Visualisation of the Lymph Node Pathway in Real Time by Laparoscopic Radioisotope- and Fluorescence-guided Sentinel Lymph Node Dissection in Prostate Cancer Staging

doi:10.1016/j.urology.2012.05.050

Urology

Volume 80, Issue 5, November 2012, Pages 1080-1087

https://doi.org/10.1016/j.urology.2012.05.050 Get rights and content

Objective

To investigate the feasibility of visualizing lymphatic drainage of the prostate using indocyanine green. The results were compared with standard radio-guided sentinel lymph node dissection and validated by extended pelvic lymph node dissection.

Methods

From March 2010 to October 2011, ^99mTc-labelled colloid (18 hours before surgery) and indocyanine green (immediately before surgery) were injected transrectally into the prostate of 26 consecutive patients. A dedicated laparoscopic fluorescence imaging system and a commercially available laparoscopic γ-probe were used. Lymphatic vessels were visualized in real time and followed to identify the sentinel lymph node. All detected hot spots (fluorescent signals and/or radioactivity) were considered as sentinel lymph nodes, dissected, and removed. Each specimen of excised tissue was labeled according to its anatomic position and whether it was positive for radioactivity or fluorescence. Every patient underwent laparoscopic extended pelvic lymph node dissection and radical prostatectomy.

Results

Five-hundred eighty-two lymph nodes (median 22, range 11-36) were removed. Two characteristic drainage patterns were identified: one was associated with the medial umbilical ligament and the other with the internal iliac region. A direct connection with para-aortic lymph nodes was found in 3 patients. A single solitary micrometastasis was visualized by fluorescence navigation alone. A strong correlation was established between radioactive and fluorescent lymph nodes. Compared with radio-guided sentinel lymph node dissection alone, additional fluorescence-guided sentinel lymph node dissection demonstrated a further 120 lymph nodes.

Conclusion

Using the described technique of fluorescence navigation, not only lymph nodes but also lymphatic vessels are visualized in real time. The technique appears to be as effective as sentinel lymph node dissection but easier to apply.

Section snippets

Material and Methods

From March 2010 to October 2011, radioisotope- and fluorescence-guided SLND was performed in 26 patients with clinically localized PCa. Indications for SLND were intermediate- and high-risk PCa.⁹ According to thresholds of risk stratification models for positive LNs, 20 (76%) and 6 (24%) patients were in the intermediate-risk and high-risk categories, respectively (Table 1).

Written informed consent was obtained from all patients in accordance with the Declaration of Helsinki. Ethics committee

Results

We studied 26 consecutive patients. Their median age was 62 years (range 49-74) and their median preoperative prostate-specific antigen (PSA) was 12 ng/mL (range 2.9-52.8). In all, 582 LNs (median 22, range 11-36) were resected.

Two-hundred seventy-one SLNs were removed (median 10 SLNs per patient, range 0-36). At least 1 SLN was identified in 21 patients (70.8%) (Fig. 1).

Almost 42% (41.7%; median 2, range 0-12) and 20.3% of the SLNs (median 1, range 0-8) were located outside the standard PLND

Comment

An important prognostic indicator of PCa is the presence of lymph node metastases (LNMs).¹¹ Staging information is usually obtained by pelvic lymphadenectomy. The extent of PLND is currently a debated subject. The standard obturator fossa and the external iliac vein template have been traditionally accepted as locations. Nomograms to predict LN involvement are usually based on these limited dissections.¹² An increasing body of evidence has shown that a large percentage of LNMs will be

Conclusions

Laparoscopic lymphatic vessel mapping in PCa with ICG is safe, feasible, and equivalent to radio-guided SLND, but is easier to apply. It has helped us to better understand LN pathways in PCa.

The procedure demonstrates LNs as well as lymph vessels in real time, thus permitting the investigator to distinguish between primary and secondary LNs. In the small number of patients we studied, we found metastases in the medial umbilical ligament, which would have been overlooked when using standard

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Cited by (98)

The application of indocyanine green in guiding prostate cancer treatment
2023, Asian Journal of Urology
Citation Excerpt :
There is no comparative study with regards to which approach is optimal but one study believes that percutaneous, robotic-guided ICG injection was proved superior to cystoscopy or transrectal delivery [37]. ICG was usually administered shortly before the surgery, or intraoperatively [29,32,47], with one study administered 18 h before the surgery [43]. There is no universal dosing for the studies so far.
Indocyanine green (ICG) with near-infrared fluorescence absorption is approved by the United States Food and Drug Administration for clinical applications in angiography, blood flow evaluation, and liver function assessment. It has strong optical absorption in the near-infrared region, where light can penetrate deepest into biological tissue. We sought to review its value in guiding prostate cancer treatment.
All related literature at PubMed from January 2000 to December 2020 were reviewed.
Multiple preclinical studies have demonstrated the usefulness of ICG in identifying prostate cancer by using different engineering techniques. Clinical studies have demonstrated the usefulness of ICG in guiding sentinel node dissection during radical prostatectomy, and possible better preservation of neurovascular bundle by identifying landmark prostatic arteries. New techniques such as adding fluorescein in additional to ICG were tested in a limited number of patients with encouraging result. In addition, the use of the ICG was shown to be safe. Even though there are encouraging results, it does not carry sufficient sensitivity and specificity in replacing extended pelvic lymph node dissection during radical prostatectomy.
Multiple preclinical and clinical studies have shown the usefulness of ICG in identifying and guiding treatment for prostate cancer. Larger randomized prospective studies are warranted to further test its usefulness and find new modified approaches.
Free-indocyanine green-guided pelvic lymph node dissection during radical prostatectomy
2022, Urologic Oncology: Seminars and Original Investigations
Extended Pelvic Lymph Node Dissection (ePLND) remains the most accurate technique for the detection of occult lymph node metastases (LNMs) in prostate cancer (CaP) patients. Here we aim to examine whether free-Indocyanine Green (F-ICG) could accurately assess the pathological nodal (pN) status in CaP patients during real-time lymphangiography as a potential replacement for ePLND.
219 consecutive patients undergoing F-ICG-guided PLND, ePLND and radical prostatectomy (RP) for clinical-localized CaPwere included in this prospective single-center study. The pathological outcomes of F-ICG-guided PLND were compared to confirmatory ePLND. Parameters of a binary diagnostic test for the proper classification of the pN status of patients (‘per-patient’ analysis) and for the probability of detecting all the metastatic LNs (‘per-node’ analysis) were calculated. Outcome measures were prevalence, accuracy (Acc), sensitivity (Se), negative predictive value (NPV), and likelihood ratio of a negative F-ICG-guided PLND test result [LR(−)].
F-ICG-guided PLND successfully visualized LNs in all procedures with no adverse events. The overall per-patient F-ICG staging Acc was 97.7%, Se was 91.4%, with a NPV of 97.0%, and LR(−) of 8.6%. At the overall per-node level, 4,780 LNs were removed and 1,535 (32.1%) were fluorescent in vivo. F-ICG-guided PLND identified LNMs with a Se of 63.4%.
This study confirms that F-ICG-guided lymphangiography correctly staged almost 98% of patients. The high per-patient NPV suggested that avoiding ePLND is safe for most patients when F-ICG stained nodes were pN0. Thus, more conservative approaches might minimise perioperative morbidity during LNMs diagnosis in selected patients.
Performance of Indocyanine Green Fluorescence for Detecting Lymph Node Metastasis in Prostate Cancer: A Systematic Review and Meta-analysis
2021, Clinical Genitourinary Cancer
: The use of sentinel lymph node dissection in several cancers has been gaining attention with the emergence of indocyanine green fluorescence. We performed a meta-analysis to assess the diagnostic performance of indocyanine green fluorescence in detecting lymph node metastasis in prostate cancer patients.
: A literature search was conducted using PubMed, Cochrane Library, and SCOPUS on November 30, 2020, to identify eligible studies. Studies were eligible if they investigated the diagnostic performance of indocyanine green fluorescence before pelvic lymph node dissection in prostate cancer patients and reported the number of true positives, false positives, false negatives, and true negatives on lymph node–based analysis in comparison to histopathologic findings in the dissected specimen.
: Our systematic review covered 11 studies published between 2011 and 2020, with 519 patients, and our meta-analysis included 9 studies with 479 patients. Based on lymph node analysis of indocyanine green fluorescence, the results showed pooled sensitivity and specificity at 0.75 (95% confidence interval [CI] 0.49 to 0.90) and 0.66 (95% CI 0.61 to 0.70), respectively. The diagnostic odds ratio was 6.0 (95%CI 2 to 21). Several lymphatic drainage routes also showed sentinel lymph nodes localized outside the ordinal pelvic lymph node template.
: We noted relatively low diagnostic performance for lymph node metastasis, suggesting that indocyanine fluorescence may not currently be a viable alternative to pelvic lymph node dissection in prostate cancer patients. However, this technique shows novel lymphatic drainage routes and underscores the importance of lymph nodes not removed in ordinary dissection.
A DROP-IN Gamma Probe for Robot-assisted Radioguided Surgery of Lymph Nodes During Radical Prostatectomy
2021, European Urology
The DROP-IN gamma probe was introduced to overcome the restricted manoeuvrability of traditional laparoscopic gamma probes. Through enhanced manoeuvrability and surgical autonomy, the DROP-IN promotes the implementation of radioguided surgery in the robotic setting.
To confirm the utility and safety profile of the DROP-IN gamma probe and to perform a comparison with the traditional laparoscopic gamma probe and fluorescence guidance.
Twenty-five prostate cancer patients were scheduled for a robot-assisted sentinel lymph node (SN) procedure, extended pelvic lymph node dissection, and prostatectomy at a single European centre.
After intraprostatic injection of indocyanine green (ICG)-^99mTc-nanocolloid (n = 12) or ^99mTc-nanocolloid + ICG (n = 13), SN locations were defined using preoperative imaging. Surgical excision of SNs was performed under image guidance using the DROP-IN gamma probe, the traditional laparoscopic gamma probe, and fluorescence imaging.
Intraoperative SN detection was assessed for the different modalities and related to anatomical locations. Patient follow-up was included (a median of 18 mo).
Overall, 47 SNs were pursued in vivo by the DROP-IN gamma probe, of which 100% were identified. No adverse events related to its use were observed. In vivo fluorescence imaging identified 91% of these SNs. The laparoscopic gamma probe identified only 76% of these SNs, where the detection inaccuracies appeared to be related to specific anatomical regions.
Owing to improved manoeuvrability, the DROP-IN probe yielded improved SN detection rates compared with the traditional gamma probe and fluorescence imaging. These findings underline that the DROP-IN technology provides a valuable tool for radioguided surgery in the robotic setting.
Radioguided robot-assisted surgery with the novel DROP-IN gamma probe is feasible and safe. It enables more efficient intraoperative identification of sentinel lymph nodes than can be achieved with a traditional laparoscopic gamma probe. The use of the DROP-IN probe in combination with fluorescence imaging allows for a complementary optical confirmation of node localisations.
Systematic review and meta-analysis concerning near-infrared imaging with fluorescent agents to identify the sentinel lymph node in oncology patients
2020, European Journal of Surgical Oncology
Sentinel node procedures (SNP) are performed with the use of tracer-agents, mainly radio-colloid and/or blue dye. Fluorescent agents have emerged as a new tracer-agent to identify the SLN intra-operatively with near-infrared imaging. Our aim is to compare the detection rate of fluorescent agents to current “golden standards” (blue dye and/or radio-colloid) for the SNP by means of a systematic review and meta-analysis without any restrictions based on tumor type.
A systematic search in PubMed, Embase and The Cochrane Library was performed. Articles that compared the detection rates of fluorescent agents with radio-colloid and/or blue dye were included. Meta-analyses were performed for breast, gynecological and dermatological cancer using a random effects model.
In total 6195 articles were screened which resulted in a final inclusion of 55 articles. All studies used indocyanine green (ICG) as fluorescent agent. Meta-analyses comparing ICG with blue dye showed a significant and clinically relevant difference in detection rate in favor of ICG, for both breast, dermatological and gynecological cancer. Meta-analyses comparing ICG with radio-colloid did not show any significant differences, with the exception of ICG versus radio-colloid + blue dye for the bilateral SLN detection in gynecological cancer.
Near-infrared fluorescence imaging using ICG provides a higher detection rate compared to blue dye for the SNP in a range of different tumor types. SLN detection rates of ICG are comparable to radio-colloid. Due to their complementary characteristics in terms of spatial resolution and transdermal sensitivity, we suggest to use a combination of both ICG and a radio-colloid.
Advances in image enhancement for sarcoma surgery
2020, Cancer Letters
The recurrence rate of soft tissue and bone sarcomas strongly correlates to the status of the surgical margin after excision, yet excessive removal of tissue may lead to distinct, otherwise avoidable morbidity. Therefore, adequate margination of sarcomas both pre- and intra-operatively is a clinical necessity that has not yet fully been met.
Current guidance for soft-tissue sarcomas recommends an ultrasound scan followed by magnetic resonance imaging (MRI). For bone sarcomas, two plane radiographs are required, followed similarly by an MRI scan. The introduction of more precise imaging modalities may reduce the morbidity associated with sarcoma surgery; the PET-CT and PET-MRI approaches in particular demonstrating high clinical efficacy.
Despite advancements in the accuracy in pre-operative imaging, translation of an image to surgical margins is difficult, regularly resulting in wider resection margins than required. For soft tissue sarcomas there is currently no standard technique for image guided resections, while for bone sarcomas fluoroscopy may be used, however margins are not easily discernible during the surgical procedure. Near infra-red (NIR) fluorescence guided surgery offers an intra-operative modality through which complete tumour resection with adequate tumour-free margins may be achieved, while simultaneously minimising surgical morbidity.
NIR imaging presents a potentially valuable adjunct to sarcoma surgery. Early reports indicate that it may be able to provide the surgeon with helpful information on anatomy, perfusion, lymphatic drainage, tumour margins and metastases. The use of NIR fluorochromes have also been demonstrated to be well tolerated by patients. However, prior to widespread implementation, studies related to cost-effectiveness and the development of protocols are essential. Nevertheless, NIR imaging may become ubiquitous in the future, carrying the potential to transform the surgical management of sarcoma.

View all citing articles on Scopus

: Financial Disclosure: The authors declare that they have no relevant financial interests.

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OncologyVisualisation of the Lymph Node Pathway in Real Time by Laparoscopic Radioisotope- and Fluorescence-guided Sentinel Lymph Node Dissection in Prostate Cancer Staging

Objective

Methods

Results

Conclusion

Section snippets

Material and Methods

Results

Comment

Conclusions

Eur J Surg Oncol

J Urol

Eur Urol

Eur Urol

J Urol

J Urol

Eur J Cancer

Eur Urol

Eur Urol

Eur J Surg Oncol

Eur Urol

Eur Urol

Laparoscopic radioisotope-guided sentinel lymph node dissection in staging of prostate cancer

Eur Urol

Validation of sentinel lymph node dissection in prostate cancer: experience in more than 2,000 patients

Eur J Nucl Med Mol Imaging

Oncology
Visualisation of the Lymph Node Pathway in Real Time by Laparoscopic Radioisotope- and Fluorescence-guided Sentinel Lymph Node Dissection in Prostate Cancer Staging