagen Molecular

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Due to poor corticosteroid response and persistent elevation of erythrocyte sedimentation rate and C-reactive protein aortitits was suspected. An 18F-FDG PET disclosed the presence of an underlying aortitis with increased FDG uptake metabolism in the thoracic aorta, supraaortic trunks, and femoral/tibioperoneal arteries. Sagittal (A and D), axial (B) and coronal (C) 18F-FDG PET views and maximum intensity projection image of the lower extremities (E)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Loricera, R. Blanco, J.L. Hernández, I. Martínez-Rodríguez, J.M. Carril, C. Lavado, M. Jiménez, C. González-Vela, M.Á. González-Gay" "autores" => array:9 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Loricera" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Blanco" ] 2 => array:2 [ "nombre" => "J.L." "apellidos" => "Hernández" ] 3 => array:2 [ "nombre" => "I." "apellidos" => "Martínez-Rodríguez" ] 4 => array:2 [ "nombre" => "J.M." 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Vidal-Sicart, R.A. Valdés Olmos" "autores" => array:2 [ 0 => array:4 [ "nombre" => "S." "apellidos" => "Vidal-Sicart" "email" => array:1 [ 0 => "svidal@clinic.ub.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "R.A." 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Median age at diagnosis is 72 years. In the United States more than 200,000 new patients are diagnosed every year. Age-standardised cases of incidence and mortality per 100,000 population per year were 96.0 and 19.3 in Europe and 96.8 and 15.2 in Spain, respectively.<a class="elsevierStyleCrossRef" href="#bib0265">1</a>In the period 1989–2008, in Spain there were 104,955 deaths due to prostate cancer, accounting for 10% of mortality among all male malignant tumors. The prostate cancer mortality pattern was not at all pronounced, indicating, as in the case of breast cancer among women, territorial uniformity in exposure to possible risk factors. A south-north pattern was in evidence during the first three quinquennia. In Andalusia, which had registered lower than expected mortality in the first three quinquennia, a change seemed to be taking place in the period 2004–2008.<a class="elsevierStyleCrossRef" href="#bib0270">2</a>The diagnosis of prostate cancer is well established, being based on the determination of the prostate-specific antigen (PSA), rectal tact, transrectal echography and prostate gland biopsy. The performance of a biopsy is guided by the ultrasound suspicious image but should be randomly performed to collect a sufficient number of samples from each lobe.<a class="elsevierStyleCrossRef" href="#bib0275">3</a>A majority of the tumors are adenocarcinomas and magnetic resonance (MRI) is the technique of choice for accurate delimitation of extension: capsular infiltration, invasion of the neurovascular bundle and infiltration of the seminal vesicles.Currently, the most used histologic grading system is the Gleason scale, which recognizes the following categories<a class="elsevierStyleCrossRef" href="#bib0280">4</a>:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">Gx, grade of differentiation cannot be evaluated.</li><li class="elsevierStyleListItem" id="lsti0010">Gleason 2–4 (G1), well differentiated (weak anaplasia).</li><li class="elsevierStyleListItem" id="lsti0015">Gleason 5–6 (G2), moderately differentiated (moderate anaplasia).</li><li class="elsevierStyleListItem" id="lsti0020">Gleason 7–10 (G3–4), poorly differentiated/undifferentiated (marked anaplasia).</li></ul>Staging follows the TNM approach, as depicted in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>On the other hand, the lymph node status serves as a key predictor for clinically localized prostate cancer. As in many other cancers, lymph node staging is important for both prognosis and therapeutic management.Prostate-specific antigen (PSA) levels, pathologic stage and Gleason score are predictors for lymph node involvement; the higher these factors, the greater is the probability of nodal involvement. The prevalence of infiltration of the lymph nodes has been shown to be approximately 25% of the patients with prostate cancer with a reduction in 5-year survival of 85% in N0 patients and of 50% in N1 patients.The presence of lymph node metastatic involvement may lead to the abandon of local curative therapy, such as radiotherapy or radical prostatectomy, and subsequently to initiate androgen deprivation therapy. Limited nodal metastases may be treated with extended pelvic lymph node dissection or with external beam radiation therapy combined with long-term androgen deprivation therapy. Currently, none of the available imaging diagnostic modalities provides a reliable assessment of lymph node metastases. Conventional imaging techniques show a low sensitivity in the localization of lymph node disease since the criteria accepted to define pathologic character is size and, on many occasions, involved lymph nodes smaller than 1cm. Thus, the sensitivity of computerized tomography (CT) varies greatly, being between 25 and 70% and from 75 to 78% for MRI. The sensitivity of these modalities is particularly limited in metastasis smaller than 5mm. This has contributed to establish the role of extended pelvic lymphadenectomy (EPL) as the gold standard for the identification of lymph node metastases in prostate cancer.<a class="elsevierStyleCrossRef" href="#bib0285">5</a>Post-operative pathologic examinations of tissue samples obtained during EPL assess metastatic spread. With an increase in the dissection template and the thorough histopathologic study of those nodes the N1 group has increased in number with improvement of staging.However, the use of EPL has been found to be associated with various complications (venous thrombosis, lymphocele, lower extremity edema and ureteral injury) and its incidence increases with the number of dissected lymph nodes varying from 10.5% for 1–5 lymph nodes to 24.3% when dissection includes more than 20 lymph nodes.<a class="elsevierStyleCrossRef" href="#bib0290">6</a>Predictive nomograms have therefore been developed, among which the most accepted is the Roach formula [(2/3) PSA+(Gleason-6)×10]. Using this tool patients who are candidates for lymphadenectomy can be selected. However, whether a standard or extended technique should be performed continues to be a controversy, due to the lack of an imaging technique to assist in the localization of lymph node infiltration.<a class="elsevierStyleCrossRef" href="#bib0295">7</a>Moreover, the area of EPL has its limits; in most descriptions the common iliac artery is only cleared up to the crossing of the ureter, the external iliac vessels as a rule are the lateral border, and the internal iliac is usually cleared from the bifurcation up to just beyond the superior vesical artery. The EPL area as well includes the obturator fossa that consists of the tissue between the external iliac vein and the obturator nerve. Nowadays, several reports indicate that EPL improves biochemical relapse-free survival, especially in patients with minimal lymphatic dissemination.<a class="elsevierStyleCrossRef" href="#bib0300">8</a>As an alternative for the EPL the sentinel lymph node (SLN) biopsy was introduced using open surgery and a gamma probe.<a class="elsevierStyleCrossRef" href="#bib0305">9</a> Subsequently the procedure was validated for laparoscopy.<a class="elsevierStyleCrossRef" href="#bib0310">10</a>SLN biopsy focuses on the identification, subsequent to minimal invasive excision and extensive histopathologic evaluation of the lymph nodes that drain directly from the primary tumor. Assuming the orderly spread of tumor cells through the lymphatic system, SLN biopsy can be used for lymph node staging and subsequent therapeutic management.The advantages of the SLN dissection are a lower incidence of complications and the possibility of identifying tumor-draining lymph nodes outside the field of EPL.<a class="elsevierStyleCrossRef" href="#bib0315">11</a> However, accurate laparoscopic localization of SLNs in the pelvis can be challenging and requires specific skill, especially when these are located near the prostatic injection site (because of the high radioactive background signal), or in the case of aberrantly located SLNs (e.g., pre-vesical or para-aortic).<a class="elsevierStyleCrossRef" href="#bib0320">12</a>For both EPL and SLN procedure the use of predictive nomograms is very important to determine the clinical indication and the probability of nodal involvement for each patient on an individual basis. As stated previously, the probability of lymph node metastases in the pelvis increases with the level of PSA, Gleason score and clinical T stage. This has resulted in the abandon of lymphadenectomy in patients with relatively favourable preoperative risk factors; the procedure is currently reserved principally for patients with intermediate or poor prognosis (clinical stage >T2b/T3, PSA>10ng/l, or Gleason >6). In the intermediate-risk group, a tumor-bearing SLN may influence the boundaries of the radiotherapy field and duration of androgen-deprivation therapy. Another possible indication is to select patients who are eligible for salvage treatment of the prostate. Since salvage treatment of the prostate may result in serious complications, it should only be considered when the prostate is actually the only tumor-bearing site. However, SLN biopsy has been able to identify metastases in 6.8–10.7% of patients of the group with favourable risk factors.<a class="elsevierStyleCrossRef" href="#bib0325">13</a>Surprisingly, the approach using lymphatic mapping and gamma detection probe is not recommended for routine use in the current surgical guidelines for management of prostate cancer.<a class="elsevierStyleCrossRef" href="#bib0330">14</a> Nevertheless, principally in Europe radioguided SLN biopsy has been thoroughly evaluated for its potential application in the surgical management of prostate cancer. The procedure was originally validated using open surgery and after the first description of the technique by Wawroschek et al. in 1999 multiple reports on the potential application of radioguided SLN biopsy in the surgical management of prostate cancer have been published.<a class="elsevierStyleCrossRef" href="#bib0305">9</a>Since its introduction, the procedure has been subject to several refinements and, in the past 15 years, the surgical technique has shifted from a mainly open procedure to a laparoscopic and later a robot-assisted procedure. For preoperative SN mapping, following the injection of a radioactive tracer, lymphoscintigrams are made. The introduction of single photon emission computed tomography with computed tomography (SPECT/CT) resulted in improved anatomic SN localisation, allowing better planning of the operation and reducing operative time. Importantly, continuous work has led to an expansion of this molecular imaging technology, including various forms of intraoperative fluorescent and optical portable imaging techniques to assist in disease identification and treatment. However, translating these interventional molecular image-guided technologies and especially, SLN approach, into real-time information available to the operating surgeon remains a challenge for the future.<a class="elsevierStyleCrossRef" href="#bib0335">15</a>Lymphatic mapping techniqueInjection and radiotracerLymphoscintigraphy for lymphatic mapping is mandatory and it is an essential component of the SLN procedure in the majority of published series.European countries have pioneered the SLN procedure for prostate cancer and this experience has been acquired by frequently using the radiopharmaceutical 99mTc-nanocolloid.<a class="elsevierStyleCrossRef" href="#bib0340">16</a>Immediately before tracer injection patients start with a 3-day prophylactic antibiotic treatment (usually, ciproﬂoxacine).Subsequently, transrectal radiocolloid injections are administered using ultrasound transrectal guidance into various sites within the peripheral zone of the prostate gland (as prostate cancer may be multifocal, injections are habitually performed in both lobes). The dosage administered ranges from 60MBq to 400MBq (1.6–10.8mCi) which is injected in a total volume of normal saline from 0.2mL to 3.0mL mostly between 6h and 24h before the planned surgery.<a class="elsevierStyleCrossRef" href="#bib0345">17</a> An alternative to transrectal injections is the transperineal administration of the radiotracer. Also for this route ultrasound transrectal guidance is necessary (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>However, investigators from the Netherlands Cancer Institute recommend a dose of 240MBq in 0.4mL because the lymph node visualization rate tends to be less optimal when lower activities are used.Moreover, adjustment of the particle concentration is also important, and a reduced labeling dilution volume (0.4mL 99mTc per 0.2mg nanocolloid) yields not only more visualized SLNs but also SLNs with higher radioactivity count rates. A three-way system is recommended, and after each depot saline is used for flushing the residual radioactivity in the needle.<a class="elsevierStyleCrossRef" href="#bib0350">18</a>According to the experience in other malignancies, the principle of SLN detection in prostate cancer is based on the assumption that accurate node identification is possible after intraprostatic injection of a radioactive tracer guided by ultrasound. As the majority of adenocarcinomas arise in the peripheral zone of the prostate, placement of tracer deposits in this zone is considered favorable for the detection of the tumor draining SLNs.<a class="elsevierStyleCrossRef" href="#bib0355">19</a>In this context, precision in the placement of the intraprostatic tracer deposits is crucial in order to increase the accuracy of the SLN procedure. However, monitoring the injection of radiotracer, even with transrectal ultrasound, is difficult because the tumour is not always visible. However, it is essential that SLNs identified preoperatively match those intraoperatively removed, since unexpected locations of SLNs outside the field of an extended pelvic lymphadenectomy are not rare and surgery's prolonged time can thus be avoided.<a class="elsevierStyleCrossRef" href="#bib0360">20</a>Interestingly, Buckle et al. demonstrated that intraprostatic tracer location may indeed be of inﬂuence on the lymphatic drainage pattern and that large variations in tracer placement in practice do occur. These authors found that lymphatic drainage from different zones of the prostate follow a distinct lymphatic drainage pattern. From the peripheral zone it seems to be more extensive than from the central zone; injection into the peripheral zone of the prostate resulted in visualization of more lymph nodes per patient.<a class="elsevierStyleCrossRef" href="#bib0365">21</a>Possibly this difference in lymphatic drainage may be explained by the fact that the prostate peripheral zone is more densely packed. Then again, injection of the radiotracer may lead to an increase of the interstitial ﬂuid pressure and to a higher lymphatic drainage. The relation between increased ﬂuid pressure after injection and lymphatic drainage may also explain why deposits situated only on the left or right side of the prostate result in a greater number of visualized SLNs and other nodes and/or higher radioactive count rates in the first SLN. Tracer placement in different regions of the prostate also resulted in visualization of different nodal basins. Radiotracer deposits located near the base of the prostate led to the visualization of lymphatic nodes in the common iliac region whereas deposits near the apex of the prostate showed paracaval SLNs. In all cases drainage tended to occur via the standard lymphatic drainage route of the prostate including the obturator fossa, internal iliac, external iliac, common iliac and presacral nodes.<a class="elsevierStyleCrossRef" href="#bib0370">22</a> (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Although these findings may have implications for SLN biopsies in prostate cancer patients, more extensive research is necessary to draw definitive conclusions. The possibility to use other imaging techniques, like T2-weighted MRI images, to guide radiotracer injection, may become attractive.<a class="elsevierStyleCrossRef" href="#bib0375">23</a><elsevierMultimedia ident="fig0010"></elsevierMultimedia>From a technical point of view, the injection procedure for prostate cancer, is probably the most frequent cause of pitfalls. Care must be taken to avoid tracer leakage during injection, possibly resulting in subsequent contamination (to be checked with a Geiger counter after tracer administration). During injection, incorrect needle placement may result in spillage of the radiocolloid to the bladder or bloodstream, which may cause SLN nonvisualization or SLN with weak uptake on lymphoscintigraphy. By monitoring the injection procedure with a portable gamma camera, it is possible to ensure adequate radiocolloid retention in the prostate.LymphoscintigraphyUsually, the tracer injection is performed outside of the Nuclear Medicine Department and therefore is not possible to adequately initiate a dynamic study. On the other hand, lymphatic ducts are seldom visualized in the pelvis and the relatively slower deep lymphatic drainage renders dynamic lymphoscintigraphy less useful. However, as mentioned before, the use of portable gamma cameras makes it possible to monitor the adequateness of tracer injection and potential early drainage in the Urology Department.<a class="elsevierStyleCrossRef" href="#bib0365">21</a> Early (15min) planar images after radiocolloid administration can visualize the first draining SLNs in almost 88% of the cases.<a class="elsevierStyleCrossRef" href="#bib0380">24</a>Delayed imaging is habitually performed 2–4h after injection. On delayed imaging, the lymph node visualization rate reaches more than 95%. The comparison between early and delayed images enables differentiation of second-echelon lymph nodes from the first draining nodes. This discrimination is based on the anatomical lymph node basins of the pelvis. As a rule, late-appearing lymph nodes located higher in the same basin are considered as second-echelon lymph nodes. Lateral planar images can help to differentiate between dorsal and more ventrally located SLNs. However, an accurate anatomical localization is only possible using SPECT/CT (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>Principally SPECT/CT devices with an improved fast high-end CT component enable incorporation of anatomical landmarks to localize SLNs in relation to vascular structures. The signal of SPECT is corrected for tissue attenuation and scatter. After fusion of SPECT/CT images the SLNs are displayed in the foreground SPECT image using a colour scale whereas a gray scale is used to display morphological aspects in the background CT image. Fused SPECT/CT, CT and SPECT may be displayed simultaneously by multiplanar reconstruction (MRP) and the use of cross-reference lines allows navigation between axial, coronal and sagittal views. Further anatomical recognition can be supported using multiple intensity projection (MIP). However, the difficulties of MIP to differentiate the vasculature from other anatomical structures have lead to the introduction of volume-rendering techniques which enable the depiction of SLNs in a 3D configuration SPECT/CT is considered as a complementary modality and does not replace conventional lymphoscintigraphy. The incorporation of SPECT/CT not only leads to increase the overall SLN visualization rate to 98% (in comparison with 95% for planar images) but also to the identification of significantly more SLNs in additional lymphatic basins (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). Also relevant is that SPECT/CT can precisely identify the SLNs within and outside the area of EPL<a class="elsevierStyleCrossRef" href="#bib0385">25</a> (<a class="elsevierStyleCrossRefs" href="#fig0025">Figs. 5 and 6</a>).<elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><elsevierMultimedia ident="fig0030"></elsevierMultimedia>In current protocols, SPECT/CT is performed following delayed planar imaging. This sequential timeline helps to clarify the role of both modalities and helps to establish some criteria for interpreting this set of images. Major criteria for labelling lymph nodes as SLNs are the visualization of lymphatic ducts, the time of appearance, the lymph node basin, and the intensity of lymph node uptake.Based on these criteria, visualized radioactive lymph nodes may be categorized as<a class="elsevierStyleCrossRef" href="#bib0390">26</a> (<a class="elsevierStyleCrossRef" href="#fig0035">Fig. 7</a>):<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025">-Definite SLNs: Including all lymph nodes draining from the site of the primary tumour through an afferent lymphatic vessel, or single radioactive lymph nodes in a regional lymph node basin.</li><li class="elsevierStyleListItem" id="lsti0030">-Highly probable SLNs: When lymph nodes appears between the injection site and a first draining node, or nodes with increasing uptake appearing in other lymph node stations.</li><li class="elsevierStyleListItem" id="lsti0035">-Less probable SLNs: All higher-echelon nodes may be included in this category.</li></ul><elsevierMultimedia ident="fig0035"></elsevierMultimedia>With these categories in mind, nuclear medicine physicians may be able to provide useful information to urological surgeons. In practical terms, the radioactive nodes included in the first two categories need to be resected during the surgical act. Moreover, in many cases early appearing lymph nodes seen as single on planar images are displayed as a two or more separate lymph nodes in different basins by SPECT/CT increasing the number of nodes considered as SLNs. In other cases intense lymph node uptake in a lymphatic basin seen on fused images may correspond with a cluster of SLNs as depicted on the CT of the SPECT/CT. Thus, SPECT/CT can depict more SLNs than planar images and in one series an average of 4.3 SLNs on SPECT/CT versus 2.2 SLNs on planar images was reported in 46 patients; 44% of the SLNs containing metastases were visualized only by SPECT/CT.<a class="elsevierStyleCrossRef" href="#bib0385">25</a> In another study, Meinhardt et al. found that SPECT/CT identified SLNs outside the area of EPL in 31% of the cases. These SLNs were found in different locations: para-aortic, abdominal wall, para-rectal, behind the common iliac artery, presacral, Cloquet's node, inguinal, and lateral to the external iliac artery.<a class="elsevierStyleCrossRef" href="#bib0380">24</a> The SLN rate outside the EPL area, as assessed by SPECT/CT, increases in patients previously treated with radiotherapy or surgery for prostate cancer to a 80% in comparison to a 34% for untreated patients.<a class="elsevierStyleCrossRef" href="#bib0395">27</a>On the other hand, SPECT/CT information may lead to a significant shortening of the time of operation of the SLN. SPECT/CT may also give important information for the planning of radiotherapy concerning treatment volume and optimization of irradiation fields in the pelvis.<a class="elsevierStyleCrossRef" href="#bib0400">28</a>In spite of bilateral tracer injection in a minority of patients only unilateral lymphatic drainage on lymphoscintigraphy and SPECT/CT is observed. Where possible tracer reinjection is recommended for SLN visualization. In cases with persistent unilateral non-visualization and to compensate for possible injection errors such as loss of tracer into the bladder, resulting in less drainage to one side, contralateral lymphadenectomy may be considered.Lymph node groups in the pelvisA thorough understanding of the anatomy and nomenclature of the pelvic and retroperitoneal lymph node nodal groups is crucial for accurate staging of prostate cancer. The mayor groups of lymph nodes, which may receive drainage from the prostate, follow the iliac vessels:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0040">-The common iliac nodal group consists of three chains: lateral, middle, and medial. The first chain is an extension of the lateral chain of external iliac nodes located lateral to the common iliac artery. The medial chain occupies the triangular area bordered by both common iliac arteries from the aortic bifurcation to the bifurcations of the external and internal iliac arteries. Nodes at the sacral promontory are included in this chain. The middle chain nodes are located in the lumbosacral fossa and between the common iliac artery and common iliac vein.</li><li class="elsevierStyleListItem" id="lsti0045">-The internal iliac nodal group, also known as hypogastric group, consists of chains accompanying each of the visceral branches of the internal iliac artery. These nodes are located more posterior in the pelvis and include the lateral sacral nodes, the presacral nodes (anterior to the sacrum and posterior to the mesorectal fascia), and the anterior nodes (at the origin of the proximal branches of the anterior division of the internal iliac artery.</li><li class="elsevierStyleListItem" id="lsti0050">-The external iliac nodal group consists of three chains: lateral, middle, and medial. The lateral chain includes nodes located along the lateral aspect of the external iliac artery. The middle chain comprises nodes between the external iliac artery and the external iliac vein. Finally, the medial chain contains nodes medial and posterior to the external iliac vein. The medial chain nodes are also known as the obturator nodes.</li></ul>With respect to the aorta and the inferior vena cava the lymph nodes are divided in seven subgroups. The lateroaortic, preaortic, and retroaortic nodes surround the aorta. The right lateroaortic, laterorocaval, precaval and retrocaval subgroups include the nodes in relation to the inferior vena cava.<a class="elsevierStyleCrossRef" href="#bib0405">29</a>Usually, prostate cancer metastasizes along four pelvic lymphatic drainage pathways: the anterior pelvic route, which drains lymph from the anterior wall of the bladder along the obliterated umbilical artery to the internal iliac (hypogastric) nodes; the lateral route, which drains lymph from the pelvic organs to the medial chain of the external iliac nodal group (a characteristic route of spread from carcinomas at the lateral aspect of the bladder and from prostate adenocarcinomas); the internal iliac (hypogastric) route, which drains lymph from most of the pelvic organs along the visceral branches of the internal iliac lymphatic ducts to the junctional nodes located between the internal and external iliac vessels; and the presacral route, which includes the lymphatic plexus anterior to the sacrum and coccyx and extending upward to the common iliac nodes.<a class="elsevierStyleCrossRef" href="#bib0410">30</a>Intraoperative sentinel node identificationTraditionally, radioguided intraoperative SLN localization is based on the acoustic signal provided by a handheld gamma probe. Surgery is performed 5–24h after tracer injection. In the original radioguided open-surgery approach, the handheld gamma probe was subsequently used to locate the active nodes in vivo and after excision, to ex vivo confirm the SLN's activity, to separate it from adjacent fatty tissue or other nodes, and to finally check the operation field for residual activity. Since its validation the SLN concept required knowledge of the state of both SLN and non-SLN metastases. Therefore, backup EPL was performed after SLNs retrieval, to get the logistics right and to make sure the method was properly executed.<a class="elsevierStyleCrossRef" href="#bib0305">9</a>Initial validation was performed under laparotomy through a lower abdominal midline incision to include the lymph node groups below the aortic bifurcation, and to identify the SLNs in the draining basins with a gamma probe. Practical problems are related to the shine-through phenomenon due to the high levels of radioactivity in the prostate after injection, which interfere with the detection of weak gamma rays from the SLN. To prevent the occurrence of this phenomenon, it was recommended to cover the prostate with a lead shield or to start the operation with its resection. Concerning the EPL, this procedure comprises separate removal of the right and left common iliac vessels, external iliac vessels, internal iliac vessels, obturator fossa and presacral lymph node basins.In the middle of the past decade, Jeschke et al., laparoscopically validated SLN biopsy and EPL. To avoid the shine-through phenomenon, they used a gamma probe with the ability to detect gamma rays from 90 degrees laterally.<a class="elsevierStyleCrossRef" href="#bib0310">10</a> Although a strict learning curve exists, laparoscopic extended pelvic lymphadenectomy for validation of the SLN concept is worth performing because this procedure yields an equivalent number of resected nodes with less morbidity.<a class="elsevierStyleCrossRef" href="#bib0415">31</a>Preoperative anatomical information about the lymphatic drainage and the site of the SLNs remains essential during laparoscopy for both planning of operation and probe detection. This has been the reason to incorporate SPECT/CT in the SLN procedure and to display it in the operation room using navigation devices. During the surgical procedure the SPECT/CT image provides guidance toward the area of the SLN, but the spatial orientation is often related to large anatomic structures such as vessels and bone. Movement of internal anatomy of the patient during the surgical procedure limits the accuracy of sole SPECT/CT-based navigation. Real-time gamma probe detection allows acoustic tracing of the SLN location. This technique, however, suffers from background signals from the injection site (e.g., prostatic fossa) and collimator issues that hamper depth perception.These limitations became an important argument for the incorporation of new devices such as portable gamma cameras for intraoperative imaging. This approach facilitates the SLN localization and resection. Using a 125I seed placed at the tip of the laparoscopic probe it is possible to use the device as a pointer to localize the SLN on screen based on the different display of the signals of 125I (circle) and 99mTc (radioactive sentinel node). After the matching of both signals on screen and the confirmation of the acoustic signals of the probe sentinel node dissection can follow (<a class="elsevierStyleCrossRef" href="#fig0040">Fig. 8</a>). After removal of all SLNs, the portable gamma camera can be used to detect any remaining SLNs that have to be removed, or to discriminate a second-echelon node that can confidently be left in place. This approach provides certainty about the completeness of the surgical procedure and complements the laparoscopic probe.<a class="elsevierStyleCrossRef" href="#bib0320">12</a><elsevierMultimedia ident="fig0040"></elsevierMultimedia>Other devices permit the “intraoperative navigation” with the aid of a fiducial reference target detected by an optical tracking system. Visualizing the SPECT/CT images from the perspective of the endoscope is the essence of the proposed navigation approach. A virtual view can be a 3D render of the combined volumetric CT and SPECT data. However, navigation systems do not always provide exact localization of the target lesions in soft movable tissues like in pelvic SLN procedures. In these areas, the intervention may alter the position of the lesions of interest relative to more rigid reference points such as the skeleton and these navigation systems cannot compensate for such deformation, rendering them less accurate.<a class="elsevierStyleCrossRef" href="#bib0420">32</a>Robot-assisted surgery is an extension of laparoscopic surgery. The robot adds enhanced vision and control and consists of several components, including an ergonomically designed console, interactive robotic arms, and a three-dimensional, high-definition vision system.Nowadays, the robotic-assisted laparoscopic procedure is increasingly used and the potential to identify nodes visually has stimulated a push toward the off-label use of the near-infrared 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 with tumor tissue. However, fluorescence imaging enables intraoperative identification of the SLNs in the areas where acoustic gamma tracing is inefficient. In the other areas fluorescence helped to identify the exact location of the SLNs with a higher precision provided that SLN location had been previously determined using preoperative SPECT/CT or intraoperative gamma camera tracing. Equally important to realize is the fact that the tissue penetration of near-infrared fluorescent signals lies below 1cm, a limitation that may prevent the identification of relevant (or distant) nodes.<a class="elsevierStyleCrossRef" href="#bib0425">33</a>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. Because ICG is in origin an angiographic imaging agent, it may yield background signals in the form of fluorescent blood vessels.The hybrid radiotracer ICG-99mTc-nanocolloid permits to combine in one signature the advantages of optical fluorescence guidance and the radiotracer properties (<a class="elsevierStyleCrossRef" href="#fig0045">Fig. 9</a>).<a class="elsevierStyleCrossRef" href="#bib0430">34</a><elsevierMultimedia ident="fig0045"></elsevierMultimedia>The development of surgical fluorescence cameras and the clinical implementation of new hybrid imaging agents are important to improve surgical efficacy. Integration of these developments into technical surgical procedures such as minimally invasive robot-assisted laparoscopy on the basis of a radioactivity/fluorescence hybrid approach, may contribute to extend the frontiers of radioguided surgery to other applications. However, limiting for these extended applications, is obtaining the approval for the clinical use of new imaging agents. The multimodal ICG-99mTc-nanocolloid imaging agent circumvents this problem because a cocktail of the ICG and 99mTc-nanocolloid, both clinically approved in Europe, is used to form the multimodal complex without requirement of any chemical modifications or altering the toxicologic profile. As such, ICG-99mTc-nanocolloid may facilitate the clinical introduction of the multimodal surgical guidance concept in the coming years.ResultsThe pioneers of the SLN biopsy in prostate cancer, based on open surgery and the use of a hand held gamma probe, performed an additional extended lymph node dissection so to demonstrate the reliability of this method.<a class="elsevierStyleCrossRef" href="#bib0305">9</a> The false-negative rate was very low when compared to the gold standard. Later on, with more experience, the SLN identification rate reached >95%.<a class="elsevierStyleCrossRef" href="#bib0325">13</a> Additional evidence for the open surgery approach and later on the reliability of the laparoscopic SLN method was found in the fact that the diagnostic yield was twice as high compared to classical pelvic node dissection series and identical to modern series of open EPL.<a class="elsevierStyleCrossRef" href="#bib0435">35</a>In most series, a SLN was generally identified in 90–100% of patients, a SLN was positive in 12–25% of cases, and false negative rates were reported in about 7% or less (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>In the largest series with more than 2000 patients evaluated using gamma probe guided SLN biopsy only 11 false negative cases (5.5%) were reported; this acceptable rate warrants the reliability of the method.<a class="elsevierStyleCrossRef" href="#bib0440">36</a>In 2006 Corvin et al. validated laparoscopic SLN pursuing to obtain a lower morbidity, less postoperative pain and shorter hospital stays. Using a gamma camera for preoperative lymph mapping and a laparoscopic gamma probe intra-operatively they proved that this approach might be an acceptable alternative to EPL.<a class="elsevierStyleCrossRef" href="#bib0415">31</a> On the other hand, if a laparoscopic prostatectomy is performed, the combination with a laparoscopic SLN procedure is the logical combination. The open and the laparoscopic SLN procedures have the same diagnostic yield.<a class="elsevierStyleCrossRef" href="#bib0435">35</a> Especially, patients opting for an external-beam radiation treatment have much to gain by a laparoscopic procedure.<a class="elsevierStyleCrossRef" href="#bib0445">37</a>In a meta-analysis performed a few years ago the pooled SLN detection rate (open and laparoscopic approaches) was 93.8% (95%CI 89–96.6%), which is high enough to be considered applicable in this malignancy (as results in similar yield than SLN detection rates for other cancer types). However, some heterogeneity, most likely attributed to different techniques applied (tracer preparation, injected activity and type of surgery), was detected among the studies. For instance, a slightly higher SLN detection rate was observed in patients who underwent open surgery in comparison with those with laparoscopic approach (94.4% vs. 92%). Also recent technological advances can have impact on the technique. The groups that used pre-operative SPECT/CT images showed a pooled detection rate higher than those using static pre-operative images (92.9% vs. 92%).<a class="elsevierStyleCrossRef" href="#bib0450">38</a>However, in some recent series SPECT/CT was up to 63% advantageous over planar imaging and recent laparoscopic and robotic-assisted approaches are based on this pre-operative information.<a class="elsevierStyleCrossRef" href="#bib0385">25</a> Moreover, SLN biopsy allows the sampling of SLNs outside the pelvic lymphadenectomy field and this can be pre-visualized with the accurate information provided by SPECT/CT. SPECT-CT scan is also a useful tool to localize the SLNs in pararectal/presacral regions. These pelvic areas are accessible for new modalities of laparoscopic surgery such as robot-assisted procedures, making excision of these nodes possible.<a class="elsevierStyleCrossRefs" href="#bib0455">39,40</a>In a series concerning 74 patients, Joniau et al. reported a total of 470 scintigraphic detected SLNs (median 6) of which 371 SLNs were removed. In total, 91 positive SLNs (median 2) were found in 34 of 74 patients. The authors identified SLNs mainly in 5 regions: obturator fossa (25%), internal iliac (25%), external iliac (19%), common iliac (14%), presacral (13%) but also in other lymphatic basins like the pararectal, paravesical and para-aortic regions, in mesenteric fat and at the aortic bifurcation.<a class="elsevierStyleCrossRef" href="#bib0465">41</a> Their findings added more evidence that SLNs are often widely spread, suggesting potential for positive lymph nodes in a large number of areas that current lymphadenectomy margins do not account for (44% of SLNs were located outside the extended pelvic lymphadenectomy field) and in 6% of patients, a positive SLN was located exclusively in the presacral or paraaortic region. They concluded that although standard EPL would have correctly staged the majority of positive-node patients, a 13% of the metastatic nodes would have been missed.The reported pooled sensitivity of SLN mapping of 94% (95% CI 91–96%) indicates that the false negative rate appears to be lower than the recommended one for breast cancer patients. Actually this provides evidence that the SLN procedure today is not only sufficiently standardized but is also a reliable technique.However, there is still some variability concerning sensitivity among the different groups reporting SLN biopsy in prostate cancer. For example, in a very recent study that comprised 74 patients with clinically node-negative localized prostate adenocarcinoma, van den Bergh et al. found that only 79% of visualized SLN were removed with the aid of gamma probe. Twenty-eight patients were node-positive based on the analysis of the resected SLN. However, the EPL that was performed as a reference revealed nine additional positive-node patients, resulting in a sensitivity of 76%. In total, 15 of 37 patients (41%) had metastases in SLN only and could have been spared EPL to remove all affected nodes. Thus, in this study a relatively low sensitivity when addressing the SLN procedure for nodal staging in prostate cancer patients.<a class="elsevierStyleCrossRef" href="#bib0470">42</a>Additional tools such as the intraoperative imaging provided by portable gamma cameras may make the (especially laparoscopic) excision of a SLN easier and even more reliable. This approach was recently evaluated in 55 patients. Out of 178 sentinel nodes visualized on SPECT-CT 16 nodes (9%) could not be reproduced with the portable gamma camera because of a weak signal and 13 (7%) because of their location in close proximity with the site of the tracer injection in the prostate. In 15 patients a 125I seed pointer was useful to directly localize nodes (principally along the aorta and common iliac artery cranial from ureter crossing) and in the other patients the portable gamma camera was used to verify adequate excision after removal of the SLN leading to the identification of 17 additional SLNs (<a class="elsevierStyleCrossRef" href="#fig0040">Fig. 8</a>). In two of these cases sentinel nodes were tumor-positive.<a class="elsevierStyleCrossRef" href="#bib0320">12</a>Pre-operative SPECT/CT and intraoperative portable gamma camera imaging provide a road map of anatomic relationships to facilitate the proposed surgery. Conversely, image-guided surgery provides in situ, real time visualization of either preoperative or intraoperative data along with the actual anatomy. In this sense, the utilization of fluorescent agents has been gaining acceptance during the last years. Manny and colleagues, reported on their initial series of fluorescence-enhanced robotic radical prostatectomy using real-time injection of ICG for tissue marking and identification of SLNs. In this study, ICG was injected into each lobe of the prostate using a robotically guided percutaneous needle. After ICG was allowed to travel through the pelvic lymphatic channels, lymphadenectomy was performed under the near-infrared visualization system integrated to the surgical robot. They found that using this technique, SLNs were identified in 76% of patients at a mean time of 30minutes after injection and had 100% sensitivity, 75.4% specificity, 14.6% positive predictive value, and 100% negative predictive value for detection of nodal metastasis. Thus, they concluded that ICG guided SLN biopsy is highly sensitive, but not specific enough for the detection of nodal metastasis.<a class="elsevierStyleCrossRef" href="#bib0475">43</a>So it seems that the time schedule and the limited penetration depth of the ICG (<1.0cm) hampers preoperative SLN mapping. This leads to a necessary meticulous scanning of, and beyond, the EPL area during operation. This issue is time-consuming and may potentially miss SLNs. Hence, the need to combine ICG with radiocolloid-based preoperative SLN mapping methods.This approach was performed in 26 consecutive patients who received 99mTc-labelled colloid (18h before surgery) and ICG (immediately before surgery) injected transrectally into the prostate. Intraoperatively, a dedicated laparoscopic fluorescence imaging system and a laparoscopic γ-probe were used. Fluorescent lymphatic vessels were visualized in real time and followed to identify the SLN. Nevertheless, all detected hot spots (fluorescent signals and/or radioactivity) were considered as SLNs and removed. A strong correlation was established between radioactive and fluorescent lymph nodes. The authors reported that, compared with radioguided SLN dissection alone, the additional fluorescence-guided procedure demonstrated a further 120 lymph nodes.<a class="elsevierStyleCrossRef" href="#bib0335">15</a>To facilitate an integrated use of preoperative imaging with fluorescence guidance, a hybrid tracer, ICG-99mTc-nanocolloid, was developed and introduced in the urological clinical setting.<a class="elsevierStyleCrossRefs" href="#bib0430">34,44</a>This hybrid tracer allowed for preoperative detection of the SLNs with SPECT/CT, whereas both the combination of the gamma detection probe and near infrared fluorescence detection of ICG enabled intraoperative localization of the SLNs.Four of 27 SLNs were preoperatively identified outside the extended lymphadenectomy field on SPECT/CT, which could thereafter be intraoperatively visualized with fluorescence. A strong correlation was found between the radioactive and fluorescent contents in the excised lymph nodes indicating that the ICG-99mTc-Nanocoll complex remained stable in the time period between injection and dissection of SLNs. This was previously demonstrated in an animal experiment.<a class="elsevierStyleCrossRef" href="#bib0485">45</a>However, 15% of the SLNs could not be intraoperatively detected with fluorescence imaging alone due to the limited tissue penetration of the ICG fluorescent signal. Especially in these instances, guidance to regions of interest by the radioactive component to the hybrid tracer remains desirable.<a class="elsevierStyleCrossRef" href="#bib0430">34</a> To increase this potential synergism of preoperative SPECT/CT imaging with fluorescence guidance, an optimization study was carried out. Following the initial feasibility study, 40 additional prostate cancer patients were included. These patients were divided in 3 groups and the authors systematically evaluated whether optimization of the tracer formulation and fluorescence hardware improvements could help increase in vivo fluorescence-based SLN identification during robot-assisted laparoscopic procedures (<a class="elsevierStyleCrossRef" href="#fig0045">Fig. 9</a>). In groups 1 and 2, SNs were pursued intraoperatively using a laparoscopic gamma probe followed by fluorescence imaging. In group 3, SLNs were initially located via fluorescence.<a class="elsevierStyleCrossRef" href="#bib0490">46</a>At least one SLN was preoperatively identified in 38 of the 40 patients. Non-visualization occurred in two patients bilateral (5.0%) and unilateral in five patients (12.5%). Lymphoscintigraphy and SPECT/CT identified a total of 119 SNs (median: 3). The change of the hybrid tracer formulation did not yield a significant difference in the number of preoperatively visualized SLNs. However, with the new tracer formulation, flushing was no longer necessary after placement of the different tracer deposits, increasing the easiness of the procedure. In 7 patients, 14 additional SLNs were removed during surgery based on their fluorescent and radioactive appearance in the same region as the SLNs detected with preoperative imaging. In 16 patients (40.0%), a SLN was located outside the extended pelvic lymphadenectomy area. Interestingly, in vivo fluorescence-based SLN visualization percentage of groups 1 and 2 was found to be 63.7% and 85.2%, respectively. Following the introduction of the upgraded laparoscopic system (group 3), the mean intraoperative visualization percentage increased to 93.5%. Ex-vivo analysis showed 123 out of 127 fluorescent SLNs (96.9%), while all 127 SLNs were radioactive (100.0%). The authors concluded that changing the hybrid tracer formulation and injection technique and upgrading the laparoscopic system significantly improve in vivo fluorescence-based SLN identification.<a class="elsevierStyleCrossRef" href="#bib0490">46</a>Additionally, Brouwer et al. reported on an intraoperative surgical navigation system based on preoperative 3D scintigraphic images that improved the efficacy of the hybrid fluorescent radiotracer. This study, designed as proof of principle, successfully showed the feasibility of combined rigid navigation based on preoperative SPECT/CT images and intraoperative fluorescence imaging for soft tissue navigation.<a class="elsevierStyleCrossRef" href="#bib0495">47</a>Navigation systems such as these remain complicated and are, at this moment, limited to the experimental realm, although more investigation is underway.Future prospectsBased on several thousand of patients, radioguided SLN biopsy using 99mTc-nanocolloids has been found to be highly sensitive for identifying lymph node metastases in prostate cancer. It has been possible to demonstrate that for this approach, the rate of lymph node involvement was higher in a sentinel cohort than was expected from the European Association of Urology guideline nomogram.<a class="elsevierStyleCrossRef" href="#bib0500">48</a>. More recently, a first SLN-based nomogram SLN to predict the probability of lymph node involvement demonstrated a high degree of accuracy.<a class="elsevierStyleCrossRef" href="#bib0505">49</a>Meanwhile, efforts are made on targeted removal of lymphatic nodes in combination with laparoscopic or robot-assisted radical prostatectomies, in order to lower the extensive effort associated with an extended pelvic lymphadenectomy.Currently this laparoscopic approach can be combined by using near-infrared fluorescence imaging to improve nodal dissection during laparoscopic or robotic surgery. The concept is that fully integrated fluorescence-aided nodal identification provides a rapid and easy-to-use technique to introduce the concept of specific SLN in conjunction with extended nodal dissection.<a class="elsevierStyleCrossRef" href="#bib0425">33</a>However, the clinical introduction of fluorescent tracers, in particular for urological applications, is still in its childhood, though rapidly emerging.Laparoscopic challenges lie in the further optimization of targeted and/or activatable (hybrid) imaging agents as well as in the integration between imaging agents and camera systems, thereby enabling more accurate fluorescence image guidance during surgical interventions.<a class="elsevierStyleCrossRef" href="#bib0510">50</a>Other non-radiactive tracers have been tested (blue dyes, fluorescent tracers,) but their results have not achieved to surpass the radiotracer outcome. Recently, a study using open surgery and paramagnetic iron-oxide particles in 20 patients has been reported. Although this feasibility study was applied for the first time ever to the prostate, the detection rate on a patient basis was found to be 90%. This procedure of magnetic marking and magnetometer-guided SLN biopsy appears to be safe for open surgery, can be performed easily and by a urologist on his own, and has the advantage of carrying no radioactive elements. However, for now it is limited to open surgery and the absence of preoperative imaging may hamper an adequate personalized lymphatic mapping with a more specific SLN identification.<a class="elsevierStyleCrossRef" href="#bib0515">51</a>On the other hand, the potential of new devices to guide the surgeon to the target is increasing. In principle they are aimed to solve two of the major limitations encountered during radioguided SLN biopsy (the identification of near-injection-site SLNs and separation of cluster nodes). This new “hybrid” radioguidance approach is, as we speak, already able to provide rapid and clear visibility of hotspots relative to the anatomic context of the patient (video feed; augmented-reality) and subsequently the possibility to virtually navigate towards these SLNs. Other novel techniques provide integration of otherwise separately used image-guided surgery technologies, namely: hand-held gamma probe, manual gamma camera, 3D-free hand SPECT, augmented-reality display, and virtual navigation. This potential, not only improves surgical logistics, but also provides perspective for more complex radioguided procedures in the future.<a class="elsevierStyleCrossRef" href="#bib0520">52</a>Key points<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0055">1.Prostate-specific antigen (PSA) levels, pathologic stage, and Gleason score are predictors for lymph node involvement. The prevalence of infiltration of the lymph nodes has been shown to be around 25% of the patients with prostate cancer with a reduction in 5-year survival of 85% in N0 patients and 50% in N1 patients.</li><li class="elsevierStyleListItem" id="lsti0060">2.The approach using lymphatic mapping and gamma detection probe is not yet recommended for routine use in the current surgical guidelines for management of prostate cancer.</li><li class="elsevierStyleListItem" id="lsti0065">3.Pre-operative SPECT/CT and intraoperative portable gamma camera imaging provide a road map of anatomic relationships to facilitate the proposed surgery. Conversely, image-guided surgery provides in situ, real time visualization of either preoperative or intraoperative data along with the actual anatomy.</li><li class="elsevierStyleListItem" id="lsti0070">4.SPECT/CT image provides anatomic guidance toward the area of the SLN. Real-time gamma probe detection allows acoustic tracing of the SLN location. Intraoperative imaging provides certainty about the completeness of the surgical procedure and complements the laparoscopic probe.</li><li class="elsevierStyleListItem" id="lsti0075">5.The tissue penetration of near-infrared fluorescent signals lies below 1cm, a limitation that may prevent the identification of relevant nodes.</li></ul>The small size of free ICG means that it flows freely through the lymphatic system and is therefore suited for real-time lymphangiography. The hybrid radiotracer ICG-99mTc-nanocolloid permits to combine in one signature the advantages of optical fluorescence guidance and the radiotracer properties.Conflict of interestThe authors declare they have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres575065" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec591834" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres575064" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec591835" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Introduction" "secciones" => array:1 [ 0 => array:3 [ "identificador" => "sec0010" "titulo" => "Lymphatic mapping technique" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Injection and radiotracer" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Lymphoscintigraphy" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Lymph node groups in the pelvis" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Intraoperative sentinel node identification" ] ] ] ] ] 5 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Future prospects" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Key points" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflict of interest" ] 9 => array:2 [ "identificador" => "xack193819" "titulo" => "Acknowledgement" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec591834" "palabras" => array:6 [ 0 => "Prostate cancer" 1 => "SPECT/TC" 2 => "Intraoperative imaging" 3 => "Fluorescence" 4 => "Intraoperative navigation" 5 => "Extended lymphadenectomy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec591835" "palabras" => array:6 [ 0 => "Cáncer de próstata" 1 => "SPECT/TC" 2 => "Imagen intraoperatoria" 3 => "Fluorescencia" 4 => "Navegación intraoperatoria" 5 => "Linfadenectomía extendida" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "In general terms, one of the main objectives of sentinel lymph node (SLN) biopsy is to identify the 20-25% of patients with occult regional metastatic involvement. This technique reduces the associated morbidity from lymphadenectomy, as well as increasing the identification rate of occult lymphatic metastases by offering the pathologist those lymph nodes with the highest probability of containing metastatic cells. Pre-surgical lymphoscintigraphy is considered a “road map” to guide the surgeon towards the sentinel nodes and to ascertain unpredictable lymphatic drainages. In prostate cancer this aspect is essential due to the multidirectional character of the lymphatic drainage in the pelvis. In this context the inclusion of SPECT/CT should be mandatory in order to improve the SLN detection rate, to clarify the location when SLNs are difficult to interpret on planar images, to achieve a better definition of them in locations close to injection site, and to provide anatomical landmarks to be recognized during operation to locate SLNs.Conventional and laparoscopic hand-held gamma probes allow the SLN technique to be applied in any kind of surgery. The introduction and combination of new tracers and devices refines this technique, and the use of intraoperative images. These aspects become of vital importance due to the recent incorporation of robot-assisted procedures for SLN biopsy. In spite of these advances various aspects of SLN biopsy in prostate cancer patients still need to be discussed, and therefore their clinical application is not widely used." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "En términos generales uno de los principales objetivos de la biopsia del ganglio centinela (GC) es identificar el 20-25% de pacientes que presentan enfermedad ganglionar regional clínicamente oculta. Esta técnica minimiza la morbilidad asociada a la linfadenectomía y aumenta también la tasa de identificación de metástasis linfáticas ocultas al ofrecer al patólogo aquel o aquellos ganglios con mayor probabilidad de contener células tumorales. La linfogammagrafía prequirúrgica se considera como un “mapa de carreteras” para guiar al cirujano hacia los GC y para la localización de patrones de drenaje impredecibles. En cáncer de próstata este aspecto adquiere especial importancia debido a su drenaje multidireccional en la pelvis. En ese contexto la inclusión de SPECT/TC aparece como esencial para lograr un mejor índice global de detección del GC, clarificar la existencia y ubicación de ganglios centinelas difíciles de interpretar a las imágenes planares, conseguir una mejor definición de los mismos en localizaciones cercanas a la inyección y entregar puntos de referencia anatómica que puedan ser reconocidos durante la operación para localizar los GC.La utilización de sondas detectoras de rayos gamma convencionales o laparoscópicas permiten la aplicación de la técnica en cualquier tipo de cirugía. La implementación y combinación de nuevos dispositivos y trazadores permite refinar la técnica, así como la utilización de imágenes intraoperatorias. Estos aspectos han ido adquiriendo especial importancia debido a la incorporación de la biopsia del GC en protocolos que emplean cirugía robótica. A pesar de ello, la aplicación clínica de la biopsia del GC en pacientes con cáncer de próstata todavía sigue incluyendo aspectos a discutir y por ello su aplicación clínica no se ha generalizado." ] ] "multimedia" => array:11 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1268 "Ancho" => 1800 "Tamanyo" => 337540 ] ] "descripcion" => array:1 [ "en" => "Transrectal ultrasound (A) guidance of radiotracer administration by means of transrectal (B) and transperineal (C) injections in two different patients. The tracer is administered in both prostatic lobes using a 3-way system with subsequent saline flushing (D). With a portable gamma camera it is possible to monitor the tracer deposition in both sides of the prostate (E)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1934 "Ancho" => 2667 "Tamanyo" => 578860 ] ] "descripcion" => array:1 [ "en" => "Distribution of sentinel lymph nodes in different pelvic basins (white caption) according to Wawroschek F. et al. (Urologe 2005; 44: 630–634). Also sentinel lymph nodes found in other locations are indicated (green caption) according to Meinhardt et al.<a class="elsevierStyleCrossRef" href="#bib0315">11</a>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1142 "Ancho" => 1750 "Tamanyo" => 304358 ] ] "descripcion" => array:1 [ "en" => "Early (A) and delayed (B) planar images showing bilateral iliac drainage. SPECT/CT with volume rendering (C) as well as transversal slices (D and E) show not only more sentinel lymph nodes in different basins, but also an accurate anatomical pelvic localization." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1251 "Ancho" => 1400 "Tamanyo" => 239641 ] ] "descripcion" => array:1 [ "en" => "Delayed planar image (A) and volume rendering SPECT/CT show bilateral pelvic drainage (B). Transversal SPECT/CT (C and D) at the same slice level show additional sentinel lymph nodes in different pelvic lymphatic basins." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1229 "Ancho" => 1800 "Tamanyo" => 310907 ] ] "descripcion" => array:1 [ "en" => "Early (A) and delayed (B) planar as well as volume rendered SPECT/CT (C) showing bilateral pelvic drainage. On transversal SPECT/CT location of sentinel lymph nodes can be related to inside (D and E) and outside of (F) the area of extended pelvic lymphadenectomy." ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Fig. 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1352 "Ancho" => 1800 "Tamanyo" => 338013 ] ] "descripcion" => array:1 [ "en" => "Early planar scintigraphy (A) and volume rendered SPECT/CT (B) showing bilateral pelvic drainage with not only iliac sentinel lymph nodes (C–E) but also para-aortic (F)." ] ] 6 => array:7 [ "identificador" => "fig0035" "etiqueta" => "Fig. 7" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr7.jpeg" "Alto" => 2255 "Ancho" => 3000 "Tamanyo" => 530297 ] ] "descripcion" => array:1 [ "en" => "Criteria to categorize radioactive lymph nodes as definite sentinel lymph nodes (SLNs 1, 2 and 3 appearing early after tracer administration as shown on left superior image), highly probable SLN (node 4 clearly defined on delayed acquired right superior image) and less probable SLN (higher-echelon node 5). Note on transversal SPECT/CT (first inferior image) that nodes 1 and 2 correspond with two SLNs in each pelvic side. The two iliac SLNs on the right correspond in turn with lymph node clusters (circles) on CT (second inferior image). Node 3 is a para-aortic SLN (third inferior image) and node 4 is a paravesical SLN on the right (last inferior image) displayed in the same slice with additional pararectal and iliac SLNs in the left pelvic side." ] ] 7 => array:7 [ "identificador" => "fig0040" "etiqueta" => "Fig. 8" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr8.jpeg" "Alto" => 1209 "Ancho" => 1750 "Tamanyo" => 306539 ] ] "descripcion" => array:1 [ "en" => "Sampling of a para-aortic sentinel lymph node (A) using a laparoscopic gamma probe with a 125I seed on the top (B) to indicate the location of the node during operation (C) as a super-imposed dotted circle on screen (D) based on the dual channel signal registration of a portable gamma camera (E) for continuous intraoperative monitoring. Note that after SLN removal no residual activity is observed on screen (F)." ] ] 8 => array:7 [ "identificador" => "fig0045" "etiqueta" => "Fig. 9" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr9.jpeg" "Alto" => 1137 "Ancho" => 1750 "Tamanyo" => 226531 ] ] "descripcion" => array:1 [ "en" => "Robot-assisted sentinel lymph node procedure (A) using laparoscopic devices for fluorescence and radioactivity detection (B) after administration of ICG-99mTc-nanocolloid in a patient with prostate cancer. The acoustic signals of the gamma probe indicate the location of the sentinel lymph node (C), which is subsequently visualized thanks to the fluorescence (D). The fluorescent node ex-vivo is clearly differentiated from the surrounding non-fluorescent fat tissue (E)." ] ] 9 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Adapted from NCCN guidelines 2015. www.nccn.org; accessed 27/2/2015." "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T: Primary tumor \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Tx: Primary tumor cannot be assessed \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T0: No evidence of primary tumor \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T1: Tumor clinically inapparent, neither palpable or visible using imaging techniques \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T1a: Tumor detected as incidental finding in an extension ≤5% of the tissue resected \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T1b: Tumor detected as incidental finding in an extension greater than 5% of the tissue resected \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T1c: Tumor identified by biopsy puncture (i.e. because of elevated PSA) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T2: Tumor confined within prostate<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T2a: The tumor involves half of a lobe or less \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T2b: The tumor involves more than half of a lobe but not both lobes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T2c: The tumor involves both lobes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T3: Tumor which extends beyond the prostatic capsule<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T3a: Extracapsular extension (uni or bilateral) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T3b: Tumor which invades the seminal vesicle(s) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T4: Tumor is fixed or invades adjacent structures other than the seminal vesicles: vesicle neck, external sphincter, rectum, elevator muscles of the anus and/or pelvic wall \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">N: Regional lymph nodes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Nx: Regional lymph nodes cannot be evaluated \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">N0: Regional lymph node metastasis not shown \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">N1: Metastasis in regional lymph nodes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">M: Distant metastasis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mx: Distant metastasis cannot be evaluated \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">M0: No distant metastasis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">M1: Distant metastasis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">M1a: Non regional lymphatic lymph node(s) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">M1b: Bone(s) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">M1c: Other localization(s) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab938477.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Tumor in one or both lobes by needle biopsy but not palpable and visible by imaging, is classified as T1c." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is not classified as T3, but as T2." ] ] ] "descripcion" => array:1 [ "en" => "TNM staging." ] ] 10 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "N/A: not available." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Author \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Year \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patients \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Radiotracer \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Surgery \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mean SN \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Identification rate (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FN \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Wawroschek \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">350 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99mTc-nanocolloid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Open \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">95.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 cases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Schafhauser \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2006 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">162 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99mTc-nanocolloid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Open \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99.3% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 case \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Brenot-Rossi \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99mTc-nanocolloid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Open \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">76% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hautmann \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">108 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99mTc-nanocolloid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Open \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Jeschke \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">140 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99mTc-HSA colloid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Laparoscopic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">94.3% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Holl \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2020 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99mTc-nanocolloid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Open \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">98% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Varga \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2010 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99mTc-HSA colloid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Open \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">89.6% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Marchioro \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2010 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">123 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99mTc-nanocolloid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Open \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">71.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Schilling \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2010 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">463 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99mTc-nanocolloid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Open/Laparoscopic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Meinhardt \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">121 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99mTc-nanocolloid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Laparoscopic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">96.6% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Winter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1229 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99mTc-nanocolloid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Open \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.4% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Muck \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">819 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99mTc-nanocolloid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Open \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">93.6% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.9% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Kleinjan \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ICG-99mTc-nanocolloid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Robot-assisted laparoscopy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 cases \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] 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Sentinel node approach in prostate cancer

El ganglio centinela en el cáncer de próstata

S. Vidal-Sicarta,

Corresponding author

svidal@clinic.ub.es

Corresponding author.

, R.A. Valdés Olmosb,c

a Nuclear Medicine Department, Hospital Clínic Barcelona, Barcelona, Spain

b Interventional Molecular Imaging and Nuclear Medicine Section, Leiden University Medical Centre, Leiden, The Netherlands

c Nuclear Medicine Department, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Prostate cancer is predominantly a tumor of older males but it is the most frequent urogenital malignancy&#44; the most common solid neoplasm and the second most common cause of death by cancer in males in Europe&#46; Median age at diagnosis is 72 years&#46; In the United States more than 200&#44;000 new patients are diagnosed every year&#46; Age-standardised cases of incidence and mortality per 100&#44;000 population per year were 96&#46;0 and 19&#46;3 in Europe and 96&#46;8 and 15&#46;2 in Spain&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In the period 1989&#8211;2008&#44; in Spain there were 104&#44;955 deaths due to prostate cancer&#44; accounting for 10&#37; of mortality among all male malignant tumors&#46; The prostate cancer mortality pattern was not at all pronounced&#44; indicating&#44; as in the case of breast cancer among women&#44; territorial uniformity in exposure to possible risk factors&#46; A south-north pattern was in evidence during the first three quinquennia&#46; In Andalusia&#44; which had registered lower than expected mortality in the first three quinquennia&#44; a change seemed to be taking place in the period 2004&#8211;2008&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The diagnosis of prostate cancer is well established&#44; being based on the determination of the prostate-specific antigen &#40;PSA&#41;&#44; rectal tact&#44; transrectal echography and prostate gland biopsy&#46; The performance of a biopsy is guided by the ultrasound suspicious image but should be randomly performed to collect a sufficient number of samples from each lobe&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A majority of the tumors are adenocarcinomas and magnetic resonance &#40;MRI&#41; is the technique of choice for accurate delimitation of extension&#58; capsular infiltration&#44; invasion of the neurovascular bundle and infiltration of the seminal vesicles&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Currently&#44; the most used histologic grading system is the Gleason scale&#44; which recognizes the following categories<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">4</span></a>&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><p id="par0030" class="elsevierStylePara elsevierViewall">Gx&#44; grade of differentiation cannot be evaluated&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><p id="par0035" class="elsevierStylePara elsevierViewall">Gleason 2&#8211;4 &#40;G1&#41;&#44; well differentiated &#40;weak anaplasia&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><p id="par0040" class="elsevierStylePara elsevierViewall">Gleason 5&#8211;6 &#40;G2&#41;&#44; moderately differentiated &#40;moderate anaplasia&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><p id="par0045" class="elsevierStylePara elsevierViewall">Gleason 7&#8211;10 &#40;G3&#8211;4&#41;&#44; poorly differentiated&#47;undifferentiated &#40;marked anaplasia&#41;&#46;</p></li></ul></p><p id="par0050" class="elsevierStylePara elsevierViewall">Staging follows the TNM approach&#44; as depicted in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">On the other hand&#44; the lymph node status serves as a key predictor for clinically localized prostate cancer&#46; As in many other cancers&#44; lymph node staging is important for both prognosis and therapeutic management&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Prostate-specific antigen &#40;PSA&#41; levels&#44; pathologic stage and Gleason score are predictors for lymph node involvement&#59; the higher these factors&#44; the greater is the probability of nodal involvement&#46; The prevalence of infiltration of the lymph nodes has been shown to be approximately 25&#37; of the patients with prostate cancer with a reduction in 5-year survival of 85&#37; in N0 patients and of 50&#37; in N1 patients&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The presence of lymph node metastatic involvement may lead to the abandon of local curative therapy&#44; such as radiotherapy or radical prostatectomy&#44; and subsequently to initiate androgen deprivation therapy&#46; Limited nodal metastases may be treated with extended pelvic lymph node dissection or with external beam radiation therapy combined with long-term androgen deprivation therapy&#46; Currently&#44; none of the available imaging diagnostic modalities provides a reliable assessment of lymph node metastases&#46; Conventional imaging techniques show a low sensitivity in the localization of lymph node disease since the criteria accepted to define pathologic character is size and&#44; on many occasions&#44; involved lymph nodes smaller than 1<span class="elsevierStyleHsp" style=""></span>cm&#46; Thus&#44; the sensitivity of computerized tomography &#40;CT&#41; varies greatly&#44; being between 25 and 70&#37; and from 75 to 78&#37; for MRI&#46; The sensitivity of these modalities is particularly limited in metastasis smaller than 5<span class="elsevierStyleHsp" style=""></span>mm&#46; This has contributed to establish the role of extended pelvic lymphadenectomy &#40;EPL&#41; as the gold standard for the identification of lymph node metastases in prostate cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">5</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Post-operative pathologic examinations of tissue samples obtained during EPL assess metastatic spread&#46; With an increase in the dissection template and the thorough histopathologic study of those nodes the N1 group has increased in number with improvement of staging&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">However&#44; the use of EPL has been found to be associated with various complications &#40;venous thrombosis&#44; lymphocele&#44; lower extremity edema and ureteral injury&#41; and its incidence increases with the number of dissected lymph nodes varying from 10&#46;5&#37; for 1&#8211;5 lymph nodes to 24&#46;3&#37; when dissection includes more than 20 lymph nodes&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">6</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Predictive nomograms have therefore been developed&#44; among which the most accepted is the Roach formula &#91;&#40;2&#47;3&#41; PSA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&#40;Gleason-6&#41;<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10&#93;&#46; Using this tool patients who are candidates for lymphadenectomy can be selected&#46; However&#44; whether a standard or extended technique should be performed continues to be a controversy&#44; due to the lack of an imaging technique to assist in the localization of lymph node infiltration&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">7</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Moreover&#44; the area of EPL has its limits&#59; in most descriptions the common iliac artery is only cleared up to the crossing of the ureter&#44; the external iliac vessels as a rule are the lateral border&#44; and the internal iliac is usually cleared from the bifurcation up to just beyond the superior vesical artery&#46; The EPL area as well includes the obturator fossa that consists of the tissue between the external iliac vein and the obturator nerve&#46; Nowadays&#44; several reports indicate that EPL improves biochemical relapse-free survival&#44; especially in patients with minimal lymphatic dissemination&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">8</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">As an alternative for the EPL the sentinel lymph node &#40;SLN&#41; biopsy was introduced using open surgery and a gamma probe&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">9</span></a> Subsequently the procedure was validated for laparoscopy&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">10</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">SLN biopsy focuses on the identification&#44; subsequent to minimal invasive excision and extensive histopathologic evaluation of the lymph nodes that drain directly from the primary tumor&#46; Assuming the orderly spread of tumor cells through the lymphatic system&#44; SLN biopsy can be used for lymph node staging and subsequent therapeutic management&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The advantages of the SLN dissection are a lower incidence of complications and the possibility of identifying tumor-draining lymph nodes outside the field of EPL&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">11</span></a> However&#44; accurate laparoscopic localization of SLNs in the pelvis can be challenging and requires specific skill&#44; especially when these are located near the prostatic injection site &#40;because of the high radioactive background signal&#41;&#44; or in the case of aberrantly located SLNs &#40;e&#46;g&#46;&#44; pre-vesical or para-aortic&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">12</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">For both EPL and SLN procedure the use of predictive nomograms is very important to determine the clinical indication and the probability of nodal involvement for each patient on an individual basis&#46; As stated previously&#44; the probability of lymph node metastases in the pelvis increases with the level of PSA&#44; Gleason score and clinical T stage&#46; This has resulted in the abandon of lymphadenectomy in patients with relatively favourable preoperative risk factors&#59; the procedure is currently reserved principally for patients with intermediate or poor prognosis &#40;clinical stage &#62;T2b&#47;T3&#44; PSA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>ng&#47;l&#44; or Gleason &#62;6&#41;&#46; In the intermediate-risk group&#44; a tumor-bearing SLN may influence the boundaries of the radiotherapy field and duration of androgen-deprivation therapy&#46; Another possible indication is to select patients who are eligible for salvage treatment of the prostate&#46; Since salvage treatment of the prostate may result in serious complications&#44; it should only be considered when the prostate is actually the only tumor-bearing site&#46; However&#44; SLN biopsy has been able to identify metastases in 6&#46;8&#8211;10&#46;7&#37; of patients of the group with favourable risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">13</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Surprisingly&#44; the approach using lymphatic mapping and gamma detection probe is not recommended for routine use in the current surgical guidelines for management of prostate cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">14</span></a> Nevertheless&#44; principally in Europe radioguided SLN biopsy has been thoroughly evaluated for its potential application in the surgical management of prostate cancer&#46; The procedure was originally validated using open surgery and after the first description of the technique by Wawroschek et al&#46; in 1999 multiple reports on the potential application of radioguided SLN biopsy in the surgical management of prostate cancer have been published&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">9</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Since its introduction&#44; the procedure has been subject to several refinements and&#44; in the past 15 years&#44; the surgical technique has shifted from a mainly open procedure to a laparoscopic and later a robot-assisted procedure&#46; For preoperative SN mapping&#44; following the injection of a radioactive tracer&#44; lymphoscintigrams are made&#46; The introduction of single photon emission computed tomography with computed tomography &#40;SPECT&#47;CT&#41; 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cipro&#64258;oxacine&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Subsequently&#44; transrectal radiocolloid injections are administered using ultrasound transrectal guidance into various sites within the peripheral zone of the prostate gland &#40;as prostate cancer may be multifocal&#44; injections are habitually performed in both lobes&#41;&#46; The dosage administered ranges from 60<span class="elsevierStyleHsp" style=""></span>MBq to 400<span class="elsevierStyleHsp" style=""></span>MBq &#40;1&#46;6&#8211;10&#46;8<span class="elsevierStyleHsp" style=""></span>mCi&#41; which is injected in a total volume of normal saline from 0&#46;2<span class="elsevierStyleHsp" style=""></span>mL to 3&#46;0<span class="elsevierStyleHsp" style=""></span>mL mostly between 6<span class="elsevierStyleHsp" style=""></span>h and 24<span class="elsevierStyleHsp" style=""></span>h before the planned surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">17</span></a> An alternative to transrectal injections is the transperineal administration of the radiotracer&#46; Also for this route ultrasound transrectal guidance is necessary &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">However&#44; investigators from the Netherlands Cancer Institute recommend a dose of 240<span class="elsevierStyleHsp" style=""></span>MBq in 0&#46;4<span class="elsevierStyleHsp" style=""></span>mL because the lymph node visualization rate tends to be less optimal when lower activities are used&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Moreover&#44; adjustment of the particle concentration is also important&#44; and a reduced labeling dilution volume &#40;0&#46;4<span class="elsevierStyleHsp" style=""></span>mL <span class="elsevierStyleSup">99m</span>Tc per 0&#46;2<span class="elsevierStyleHsp" style=""></span>mg nanocolloid&#41; yields not only more visualized SLNs but also SLNs with higher radioactivity count rates&#46; A three-way system is recommended&#44; and after each depot saline is used for flushing the residual radioactivity in the needle&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">18</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">According to the experience in other malignancies&#44; the principle of SLN detection in prostate cancer is based on the assumption that accurate node identification is possible after intraprostatic injection of a radioactive tracer guided by ultrasound&#46; As the majority of adenocarcinomas arise in the peripheral zone of the prostate&#44; placement of tracer deposits in this zone is considered favorable for the detection of the tumor draining SLNs&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">19</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">In this context&#44; precision in the placement of the intraprostatic tracer deposits is crucial in order to increase the accuracy of the SLN procedure&#46; However&#44; monitoring the injection of radiotracer&#44; even with transrectal ultrasound&#44; is difficult because the tumour is not always visible&#46; However&#44; it is essential that SLNs identified preoperatively match those intraoperatively removed&#44; since unexpected locations of SLNs outside the field of an extended pelvic lymphadenectomy are not rare and surgery&#39;s prolonged time can thus be avoided&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">20</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Interestingly&#44; Buckle et al&#46; demonstrated that intraprostatic tracer location may indeed be of in&#64258;uence on the lymphatic drainage pattern and that large variations in tracer placement in practice do occur&#46; These authors found that lymphatic drainage from different zones of the prostate follow a distinct lymphatic drainage pattern&#46; From the peripheral zone it seems to be more extensive than from the central zone&#59; injection into the peripheral zone of the prostate resulted in visualization of more lymph nodes per patient&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">21</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Possibly this difference in lymphatic drainage may be explained by the fact that the prostate peripheral zone is more densely packed&#46; Then again&#44; injection of the radiotracer may lead to an increase of the interstitial &#64258;uid pressure and to a higher lymphatic drainage&#46; The relation between increased &#64258;uid pressure after injection and lymphatic drainage may also explain why deposits situated only on the left or right side of the prostate result in a greater number of visualized SLNs and other nodes and&#47;or higher radioactive count rates in the first SLN&#46; Tracer placement in different regions of the prostate also resulted in visualization of different nodal basins&#46; Radiotracer deposits located near the base of the prostate led to the visualization of lymphatic nodes in the common iliac region whereas deposits near the apex of the prostate showed paracaval SLNs&#46; In all cases drainage tended to occur via the standard lymphatic drainage route of the prostate including the obturator fossa&#44; internal iliac&#44; external iliac&#44; common iliac and presacral nodes&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">22</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Although these findings may have implications for SLN biopsies in prostate cancer patients&#44; more extensive research is necessary to draw definitive conclusions&#46; The possibility to use other imaging techniques&#44; like T2-weighted MRI images&#44; to guide radiotracer injection&#44; may become attractive&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">23</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">From a technical point of view&#44; the injection procedure for prostate cancer&#44; is probably the most frequent cause of pitfalls&#46; Care must be taken to avoid tracer leakage during injection&#44; possibly resulting in subsequent contamination &#40;to be checked with a Geiger counter after tracer administration&#41;&#46; During injection&#44; incorrect needle placement may result in spillage of the radiocolloid to the bladder or bloodstream&#44; which may cause SLN nonvisualization or SLN with weak uptake on lymphoscintigraphy&#46; By monitoring the injection procedure with a portable gamma camera&#44; it is possible to ensure adequate radiocolloid retention in the prostate&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Lymphoscintigraphy</span><p id="par0175" class="elsevierStylePara elsevierViewall">Usually&#44; the tracer injection is performed outside of the Nuclear Medicine Department and therefore is not possible to adequately initiate a dynamic study&#46; On the other hand&#44; lymphatic ducts are seldom visualized in the pelvis and the relatively slower deep lymphatic drainage renders dynamic lymphoscintigraphy less useful&#46; However&#44; as mentioned before&#44; the use of portable gamma cameras makes it possible to monitor the adequateness of tracer injection and potential early drainage in the Urology Department&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">21</span></a> Early &#40;15<span class="elsevierStyleHsp" style=""></span>min&#41; planar images after radiocolloid administration can visualize the first draining SLNs in almost 88&#37; of the cases&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">24</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Delayed imaging is habitually performed 2&#8211;4<span class="elsevierStyleHsp" style=""></span>h after injection&#46; On delayed imaging&#44; the lymph node visualization rate reaches more than 95&#37;&#46; The comparison between early and delayed images enables differentiation of second-echelon lymph nodes from the first draining nodes&#46; This discrimination is based on the anatomical lymph node basins of the pelvis&#46; As a rule&#44; late-appearing lymph nodes located higher in the same basin are considered as second-echelon lymph nodes&#46; Lateral planar images can help to differentiate between dorsal and more ventrally located SLNs&#46; However&#44; an accurate anatomical localization is only possible using SPECT&#47;CT &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall">Principally SPECT&#47;CT devices with an improved fast high-end CT component enable incorporation of anatomical landmarks to localize SLNs in relation to vascular structures&#46; The signal of SPECT is corrected for tissue attenuation and scatter&#46; After fusion of SPECT&#47;CT images the SLNs are displayed in the foreground SPECT image using a colour scale whereas a gray scale is used to display morphological aspects in the background CT image&#46; Fused SPECT&#47;CT&#44; CT and SPECT may be displayed simultaneously by multiplanar reconstruction &#40;MRP&#41; and the use of cross-reference lines allows navigation between axial&#44; coronal and sagittal views&#46; Further anatomical recognition can be supported using multiple intensity projection &#40;MIP&#41;&#46; However&#44; the difficulties of MIP to differentiate the vasculature from other anatomical structures have lead to the introduction of volume-rendering techniques which enable the depiction of SLNs in a 3D configuration SPECT&#47;CT is considered as a complementary modality and does not replace conventional lymphoscintigraphy&#46; The incorporation of SPECT&#47;CT not only leads to increase the overall SLN visualization rate to 98&#37; &#40;in comparison with 95&#37; for planar images&#41; but also to the identification of significantly more SLNs in additional lymphatic basins &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; Also relevant is that SPECT&#47;CT can precisely identify the SLNs within and outside the area of EPL<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">25</span></a> &#40;<a class="elsevierStyleCrossRefs" href="#fig0025">Figs&#46; 5 and 6</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0190" class="elsevierStylePara elsevierViewall">In current protocols&#44; SPECT&#47;CT is performed following delayed planar imaging&#46; This sequential timeline helps to clarify the role of both modalities and helps to establish some criteria for interpreting this set of images&#46; Major criteria for labelling lymph nodes as SLNs are the visualization of lymphatic ducts&#44; the time of appearance&#44; the lymph node basin&#44; and the intensity of lymph node uptake&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Based on these criteria&#44; visualized radioactive lymph nodes may be categorized as<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">26</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0035">Fig&#46; 7</a>&#41;&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0200" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Definite SLNs</span>&#58; Including all lymph nodes draining from the site of the primary tumour through an afferent lymphatic vessel&#44; or single radioactive lymph nodes in a regional lymph node basin&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0205" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Highly probable SLNs</span>&#58; When lymph nodes appears between the injection site and a first draining node&#44; or nodes with increasing uptake appearing in other lymph node stations&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0210" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Less probable SLNs</span>&#58; All higher-echelon nodes may be included in this category&#46;</p></li></ul></p><elsevierMultimedia ident="fig0035"></elsevierMultimedia><p id="par0215" class="elsevierStylePara elsevierViewall">With these categories in mind&#44; nuclear medicine physicians may be able to provide useful information to urological surgeons&#46; In practical terms&#44; the radioactive nodes included in the first two categories need to be resected during the surgical act&#46; Moreover&#44; in many cases early appearing lymph nodes seen as single on planar images are displayed as a two or more separate lymph nodes in different basins by SPECT&#47;CT increasing the number of nodes considered as SLNs&#46; In other cases intense lymph node uptake in a lymphatic basin seen on fused images may correspond with a cluster of SLNs as depicted on the CT of the SPECT&#47;CT&#46; Thus&#44; SPECT&#47;CT can depict more SLNs than planar images and in one series an average of 4&#46;3 SLNs on SPECT&#47;CT versus 2&#46;2 SLNs on planar images was reported in 46 patients&#59; 44&#37; of the SLNs containing metastases were visualized only by SPECT&#47;CT&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">25</span></a> In another study&#44; Meinhardt et al&#46; found that SPECT&#47;CT identified SLNs outside the area of EPL in 31&#37; of the cases&#46; These SLNs were found in different locations&#58; para-aortic&#44; abdominal wall&#44; para-rectal&#44; behind the common iliac artery&#44; presacral&#44; Cloquet&#39;s node&#44; inguinal&#44; and lateral to the external iliac artery&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">24</span></a> The SLN rate outside the EPL area&#44; as assessed by SPECT&#47;CT&#44; increases in patients previously treated with radiotherapy or surgery for prostate cancer to a 80&#37; in comparison to a 34&#37; for untreated patients&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">27</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">On the other hand&#44; SPECT&#47;CT information may lead to a significant shortening of the time of operation of the SLN&#46; SPECT&#47;CT may also give important information for the planning of radiotherapy concerning treatment volume and optimization of irradiation fields in the pelvis&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">28</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">In spite of bilateral tracer injection in a minority of patients only unilateral lymphatic drainage on lymphoscintigraphy and SPECT&#47;CT is observed&#46; Where possible tracer reinjection is recommended for SLN visualization&#46; In cases with persistent unilateral non-visualization and to compensate for possible injection errors such as loss of tracer into the bladder&#44; resulting in less drainage to one side&#44; contralateral lymphadenectomy may be considered&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Lymph node groups in the pelvis</span><p id="par0230" class="elsevierStylePara elsevierViewall">A thorough understanding of the anatomy and nomenclature of the pelvic and retroperitoneal lymph node nodal groups is crucial for accurate staging of prostate cancer&#46; The mayor groups of lymph nodes&#44; which may receive drainage from the prostate&#44; follow the iliac vessels&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0235" class="elsevierStylePara elsevierViewall">The common iliac nodal group consists of three chains&#58; lateral&#44; middle&#44; and medial&#46; The first chain is an extension of the lateral chain of external iliac nodes located lateral to the common iliac artery&#46; The medial chain occupies the triangular area bordered by both common iliac arteries from the aortic bifurcation to the bifurcations of the external and internal iliac arteries&#46; Nodes at the sacral promontory are included in this chain&#46; The middle chain nodes are located in the lumbosacral fossa and between the common iliac artery and common iliac vein&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0240" class="elsevierStylePara elsevierViewall">The internal iliac nodal group&#44; also known as hypogastric group&#44; consists of chains accompanying each of the visceral branches of the internal iliac artery&#46; These nodes are located more posterior in the pelvis and include the lateral sacral nodes&#44; the presacral nodes &#40;anterior to the sacrum and posterior to the mesorectal fascia&#41;&#44; and the anterior nodes &#40;at the origin of the proximal branches of the anterior division of the internal iliac artery&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0245" class="elsevierStylePara elsevierViewall">The external iliac nodal group consists of three chains&#58; lateral&#44; middle&#44; and medial&#46; The lateral chain includes nodes located along the lateral aspect of the external iliac artery&#46; The middle chain comprises nodes between the external iliac artery and the external iliac vein&#46; Finally&#44; the medial chain contains nodes medial and posterior to the external iliac vein&#46; The medial chain nodes are also known as the obturator nodes&#46;</p></li></ul></p><p id="par0250" class="elsevierStylePara elsevierViewall">With respect to the aorta and the inferior vena cava the lymph nodes are divided in seven subgroups&#46; The lateroaortic&#44; preaortic&#44; and retroaortic nodes surround the aorta&#46; The right lateroaortic&#44; laterorocaval&#44; precaval and retrocaval subgroups include the nodes in relation to the inferior vena cava&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">29</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Usually&#44; prostate cancer metastasizes along four pelvic lymphatic drainage pathways&#58; the anterior pelvic route&#44; which drains lymph from the anterior wall of the bladder along the obliterated umbilical artery to the internal iliac &#40;hypogastric&#41; nodes&#59; the lateral route&#44; which drains lymph from the pelvic organs to the medial chain of the external iliac nodal group &#40;a characteristic route of spread from carcinomas at the lateral aspect of the bladder and from prostate adenocarcinomas&#41;&#59; the internal iliac &#40;hypogastric&#41; route&#44; which drains lymph from most of the pelvic organs along the visceral branches of the internal iliac lymphatic ducts to the junctional nodes located between the internal and external iliac vessels&#59; and the presacral route&#44; which includes the lymphatic plexus anterior to the sacrum and coccyx and extending upward to the common iliac nodes&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">30</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Intraoperative sentinel node identification</span><p id="par0260" class="elsevierStylePara elsevierViewall">Traditionally&#44; radioguided intraoperative SLN localization is based on the acoustic signal provided by a handheld gamma probe&#46; Surgery is performed 5&#8211;24<span class="elsevierStyleHsp" style=""></span>h after tracer injection&#46; In the original radioguided open-surgery approach&#44; the handheld gamma probe was subsequently used to locate the active nodes in vivo and after excision&#44; to ex vivo confirm the SLN&#39;s activity&#44; to separate it from adjacent fatty tissue or other nodes&#44; and to finally check the operation field for residual activity&#46; Since its validation the SLN concept required knowledge of the state of both SLN and non-SLN metastases&#46; Therefore&#44; backup EPL was performed after SLNs retrieval&#44; to get the logistics right and to make sure the method was properly executed&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">9</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">Initial validation was performed under laparotomy through a lower abdominal midline incision to include the lymph node groups below the aortic bifurcation&#44; and to identify the SLNs in the draining basins with a gamma probe&#46; Practical problems are related to the shine-through phenomenon due to the high levels of radioactivity in the prostate after injection&#44; which interfere with the detection of weak gamma rays from the SLN&#46; To prevent the occurrence of this phenomenon&#44; it was recommended to cover the prostate with a lead shield or to start the operation with its resection&#46; Concerning the EPL&#44; this procedure comprises separate removal of the right and left common iliac vessels&#44; external iliac vessels&#44; internal iliac vessels&#44; obturator fossa and presacral lymph node basins&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">In the middle of the past decade&#44; Jeschke et al&#46;&#44; laparoscopically validated SLN biopsy and EPL&#46; To avoid the shine-through phenomenon&#44; they used a gamma probe with the ability to detect gamma rays from 90 degrees laterally&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">10</span></a> Although a strict learning curve exists&#44; laparoscopic extended pelvic lymphadenectomy for validation of the SLN concept is worth performing because this procedure yields an equivalent number of resected nodes with less morbidity&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">31</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">Preoperative anatomical information about the lymphatic drainage and the site of the SLNs remains essential during laparoscopy for both planning of operation and probe detection&#46; This has been the reason to incorporate SPECT&#47;CT in the SLN procedure and to display it in the operation room using navigation devices&#46; During the surgical procedure the SPECT&#47;CT image provides guidance toward the area of the SLN&#44; but the spatial orientation is often related to large anatomic structures such as vessels and bone&#46; Movement of internal anatomy of the patient during the surgical procedure limits the accuracy of sole SPECT&#47;CT-based navigation&#46; Real-time gamma probe detection allows acoustic tracing of the SLN location&#46; This technique&#44; however&#44; suffers from background signals from the injection site &#40;e&#46;g&#46;&#44; prostatic fossa&#41; and collimator issues that hamper depth perception&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">These limitations became an important argument for the incorporation of new devices such as portable gamma cameras for intraoperative imaging&#46; This approach facilitates the SLN localization and resection&#46; Using a <span class="elsevierStyleSup">125</span>I seed placed at the tip of the laparoscopic probe it is possible to use the device as a pointer to localize the SLN on screen based on the different display of the signals of <span class="elsevierStyleSup">125</span>I &#40;circle&#41; and <span class="elsevierStyleSup">99m</span>Tc &#40;radioactive sentinel node&#41;&#46; After the matching of both signals on screen and the confirmation of the acoustic signals of the probe sentinel node dissection can follow &#40;<a class="elsevierStyleCrossRef" href="#fig0040">Fig&#46; 8</a>&#41;&#46; After removal of all SLNs&#44; the portable gamma camera can be used to detect any remaining SLNs that have to be removed&#44; or to discriminate a second-echelon node that can confidently be left in place&#46; This approach provides certainty about the completeness of the surgical procedure and complements the laparoscopic probe&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">12</span></a></p><elsevierMultimedia ident="fig0040"></elsevierMultimedia><p id="par0285" class="elsevierStylePara elsevierViewall">Other devices permit the &#8220;intraoperative navigation&#8221; with the aid of a fiducial reference target detected by an optical tracking system&#46; Visualizing the SPECT&#47;CT images from the perspective of the endoscope is the essence of the proposed navigation approach&#46; A virtual view can be a 3D render of the combined volumetric CT and SPECT data&#46; However&#44; navigation systems do not always provide exact localization of the target lesions in soft movable tissues like in pelvic SLN procedures&#46; In these areas&#44; the intervention may alter the position of the lesions of interest relative to more rigid reference points such as the skeleton and these navigation systems cannot compensate for such deformation&#44; rendering them less accurate&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">32</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">Robot-assisted surgery is an extension of laparoscopic surgery&#46; The robot adds enhanced vision and control and consists of several components&#44; including an ergonomically designed console&#44; interactive robotic arms&#44; and a three-dimensional&#44; high-definition vision system&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Nowadays&#44; the robotic-assisted laparoscopic procedure is increasingly used and the potential to identify nodes visually has stimulated a push toward the off-label use of the near-infrared fluorescent dye indocyanine green &#40;ICG&#41;&#46; ICG has been used as a free chemical entity or as the hybrid tracer ICG-technetium &#40;<span class="elsevierStyleSup">99m</span>Tc&#41; nanocolloid&#46; Neither of these compounds has an affinity with tumor tissue&#46; However&#44; fluorescence imaging enables intraoperative identification of the SLNs in the areas where acoustic gamma tracing is inefficient&#46; In the other areas fluorescence helped to identify the exact location of the SLNs with a higher precision provided that SLN location had been previously determined using preoperative SPECT&#47;CT or intraoperative gamma camera tracing&#46; Equally important to realize is the fact that the tissue penetration of near-infrared fluorescent signals lies below 1<span class="elsevierStyleHsp" style=""></span>cm&#44; a limitation that may prevent the identification of relevant &#40;or distant&#41; nodes&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">33</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">The small size of free ICG means that it flows freely through the lymphatic system and is therefore suited for real-time lymphangiography&#46; This approach enables accurate identification of both lymph nodes and draining lymphatic vessels&#46; Because ICG is in origin an angiographic imaging agent&#44; it may yield background signals in the form of fluorescent blood vessels&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">The hybrid radiotracer ICG-<span class="elsevierStyleSup">99m</span>Tc-nanocolloid permits to combine in one signature the advantages of optical fluorescence guidance and the radiotracer properties &#40;<a class="elsevierStyleCrossRef" href="#fig0045">Fig&#46; 9</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">34</span></a></p><elsevierMultimedia ident="fig0045"></elsevierMultimedia><p id="par0310" class="elsevierStylePara elsevierViewall">The development of surgical fluorescence cameras and the clinical implementation of new hybrid imaging agents are important to improve surgical efficacy&#46; Integration of these developments into technical surgical procedures such as minimally invasive robot-assisted laparoscopy on the basis of a radioactivity&#47;fluorescence hybrid approach&#44; may contribute to extend the frontiers of radioguided surgery to other applications&#46; However&#44; limiting for these extended applications&#44; is obtaining the approval for the clinical use of new imaging agents&#46; The multimodal ICG-<span class="elsevierStyleSup">99m</span>Tc-nanocolloid imaging agent circumvents this problem because a cocktail of the ICG and <span class="elsevierStyleSup">99m</span>Tc-nanocolloid&#44; both clinically approved in Europe&#44; is used to form the multimodal complex without requirement of any chemical modifications or altering the toxicologic profile&#46; As such&#44; ICG-<span class="elsevierStyleSup">99m</span>Tc-nanocolloid may facilitate the clinical introduction of the multimodal surgical guidance concept in the coming years&#46;</p></span></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Results</span><p id="par0315" class="elsevierStylePara elsevierViewall">The pioneers of the SLN biopsy in prostate cancer&#44; based on open surgery and the use of a hand held gamma probe&#44; performed an additional extended lymph node dissection so to demonstrate the reliability of this method&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">9</span></a> The false-negative rate was very low when compared to the gold standard&#46; Later on&#44; with more experience&#44; the SLN identification rate reached &#62;95&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">13</span></a> Additional evidence for the open surgery approach and later on the reliability of the laparoscopic SLN method was found in the fact that the diagnostic yield was twice as high compared to classical pelvic node dissection series and identical to modern series of open EPL&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">35</span></a></p><p id="par0320" class="elsevierStylePara elsevierViewall">In most series&#44; a SLN was generally identified in 90&#8211;100&#37; of patients&#44; a SLN was positive in 12&#8211;25&#37; of cases&#44; and false negative rates were reported in about 7&#37; or less &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0325" class="elsevierStylePara elsevierViewall">In the largest series with more than 2000 patients evaluated using gamma probe guided SLN biopsy only 11 false negative cases &#40;5&#46;5&#37;&#41; were reported&#59; this acceptable rate warrants the reliability of the method&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">36</span></a></p><p id="par0330" class="elsevierStylePara elsevierViewall">In 2006 Corvin et al&#46; validated laparoscopic SLN pursuing to obtain a lower morbidity&#44; less postoperative pain and shorter hospital stays&#46; Using a gamma camera for preoperative lymph mapping and a laparoscopic gamma probe intra-operatively they proved that this approach might be an acceptable alternative to EPL&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">31</span></a> On the other hand&#44; if a laparoscopic prostatectomy is performed&#44; the combination with a laparoscopic SLN procedure is the logical combination&#46; The open and the laparoscopic SLN procedures have the same diagnostic yield&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">35</span></a> Especially&#44; patients opting for an external-beam radiation treatment have much to gain by a laparoscopic procedure&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">37</span></a></p><p id="par0335" class="elsevierStylePara elsevierViewall">In a meta-analysis performed a few years ago the pooled SLN detection rate &#40;open and laparoscopic approaches&#41; was 93&#46;8&#37; &#40;95&#37;CI 89&#8211;96&#46;6&#37;&#41;&#44; which is high enough to be considered applicable in this malignancy &#40;as results in similar yield than SLN detection rates for other cancer types&#41;&#46; However&#44; some heterogeneity&#44; most likely attributed to different techniques applied &#40;tracer preparation&#44; injected activity and type of surgery&#41;&#44; was detected among the studies&#46; For instance&#44; a slightly higher SLN detection rate was observed in patients who underwent open surgery in comparison with those with laparoscopic approach &#40;94&#46;4&#37; vs&#46; 92&#37;&#41;&#46; Also recent technological advances can have impact on the technique&#46; The groups that used pre-operative SPECT&#47;CT images showed a pooled detection rate higher than those using static pre-operative images &#40;92&#46;9&#37; vs&#46; 92&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">38</span></a></p><p id="par0340" class="elsevierStylePara elsevierViewall">However&#44; in some recent series SPECT&#47;CT was up to 63&#37; advantageous over planar imaging and recent laparoscopic and robotic-assisted approaches are based on this pre-operative information&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">25</span></a> Moreover&#44; SLN biopsy allows the sampling of SLNs outside the pelvic lymphadenectomy field and this can be pre-visualized with the accurate information provided by SPECT&#47;CT&#46; SPECT-CT scan is also a useful tool to localize the SLNs in pararectal&#47;presacral regions&#46; These pelvic areas are accessible for new modalities of laparoscopic surgery such as robot-assisted procedures&#44; making excision of these nodes possible&#46;<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">39&#44;40</span></a></p><p id="par0345" class="elsevierStylePara elsevierViewall">In a series concerning 74 patients&#44; Joniau et al&#46; reported a total of 470 scintigraphic detected SLNs &#40;median 6&#41; of which 371 SLNs were removed&#46; In total&#44; 91 positive SLNs &#40;median 2&#41; were found in 34 of 74 patients&#46; The authors identified SLNs mainly in 5 regions&#58; obturator fossa &#40;25&#37;&#41;&#44; internal iliac &#40;25&#37;&#41;&#44; external iliac &#40;19&#37;&#41;&#44; common iliac &#40;14&#37;&#41;&#44; presacral &#40;13&#37;&#41; but also in other lymphatic basins like the pararectal&#44; paravesical and para-aortic regions&#44; in mesenteric fat and at the aortic bifurcation&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">41</span></a> Their findings added more evidence that SLNs are often widely spread&#44; suggesting potential for positive lymph nodes in a large number of areas that current lymphadenectomy margins do not account for &#40;44&#37; of SLNs were located outside the extended pelvic lymphadenectomy field&#41; and in 6&#37; of patients&#44; a positive SLN was located exclusively in the presacral or paraaortic region&#46; They concluded that although standard EPL would have correctly staged the majority of positive-node patients&#44; a 13&#37; of the metastatic nodes would have been missed&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">The reported pooled sensitivity of SLN mapping of 94&#37; &#40;95&#37; CI 91&#8211;96&#37;&#41; indicates that the false negative rate appears to be lower than the recommended one for breast cancer patients&#46; Actually this provides evidence that the SLN procedure today is not only sufficiently standardized but is also a reliable technique&#46;</p><p id="par0355" class="elsevierStylePara elsevierViewall">However&#44; there is still some variability concerning sensitivity among the different groups reporting SLN biopsy in prostate cancer&#46; For example&#44; in a very recent study that comprised 74 patients with clinically node-negative localized prostate adenocarcinoma&#44; van den Bergh et al&#46; found that only 79&#37; of visualized SLN were removed with the aid of gamma probe&#46; Twenty-eight patients were node-positive based on the analysis of the resected SLN&#46; However&#44; the EPL that was performed as a reference revealed nine additional positive-node patients&#44; resulting in a sensitivity of 76&#37;&#46; In total&#44; 15 of 37 patients &#40;41&#37;&#41; had metastases in SLN only and could have been spared EPL to remove all affected nodes&#46; Thus&#44; in this study a relatively low sensitivity when addressing the SLN procedure for nodal staging in prostate cancer patients&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">42</span></a></p><p id="par0360" class="elsevierStylePara elsevierViewall">Additional tools such as the intraoperative imaging provided by portable gamma cameras may make the &#40;especially laparoscopic&#41; excision of a SLN easier and even more reliable&#46; This approach was recently evaluated in 55 patients&#46; Out of 178 sentinel nodes visualized on SPECT-CT 16 nodes &#40;9&#37;&#41; could not be reproduced with the portable gamma camera because of a weak signal and 13 &#40;7&#37;&#41; because of their location in close proximity with the site of the tracer injection in the prostate&#46; In 15 patients a <span class="elsevierStyleSup">125</span>I seed pointer was useful to directly localize nodes &#40;principally along the aorta and common iliac artery cranial from ureter crossing&#41; and in the other patients the portable gamma camera was used to verify adequate excision after removal of the SLN leading to the identification of 17 additional SLNs &#40;<a class="elsevierStyleCrossRef" href="#fig0040">Fig&#46; 8</a>&#41;&#46; In two of these cases sentinel nodes were tumor-positive&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">12</span></a></p><p id="par0365" class="elsevierStylePara elsevierViewall">Pre-operative SPECT&#47;CT and intraoperative portable gamma camera imaging provide a road map of anatomic relationships to facilitate the proposed surgery&#46; Conversely&#44; image-guided surgery provides in situ&#44; real time visualization of either preoperative or intraoperative data along with the actual anatomy&#46; In this sense&#44; the utilization of fluorescent agents has been gaining acceptance during the last years&#46; Manny and colleagues&#44; reported on their initial series of fluorescence-enhanced robotic radical prostatectomy using real-time injection of ICG for tissue marking and identification of SLNs&#46; In this study&#44; ICG was injected into each lobe of the prostate using a robotically guided percutaneous needle&#46; After ICG was allowed to travel through the pelvic lymphatic channels&#44; lymphadenectomy was performed under the near-infrared visualization system integrated to the surgical robot&#46; They found that using this technique&#44; SLNs were identified in 76&#37; of patients at a mean time of 30<span class="elsevierStyleHsp" style=""></span>minutes after injection and had 100&#37; sensitivity&#44; 75&#46;4&#37; specificity&#44; 14&#46;6&#37; positive predictive value&#44; and 100&#37; negative predictive value for detection of nodal metastasis&#46; Thus&#44; they concluded that ICG guided SLN biopsy is highly sensitive&#44; but not specific enough for the detection of nodal metastasis&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">43</span></a></p><p id="par0370" class="elsevierStylePara elsevierViewall">So it seems that the time schedule and the limited penetration depth of the ICG &#40;&#60;1&#46;0<span class="elsevierStyleHsp" style=""></span>cm&#41; hampers preoperative SLN mapping&#46; This leads to a necessary meticulous scanning of&#44; and beyond&#44; the EPL area during operation&#46; This issue is time-consuming and may potentially miss SLNs&#46; Hence&#44; the need to combine ICG with radiocolloid-based preoperative SLN mapping methods&#46;</p><p id="par0375" class="elsevierStylePara elsevierViewall">This approach was performed in 26 consecutive patients who received <span class="elsevierStyleSup">99m</span>Tc-labelled colloid &#40;18<span class="elsevierStyleHsp" style=""></span>h before surgery&#41; and ICG &#40;immediately before surgery&#41; injected transrectally into the prostate&#46; Intraoperatively&#44; a dedicated laparoscopic fluorescence imaging system and a laparoscopic &#947;-probe were used&#46; Fluorescent lymphatic vessels were visualized in real time and followed to identify the SLN&#46; Nevertheless&#44; all detected hot spots &#40;fluorescent signals and&#47;or radioactivity&#41; were considered as SLNs and removed&#46; A strong correlation was established between radioactive and fluorescent lymph nodes&#46; The authors reported that&#44; compared with radioguided SLN dissection alone&#44; the additional fluorescence-guided procedure demonstrated a further 120 lymph nodes&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">15</span></a></p><p id="par0380" class="elsevierStylePara elsevierViewall">To facilitate an integrated use of preoperative imaging with fluorescence guidance&#44; a hybrid tracer&#44; ICG-<span class="elsevierStyleSup">99m</span>Tc-nanocolloid&#44; was developed and introduced in the urological clinical setting&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">34&#44;44</span></a></p><p id="par0385" class="elsevierStylePara elsevierViewall">This hybrid tracer allowed for preoperative detection of the SLNs with SPECT&#47;CT&#44; whereas both the combination of the gamma detection probe and near infrared fluorescence detection of ICG enabled intraoperative localization of the SLNs&#46;</p><p id="par0390" class="elsevierStylePara elsevierViewall">Four of 27 SLNs were preoperatively identified outside the extended lymphadenectomy field on SPECT&#47;CT&#44; which could thereafter be intraoperatively visualized with fluorescence&#46; A strong correlation was found between the radioactive and fluorescent contents in the excised lymph nodes indicating that the ICG-<span class="elsevierStyleSup">99m</span>Tc-Nanocoll complex remained stable in the time period between injection and dissection of SLNs&#46; This was previously demonstrated in an animal experiment&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">45</span></a></p><p id="par0395" class="elsevierStylePara elsevierViewall">However&#44; 15&#37; of the SLNs could not be intraoperatively detected with fluorescence imaging alone due to the limited tissue penetration of the ICG fluorescent signal&#46; Especially in these instances&#44; guidance to regions of interest by the radioactive component to the hybrid tracer remains desirable&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">34</span></a> To increase this potential synergism of preoperative SPECT&#47;CT imaging with fluorescence guidance&#44; an optimization study was carried out&#46; Following the initial feasibility study&#44; 40 additional prostate cancer patients were included&#46; These patients were divided in 3 groups and the authors systematically evaluated whether optimization of the tracer formulation and fluorescence hardware improvements could help increase in vivo fluorescence-based SLN identification during robot-assisted laparoscopic procedures &#40;<a class="elsevierStyleCrossRef" href="#fig0045">Fig&#46; 9</a>&#41;&#46; In groups 1 and 2&#44; SNs were pursued intraoperatively using a laparoscopic gamma probe followed by fluorescence imaging&#46; In group 3&#44; SLNs were initially located via fluorescence&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">46</span></a></p><p id="par0400" class="elsevierStylePara elsevierViewall">At least one SLN was preoperatively identified in 38 of the 40 patients&#46; Non-visualization occurred in two patients bilateral &#40;5&#46;0&#37;&#41; and unilateral in five patients &#40;12&#46;5&#37;&#41;&#46; Lymphoscintigraphy and SPECT&#47;CT identified a total of 119 SNs &#40;median&#58; 3&#41;&#46; The change of the hybrid tracer formulation did not yield a significant difference in the number of preoperatively visualized SLNs&#46; However&#44; with the new tracer formulation&#44; flushing was no longer necessary after placement of the different tracer deposits&#44; increasing the easiness of the procedure&#46; In 7 patients&#44; 14 additional SLNs were removed during surgery based on their fluorescent and radioactive appearance in the same region as the SLNs detected with preoperative imaging&#46; In 16 patients &#40;40&#46;0&#37;&#41;&#44; a SLN was located outside the extended pelvic lymphadenectomy area&#46; Interestingly&#44; in vivo fluorescence-based SLN visualization percentage of groups 1 and 2 was found to be 63&#46;7&#37; and 85&#46;2&#37;&#44; respectively&#46; Following the introduction of the upgraded laparoscopic system &#40;group 3&#41;&#44; the mean intraoperative visualization percentage increased to 93&#46;5&#37;&#46; Ex-vivo analysis showed 123 out of 127 fluorescent SLNs &#40;96&#46;9&#37;&#41;&#44; while all 127 SLNs were radioactive &#40;100&#46;0&#37;&#41;&#46; The authors concluded that changing the hybrid tracer formulation and injection technique and upgrading the laparoscopic system significantly improve in vivo fluorescence-based SLN identification&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">46</span></a></p><p id="par0405" class="elsevierStylePara elsevierViewall">Additionally&#44; Brouwer et al&#46; reported on an intraoperative surgical navigation system based on preoperative 3D scintigraphic images that improved the efficacy of the hybrid fluorescent radiotracer&#46; This study&#44; designed as proof of principle&#44; successfully showed the feasibility of combined rigid navigation based on preoperative SPECT&#47;CT images and intraoperative fluorescence imaging for soft tissue navigation&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">47</span></a></p><p id="par0410" class="elsevierStylePara elsevierViewall">Navigation systems such as these remain complicated and are&#44; at this moment&#44; limited to the experimental realm&#44; although more investigation is underway&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Future prospects</span><p id="par0415" class="elsevierStylePara elsevierViewall">Based on several thousand of patients&#44; radioguided SLN biopsy using <span class="elsevierStyleSup">99m</span>Tc-nanocolloids has been found to be highly sensitive for identifying lymph node metastases in prostate cancer&#46; It has been possible to demonstrate that for this approach&#44; the rate of lymph node involvement was higher in a sentinel cohort than was expected from the European Association of Urology guideline nomogram&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">48</span></a>&#46; More recently&#44; a first SLN-based nomogram SLN to predict the probability of lymph node involvement demonstrated a high degree of accuracy&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">49</span></a></p><p id="par0420" class="elsevierStylePara elsevierViewall">Meanwhile&#44; efforts are made on targeted removal of lymphatic nodes in combination with laparoscopic or robot-assisted radical prostatectomies&#44; in order to lower the extensive effort associated with an extended pelvic lymphadenectomy&#46;</p><p id="par0425" class="elsevierStylePara elsevierViewall">Currently this laparoscopic approach can be combined by using near-infrared fluorescence imaging to improve nodal dissection during laparoscopic or robotic surgery&#46; The concept is that fully integrated fluorescence-aided nodal identification provides a rapid and easy-to-use technique to introduce the concept of specific SLN in conjunction with extended nodal dissection&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">33</span></a></p><p id="par0430" class="elsevierStylePara elsevierViewall">However&#44; the clinical introduction of fluorescent tracers&#44; in particular for urological applications&#44; is still in its childhood&#44; though rapidly emerging&#46;</p><p id="par0435" class="elsevierStylePara elsevierViewall">Laparoscopic challenges lie in the further optimization of targeted and&#47;or activatable &#40;hybrid&#41; imaging agents as well as in the integration between imaging agents and camera systems&#44; thereby enabling more accurate fluorescence image guidance during surgical interventions&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">50</span></a></p><p id="par0440" class="elsevierStylePara elsevierViewall">Other non-radiactive tracers have been tested &#40;blue dyes&#44; fluorescent tracers&#44;&#41; but their results have not achieved to surpass the radiotracer outcome&#46; Recently&#44; a study using open surgery and paramagnetic iron-oxide particles in 20 patients has been reported&#46; Although this feasibility study was applied for the first time ever to the prostate&#44; the detection rate on a patient basis was found to be 90&#37;&#46; This procedure of magnetic marking and magnetometer-guided SLN biopsy appears to be safe for open surgery&#44; can be performed easily and by a urologist on his own&#44; and has the advantage of carrying no radioactive elements&#46; However&#44; for now it is limited to open surgery and the absence of preoperative imaging may hamper an adequate personalized lymphatic mapping with a more specific SLN identification&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">51</span></a></p><p id="par0445" class="elsevierStylePara elsevierViewall">On the other hand&#44; the potential of new devices to guide the surgeon to the target is increasing&#46; In principle they are aimed to solve two of the major limitations encountered during radioguided SLN biopsy &#40;the identification of near-injection-site SLNs and separation of cluster nodes&#41;&#46; This new &#8220;hybrid&#8221; radioguidance approach is&#44; as we speak&#44; already able to provide rapid and clear visibility of hotspots relative to the anatomic context of the patient &#40;video feed&#59; augmented-reality&#41; and subsequently the possibility to virtually navigate towards these SLNs&#46; Other novel techniques provide integration of otherwise separately used image-guided surgery technologies&#44; namely&#58; hand-held gamma probe&#44; manual gamma camera&#44; 3D-free hand SPECT&#44; augmented-reality display&#44; and virtual navigation&#46; This potential&#44; not only improves surgical logistics&#44; but also provides perspective for more complex radioguided procedures in the future&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">52</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Key points</span><p id="par0450" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">1&#46;</span><p id="par0455" class="elsevierStylePara elsevierViewall">Prostate-specific antigen &#40;PSA&#41; levels&#44; pathologic stage&#44; and Gleason score are predictors for lymph node involvement&#46; The prevalence of infiltration of the lymph nodes has been shown to be around 25&#37; of the patients with prostate cancer with a reduction in 5-year survival of 85&#37; in N0 patients and 50&#37; in N1 patients&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">2&#46;</span><p id="par0460" class="elsevierStylePara elsevierViewall">The approach using lymphatic mapping and gamma detection probe is not yet recommended for routine use in the current surgical guidelines for management of prostate cancer&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">3&#46;</span><p id="par0465" class="elsevierStylePara elsevierViewall">Pre-operative SPECT&#47;CT and intraoperative portable gamma camera imaging provide a road map of anatomic relationships to facilitate the proposed surgery&#46; Conversely&#44; image-guided surgery provides in situ&#44; real time visualization of either preoperative or intraoperative data along with the actual anatomy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">4&#46;</span><p id="par0470" class="elsevierStylePara elsevierViewall">SPECT&#47;CT image provides anatomic guidance toward the area of the SLN&#46; Real-time gamma probe detection allows acoustic tracing of the SLN location&#46; Intraoperative imaging provides certainty about the completeness of the surgical procedure and complements the laparoscopic probe&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">5&#46;</span><p id="par0475" class="elsevierStylePara elsevierViewall">The tissue penetration of near-infrared fluorescent signals lies below 1<span class="elsevierStyleHsp" style=""></span>cm&#44; a limitation that may prevent the identification of relevant nodes&#46;</p></li></ul></p><p id="par0480" class="elsevierStylePara elsevierViewall">The small size of free ICG means that it flows freely through the lymphatic system and is therefore suited for real-time lymphangiography&#46; The hybrid radiotracer ICG-<span class="elsevierStyleSup">99m</span>Tc-nanocolloid permits to combine in one signature the advantages of optical fluorescence guidance and the radiotracer properties&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflict of interest</span><p id="par0485" class="elsevierStylePara elsevierViewall">The authors declare they have no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">In general terms&#44; one of the main objectives of sentinel lymph node &#40;SLN&#41; biopsy is to identify the 20-25&#37; of patients with occult regional metastatic involvement&#46; This technique reduces the associated morbidity from lymphadenectomy&#44; as well as increasing the identification rate of occult lymphatic metastases by offering the pathologist those lymph nodes with the highest probability of containing metastatic cells&#46; Pre-surgical lymphoscintigraphy is considered a &#8220;road map&#8221; to guide the surgeon towards the sentinel nodes and to ascertain unpredictable lymphatic drainages&#46; In prostate cancer this aspect is essential due to the multidirectional character of the lymphatic drainage in the pelvis&#46; In this context the inclusion of SPECT&#47;CT should be mandatory in order to improve the SLN detection rate&#44; to clarify the location when SLNs are difficult to interpret on planar images&#44; to achieve a better definition of them in locations close to injection site&#44; and to provide anatomical landmarks to be recognized during operation to locate SLNs&#46;</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Conventional and laparoscopic hand-held gamma probes allow the SLN technique to be applied in any kind of surgery&#46; The introduction and combination of new tracers and devices refines this technique&#44; and the use of intraoperative images&#46; These aspects become of vital importance due to the recent incorporation of robot-assisted procedures for SLN biopsy&#46; In spite of these advances various aspects of SLN biopsy in prostate cancer patients still need to be discussed&#44; and therefore their clinical application is not widely used&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">En t&#233;rminos generales uno de los principales objetivos de la biopsia del ganglio centinela &#40;GC&#41; es identificar el 20-25&#37; de pacientes que presentan enfermedad ganglionar regional cl&#237;nicamente oculta&#46; Esta t&#233;cnica minimiza la morbilidad asociada a la linfadenectom&#237;a y aumenta tambi&#233;n la tasa de identificaci&#243;n de met&#225;stasis linf&#225;ticas ocultas al ofrecer al pat&#243;logo aquel o aquellos ganglios con mayor probabilidad de contener c&#233;lulas tumorales&#46; La linfogammagraf&#237;a prequir&#250;rgica se considera como un &#8220;mapa de carreteras&#8221; para guiar al cirujano hacia los GC y para la localizaci&#243;n de patrones de drenaje impredecibles&#46; En c&#225;ncer de pr&#243;stata este aspecto adquiere especial importancia debido a su drenaje multidireccional en la pelvis&#46; En ese contexto la inclusi&#243;n de SPECT&#47;TC aparece como esencial para lograr un mejor &#237;ndice global de detecci&#243;n del GC&#44; clarificar la existencia y ubicaci&#243;n de ganglios centinelas dif&#237;ciles de interpretar a las im&#225;genes planares&#44; conseguir una mejor definici&#243;n de los mismos en localizaciones cercanas a la inyecci&#243;n y entregar puntos de referencia anat&#243;mica que puedan ser reconocidos durante la operaci&#243;n para localizar los GC&#46;</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">La utilizaci&#243;n de sondas detectoras de rayos gamma convencionales o laparosc&#243;picas permiten la aplicaci&#243;n de la t&#233;cnica en cualquier tipo de cirug&#237;a&#46; La implementaci&#243;n y combinaci&#243;n de nuevos dispositivos y trazadores permite refinar la t&#233;cnica&#44; as&#237; como la utilizaci&#243;n de im&#225;genes intraoperatorias&#46; Estos aspectos han ido adquiriendo especial importancia debido a la incorporaci&#243;n de la biopsia del GC en protocolos que emplean cirug&#237;a rob&#243;tica&#46; A pesar de ello&#44; la aplicaci&#243;n cl&#237;nica de la biopsia del GC en pacientes con c&#225;ncer de pr&#243;stata todav&#237;a sigue incluyendo aspectos a discutir y por ello su aplicaci&#243;n cl&#237;nica no se ha generalizado&#46;</p></span>"
      ]
    ]
    "multimedia" => array:11 [
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        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
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          0 => array:4 [
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Transrectal ultrasound &#40;A&#41; guidance of radiotracer administration by means of transrectal &#40;B&#41; and transperineal &#40;C&#41; injections in two different patients&#46; The tracer is administered in both prostatic lobes using a 3-way system with subsequent saline flushing &#40;D&#41;&#46; With a portable gamma camera it is possible to monitor the tracer deposition in both sides of the prostate &#40;E&#41;&#46;</p>"
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Distribution of sentinel lymph nodes in different pelvic basins &#40;white caption&#41; according to Wawroschek F&#46; et al&#46; &#40;Urologe 2005&#59; 44&#58; 630&#8211;634&#41;&#46; Also sentinel lymph nodes found in other locations are indicated &#40;green caption&#41; according to Meinhardt et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">11</span></a></p>"
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        "identificador" => "fig0015"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Early &#40;A&#41; and delayed &#40;B&#41; planar images showing bilateral iliac drainage&#46; SPECT&#47;CT with volume rendering &#40;C&#41; as well as transversal slices &#40;D and E&#41; show not only more sentinel lymph nodes in different basins&#44; but also an accurate anatomical pelvic localization&#46;</p>"
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      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Delayed planar image &#40;A&#41; and volume rendering SPECT&#47;CT show bilateral pelvic drainage &#40;B&#41;&#46; Transversal SPECT&#47;CT &#40;C and D&#41; at the same slice level show additional sentinel lymph nodes in different pelvic lymphatic basins&#46;</p>"
        ]
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      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Fig&#46; 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Early &#40;A&#41; and delayed &#40;B&#41; planar as well as volume rendered SPECT&#47;CT &#40;C&#41; showing bilateral pelvic drainage&#46; On transversal SPECT&#47;CT location of sentinel lymph nodes can be related to inside &#40;D and E&#41; and outside of &#40;F&#41; the area of extended pelvic lymphadenectomy&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "fig0030"
        "etiqueta" => "Fig&#46; 6"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr6.jpeg"
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            "Tamanyo" => 338013
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Early planar scintigraphy &#40;A&#41; and volume rendered SPECT&#47;CT &#40;B&#41; showing bilateral pelvic drainage with not only iliac sentinel lymph nodes &#40;C&#8211;E&#41; but also para-aortic &#40;F&#41;&#46;</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "fig0035"
        "etiqueta" => "Fig&#46; 7"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr7.jpeg"
            "Alto" => 2255
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            "Tamanyo" => 530297
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        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Criteria to categorize radioactive lymph nodes as definite sentinel lymph nodes &#40;SLNs 1&#44; 2 and 3 appearing early after tracer administration as shown on left superior image&#41;&#44; highly probable SLN &#40;node 4 clearly defined on delayed acquired right superior image&#41; and less probable SLN &#40;higher-echelon node 5&#41;&#46; Note on transversal SPECT&#47;CT &#40;first inferior image&#41; that nodes 1 and 2 correspond with two SLNs in each pelvic side&#46; The two iliac SLNs on the right correspond in turn with lymph node clusters &#40;circles&#41; on CT &#40;second inferior image&#41;&#46; Node 3 is a para-aortic SLN &#40;third inferior image&#41; and node 4 is a paravesical SLN on the right &#40;last inferior image&#41; displayed in the same slice with additional pararectal and iliac SLNs in the left pelvic side&#46;</p>"
        ]
      ]
      7 => array:7 [
        "identificador" => "fig0040"
        "etiqueta" => "Fig&#46; 8"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr8.jpeg"
            "Alto" => 1209
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            "Tamanyo" => 306539
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Sampling of a para-aortic sentinel lymph node &#40;A&#41; using a laparoscopic gamma probe with a <span class="elsevierStyleSup">125</span>I seed on the top &#40;B&#41; to indicate the location of the node during operation &#40;C&#41; as a super-imposed dotted circle on screen &#40;D&#41; based on the dual channel signal registration of a portable gamma camera &#40;E&#41; for continuous intraoperative monitoring&#46; Note that after SLN removal no residual activity is observed on screen &#40;F&#41;&#46;</p>"
        ]
      ]
      8 => array:7 [
        "identificador" => "fig0045"
        "etiqueta" => "Fig&#46; 9"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr9.jpeg"
            "Alto" => 1137
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            "Tamanyo" => 226531
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Robot-assisted sentinel lymph node procedure &#40;A&#41; using laparoscopic devices for fluorescence and radioactivity detection &#40;B&#41; after administration of ICG-<span class="elsevierStyleSup">99m</span>Tc-nanocolloid in a patient with prostate cancer&#46; The acoustic signals of the gamma probe indicate the location of the sentinel lymph node &#40;C&#41;&#44; which is subsequently visualized thanks to the fluorescence &#40;D&#41;&#46; The fluorescent node ex-vivo is clearly differentiated from the surrounding non-fluorescent fat tissue &#40;E&#41;&#46;</p>"
        ]
      ]
      9 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "Adapted from NCCN guidelines 2015&#46; <span class="elsevierStyleInterRef" id="intr0005" href="http://www.nccn.org/">www&#46;nccn&#46;org</span>&#59; accessed 27&#47;2&#47;2015&#46;"
        "tabla" => array:2 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">T&#58; Primary tumor</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Tx&#58; Primary tumor cannot be assessed</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">T0&#58; No evidence of primary tumor</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">T1&#58; Tumor clinically inapparent&#44; neither palpable or visible using imaging techniques</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>T1a&#58; Tumor detected as incidental finding in an extension &#8804;5&#37; of the tissue resected&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>T1b&#58; Tumor detected as incidental finding in an extension greater than 5&#37; of the tissue resected&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>T1c&#58; Tumor identified by biopsy puncture &#40;i&#46;e&#46; because of elevated PSA&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">T2&#58; Tumor confined within prostate</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>T2a&#58; The tumor involves half of a lobe or less&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>T2b&#58; The tumor involves more than half of a lobe but not both lobes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>T2c&#58; The tumor involves both lobes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">T3&#58; Tumor which extends beyond the prostatic capsule</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>T3a&#58; Extracapsular extension &#40;uni or bilateral&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>T3b&#58; Tumor which invades the seminal vesicle&#40;s&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">T4&#58; Tumor is fixed or invades adjacent structures other than the seminal vesicles&#58; vesicle neck&#44; external sphincter&#44; rectum&#44; elevator muscles of the anus and&#47;or pelvic wall</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">N&#58; Regional lymph nodes</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Nx&#58; Regional lymph nodes cannot be evaluated</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">N0&#58; Regional lymph node metastasis not shown</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">N1&#58; Metastasis in regional lymph nodes</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">M&#58; Distant metastasis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Mx&#58; Distant metastasis cannot be evaluated</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">M0&#58; No distant metastasis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">M1&#58; Distant metastasis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>M1a&#58; Non regional lymphatic lymph node&#40;s&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>M1b&#58; Bone&#40;s&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>M1c&#58; Other localization&#40;s&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab938477.png"
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Tumor in one or both lobes by needle biopsy but not palpable and visible by imaging&#44; is classified as T1c&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Invasion into the prostatic apex or into &#40;but not beyond&#41; the prostatic capsule is not classified as T3&#44; but as T2&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">TNM staging&#46;</p>"
        ]
      ]
      10 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">N&#47;A&#58; not available&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Author&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Radiotracer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mean SN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Identification rate &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Wawroschek&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">350&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSup">99m</span>Tc-nanocolloid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&#46;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Schafhauser&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">162&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSup">99m</span>Tc-nanocolloid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">99&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 case&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Brenot-Rossi&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSup">99m</span>Tc-nanocolloid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">76&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Hautmann&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">108&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSup">99m</span>Tc-nanocolloid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90&#46;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Jeschke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">140&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSup">99m</span>Tc-HSA colloid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Laparoscopic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">94&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Holl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSup">99m</span>Tc-nanocolloid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">98&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Varga&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSup">99m</span>Tc-HSA colloid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">89&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Marchioro&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">123&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSup">99m</span>Tc-nanocolloid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">71&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Schilling&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">463&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSup">99m</span>Tc-nanocolloid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&#47;Laparoscopic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Meinhardt&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">121&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSup">99m</span>Tc-nanocolloid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Laparoscopic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">96&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Winter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1229&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSup">99m</span>Tc-nanocolloid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">99&#46;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Muck&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">819&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSup">99m</span>Tc-nanocolloid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Open&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">93&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Kleinjan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ICG-<span class="elsevierStyleSup">99m</span>Tc-nanocolloid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Robot-assisted laparoscopy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Summary of some studies involving SLN biopsy in prostate cancer patients&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
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            0 => array:3 [
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "autores" => array:1 [
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                          "etal" => false
                          "autores" => array:5 [
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                            1 => "M&#46;A&#46; Climent"
                            2 => "A&#46; Gonz&#225;lez del Alba"
                            3 => "B&#46; Mellado"
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                    ]
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                    0 => array:2 [
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                      "Revista" => array:6 [
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                        "link" => array:1 [
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                            "web" => "Medline"
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              ]
            ]
            1 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; L&#243;pez-Abente"
                            1 => "N&#46; Aragon&#233;s"
                            2 => "B&#46; P&#233;rez-G&#243;mez"
                            3 => "M&#46; Poll&#225;n"
                            4 => "J&#46; Garc&#237;a-P&#233;rez"
                            5 => "R&#46; Ramis"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2407-14-535"
                      "Revista" => array:5 [
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            ]
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              "identificador" => "bib0275"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;E&#46; Damber"
                            1 => "G&#46; Aus"
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                        ]
                      ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
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                        "fecha" => "2008"
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            3 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Update on the use of radiopharmaceuticals for positron emission tomography imaging of prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "J&#46;R&#46; Garc&#237;a"
                          ]
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                      ]
                    ]
                  ]
                  "host" => array:1 [
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            ]
            4 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "EAU guidelines on prostate cancer&#46; Part 1&#58; screening&#44; diagnosis&#44; and local treatment with curative intent-update 2013"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "European Association of Urology"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Heidenreich"
                            1 => "P&#46;J&#46; Bastian"
                            2 => "J&#46; Bellmunt"
                            3 => "M&#46; Bolla"
                            4 => "S&#46; Joniau"
                            5 => "T&#46; van der Kwast"
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                      ]
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.eururo.2013.09.046"
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                        "tituloSerie" => "Eur Urol"
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                        "paginaInicial" => "124"
                        "paginaFinal" => "137"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24207135"
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                          ]
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                      ]
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              ]
            ]
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lymphadenectomy in prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Winter"
                            1 => "F&#46; Wawroschek"
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Article information

ISSN: 2253654X
Original language: English

DOI:10.1016/j.remn.2015.07.007

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 October	1	2	3
2024 February	1	2	3
2023 June	1	0	1
2023 May	1	0	1
2023 March	2	0	2
2023 February	1	2	3
2022 March	3	0	3
2021 October	1	2	3
2021 May	1	2	3
2021 March	2	2	4
2021 February	10	2	12
2020 December	2	4	6
2020 November	1	2	3
2020 September	0	3	3
2020 July	2	4	6
2020 June	1	2	3
2020 March	3	4	7
2020 January	2	2	4
2019 August	1	0	1
2019 July	3	2	5
2019 February	3	0	3
2018 September	1	0	1
2018 August	1	0	1
2018 June	2	0	2
2018 May	1	0	1
2018 April	1	0	1
2018 March	3	2	5
2018 February	52	5	57
2018 January	68	2	70
2017 December	46	1	47
2017 November	48	2	50
2017 October	52	8	60
2017 September	46	6	52
2017 August	71	6	77
2017 July	76	2	78
2017 June	67	7	74
2017 May	93	17	110
2017 April	63	39	102
2017 March	43	12	55
2017 February	20	7	27
2017 January	12	3	15
2016 December	27	10	37
2016 November	28	2	30
2016 October	2	1	3
2016 September	0	3	3
2016 July	1	1	2
2016 June	0	4	4
2016 May	1	13	14
2016 April	2	13	15
2016 March	2	4	6
2016 February	2	9	11
2016 January	56	48	104
2015 December	23	39	62
2015 November	17	32	49

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