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.

Changes in femoral rollback and rotation with increasing coupling in knee arthroplasty-a biomechanical in-vitro study.

BACKGROUND: After total knee arthroplasty, 10-30% of patients still complain about knee pain, even after exact positioning of the components. Altered knee kinematics are crucial in this regard. The aim of our study was to experimentally determine the influence of different degrees of component coupling of knee prostheses on joint kinematics during muscle-loaded knee flexion in-vitro. METHODS: Femoral rollback and femoral rotation of a standard cruciate retaining (GCR), a posterior stabilized (GPS), a rotational hinge (RSL) and a total hinge (SSL) design of the same series of knee replacement implants (SL-series) of one single manufacturer (Waldemar Link GmbH, Hamburg, Germany) were analyzed and set in relation to the motion of the corresponding native knee in a paired study design. All different coupling degrees were analyzed in the same human knees. To simulate muscle loaded knee flexion, a knee simulator was used. Kinematics were measured with an ultrasonic motion capture system and integrated in a calculated coordinate system via CT-imaging. RESULTS: The largest posterior motion on the lateral side was found for the native knee (8.7 ± 7.0 mm), followed by the GPS (3.2 ± 5.1 mm) and GCR (2.8 ± 7.3 mm) implants, while no motion was found for the RSL (0.1 ± 3.0 mm) and the SSL (-0.6 ± 2.7 mm) implants. In contrast, on the medial side, only the native knee showed a posterior motion (2.1 ± 3.2 mm). Regarding femoral external rotation, the only implant where the observed difference did not reach statistical significance when compared to the native knee was the GCR (p = 0.007). CONCLUSION: The GCR and GPS kinematics closely imitate those of the native joint. Medial femoral rollback is reduced, however, with the joint pivoting around a rotational center located in the medial plateau. Without additional rotational forces, the coupled RSL and SSL prostheses closely resemble each other with no femoral rollback or relevant rotational component. The femoral axis, however, shifts ventrally in both models when compared with their primary counterparts. The positioning of the coupling mechanism in the femoral and tibial component thus can already lead to altered joint kinematics even in prostheses with an identical surface geometry.

Associations of serum levels of microRNA-371a-3p (M371) with risk factors for progression in nonseminomatous testicular germ cell tumours clinical stage 1.

PURPOSE: Lymphovascular invasion (LV1) and presence of > 50% embryonal carcinoma (> 50% EC) represent risk factors for progression in patients with clinical stage 1 (CS1) nonseminomatous (NS) testicular germ cell tumours. As serum levels of microRNA-371a-3p (M371) are capable of detecting small amounts of GCT, we evaluated if LV1 and > 50% EC are associated with M371 levels. METHODS: M371 serum levels were measured postoperatively in 153 NS CS1 patients and both pre- and postoperatively in 131 patients. We registered the following factors: age, tumour size, LV status, > 50% EC, teratoma in primary, preoperative elevation of classical tumour markers. M371 expression was compared among subgroups. The ability of M371 to predict LV1 was calculated by receiver operating characteristics (ROC) curves. Multiple regression analysis was used to look for associations of M371 levels with other factors. RESULTS: Postoperatively elevated M371 levels were found in 29.4% of the patients, but were neither associated with LV status nor with > 50% EC. Likewise, relative decrease of M371 was not associated. ROC analysis of postoperative M371 levels revealed an AUC of 0.5 for the ability to predict LV1 while preoperative M371 had an AUC of 0.732. Multiple regression analysis revealed significant associations of preoperative M371 levels with LV status (p = 0.003), tumour size (p = 0.001), > 50% EC (p = 0.004), and teratoma component (p = 0.045). CONCLUSION: Postoperatively elevated M371 levels are not associated with risk factors for progression in NS CS1 patients. However, the significant association of preoperative M371 expression with LV1 deserves further evaluation.

Stone Localization Is Pivotal for the Success of Percutaneous Nephrolithotomy.

OBJECTIVE: The objective of this study was to predict computed tomography (CT)-controlled treatment success after minimally invasive percutaneous nephrolithotomy (Mini-PCNL). PATIENTS AND METHODS: We relied on retrospective single institutional data from 92 kidney stone patients treated with Mini-PCNL. Residual stones after treatment were evaluated by post-Mini-PCNL CT scans. Stone-free status was defined as clinically insignificant residual stones ≤3 mm after surgery. Multivariable logistic regression analyses predicted stone-free status after Mini-PCNL. RESULTS: Overall, 53 (57.6%) patients achieved stone-free status after Mini-PCNL treatment. In multivariable logistic regression analyses, stone localization was the strongest predictor for stone-free status after Mini-PCNL. Specifically, patients with exclusively pelvic stones were 7.1-fold more likely to achieve stone-free status than those patients with stones at multiple localizations (OR: 7.1; p = 0.005). Additionally, stone size represented a barrier for stone-free status (OR: 0.9; p = 0.03). CONCLUSIONS: Stone localization revealed the highest impact on treatment success after Mini-PCNL. Especially, those patients with exclusively pelvic stones were most likely to achieve stone-free status. Conversely, patients with multiple stone localizations were less likely to achieve stone-free status and need to be informed about higher risk of additional interventions after initial Mini-PCNL.

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.

Elastography Targeted Prostate Biopsy in Patients under Active Surveillance.

OBJECTIVE: The aim of this study was to examine elastography-based prostate biopsy in prostate cancer (PCa) patients under active surveillance. PATIENTS AND METHODS: We relied on PCa patients who opted for active surveillance and underwent elastography targeted and systematic follow-up biopsy at the Braunschweig Prostate Cancer Center between October 2009 and February 2015. Each prostate sextant was considered as an individual case. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC) for elastography to predict follow-up biopsy results were analyzed, respectively, and 95 % confidence intervals (CIs) were carried out by using 2000 bootstrapping sample analyses. RESULTS: Overall, 50 men and 300 sextants were identified. Overall, 27 (54%) men and 66 (22%) sextants harbored PCa at follow-up biopsy. Sensitivity, specificity, PPV, NPV, and ACC for elastography to predict follow-up biopsy results were: 19.7 (95% CI: 11.9-27.3), 86.8 (95% CI: 82.7-90.3), 29.6 (95% CI: 14.6-46.0), 79.3 (95% CI: 71.6-86.5), and 72.0% (95% CI: 65.7-78.3), respectively. CONCLUSIONS: We recorded limited reliability of elastography-based prediction of follow-up biopsy results in active surveillance patients. Based on our analyses, we can neither recommend to rely exclusively on elastography-based targeted biopsies nor to delay or to omit follow-up biopsies based on elastography results during active surveillance.

Only Size Matters in Stone Patients: Computed Tomography Controlled Stone-Free Rates after Mini-Percutaneous Nephrolithotomy.

OBJECTIVE: To examine and predicting stone-free rates (SFRs) after minimally invasive-percutaneous nephrolithotomy (mini-PNL) based on computed tomography (CT), instead of X-ray or ultrasound control. PATIENTS AND METHODS: We identified 146 mini-PNL patients with pre- and postoperative CT scans. Patient and stone characteristics were assessed. Stone-free status was defined as ≤3 mm residual fragment after mini-PNL according to postsurgery CT scan. Multivariable logistic regression analyses predicted stone-free status after mini-PNL. RESULTS: Overall, 62 (42.5%) patients achieved stone-free status after mini-PNL. In multivariable analyses, stone size was the only independent predictor for stone-free status (OR 0.9; p = 0.02). Patients with stones > 20 mm were less likely to achieve stone-free status, than those harboring stones 10-20 mm (OR 0.3; p = 0.009). SFRs according to stone size categories (< 10, 10-20, and > 20 mm) were 33.3, 50.5, and 25%. Body mass index (BMI) and stone density (Houndsfield units) were no independent predictors for stone-free status after mini-PNL. CONCLUSIONS: We report lower SFRs than expected. Stone size was the only independent predictor for stone-free status after mini-PNL. Patients with larger stones need to be informed about high risk of additional interventions. High BMI and high stone density do not represent a barrier for stone-free status after mini-PNL.

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.

Real-Life Implementation of a GPS-Based Path-Following System for an Autonomous Vehicle.

This work is meant to report on activities at TU Delft on the design and implementation of a path-following system for an autonomous Toyota Prius. The design encompasses: finding the vehicle parameters for the actual vehicle to be used for control design; lateral and longitudinal controllers for steering and acceleration, respectively. The implementation covers the real-time aspects via LabVIEW from National Instruments and the real-life tests. The deployment of the system was enabled by a Spatial Dual Global Positioning System (GPS) system providing more accuracy than the regular GPS. The results discussed in this work represent the first autonomous tests on the Toyota Prius at TU Delft, and we expect the proposed system to be a benchmark against which to test more advanced solutions. The tests show that the system is able to perform in real-time while satisfying comfort and trajectory tracking requirements: in particular, the tracking error was within 16 cm, which is compatible with the 13 cm precision of the Spatial Dual GPS, whereas the longitudinal and lateral acceleration are within comfort levels as defined by available experimental studies.

Validation and head-to-head comparison of three nomograms predicting probability of lymph node invasion of prostate cancer in patients undergoing extended and/or sentinel lymph node dissection.

PURPOSE: The updated Winter nomogram is the only nomogram predicting lymph node invasion (LNI) in prostate cancer (PCa) patients based on sentinel node (SN) dissection (sLND). The aim of the study was to externally validate the Winter nomogram and examine its performance in patients undergoing extended pelvic lymph node dissection (ePLND), ePLND combined with SN biopsy (SNB) and sLND only. The results were compared with the Memorial Sloan Kettering Cancer Center (MSKCC) and updated Briganti nomograms. METHODS: This retrospective study included 1183 patients with localized PCa undergoing robot-assisted laparoscopic radical prostatectomy (RARP) combined with pelvic lymphadenectomy and 224 patients treated with sLND and external beam radiotherapy (EBRT), aiming to offer pelvic radiotherapy only in case of histologically positive SNs. In the RARP population, ePLND was applied in 956 (80.8%) patients,while 227 (19.2%) patients were offered ePLND combined with additional SNB. RESULTS: The median numbers of removed nodes were 10 (interquartile range, IQR = 6-14), 15 (IQR = 10-20) and 7 (IQR = 4-10) in the ePLND, ePLND + SNB, and sLND groups, respectively. Corresponding LNI rates were 16.6%, 25.5% and 42%. Based on the AUC, the performance of the Briganti nomogram (0.756) in the ePLND group was superior to both the MSKCC (0.744) and Winter nomogram (0.746). The Winter nomogram, however, was the best predictor of LNI in both the ePLND + SNB (0.735) and sLND (0.709) populations. In the calibration analysis, all nomograms showed better accuracy in the low/intermediate risk patients, while in the high-risk population, an overestimation of the risk for LNI was observed. CONCLUSION: The SN-based updated nomogram showed better prediction in the SN population. The results were also comparable, relative to predictive tools developed with (e)PLND, suggesting a difference in sampling accuracy between SNB and non-SNB. Patients who benefit most from the nomogram would be those with a low/intermediate risk of LN metastasis.

Comparison of prostate cancer survival in Germany and the USA: can differences be attributed to differences in stage distributions?

OBJECTIVES: To better understand the influence of prostate-specific antigen (PSA) screening and other health system determinants on prognosis of prostate cancer, up-to-date relative survival (RS), stage distributions, and trends in survival and incidence in Germany were evaluated and compared with the United States of America (USA). PATIENTS AND METHODS: Incidence and mortality rates for Germany and the USA for the period 1999-2010 were obtained from the Centre for Cancer Registry Data at the Robert Koch Institute and the USA Surveillance Epidemiology and End Results (SEER) database. For analyses on stage and survival, data from 12 population-based cancer registries in Germany and from the SEER-13 database were analysed. Patients (aged ≥ 15 years) diagnosed with prostate cancer (1997-2010) and mortality follow-up to December 2010 were included. The 5- and 10-year RS and survival trends (2002-2010) were calculated using standard and model-based period analysis. RESULTS: Between 1999 and 2010, prostate cancer incidence decreased in the USA but increased in Germany. Nevertheless, incidence remained higher in the USA throughout the study period (99.8 vs 76.0 per 100,000 in 2010). The proportion of localised disease significantly increased from 51.9% (1998-2000) to 69.6% (2007-2010) in Germany and from 80.5% (1998-2000) to 82.6% (2007-2010) in the USA. Mortality slightly decreased in both countries (1999-2010). Overall, 5- and 10-year RS was lower in Germany (93.3%; 90.7%) than in the USA (99.4%; 99.6%) but comparable after adjustment for stage. The same patterns were seen in age-specific analyses. Improvements seen in prostate cancer survival between 2002-2004 and 2008-2010 (5-year RS: 87.4% and 91.2%; +3.8% units) in Germany disappeared after adjustment for stage (P = 0.8). CONCLUSION: The survival increase in Germany and the survival advantage in the USA might be explained by differences in incidence and stage distributions over time and across countries. Effects of early detection or a lead-time bias due to the more widespread utilisation and earlier introduction of PSA testing in the USA are likely to explain the observed patterns.

Sentinel node biopsy for prostate cancer: report from a consensus panel meeting.

OBJECTIVE: To explore the evidence and knowledge gaps in sentinel node biopsy (SNB) in prostate cancer through a consensus panel of experts. METHODS: A two-round Delphi survey among experts was followed by a consensus panel meeting of 16 experts in February 2016. Agreement voting was performed using the research and development project/University of California, Los Angeles Appropriateness Methodology on 150 statements in nine domains. The disagreement index based on the interpercentile range, adjusted for symmetry score, was used to assess consensus and non-consensus among panel members. RESULTS: Consensus was obtained on 91 of 150 statements (61%). The main outcomes were: (1) the results from an extended lymph node dissection (eLND) are still considered the 'gold standard', and sentinel node (SN) detection should be combined with eLND, at least in patients with intermediate- and high-risk prostate cancer; (2) the role of SN detection in low-risk prostate cancer is unclear; and (3) future studies should contain oncological endpoints as number of positive nodes outside the eLND template, false-negative and false-positive SN procedures, and recurrence-free survival. A high rate of consensus was obtained regarding outcome measures of future clinical trials on SNB (89%). Consensus on tracer technology was only obtained in 47% of statements, reflecting a need for further research and standardization in this area. The low-level evidence in the available literature and the composition of mainly SNB users in the panel constitute the major limitations of the study. CONCLUSIONS: Consensus on a majority of elementary statements on SN detection in prostate cancer was obtained.; therefore, the results from this consensus report will provide a basis for the design of further studies in the field. A group of experts identified evidence and knowledge gaps on SN detection in prostate cancer and its application in daily practice. Information from the consensus statements can be used to direct further studies.

Transvesical Suprapubic Externalization of Ureteral Stents - Introduction of a Surgical Innovation at the Development Stage.

BACKGROUND AND OBJECTIVES: In this study, we describe our first experiences with the new method of transvesical suprapubic externalization of ureteral stents. This method is assessed in patients with incurable ureteral obstruction and concomitant bladder dysfunction, and is classified according to the Idea, Development, Exploration, Assessment, Long-Term Study (IDEAL) recommendations. PATIENTS AND METHODS: From 2009 to 2015, transvesical suprapubic externalization of ureteral stents was applied in 14 (8 males, 6 females) patients with incurable ureteral obstruction of malignant (n = 9, 64%) or benign (n = 5; 36%) etiology. All the patients had concomitant bladder pathologies that impaired quality of life (QoL). Classification according to IDEAL followed the respective recommendations. RESULTS: Only minor complications, except 1 major complication not directly related to the procedure, were observed. QoL improvement was reported in all patients. The duration for this surgery was 45 (17-86) min; however, it varied between genders (female 37 min, male 51 min). The mean follow-up period was 26.6 months ranging from 12 to 73 months. Transvesical suprapubic externalization of ureteral stents resulted in a stable renal function and the elimination of urinary leakage via a compromised bladder in all patients. CONCLUSIONS: Transvesical externalization of ureteral stents is a feasible method for urinary diversion, which seems to improve patients' QoL in appropriate indications. The method can be classified as IDEAL stage 2a.

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.

Targeted salvage lymphadenectomy in patients treated with radical prostatectomy with biochemical recurrence: complete biochemical response without adjuvant therapy in patients with low volume lymph node recurrence over a long-term follow-up.

BACKGROUND: Choline positron emission tomography/computed tomography (PET/CT) represents an option in restaging of prostate cancer patients with disease relapse after local treatment. The present study assess whether salvage resection of lymph node metastases detected on choline PET/CT imaging in prostate cancer patients with biochemical recurrence after radical prostatectomy can result in a long-term complete biochemical remission, without adjuvant therapy. METHODS: We analysed 13 patients with prostate specific antigen (PSA) recurrence (PSA median 1.64 ng/ml, range 0.5-9.55) after radical prostatectomy and suspicious lymph nodes (median 1; range 1-3) detected on [11C]choline and [18F]fluoroethylcholine PET/CT scans. An open salvage lymphadenectomy of positive lymph nodes in a PET/CT scan and nearby lymph nodes was carried out. We examined PSA outcome without adjuvant therapy; defined complete biochemical remission as PSA <0.01 ng/ml. Histological and PET/CT findings were compared. RESULTS: Ten of 11 patients with histologically confirmed lymph node metastases showed a PSA response. Three of ten patients with single lymph node metastases had a complete biochemical remission (median follow-up 72 months, range 31.0-83). In five cases with single lymph node metastasis PSA decreased <0.02 ng/ml. Histologically confirmed 13 of 16 metastasis suspicious lymph nodes. No lymph node metastases were detected in two patients. All of the additionally removed 30 lymph nodes were correctly negative. CONCLUSIONS: This is the first confirmation of a complete biochemical remission after PET/CT guided secondary resection of a single lymph node metastasis in prostate cancer patients with biochemical recurrence after radical prostatectomy, over the long-term (>6.5 years), without adjuvant therapy. In order to improve these promising results, longer-term studies with more patients are required.

Reliability of radioisotope-guided sentinel lymph node biopsy in penile cancer: verification in consideration of the European guidelines.

BACKGROUND: Lymph node (LN) staging in penile cancer has strong prognostic implications. This contrasts with the high morbidity of extended inguinal LN dissection (LND) or over-treatment of many patients. Therefore, inguinal dynamic sentinel node biopsy (DSNB) or modified LND is recommended by the European Association of Urology (EAU) guidelines to evaluate the nodal status of patients with clinically node-negative penile cancer. This study analyzed the reliability and morbidity of radioguided DSNB in penile cancer under consideration of the current EAU recommendations in an experienced center with long-term follow-up. METHODS: Thirty-four patients who received primary surgery and had radioguided inguinal DSNB for penile cancer (≥ T1G2) were included (July 2004 to July 2013). Preoperative sentinel LN (SLN) mapping was performed using lymphoscintigraphy after peritumoral injection of (99m)Technetium nanocolloid on the day of surgery. During surgery, SLNs were detected using a gamma probe. According to the EAU guidelines, a secondary ipsilateral radical inguinal LND was performed in patients who had positive SLNs. The false-negative and complication rates of DSNB were assessed. RESULTS: A total of 32 patients were analyzed. Two patients were lost to follow-up. A total of 166 SLNs (median, 5; range, 1-15) were removed and 216 LNs (SLNs + non-SLNs; median, 6; range, 2-19) were dissected. LN metastases were found in five of the 32 (15.6 %) patients and nine of the 166 (5.4 %) SLNs were found to contain metastases. None of the remaining 50 non-SLNs contained metastases. In only one of the five SLN-positive patients, a singular further metastasis was detected by secondary radical inguinal LND. During follow-up (median, 30.5; range, 5-95 months) no inguinal nodal recurrence was detected. DSNB-related complications occurred in 11.1 % of explored groins. DISCUSSION AND CONCLUSIONS: Radioguided DSNB is a suitable procedure for LN staging in penile cancer considering the EAU recommendations and with the required experience. Under these circumstances, patients can be spared from higher morbidity without compromising the detection of LN metastases or therapeutic implications. Improvement of the methodology used to perform DSNB should be developed further to decrease the risk of missing LN metastases and to simplify the procedure.

First Nomogram Predicting the Probability of Lymph Node Involvement in Prostate Cancer Patients Undergoing Radioisotope Guided Sentinel Lymph Node Dissection.

INTRODUCTION: Existing nomograms predicting lymph node involvement (LNI) in prostate cancer (PCa) are based on conventional lymphadenectomy. The aim of the study was to develop the first nomogram for predicting LNI in PCa patients undergoing sentinel guided pelvic lymph node dissection (sPLND). MATERIALS AND METHODS: Analysis was performed on 1,296 patients with PCa who underwent radioisotope guided sPLND and retropubic radical prostatectomy (2005-2010). Median prostate specific antigen (PSA): 7.4 ng/ml (IQR 5.3-11.5 ng/ml). Clinical T-categories: T1: 54.8%, T2: 42.4%, T3: 2.8%. Biopsy Gleason sums: ≤ 6: 55.1%, 7: 39.5%, ≥ 8: 5.4%. Multivariate logistic regression models tested the association between all of the above predictors and LNI. Regression-based coefficients were used to develop a nomogram for predicting LNI. Accuracy was quantified using the area under the curve (AUC). RESULTS: The median number of LNs removed was 10 (IQR 7-13). Overall, 17.8% of patients (n = 231) had LNI. The nomogram had a high predictive accuracy (AUC of 82%). All the variables were statistically significant multivariate predictors of LNI (p = 0.001). Univariate predictive accuracy for PSA, Gleason sum and clinical stage was 69, 75 and 69%, respectively. CONCLUSIONS: The sentinel nomogram can predict LNI at a sPLND very accurately and, for the first time, aid clinicians and patients in making important decisions on the indication of a sPLND. The high rate of LN+ patients underscores the sensitivity of sPLND.

Enhanced proton translocating pyrophosphatase activity improves nitrogen use efficiency in Romaine lettuce.

Plant nitrate (NO3(-)) acquisition depends on the combined activities of root high- and low-affinity NO3(-) transporters and the proton gradient generated by the plasma membrane H(+)-ATPase. These processes are coordinated with photosynthesis and the carbon status of the plant. Here, we present the characterization of romaine lettuce (Lactuca sativa 'Conquistador') plants engineered to overexpress an intragenic gain-of-function allele of the type I proton translocating pyrophosphatase (H(+)-PPase) of Arabidopsis (Arabidopsis thaliana). The proton-pumping and inorganic pyrophosphate hydrolytic activities of these plants are augmented compared with control plants. Immunohistochemical data show a conspicuous increase in H(+)-PPase protein abundance at the vasculature of the transgenic plants. Transgenic plants displayed an enhanced rhizosphere acidification capacity consistent with the augmented plasma membrane H(+)-ATPase proton transport values, and ATP hydrolytic capacities evaluated in vitro. These transgenic lines outperform control plants when challenged with NO3(-) limitations in laboratory, greenhouse, and field scenarios. Furthermore, we report the characterization of a lettuce LsNRT2.1 gene that is constitutive up-regulated in the transgenic plants. Of note, the expression of the LsNRT2.1 gene in control plants is regulated by NO3(-) and sugars. Enhanced accumulation of (15)N-labeled fertilizer by transgenic lettuce compared with control plants was observed in greenhouse experiments. A negative correlation between the level of root soluble sugars and biomass is consistent with the strong root growth that characterizes these transgenic plants.

A novel method for intraoperative sentinel lymph node detection in prostate cancer patients using superparamagnetic iron oxide nanoparticles and a handheld magnetometer: the initial clinical experience.

BACKGROUND: A sentinel lymph node (SLN) biopsy using superparamagnetic iron oxide nanoparticles (SPIOs) as a tracer instead of radioisotopes was first applied successfully in breast cancer. This study determined the feasibility of this new technique using SPIOs and a handheld magnetometer to detect SLNs in prostate cancer (PC). METHODS: Enrolled 20 patients with intermediate and high-risk PC (PSA >10 and/or Gleason score >7) in a prospective study (12/2013-1/2014; DRKS00005473), following an ethics committee approval. After transrectal intraprostatic SPIOs injection a day earlier, patients (19/20) underwent magnetometer-guided sentinel lymphadenectomy (sPLND) and extended PLND, followed by radical prostatectomy. One patient was not operated because of an unrelated coagulation disorder. The ex vivo magnetic activity of all lymph nodes (LNs) removed was measured. The detection rate, rate of in vivo detected SLNs, and sensitivity of sPLND was established. RESULTS: No adverse events attributable to SPIOs injection were observed. Identified 126 SLNs (median 7, IQR 4-9) and resected 334 LNs (median 17, IQR 14-19); 37 % (7/19) of the patients had LN metastases (median 1, IQR 1-3.5). The detection rate and rate of in vivo detected SLNs were 90 % (17/19) and 94 % (118/126) respectively. Using sPLND, all LN metastases were detected (15/15, sensitivity 100 %) in all patients identified with SLNs. One LN + patient showed no SLNs following transurethral prostate resection. CONCLUSIONS: This is the first study using a magnetic tracer and magnetometer to detect SLNs in PC. Initial data indicate that this simple, radiation-free procedure is safe, feasible, and reliably identifies SLN and LN metastases in most patients.