A new bimodal approach for sentinel lymph node imaging in prostate cancer using a magnetic and fluorescent hybrid tracer.

PURPOSE: To obtain initial data on sentinel lymph node (SLN) visualisation by pre-operative magnetic resonance imaging (MRI) and intra-operative bimodal SLN identification using a new magnetic fluorescent hybrid tracer in prostate cancer (PCa) patients. METHODS: Ten patients at > 5% risk for lymph node (LN) invasion were included. The day before surgery, a magnetic fluorescent hybrid tracer consisting of superparamagnetic iron oxide nanoparticles (SPION) and indocyanine green was transrectally injected into the prostate. Five hours after injection, transversal pelvic MRI scans were recorded and T2*-weighed images were screened for pelvic LNs with SPION uptake. Intra-operatively, magnetically active and/or fluorescent SLNs were detected by a handheld magnetometer and near-infrared fluorescence imaging (FI). Extended pelvic lymph node dissection (PLND) and radical prostatectomy completed the surgery. All resected specimens were checked ex situ for magnetic activity and fluorescence and were histopathologically examined. RESULTS: Pre-operative MRI identified 145 pelvic LNs with SPION uptake. In total, 75 (median 6, range 3‒13) magnetically active SLNs were resected, including 14 SLNs not seen on MRI. FI identified 89 fluorescent LNs (median 8.5, range 4‒13) of which 15 LNs were not magnetically active. Concordance of the different techniques was 70% for pre-operative MRI vs. magnetometer-guided PLND and 88% for magnetic vs. fluorescent SLN detection. CONCLUSION: These are the first promising results of bimodal, magnetic fluorescent SLN detection in PCa patients. Our magnetic fluorescent hybrid approach provides the surgeon a pre-operative lymphatic roadmap by using MRI and intra-operative visual guidance through the application of a fluorescent lymphatic agent. The diagnostic accuracy of our new hybrid approach has to be evaluated in further studies. TRIAL REGISTRATION: DRKS00032808. Registered 04 October 2023, retrospectively registered.

Can contralateral lymph-node metastases be ruled out in prostate cancer patients with only unilaterally positive prostate biopsy?

PURPOSE: Our study evaluated the diagnostic benefits of bilateral pelvic lymphadenectomy in prostate cancer patients with unilaterally positive prostate biopsy. METHODS: Our retrospective analysis included clinical, surgical, and histopathological data of 440 prostate cancer patients treated with radical prostatectomy and bilateral sentinel-guided and risk-adapted complementary extended pelvic lymphadenectomy at our hospital between 2015 and 2022. We performed multiparametric logistic regression analysis to identify the most relevant predictive factors for detecting lymph-node metastasis in this group of patients. RESULTS: Overall, 373 patients (85%) had histopathologically bilateral tumours and 45 (10%) pN1 status, of which 22 (49%) also had lymph-node metastasis contralateral to the side of the positive prostate biopsy. In two patients with confirmed unilateral disease in prostatectomy specimens, bilateral lymph-node metastases were observed. Eight pN1 patients would have been missed by unilateral pelvic lymphadenectomy, resulting in a false-negative rate of 18%, 82% sensitivity, and 98% accuracy. Clinical tumour category, International Society of Urological Pathology grade, and percentage of prostate biopsy cores that are positive, as well as number of dissected lymph nodes contralateral to positive prostate biopsy, were determined as the most relevant predictive factors for detecting lymph-node metastasis. Our analysis was limited by its retrospective nature as well as by the fact that 80% of the patients did not receive MRI-targeted biopsy. CONCLUSION: Our study highlights the diagnostic value of bilateral pelvic lymphadenectomy and the need for careful planning in surgery for prostate cancer patients with unilaterally positive prostate biopsy.

A newly identified trigeminal brain pathway in a night-migratory bird could be dedicated to transmitting magnetic map information.

Night-migratory songbirds can use geomagnetic information to navigate over thousands of kilometres with great precision. A crucial part of the magnetic 'map' information used by night-migratory songbirds is conveyed via the ophthalmic branches of the trigeminal nerves to the trigeminal brainstem complex, where magnetic-driven neuronal activation has been observed. However, it is not known how this information reaches the forebrain for further processing. Here, we show that the magnetically activated region in the trigeminal brainstem of migratory Eurasian blackcaps (Sylvia atricapilla) represents a morphologically distinctive neuronal population with an exclusive and previously undescribed projection to the telencephalic frontal nidopallium. This projection is clearly different from the known trigeminal somatosensory pathway that we also confirmed both by neuronal tracing and by a thorough morphometric analysis of projecting neurons. The new pathway we identified here represents part of a brain circuit that-based on the known nidopallial connectivities in birds-could potentially transmit magnetic 'map' information to key multisensory integration centres in the brain known to be critically involved in spatial memory formation, cognition and/or controlling executive behaviour, such as navigation, in birds.

A Fluorescent and Magnetic Hybrid Tracer for Improved Sentinel Lymphadenectomy in Prostate Cancer Patients.

In prostate cancer, sentinel lymph node dissection (sLND) offers a personalized procedure with staging ability which is at least equivalent to extended LND while inducing lower morbidity. A bimodal fluorescent-radioactive approach was introduced to improve sentinel LN (SLN) detection. We present the first in-human case series on exploring the use of a fluorescent-magnetic hybrid tracer in a radiation-free sLND procedure. Superparamagnetic iron oxide nanoparticles and indocyanine green were administered simultaneously in five prostate cancer patients scheduled for extended LND, sLND and radical prostatectomy. In situ and ex vivo fluorescence and magnetic signals were documented for each LN sample detected via a laparoscopic fluorescence imaging and magnetometer system. Fluorescence and magnetic activity could be detected in all patients. Overall, 19 lymph node spots could be detected in situ, 14 of which were fluorescently active and 18 of which were magnetically active. In two patients, no fluorescent LNs could be detected in situ. The separation of the LN samples resulted in a total number of 30 SLNs resected. Ex vivo measurements confirmed fluorescence in all but two magnetically active SLNs. One LN detected in situ with both modalities was subsequently shown to contain a metastasis. This study provides the first promising results of a bimodal, radiation-free sLND, combining the advantages of both the magnetic and fluorescence approaches.

Radioisotope-Guided Sentinel Lymph Node Biopsy in Penile Cancer: A Long-Term Follow-Up Study.

Lymph node (LN) management is critical for survival in patients with penile cancer. However, radical inguinal lymphadenectomy carries a high risk of postoperative complications such as lymphedema, lymphocele, wound infection, and skin necrosis. The European Association of Urology guidelines therefore recommend invasive LN staging by modified inguinal lymphadenectomy or dynamic sentinel node biopsy (DSNB) in clinically node-negative patients (cN0) with intermediate- and high-risk tumors (≥ T1G2). However, the timing of DSNB (simultaneous vs. subsequent to partial or total penile resection) is controversial and the low incidence of penile cancer means that data on the long-term outcomes of DSNB are limited. The present study aimed to analyze the reliability and morbidity of DSNB in patients with penile cancer during long-term follow-up. This retrospective study included 41 patients (76 groins) who underwent radioisotope-guided DSNB simultaneously or secondarily after penile surgery from June 2004 to November 2018. In total, 193 sentinel LNs (SLNs) and 39 non-SLNs were removed. The median number of dissected LNs was 2.5 (interquartile range 2-4). Histopathological analysis showed that five of the 76 groins (6.6%) contained metastases. None of the non-SLNs were tumor-positive. In accordance with the guidelines, all inguinal regions with positive SLNs underwent secondary radical inguinal lymphadenectomy, which revealed three additional metastases in one groin. Regional LN recurrence was detected in three patients (four groins) during a median follow-up of 70 months, including two patients in whom DSNB had been performed secondarily after repetitive penile tumor resections. DSNB-related complications occurred in 15.8% of groins. Most complications were mild (Clavien-Dindo grade I; 50%) or moderate (II; 25%), and invasive intervention was only required in 3.9% of groins (IIIa: n = 1; IIIb: n = 2). In summary, this study suggests that the current radioisotope-guided DSNB procedure may reduce the complication rate of inguinal lymphadenectomy in patients with cN0 penile cancer. However, DSNB and penile surgery should be performed simultaneously to minimize the false-negative rate. Recent advances, such as new tracers and imaging techniques, may help to reduce the false-negative rate of DSNB further.

Magnetometer-Guided Sentinel Lymph Node Dissection in Prostate Cancer: Rate of Lymph Node Involvement Compared with Radioisotope Marking.

Sentinel pelvic lymph node dissection (sPLND) enables the targeted removal of lymph nodes (LNs) bearing the highest metastasis risk. In prostate cancer (PCa), sPLND alone or combined with extended PLND (ePLND) reveals more LN metastases along with detecting sentinel LNs (SLNs) outside the conventional ePLND template. To overcome the disadvantages of radioisotope-guided sPLND in PCa treatment, magnetometer-guided sPLND applying superparamagnetic iron oxide nanoparticles as a tracer was established. This retrospective study compared the nodal staging ability between magnetometer- and radioisotope-guided sPLNDs. We analyzed data of PCa patients undergoing radical prostatectomy and magnetometer- (848 patients, 2015-2021) or radioisotope-guided (2092 patients, 2006-2015) sPLND. To reduce heterogeneity among cohorts, we performed propensity score matching and compared data considering sentinel nomogram-based probabilities for LN involvement (LNI). Magnetometer- and radioisotope-guided sPLNDs had SLN detection rates of 98.12% and 98.09%, respectively; the former detected more SLNs per patient. The LNI rates matched nomogram-based predictions in both techniques equally well. Approximately 7% of LN metastases were detected outside the conventional ePLND template. Thus, we confirmed the reliability of magnetometer-guided sPLND in nodal staging, with results comparable with or better than radioisotope-guided sPLND. Our findings highlight the importance of the sentinel technique for detecting LN metastases in PCa.

Are movements of daytime and nighttime passerine migrants as different as day and night?

Even after decades of research, the migration of songbirds still holds numerous secrets. Distinct stopover and routing behavior of diurnally and nocturnally migrating songbirds has been stated in the 1960s, but empirical confirmation is yet lacking widely. We studied the behavior of individual diurnally migrating dunnocks and nocturnally migrating blackcaps by means of large-scale automated radio-telemetry. Birds were radio-tagged during their stopover at the German North Sea coast. Our data indicate longer initial stopover duration in the diurnally migrating dunnocks, opposing the hypothesis of nocturnal migrants needing more time to recover due to their longer migratory flights. Nonetheless, dunnocks stopped over more often along their tracks as when compared to the nocturnally migrating blackcaps. Behavior en route did not differ as clearly between species challenging the general view of contrasting routings of diurnal and nocturnal migrants with regard to landscape and open water. Our results imply additional factors of relevance other than differences in species or daily migration timing per se. We discuss and highlight the need of detailed and individual based data to better understand stopover and routing behavior of songbirds in the environmental context.

To cross or not to cross - thrushes at the German North Sea coast adapt flight and routing to wind conditions in autumn.

BACKGROUND: Although many aspects of passerine migration are genetically determined, routing appears to be flexibly adjusted to the conditions experienced on each individual journey. This holds especially true for routing decisions taken when confronted with large bodies of water. Once taken, these decisions can be hardly altered or revised. In this paper, we analysed stopover and routing decisions taken by three species of thrushes, blackbirds, redwings and song thrushes, at the German North Sea coast. METHODS: Birds were equipped with radio-telemetry tags at stopover sites along the coast during autumn migration and subsequently tracked by an automated receiver network covering the coastline and islands of the German Bight. RESULTS: The thrushes resumed migration in nights with a favourable northward wind component and clear skies. About 40% of the tagged individuals have taken an offshore instead of an alongshore oriented flight route. Routing decisions were influenced by the strength of the eastward wind component with offshore oriented flights taking place primarily under weak winds or winds blowing towards the west. Thrushes that took an offshore oriented route stopped over at the coast longer than those flying alongshore. Interestingly, offshore as well as alongshore oriented flights co-occurred within single nights and under comparable weather conditions. CONCLUSIONS: Migratory flight and routing decisions of thrushes at the German North Sea coast are highly dependent on weather, in particular wind. Still, we found evidence that weather may not be the sole reason for individual routes taken. Physical condition, morphology or animal personality lend themselves as possible additional factors of influence. Enabling a more detailed understanding of thrush migration over and along the German North Sea, our data help to better judge risks that migratory birds are facing when en route conditions are altered, for example by artificial obstacles such as offshore wind turbines.