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.

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.

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.

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.

Evaluation of Fast Molecular Detection of Lymph Node Metastases in Prostate Cancer Patients Using One-Step Nucleic Acid Amplification (OSNA).

Background: In clinical routine, only fractions of lymph nodes (LNs) are examined histopathologically, often resulting in missed (micro-)metastases and incorrect staging of prostate cancer (PCa). One-step nucleic acid amplification (OSNA) analyzes the entire LN by detecting cytokeratin 19 (CK19) mRNA as a surrogate for LN metastases requiring less effort than conventional biomolecular techniques. We aimed to evaluate performance of OSNA in detecting sentinel LN (SLN) metastases in PCa. Methods: SLNs (n = 534) of 64 intermediate- or high-risk PCa patients undergoing radical prostatectomy with extended and sentinel-guided lymphadenectomy were cut into slices and alternatingly assigned to OSNA and histopathology (hematoxylin-eosin staining, CK19, and CK AE1/AE3 immunohistochemistry). Sensitivity and specificity of OSNA and concordance and measure of agreement (Cohen's kappa (κ)) between OSNA and histopathology were assessed. Results: Histopathology revealed metastases in 76 SLNs. Sensitivity and specificity of OSNA were 84.2% and 96.1%, respectively. Discordant results were recorded for 30 of 534 SLNs, revealing high concordance (94.4%). Twenty-four discordant cases were classified as micrometastases, indicating a possible allocation bias. In 18 cases, positive results were conferred only by OSNA resulting in seven LN-positive patients who were missed by histopathology. Overall, the level of agreement was high (κ = 0.78). Conclusions: OSNA provided a diagnosis that was as least as accurate as detailed histological examination and might improve LN staging in PCa.

Magnetic Resonance Sentinel Lymph Node Imaging and Magnetometer-Guided Intraoperative Detection in Penile Cancer, using Superparamagnetic Iron Oxide Nanoparticles: First Results.

In penile cancer, lymph node (LN) metastasis is the main known prognostic factor that affects survival. Inguinal sentinel LN (SLN) dissection (sLND) using radioactive marking is recommended by the European Association of Urology guidelines to evaluate the nodal status in clinically node-negative penile cancer (cN0; ≥pT1, G2). Dependence on radioisotopes limits the application of this procedure to small parts of the developed world, and imposes restrictions on hospital logistics. To overcome these issues, SLN visualization using magnetic resonance imaging (MRI) and magnetometer-guided detection after intraprostatic injection of superparamagnetic iron oxide nanoparticles (SPION) has been successfully applied in prostate cancer. Here, we present the first results of magnetic sLND in penile cancer. After peritumoral SPION injection, MR SLN imaging and magnetometer-guided sLND were performed in one cN0 penile cancer patient. Another patient underwent magnetometer-guided sLND only. In the first case, 5 SLNs could be visualized on MRI and intraoperatively detected by magnetometer-guided sLND. In the second patient, 3 SLNs could be detected by magnetic sLND. Neither patient exhibited adverse events attributable to SPION-injection. In conclusion, SPION-guided SLN identification using MRI and a handheld magnetometer is feasible and could provide a radiation-free technique for SLN identification in penile cancer. For further clarification, a multicenter study should be carried out.

Accuracy of Magnetometer-Guided Sentinel Lymphadenectomy after Intraprostatic Injection of Superparamagnetic Iron Oxide Nanoparticles in Prostate Cancer: The SentiMag Pro II Study.

Radioisotope-guided sentinel lymph node dissection (sLND) has shown high diagnostic reliability in prostate (PCa) and other cancers. To overcome the limitations of the radioactive tracers, magnetometer-guided sLND using superparamagnetic iron oxide nanoparticles (SPIONs) has been successfully used in PCa. This prospective study (SentiMag Pro II, DRKS00007671) determined the diagnostic accuracy of magnetometer-guided sLND in intermediate- and high-risk PCa. Fifty intermediate- or high-risk PCa patients (prostate-specific antigen (PSA) ≥ 10 ng/mL and/or Gleason score ≥ 7; median PSA 10.8 ng/mL, IQR 7.4-19.2 ng/mL) were enrolled. After the intraprostatic SPIONs injection a day earlier, patients underwent magnetometer-guided sLND and extended lymph node dissection (eLND, followed by radical prostatectomy. SLNs were detected in in vivo and in ex vivo samples. Diagnostic accuracy of sLND was assessed using eLND as the reference. SLNs were detected in all patients (detection rate 100%), with 447 sentinel lymph nodes SLNs (median 9, IQR 6-12) being identified and 966 LNs (median 18, IQR 15-23) being removed. Thirty-six percent (18/50) of patients had LN metastases (median 2, IQR 1-3). Magnetometer-guided sLND had 100% sensitivity, 97.0% specificity, 94.4% positive predictive value, 100% negative predictive value, 0.0% false negative rate, and 3.0% additional diagnostic value (LN metastases only in SLNs outside the eLND template). In vivo, one positive SLN/LN-positive patient was missed, resulting in a sensitivity of 94.4%. In conclusion, this new magnetic sentinel procedure has high accuracy for nodal staging in intermediate- and high-risk PCa. The reliability of intraoperative SLN detection using this magnetometer system requires verification in further multicentric studies.

Diagnostic Accuracy of Magnetometer-Guided Sentinel Lymphadenectomy After Intraprostatic Injection of Superparamagnetic Iron Oxide Nanoparticles in Intermediate- and High-Risk Prostate Cancer Using the Magnetic Activity of Sentinel Nodes.

Due to the high morbidity of extended lymph node dissection (eLND) and the low detection rate of limited lymph node dissection (LND), targeted sentinel lymph node dissection (sLND) was implemented in prostate cancer (PCa). Subsequently, nonradioactive sentinel lymph node (SLN) detection using magnetic resonance imaging (MRI) and a magnetometer after intraprostatic injection of superparamagnetic iron oxide nanoparticles (SPIONs) was successfully applied in PCa. To validate the reliability of this approach, considering the magnetic activity of SLNs or whether it is sufficient to dissect only the most active SLNs as shown in other tumor entities for radio-guided sLND, we analyzed magnetometer-guided sLND results in 218 high- and intermediate-risk PCa patients undergoing eLND as a reference standard. Using a sentinel nomogram to predict lymph node invasion (LNI), a risk range was determined up to which LND could be dispensed with or sLND only would be adequate. In total, 3,711 LNs were dissected, and 1,779 SLNs (median, 8) were identified. Among 78 LN-positive patients, there were 264 LN metastases (median, 2). sLND had a 96.79% diagnostic rate, 88.16% sensitivity, 98.59% specificity, 97.1% positive predictive value (PPV), 93.96% negative predictive value (NPV), 4.13% false-negative rate, and 0.92% additional diagnostic value (LN metastases only outside the eLND template). For intermediate-risk patients only, the sensitivity, specificity, PPV, and NPV were 100%. Magnetic activities of SLNs were heterogeneous regardless of metastasis. The accuracy of predicting the presence of metastases for each LN from the proportion of activity was only 57.3% in high- and 65% in intermediate-risk patients. Patients with LNI risk of less than 5% could have been spared LND, as no positive LNs were found in this group. For patients with an LNI risk between 5% and 20%, sLND-only would have been sufficient to detect almost all LN metastases; thus, eLND could be dispensed with in 36% of patients. In conclusion, SPION-guided sLND is a reliable alternative to eLND in intermediate-/high-risk PCa. No conclusions can be drawn from magnetic SLN activity regarding the presence of metastases. LND could be dispensed with according to a nomogram of predicted probability for LNI of 5% without losing any LN-positive patient. Patients with LNI risk between 5% and 20% could be spared eLND by performing sLND.

Detection of CK19 mRNA Using One-step Nucleic Acid Amplification (OSNA) in Prostate Cancer: Preliminary Results.

Background: Accurate histopathological evaluation of lymph nodes (LNs) is essential for reliable staging in prostate cancer. In routine practice, conventional techniques only examine parts of the LN. Molecular nodal staging methods are limited by their high costs and extensive time requirement. One-step nucleic acid amplification (OSNA) determines the metastatic status of the complete LN and allows for rapid intraoperative detection of LN metastases. OSNA has been proposed for diagnosis of LN metastases from breast cancer by quantifying the CK19 mRNA copy number. To provide basic data for OSNA development for prostate cancer, we conducted an investigation of CK19 and OSNA in prostate cancer specimens. Methods: OSNA is based on a short homogenization step and subsequent automated amplification of CK19 mRNA directly from the sample lysate, with results available in 30-40 min. A total of 20 prostate cancer specimens from consecutive patients with intermediate or high-risk prostate cancer (Gleason-Score ≥7) were investigated by both OSNA and conventional histopathology (H&E staining, CK19 immunohistochemistry). OSNA was performed on frozen samples using a ready-to-use amplification kit in an automated real-time detection system. Samples were defined as 'negative' or 'positive' according to mRNA copy number: >5000 copies/µl (++), 250-5000 copies/µl (+), and <250 copies/µl (-). Results: Histopathological analysis confirmed prostate cancer in all samples: Gleason score 7 (n=11), Gleason score 8 (n=2), and Gleason score 9 (n=6). Gleason score could not be given for one patient who previously underwent hormonal treatment. OSNA analysis detected CK19 expression in 100% of the specimens and high numbers of CK19 mRNA copies in all cases (9 samples ++; 11 samples +). Immunohistochemistry confirmed CK19 expression in 19 of 20 cases. In the immunohistochemistry CK19-negative patient, a Gleason score 9 prostate cancer was diagnosed. Conclusions: This is the first study using OSNA to detect CK19 expression in prostate cancer. Initial data indicate that this rapid method for molecular LN staging reliably identifies CK19 mRNA in prostate cancer. These results suggest that the OSNA assay may be suitable to improve (intraoperative) LN staging in prostate cancer. For further verification, OSNA analysis of LN specimens from prostate cancer patients is required.

Magnetic resonance sentinel lymph node imaging and magnetometer-guided intraoperative detection in prostate cancer using superparamagnetic iron oxide nanoparticles.

PURPOSE: Sentinel lymph node (LN) dissection (sLND) using a magnetometer and superpara-magnetic iron oxide nanoparticles (SPION) as a tracer was successfully applied in prostate cancer (PCa). The feasibility of sentinel LN (SLN) visualization on MRI after intraprostatic SPION injection has been reported. In the present study, results of preoperative MRI identification of SLNs and the outcome of subsequent intraoperative magnetometer-guided sLND following intraprostatic SPION injection were studied in intermediate- and high-risk PCa. PATIENTS AND METHODS: A total of 50 intermediate- and high-risk PCa patients (prostate-specific antigen >10 ng/mL and/or Gleason score ≥7) scheduled for radical prostatectomy with magnetometer-guided sLND and extended pelvic LND (eLND), were included. Patients underwent MRI before and one day after intraprostatic SPION injection using T1-, T2-, and T2*-weighted sequences. Diagnostic rate per patient was established. Distribution of SLNs per anatomic region was registered. Diagnostic accuracy of sLND was assessed by using eLND as a reference standard. RESULTS: SPION-MRI identified a total of 890 SLNs (median 17.5; IQR 12-22.5). SLNs could be successfully detected using MRI in all patients (diagnostic rate 100%). Anatomic SLN distribution: external iliac 19.2%, common iliac 16.6%, fossa obturatoria 15.8%, internal iliac 13.8%, presacral 12.1%, perirectal 12.0%, periprostatic 3.7%, perivesical 2.3%, and other regions 4.4%. LN metastases were intraoperatively found in 15 of 50 patients (30%). sLND had a 100% diagnostic rate, 85.7% sensitivity, 97.2% specificity, 92.3% positive predictive value, 94.9% negative predictive value, false negative rate 14.3%, and 2.8% additional diagnostic value (LN metastases only outside the eLND template). CONCLUSION: MR scintigraphy after intraprostatic SPION injection provides a roadmap for intraoperative magnetometer-guided SLN detection and can be useful to characterize a reliable lymphadenectomy template. Draining LN from the prostate can be identified in an unexpectedly high number, especially outside the established eLND template. Further studies are required to analyze discordance between the number of pre- and intraoperatively identified SLNs.

Lidocaine is a nocebo treatment for trigeminally mediated magnetic orientation in birds.

Even though previously described iron-containing structures in the upper beak of pigeons were almost certainly macrophages, not magnetosensitive neurons, behavioural and neurobiological evidence still supports the involvement of the ophthalmic branch of the trigeminal nerve (V1) in magnetoreception. In previous behavioural studies, inactivation of putative V1-associated magnetoreceptors involved either application of the surface anaesthetic lidocaine to the upper beak or sectioning of V1. Here, we compared the effects of lidocaine treatment, V1 ablations and sham ablations on magnetic field-driven neuronal activation in V1-recipient brain regions in European robins. V1 sectioning led to significantly fewer Egr-1-expressing neurons in the trigeminal brainstem than in the sham-ablated birds, whereas lidocaine treatment had no effect on neuronal activation. Furthermore, Prussian blue staining showed that nearly all iron-containing cells in the subepidermal layer of the upper beak are nucleated and are thus not part of the trigeminal nerve, and iron-containing cells appeared in highly variable numbers at inconsistent locations between individual robins and showed no systematic colocalization with a neuronal marker. Our data suggest that lidocaine treatment has been a nocebo to the birds and a placebo for the experimenters. Currently, the nature and location of any V1-associated magnetosensor remains elusive.

Sentinel lymph node surgery in prostate cancer using magnetic particles.

PURPOSE OF REVIEW: Superparamagnetic iron oxide nanoparticles (SPIONs) are tested to identify sentinel lymph nodes (SLNs) to exploit the advantages of targeted pelvic SLN dissection (sPLND), while circumventing the disadvantages of established radioactive labeling. Here we review recent studies about sPLND in prostate cancer (PCa), including the first results of SLN detection using intraprostatic SPION-injection. RECENT FINDINGS: A recent systematic literature review reveals that the diagnostic accuracy of sPLND is comparable with extended PLND (ePLND). sPLND combined with ePLND achieve better node removal by increasing the number of affected nodes. The first sentinel-based nomogram predicting lymph node invasion is established. A sentinel-nomogram update provides comparative predictions relative to ePLND models. sPLND using a magnetometer and SPIONs as a tracer is successful whenever applied to PCa, and SLN identification using MRI after intraprostatic injection of SPIONs is feasible. SLNs are present in an unexpectedly high number outside the ePLND template. SUMMARY: SLN detection outside the ePLND template and the increased diagnostic value of sPLND compared with ePLND supports the individualized extension of PLND using sPLND in PCa. SPION-MRI, combined with a hand-held magnetometer, provides a nonradioactive technique for preoperative and intraoperative SLN localization. Further studies are required to evaluate the effects of sPLND on oncological outcomes.

Magnetic Marking and Intraoperative Detection of Primary Draining Lymph Nodes in High-Risk Prostate Cancer Using Superparamagnetic Iron Oxide Nanoparticles: Additional Diagnostic Value.

Sentinel lymph node dissection (sLND) using a magnetometer and superparamagnetic iron oxide nanoparticles (SPIONs) as a tracer was successfully applied in prostate cancer (PCa). Radioisotope-guided sLND combined with extended pelvic LND (ePLND) achieved better node removal, increasing the number of affected nodes or the detection of sentinel lymph nodes outside the established ePLND template. We determined the diagnostic value of additional magnetometer-guided sLND after intraprostatic SPION-injection in high-risk PCa. This retrospective study included 104 high-risk PCa patients (PSA >20 ng/mL and/or Gleason score ≥ 8 and/or cT2c) from a prospective cohort who underwent radical prostatectomy with magnetometer-guided sLND and ePLND. The diagnostic accuracy of sLND was assessed using ePLND as a reference standard. Lymph node metastases were found in 61 of 104 patients (58.7%). sLND had a 100% diagnostic rate, 96.6% sensitivity, 95.6% specificity, 96.6% positive predictive value, 95.6% negative predictive value, 3.4% false negative rate, and 4.4% false positive rate (detecting lymph node metastases outside the ePLND template). These findings demonstrate the high sensitivity and additional diagnostic value of magnetometer-guided sLND, exceeding that of ePLND through the individualized extension of PLND or the detection of sentinel lymph nodes/lymph node metastases outside the established node template in high-risk PCa.

Updated Nomogram Incorporating Percentage of Positive Cores to Predict Probability of Lymph Node Invasion in Prostate Cancer Patients Undergoing Sentinel Lymph Node Dissection.

Objectives: To update the first sentinel nomogram predicting the presence of lymph node invasion (LNI) in prostate cancer patients undergoing sentinel lymph node dissection (sPLND), taking into account the percentage of positive cores. Patients and Methods: Analysis included 1,870 prostate cancer patients who underwent radioisotope-guided sPLND and retropubic radical prostatectomy. Prostate-specific antigen (PSA), clinical T category, primary and secondary biopsy Gleason grade, and percentage of positive cores were included in univariate and multivariate logistic regression models predicting LNI, and constituted the basis for the regression coefficient-based nomogram. Bootstrapping was applied to generate 95% confidence intervals for predicted probabilities. The area under the receiver operator characteristic curve (AUC) was obtained to quantify accuracy. Results: Median PSA was 7.68 ng/ml (interquartile range (IQR) 5.5-12.3). The number of lymph nodes removed was 10 (IQR 7-13). Overall, 352 patients (18.8%) had LNI. All preoperative prostate cancer characteristics differed significantly between LNI-positive and LNI-negative patients (P<0.001). In univariate accuracy analyses, the proportion of positive cores was the foremost predictor of LNI (AUC, 77%) followed by PSA (71.1%), clinical T category (69.9%), and primary and secondary Gleason grade (66.6% and 61.3%, respectively). For multivariate logistic regression models, all parameters were independent predictors of LNI (P<0.001). The nomogram exhibited a high predictive accuracy (AUC, 83.5%). Conclusion: The first update of the only available sentinel nomogram predicting LNI in prostate cancer patients demonstrates even better predictive accuracy and improved calibration. As an additional factor, the percentage of positive cores represents the leading predictor of LNI. This updated sentinel model should be externally validated and compared with results of extended PLND-based nomograms.

[Magnetic Sentinel Lymph Node Detection in Prostate Cancer after intraprostatic Injection of Superparamagnetic Iron Oxide Nanoparticles]. / Magnetische Detektion von Sentinel-Lymphknoten beim Prostatakarzinom nach intraprostatischer Injektion von superparamagnetischen Eisenoxid-Nanopartikeln.

In prostate cancer, reliable information about the lymph node status is of great importance for accurate staging and the optimal planning of treatment. Despite recent advances in imaging, the histological detection of metastases, or pelvic lymphadenectomy (PLND), continues to be the most reliable method for lymph node staging in clinically localised prostate cancer, especially as this procedure enables the detection of small or micrometastases. Radioisotope-guided sentinel PLND (sPLND) demonstrates high sensitivity in the detection of lymph node metastases as well as low morbidity in prostate cancer because of the targeted removal of a relatively small number of lymph nodes. However, radioactive labelling is associated with limitations such as strict legal regulations, the need for a nuclear medicine department and the radioactive exposure of patients and medical staff. In order to take advantage of the targeted sentinel method while avoiding the disadvantages of radioactive labelling, the identification of sentinel lymph nodes (SLNs) by means of superparamagnetic iron oxide nanoparticles (SPIONs) was studied in breast carcinoma, and its non-inferiority compared with the established procedure with 99mtechnetium nanocolloid was demonstrated. Just like the radioactive identification of SLNs, this innovative new method for magnetic labelling and the intraoperative identification of SLNs using a hand-held magnetometer were successfully transferred to prostate cancer. Initial studies demonstrated high sensitivity in the detection of lymph node-positive patients. This method offers the additional advantage of being safe and easy to perform for a single urologist. In addition, the visualisation of SPION-marked SLNs through magnetic resonance tomography enables a precise preoperative SLN identification comparable to lymphoscintigraphy in the radioactive approach. Therefore, SLNs can be identified before and during surgical procedures in prostate cancer patients without exposure to irradiation.

Weak Broadband Electromagnetic Fields are More Disruptive to Magnetic Compass Orientation in a Night-Migratory Songbird (Erithacus rubecula) than Strong Narrow-Band Fields.

Magnetic compass orientation in night-migratory songbirds is embedded in the visual system and seems to be based on a light-dependent radical pair mechanism. Recent findings suggest that both broadband electromagnetic fields ranging from ~2 kHz to ~9 MHz and narrow-band fields at the so-called Larmor frequency for a free electron in the Earth's magnetic field can disrupt this mechanism. However, due to local magnetic fields generated by nuclear spins, effects specific to the Larmor frequency are difficult to understand considering that the primary sensory molecule should be organic and probably a protein. We therefore constructed a purpose-built laboratory and tested the orientation capabilities of European robins in an electromagnetically silent environment, under the specific influence of four different oscillating narrow-band electromagnetic fields, at the Larmor frequency, double the Larmor frequency, 1.315 MHz or 50 Hz, and in the presence of broadband electromagnetic noise covering the range from ~2 kHz to ~9 MHz. Our results indicated that the magnetic compass orientation of European robins could not be disrupted by any of the relatively strong narrow-band electromagnetic fields employed here, but that the weak broadband field very efficiently disrupted their orientation.

Magnetic field-driven induction of ZENK in the trigeminal system of pigeons (Columba livia).

Magnetoreception remains one of the few unsolved mysteries in sensory biology. The upper beak, which is innervated by the ophthalmic branch of the trigeminal nerve (V1), has been suggested to contain magnetic sensors based on ferromagnetic structures. Recently, its existence in pigeons has been seriously challenged by studies suggesting that the previously described iron-accumulations are macrophages, not magnetosensitive nerve endings. This raised the fundamental question of whether V1 is involved in magnetoreception in pigeons at all. We exposed pigeons to either a constantly changing magnetic field (CMF), to a zero magnetic field providing no magnetic information, or to CMF conditions after V1 was cut bilaterally. Using immediate early genes as a marker of neuronal responsiveness, we report that the trigeminal brainstem nuclei of pigeons, which receive V1 input, are activated under CMF conditions and that this neuronal activation disappears if the magnetic stimuli are removed or if V1 is cut. Our data suggest that the trigeminal system in pigeons is involved in processing magnetic field information and that V1 transmits this information from currently unknown, V1-associated magnetosensors to the brain.

Anthropogenic electromagnetic noise disrupts magnetic compass orientation in a migratory bird.

Electromagnetic noise is emitted everywhere humans use electronic devices. For decades, it has been hotly debated whether man-made electric and magnetic fields affect biological processes, including human health. So far, no putative effect of anthropogenic electromagnetic noise at intensities below the guidelines adopted by the World Health Organization has withstood the test of independent replication under truly blinded experimental conditions. No effect has therefore been widely accepted as scientifically proven. Here we show that migratory birds are unable to use their magnetic compass in the presence of urban electromagnetic noise. When European robins, Erithacus rubecula, were exposed to the background electromagnetic noise present in unscreened wooden huts at the University of Oldenburg campus, they could not orient using their magnetic compass. Their magnetic orientation capabilities reappeared in electrically grounded, aluminium-screened huts, which attenuated electromagnetic noise in the frequency range from 50 kHz to 5 MHz by approximately two orders of magnitude. When the grounding was removed or when broadband electromagnetic noise was deliberately generated inside the screened and grounded huts, the birds again lost their magnetic orientation capabilities. The disruptive effect of radiofrequency electromagnetic fields is not confined to a narrow frequency band and birds tested far from sources of electromagnetic noise required no screening to orient with their magnetic compass. These fully double-blinded tests document a reproducible effect of anthropogenic electromagnetic noise on the behaviour of an intact vertebrate.

Night-migratory songbirds possess a magnetic compass in both eyes.

Previous studies on European robins, Erithacus rubecula, and Australian silvereyes, Zosterops lateralis, had suggested that magnetic compass information is being processed only in the right eye and left brain hemisphere of migratory birds. However, recently it was demonstrated that both garden warblers, Sylvia borin, and European robins have a magnetic compass in both eyes. These results raise the question if the strong lateralization effect observed in earlier experiments might have arisen from artifacts or from differences in experimental conditions rather than reflecting a true all-or-none lateralization of the magnetic compass in European robins. Here we show that (1) European robins having only their left eye open can orient in their seasonally appropriate direction both during autumn and spring, i.e. there are no strong lateralization differences between the outward journey and the way home, that (2) their directional choices are based on the standard inclination compass as they are turned 180° when the inclination is reversed, and that (3) the capability to use the magnetic compass does not depend on monocular learning or intraocular transfer as it is already present in the first tests of the birds with only one eye open.