Baseline neutrophil-to-eosinophil-ratio and outcome in metastatic clear-cell renal cell carcinoma treated with nivolumab or ipilimumab/nivolumab.

BACKGROUND AND PURPOSE: This study aims to evaluate neutrophil-to-eosinophil ratio (NER) as a prognostic and/or predictive biomarker in metastatic clear cell renal cell carcinoma (m-ccRCC) treated with nivolumab or ipilimumab/nivolumab. PATIENTS/MATERIALS AND METHODS: We performed a retrospective study on m-ccRCC patients treated with nivolumab or ipilimumab/nivolumab (2012-2022). Baseline NER was calculated and correlated with clinical outcomes: response rate (RR), progression free survival (PFS) and overall survival (OS). Corresponding transcriptomic data were analysed. RESULTS: We included 201 m-ccRCC patients, 76 treated with ipilimumab/nivolumab and 125 with nivolumab. Baseline NER was statistically significantly associated with International Metastatic RCC Database Consortium (IMDC) risk groups. Increased NER was associated with shorter PFS and OS in the total patient series and nivolumab-treated patients. In patients treated with ipilimumab/nivolumab, increased NER was only statistically significantly associated with shorter OS. The impact of baseline NER on PFS and OS was independent of IMDC risk stratification. No clear correlation was found between baseline NER and RECIST response or maximal tumour shrinkage. In two additional databases, NER was also associated with PFS and OS in first-line vascular-endothelial-growth-factor-receptor tyrosine-kinase-inhibitors (VEGFR-TKIs), but not to disease-free survival in the post-nephrectomy setting. Lower NER was associated with intratumoural molecular features possibly associated with better outcome on immune checkpoint inhibitors. INTERPRETATION: Lower baseline NER is associated with better PFS and OS, independent of IMDC risk score, in m-ccRCC patients treated with ipilimumab/nivolumab or nivolumab. It correlates with intratumoural molecular features possibly associated with better outcome on immune checkpoint inhibitors. The predictive power of this biomarker is probably limited and insufficient for patient selection.

Posttraumatic hemorrhagic bladder rupture managed with transurethral foley catheter placement and bilateral transcatheter vesical artery embolization.

BACKGROUND: Outcome of minimally invasive treatment of posttraumatic, hemorrhagic bladder rupture is unknown. METHODS: A 41-year-old male presented at the emergency department with pelvic and scrotal pain and macroscopic hematuria after a motor vehicle accident. Contrast-enhanced computed tomography revealed an open book fracture and an arterial phase contrast media extravasation posterior to the symphysis pubis and anterior to the urethra-vesical junction. RESULTS: The open book fracture was treated with an external fixation and the persistent bleeding was managed with insertion of a Foley catheter and bilateral embolization of the vesical arteries. CONCLUSION: Minimally invasive treatment, including vesical artery embolization and placement of a Foley catheter can be effective in the treatment of posttraumatic, hemorrhagic bladder rupture.

The key role of levator ani thickness for early urinary continence recovery in patients undergoing robot-assisted radical prostatectomy: A multi-institutional study.

BACKGROUND: Urinary continence (UC) recovery dramatically affects quality of life after robot-assisted radical prostatectomy (RARP). Membranous urethral length (MUL) has been the most studied anatomical variable associated with UC recovery. OBJECTIVE: To investigate whether levator ani thickness (LAT), assessed with multi-parametric magnetic resonance imaging (mpMRI), correlates with UC recovery after RARP. DESIGN, SETTING, AND PARTICIPANTS: The study included 209 patients treated with RARP by expert surgeons with extensive robotic experience from 2017 to 2019. All patients had complete, clinical, mpMRI, pathological, and postoperative data including pelvic floor muscle training (PFMT) protocols. INTERVENTION: After a radiologist-specific training, two urologists independently examined the files, blinded to clinical and pathological findings as well as to postoperative continence status. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: On mpMRI, LAT, bladder neck (BN) shape, MUL, and apex overlapping (AO) were measured. UC recovery was defined as use of 0 or 1 safety pad at follow-up. Multivariable models were used to assess the association between variables and UC recovery. RESULTS AND LIMITATIONS: Overall, 173 (82.8%) patients were continent after a median follow-up of 23 months (interquartile range [IQR]: 17-28). Of these, 98 (46.9%) recovered within 3 months after surgery, 42 (20.1%) from 3 to 6 months, and 33 (15.8%) from 6 months onwards. A significant higher rate of patients with LAT > 10 mm (88.1 vs.75.8%; p = 0.03) experienced UC recovery, compared to those with LAT < 10 mm. This difference was observed in the first 3 months after surgery. At multivariable analysis, LAT (odds ratio [OR]: 1.18, 95% confidence interval [CI]: 1.02-1.37; p = 0.02), Preoperative ICIQ score (OR: 0.91, 95% CI: 0.82-0.98, p = 0.03) and PFMT (OR: 1.98, 95% CI: 1.01-3.93; p = 0.04) independently predict higher UC recovery within 3 months, after accounting for age, BMI, preoperative PSA, D'Amico risk group, MUL, BN shape and AO. CONCLUSIONS: LAT greater than 1 cm was associated with greater UC recovery. Specifically, LAT greater than 1 cm seems to be associated with higher UC rate at 3 months after RARP, compared to those with LAT < 1 cm. PATIENT SUMMARY: Magnetic resonance features can help in predicting the risk of incontinence after robot-assisted radical prostatectomy and should be taken into account when counseling patients before surgery.

Human and animal fertility studies in cystinosis reveal signs of obstructive azoospermia, an altered blood-testis barrier and a subtherapeutic effect of cysteamine in testis.

Cystinosis is an inherited metabolic disorder caused by autosomal recessive mutations in the CTNS gene leading to lysosomal cystine accumulation. The disease primarily affects the kidneys followed by extra-renal organ involvement later in life. Azoospermia is one of the unclarified complications which are not improved by cysteamine, which is the only available disease-modifying treatment. We aimed at unraveling the origin of azoospermia in cysteamine-treated cystinosis by confirming or excluding an obstructive factor, and investigating the effect of cysteamine on fertility in the Ctns-/- mouse model compared with wild type. Azoospermia was present in the vast majority of infantile type cystinosis patients. While spermatogenesis was intact, an enlarged caput epididymis and reduced levels of seminal markers for obstruction neutral α-glucosidase (NAG) and extracellular matrix protein 1 (ECM1) pointed towards an epididymal obstruction. Histopathological examination in human and mouse testis revealed a disturbed blood-testis barrier characterized by an altered zonula occludens-1 (ZO-1) protein expression. Animal studies ruled out a negative effect of cysteamine on fertility, but showed that cystine accumulation in the testis is irresponsive to regular cysteamine treatment. We conclude that the azoospermia in infantile cystinosis is due to an obstruction related to epididymal dysfunction, irrespective of the severity of an evolving primary hypogonadism. Regular cysteamine treatment does not affect fertility but has subtherapeutic effects on cystine accumulation in testis.

Development and External Validation of a Multiparametric Magnetic Resonance Imaging and International Society of Urological Pathology Based Add-On Prediction Tool to Identify Prostate Cancer Candidates for Pelvic Lymph Node Dissection.

PURPOSE: We sought to expand current prediction tools for lymph node invasion in patients with prostate cancer using current state-of-the-art available tumor information, including multiparametric magnetic resonance imaging based tumor stage and detailed biopsy information. MATERIALS AND METHODS: We selected patients with prostate cancer for study who had available registered information on ISUP (International Society of Urological Pathology) based biopsy grading and multiparametric magnetic resonance imaging, and who had undergone radical prostatectomy with extended pelvic lymph node dissection. We developed a lymph node invasion prediction tool in 420 patients and externally validated it in 187. A concordance index was estimated to quantify the discriminative performance of the model. RESULTS: In the development cohort a median of 21 lymph nodes were removed per patient and 71 patients (16.9%) were diagnosed with lymph node invasion. Statistically significant predictors of lymph node invasion were the initial prostate specific antigen value, multiparametric magnetic resonance imaging based T stage, maximum tumor length in 1 core in mm and ISUP grade group corresponding to the maximum tumor involvement in 1 core. The predictive accuracy of this lymph node invasion prediction tool was 79.7% after fivefold internal cross validation and 72.5% after external validation. CONCLUSIONS: We report a contemporary, externally validated prediction tool for lymph node invasion in patients with prostate cancer. This prediction tool is a response to the paradigm shift from systematic to targeted biopsies by incorporating additional core specific biopsy information instead of the percent of positive cores. This new tool will also overcome stage migration, which is a potential risk when multiparametric magnetic resonance imaging information is used in digital rectal examination based nomograms.

Whole-body diffusion-weighted magnetic resonance imaging for the detection of bone metastases and their prognostic impact in metastatic renal cell carcinoma patients treated with angiogenesis inhibitors.

Background: Metastatic renal cell carcinoma (mRCC) patients with bone metastases (BM) are at high risk for skeletal related events and have a poorer outcome when treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs). Computed tomography (CT) lacks sensitivity to detect BM in mRCC. We aimed to determine the added value of whole body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) to CT for the detection of BM in mRCC and to estimate the prognostic impact of the number of BM in mRCC patients treated with VEGFR-TKIs.Material and methods: We conducted a prospective study including consecutive mRCC patients treated with a first-line VEGFR-TKI in the metastatic setting. All patients underwent a pretreatment thoracic-abdominal-pelvic CT and WB-DWI/MRI. CT and WB-DWI/MRI were compared for the detection of BM. The number of detected BM was correlated with response rate (RR), progression-free survival (PFS) and overall survival (OS) after start of the VEGFR-TKI.Results: Ninety-two patients were included. BM were found in 55% of the patients by WB-DWI/MRI and in 43% of the patients by CT (p = .003). Mean number of BM discovered per patient was 6.8 by WB-DWI/MRI versus 1.9 by CT (p = .006). The cutoff of ≤5 versus >5 BM on WB-DWI/MRI had the highest discriminative power for all outcome measures. Patients with >5 BM had a lower RR (10% versus 42%), more frequently early progressive disease (43% versus 13%, p = .003), shorter PFS (4 versus 10 months, p = .006) and shorter OS (10 versus 35 months, p < .0001) compared to patients with ≤5 BM.Conclusion: WB-DWI/MRI detects significantly more BM in mRCC patients than CT, allowing better estimation of the prognostic impact of BM in mRCC patients treated with VEGFR-TKIs. The prognostic impact should now be validated in patients treated with immune checkpoint inhibitors.

Safety and efficacy of embolotherapy for severe hemorrhage after partial nephrectomy.

BACKGROUND: Partial nephrectomy may be complicated by postoperative hemorrhage, which may be treated by transcatheter embolization. PURPOSE: To assess the safety and efficacy of embolotherapy for hemorrhagic complications of partial nephrectomy and to analyze the potential correlation between multiple bleeding sites on angiography and surgical complexity. MATERIAL AND METHODS: A cohort of 25 patients presenting with severe, postoperative bleeding after partial nephrectomy and treated with catheter-directed superselective embolization was included. Patients' demographics, radiological investigations before the embolization, and clinical outcome after embolization were analyzed. Mann-Whitney U test was used to analyze the potential difference in the RENAL score between patients with one or more bleeding sites in the resection area. RESULTS: Selective renal angiography revealed multiple bleeding sites at the resection bed in 8 (32%) patients with amorphous contrast extravasation in 10 (40%) patients. Embolization with use of a microcatheter and microcoils was effective to stop the bleeding in all but one patient, the latter requiring a second embolization two days later. Transient decrease in renal function was noted in 3/25 (12%) patients with full recovery in two of the three. Patients with multiple bleeding sites did not show significantly different RENAL scores compared to patients with a single bleeding site (P = 0.148). CONCLUSION: Embolotherapy for postoperative partial nephrectomy-related bleeding is safe and effective with a low rate of recurrent bleeding. The number of bleeding sites at the resection area did not correlate to the RENAL score.

Intrarenal resistive index after renal transplantation.

BACKGROUND: The intrarenal resistive index is routinely measured in many renal-transplantation centers for assessment of renal-allograft status, although the value of the resistive index remains unclear. METHODS: In a single-center, prospective study involving 321 renal-allograft recipients, we measured the resistive index at baseline, at the time of protocol-specified renal-allograft biopsies (3, 12, and 24 months after transplantation), and at the time of biopsies performed because of graft dysfunction. A total of 1124 renal-allograft resistive-index measurements were included in the analysis. All patients were followed for at least 4.5 years after transplantation. RESULTS: Allograft recipients with a resistive index of at least 0.80 had higher mortality than those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 5.20 [95% confidence interval {CI}, 2.14 to 12.64; P<0.001]; 3.46 [95% CI, 1.39 to 8.56; P=0.007]; and 4.12 [95% CI, 1.26 to 13.45; P=0.02], respectively). The need for dialysis did not differ significantly between patients with a resistive index of at least 0.80 and those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 1.95 [95% CI, 0.39 to 9.82; P=0.42]; 0.44 [95% CI, 0.05 to 3.72; P=0.45]; and 1.34 [95% CI, 0.20 to 8.82; P=0.76], respectively). At protocol-specified biopsy time points, the resistive index was not associated with renal-allograft histologic features. Older recipient age was the strongest determinant of a higher resistive index (P<0.001). At the time of biopsies performed because of graft dysfunction, antibody-mediated rejection or acute tubular necrosis, as compared with normal biopsy results, was associated with a higher resistive index (0.87 ± 0.12 vs. 0.78 ± 0.14 [P=0.05], and 0.86 ± 0.09 vs. 0.78 ± 0.14 [P=0.007], respectively). CONCLUSIONS: The resistive index, routinely measured at predefined time points after transplantation, reflects characteristics of the recipient but not those of the graft. (ClinicalTrials.gov number, NCT01879124 .).

Palliative endovascular treatment of cancer-related iliocaval obstructive disease: technical and clinical outcomes.

BACKGROUND: Cancer-related obstruction of large abdominal and pelvic veins might become symptomatic with clinical signs of lower limb venous congestion. Technical and clinical outcome after interventional treatment is not well studied yet. PURPOSE: To retrospectively assess the technical and clinical outcome of endovascular management of symptomatic cancer-related iliocaval venous obstructive disease. MATERIAL AND METHODS: From 1998 to 2013, 19 patients (15 men, 4 women; mean age, 63.6 years) referred for interventional treatment of cancer-related iliocaval obstructive disease were identified. Patients' symptoms included unilateral (n = 16; 84%) or bilateral (n = 3; 16%) painful swelling of the lower limbs. Patients' demographics as well as interventional and clinical outcome data were collected. RESULTS: All 19 patients underwent, under local anesthesia, stenting of the iliac vein (n = 16; 84%) or inferior vena cava (n = 3; 16%). Immediate technical success (n = 19) was 100%; immediate clinical success (n = 18) was 94.7%. During follow-up, seven patients (36.8%) presented with recurrent symptoms of painful limb swelling. Estimated survival after 3 and 6 months was 68.4% (95% confidence interval [CI], 47.8-82.3%) and 19.8% (95% CI, 11.9-29.2%), respectively. CONCLUSION: Endovascular stenting of cancer-related iliocaval venous obstructive disease is safe and results in immediate relief of symptoms. However, recurrent venous obstruction is common. At 3 months follow-up, the majority of patients with iliac vein stenting were still alive.

Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Syndrome.

In hereditary leiomyomatosis and renal cell carcinoma syndrome, fumarate hydratase-deficient renal cell carcinomas typically present as aggressive, unilateral, often cystic masses with heterogeneous enhancement. These tumors can metastasize early, making appropriate imaging and staging critical for diagnosis and management. Teaching point: When a renal lesion suspected of RCC is identified in a patient with cutaneous and uterine leiomyomas, HLRCC should be evaluated, which is important for future genetic counseling.

Segmentation-based quantitative measurements in renal CT imaging using deep learning.

BACKGROUND: Renal quantitative measurements are important descriptors for assessing kidney function. We developed a deep learning-based method for automated kidney measurements from computed tomography (CT) images. METHODS: The study datasets comprised potential kidney donors (n = 88), both contrast-enhanced (Dataset 1 CE) and noncontrast (Dataset 1 NC) CT scans, and test sets of contrast-enhanced cases (Test set 2, n = 18), cases from a photon-counting (PC)CT scanner reconstructed at 60 and 190 keV (Test set 3 PCCT, n = 15), and low-dose cases (Test set 4, n = 8), which were retrospectively analyzed to train, validate, and test two networks for kidney segmentation and subsequent measurements. Segmentation performance was evaluated using the Dice similarity coefficient (DSC). The quantitative measurements' effectiveness was compared to manual annotations using the intraclass correlation coefficient (ICC). RESULTS: The contrast-enhanced and noncontrast models demonstrated excellent reliability in renal segmentation with DSC of 0.95 (Test set 1 CE), 0.94 (Test set 2), 0.92 (Test set 3 PCCT) and 0.94 (Test set 1 NC), 0.92 (Test set 3 PCCT), and 0.93 (Test set 4). Volume estimation was accurate with mean volume errors of 4%, 3%, 6% mL (contrast test sets) and 4%, 5%, 7% mL (noncontrast test sets). Renal axes measurements (length, width, and thickness) had ICC values greater than 0.90 (p < 0.001) for all test sets, supported by narrow 95% confidence intervals. CONCLUSION: Two deep learning networks were shown to derive quantitative measurements from contrast-enhanced and noncontrast renal CT imaging at the human performance level. RELEVANCE STATEMENT: Deep learning-based networks can automatically obtain renal clinical descriptors from both noncontrast and contrast-enhanced CT images. When healthy subjects comprise the training cohort, careful consideration is required during model adaptation, especially in scenarios involving unhealthy kidneys. This creates an opportunity for improved clinical decision-making without labor-intensive manual effort. KEY POINTS: Trained 3D UNet models quantify renal measurements from contrast and noncontrast CT. The models performed interchangeably to the manual annotator and to each other. The models can provide expert-level, quantitative, accurate, and rapid renal measurements.

Impact of the Standardization of Penile Cancer Care on the Quality of Care, Outcomes, and Academic-driven Centralization in a Single eUROGEN Referral Center.

BACKGROUND: Penile cancer (PeCa) represents a diagnostic and therapeutic challenge given the low patient volume, which may result in inadequate physician expertise and poor guideline adherence. Since 2015, we have developed a specific care pathway for PeCa in our tertiary referral center. OBJECTIVE: To evaluate the impact of a dedicated PeCa care pathway on patient management, the adequacy of pathological reporting, and oncological outcomes. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively queried our institutional registry (S-66482) to identify patients who were surgically treated for PeCa between January 1989 and April 2022. The patient numbers were evaluated within a broader national context. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We compared patient, surgery, tumor, and pathological data before and after 2015. Kaplan-Meier analysis was used to compare local and regional recurrence rates and cancer-specific survival (CSS). RESULTS AND LIMITATIONS: Overall, 313 patients were included, of whom 204 (65.1%) were surgically treated after 2015. The median number of patients treated yearly was significantly higher after 2015 (26 vs 5; p < 0.01). Patients treated after 2015 more frequently had no palpable lymph nodes at diagnosis, despite similar primary tumor stage. After adoption of the PeCa care pathway, organ-sparing surgery (OSS) was more commonly performed (79.9% vs 57.8%; p < 0.01) despite local staging being similar and without observing a significant increase in positive margins. Surgical staging in patients with European Association of Urology intermediate- or high-risk tumors was conducted more frequently after 2015 (90% vs 41%; p < 0.01). Pathology reporting was standardized, and there was more frequent reporting of p16 staining status (81.4% vs 8.3%; p < 0.01), lymphovascular invasion (93.8% vs 44.3%; p < 0.01), and perineural invasion (92.4% vs 44.3%; p < 0.01) following implementation. CONCLUSIONS: Implementation of a standardized care pathway for PeCa resulted in higher rates of OSS and pathological nodal staging and more complete pathology reports. Considering that these changes were associated with an increase in the number of patients treated, academic-driven centralization may play a role in optimizing the management of these patients. PATIENT SUMMARY: We evaluated the impact of a care pathway for patients with penile cancer on patient management, the completeness of pathology reporting, and cancer control. We found that implementation of this pathway was associated with an increase in the number of patients treated, higher rates of organ-sparing surgery and lymph node staging, and more complete pathology reports. Centralization of care may play a role in optimizing the management of penile cancer.

Multiparametric MRI for prostate cancer localization in correlation to whole-mount histopathology.

PURPOSE: To prospectively evaluate multiparametric magnetic resonance imaging (MRI) for accurate localization of intraprostatic tumor nodules, with whole-mount histopathology as the gold standard. MATERIALS AND METHODS: Seventy-five patients with biopsy-proven, intermediate, and high-risk prostate cancer underwent preoperative T2-weighted (T2w), dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MRI at 1.5T. Localization of suspicious lesions was recorded for each of 24 standardized regions of interest on the different MR images and correlated with the pathologic findings. Generalized estimating equations (GEE) were used to estimate the sensitivity, specificity, accuracy, positive, and negative predictive value for every MRI modality, as well as to evaluate the influence of Gleason score and pT-stage. Tumor volume measurements on histopathological specimens were correlated with those on the different MR modalities (Pearson correlation). RESULTS: DW MRI had the highest sensitivity for tumor localization (31.1% vs. 27.4% vs. 44.5% for T2w, DCE, and DW MRI, respectively; P < 0.005), with more aggressive or more advanced tumors being more easily detected with this imaging modality. Significantly higher sensitivity values were obtained for the combination of T2w, DCE, and DW MRI (58.8%) as compared to each modality alone or any combination of two modalities (P < 0.0001). Tumor volume can most accurately be assessed by means of DW MRI (r = 0.75; P < 0.0001). CONCLUSION: Combining T2w, DCE, and DW imaging significantly improves prostate cancer localization.

Tumour-related imaging parameters predicting the percentage of preserved normal renal parenchyma following nephron sparing surgery: a retrospective study.

OBJECTIVES: To examine pre-operative imaging parameters that predict the residual amount of healthy renal parenchyma after nephron sparing surgery (NSS) for renal tumours, as this can help stratify patients towards the optimal surgical choice. METHODS: Ninety-eight patients with the diagnosis of a solitary unilateral renal tumour and with pre- and post-operative imaging were included in this retrospective study. Imaging, patient and surgical parameters were acquired and their correlation to the percentage decrease of healthy renal parenchyma following surgery was statistically examined to find the most significant predictor of nephron sparing. RESULTS: Loss of healthy renal parenchyma was highest in patients with renal sinus tumour involvement (P = 0.003) and anterior tumours (P = 0.006), but not significantly correlated with medial/lateral location (P = 0.940) or exophytic/endophytic tumour growth (P = 0.244). The correlation of tumour size with the percentage of parenchymal sparing did not quite reach statistical significance (P = 0.053), but involvement of the urinary collecting system (P = 0.008) was a very good predictor of complications. Loss of healthy renal parenchyma was higher in patients with high-grade surgical complications (P = 0.001). CONCLUSIONS: Several pre-operative parameters correlate to percentage nephron sparing after NSS. Anterior tumour location and renal sinus involvement proved to be the best predictors of loss of healthy renal parenchyma.

Accuracy of dynamic sentinel lymph node biopsy for inguinal lymph node staging in cN0 penile cancer.

BACKGROUND: Penile cancer is characterized by an early lymphatic dissemination. In intermediate and high-risk primary tumors without palpable inguinal lymph nodes, there is a 6-30% risk of micro-metastatic disease. Invasive lymph node staging in these patients is performed using dynamic sentinel lymph node biopsy (DSNB). In this study, the role of DSNB in cN0 penile cancer was studied, evaluating features of sentinel lymph node (SN) visualization and outcome parameters. Patients with penile cancer without inguinal lymph node metastases who were referred for DSNB at our center between January 2015 and May 2021 and had a follow-up period of at least 18 months, were retrospectively included. After injection of 85 ± 20 MBq [99mTc]Tc-nanocolloid peritumorally, dynamic, static planar and SPECT/CT imaging was performed. Primary endpoints were sensitivity of the diagnostic procedure, disease-free survival and DSNB-related adverse events. Secondary endpoints were SN detection rate, number of SNs and the number of counts of the most active SN. RESULTS: Seventy-seven penile DSNB procedures in 75 patients (67 ± 11 years) were included. The detection rate of DSNB was 91% and 96% per procedure and groin, respectively. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were 79%, 100%, 97% and 100%, respectively. More SNs were seen on SPECT/CT than on static planar imaging (1.33 vs. 1.17, p = 0.001). The mean counts per SN on static planar imaging was lower compared to SPECT/CT (1343 vs. 5008; p < 0.0001). There was a positive correlation between the total counts of the SN on the static planar image and the SPECT/CT (r = 0.79, p < 0.0001). Only one out of seventy-five patients (1%) experienced DSNB-related adverse events. After 18 months, 58 patients remained disease free (77%), 13 developed local recurrence (17%), and 4 developed lymphatic or distant metastases (5%). CONCLUSION: DNSB is a safe diagnostic procedure with a good detection rate and in particular high negative predictive value. It can therefore prevent overtreatment of patients with negative inguinal groins on clinical examination and DSNB examination. Finally, DSNB enables an early detection of occult metastases which would not be visualized with standardized imaging modalities.

Safety, Efficacy, and Predictors for Late Reintervention After Embolization of Renal Angiomyolipomas - Embolization renal angiomyolipoma.

PURPOSE: To retrospectively analyze the procedural and long-term clinical outcome of the selective embolization of renal angiomyolipoma. In addition, potential predictive factors for higher risk of late re-intervention were analyzed. METHODS: Retrospective monocentric study, including 34 consecutive patients, analyzing the safety, efficiency, and long-term clinical outcome of catheter-directed embolization of renal AML. Additionally, the difference in postembolization renal function between patients embolized in the acute and in the elective setting was analyzed. Secondly, we also evaluated whether volume/diameter of the AML and presence of intralesional aneurysms are risk factors for late re-intervention. RESULTS: Embolization of renal AML was performed to control volume (n = 21; 62 %) or to stop spontaneous hemorrhage (n = 13; 38 %) with angiographic success in all cases but was associated with renal abscess (n = 1) and pulmonary embolism (n = 1) without a significant difference in renal function before and after embolization (P = 0.513). Volume/diameter (P = 0.276/P = 0.21) and presence of aneurysms before embolization (P = 0.37) are not predictive for a higher risk of late re-intervention. CONCLUSION: Catheter-directed embolization is a safe and effective treatment modality for asymptomatic and bleeding renal AML, without a negative impact on renal function. Initial mass volume/diameter or presence/absence of intralesional aneurysms does not seem to be predictive for late re-intervention. KEY POINTS: · Complications related to renal angiomyolipoma embolization are rare.. · Embolization of angiomyolipoma will not reduce renal function.. · Initial volume or diameter of angiomyolipoma is not predictive for late re-intervention.. CITATION FORMAT: · Claesen E, Bonne L, Laenen A et al. Safety, Efficacy, and Predictors for Late Reintervention After Embolization of Renal Angiomyolipomas. Fortschr Röntgenstr 2023; 195: 319 - 325.

Pseudoprogression and Mixed Responses in Metastatic Renal Cell Carcinoma Patients Treated With Nivolumab: A Retrospective Analysis.

INTRODUCTION: Immune checkpoint inhibitors (ICI) are part of the current standard of care for metastatic clear-cell renal cell carcinoma (m-ccRCC). ICI can elicit diverse tumor response, including atypical responses such as pseudoprogression (psPD), mixed responses (MR) and late responses. We aimed to analyze the occurrence and prognostic impact of atypical responses in m-ccRCC patients treated with nivolumab. MATERIALS AND METHODS: A retrospective analysis of m-ccRCC patients treated with nivolumab in first or subsequent therapy line between November 2012 and July 2022 was performed. All radiographic evaluations of eligible patients were analyzed using the iRECIST consensus guideline. RESULTS: We assessed 247 baseline target lesions in 94 eligible patients. MR occurred in 11 (11.7%) patients: in 7 at first CT (computed tomography) evaluation (CT1) and in 4 at second CT evaluation (CT2). In 8 patients (73%), MR evolved to confirmed PD. In 3 patients (27%), MR evolved towards a partial response (PR) and was thus a psPD. psPD occurred in 8 (8.5%) patients: with psPD features at CT1 in 3 patients, with psPD features at CT2 in 2 patients, and with MR features at CT1 in 3 patients. psPD patients had similar progression-free survival and overall survival compared to patients displaying PR as best response without a phase of psPD. 76 patients were treated beyond immune unconfirmed progressive disease (iUPD) at any moment: 12 (16%) of them evolved towards PR or stable disease (SD). Treatment beyond immune confirmed PD (iCPD) in 20 patients did not lead to PR or SD. CONCLUSION: Atypical responses such as psPD and MR occurred in 8.5% and 11.7% of m-ccRCC patients treated with nivolumab at CT1 and CT2. Patients with psPD had favorable outcomes, while MR most often evolved to progression. Treatment with nivolumab beyond iCPD did not lead to tumor stabilization or regression.

Parameters predicting [18F]PSMA-1007 scan positivity and type and number of detected lesions in patients with biochemical recurrence of prostate cancer.

BACKGROUND: Detection of the site of recurrence using PSMA-PET/CT is important to guide treatment in patients with biochemical recurrence of prostate cancer (PCa). The aim of this study was to evaluate the positivity rate of [18F]PSMA-1007-PET/CT in patients with biochemically recurrent PCa and identify parameters that predict scan positivity as well as the type and number of detected lesions. This monocentric retrospective study included 137 PCa patients with biochemical recurrence who underwent one or more [18F]PSMA-1007-PET/CT scans between August 2018 and June 2019. PET-positive malignant lesions were classified as local recurrence, lymph node (LN), bone or soft tissue lesions. The association between biochemical/paraclinical parameters, as PSA value, PSA doubling time, PSA velocity, Gleason score (GS) and androgen deprivation therapy (ADT), and scan positivity as well as type and number of detected lesions was evaluated using logistic regression analysis (binary outcomes) and Poisson models (count-type outcomes). RESULTS: We included 175 [18F]PSMA-1007-PET/CT scans after radical prostatectomy (78%), external beam radiation therapy (8.8%), ADT (7.3%), brachytherapy (5.1%) and high intensity focused ultrasound (0.7%) as primary treatment (median PSA value 1.6 ng/ml). Positivity rate was 80%. PSA value and PSA velocity were significant predictors of scan positivity as well as of the presence of bone and soft tissue lesions and number of bone, LN and soft tissue lesions, both in uni- and/or multivariable analysis. Multivariable analysis also showed prior ADT as predictor of bone and soft tissue lesions, GS as predictor of the number of bone lesions and ongoing ADT as predictor of the number of LN lesions. CONCLUSION: [18F]PSMA-1007-PET/CT showed a high positivity rate in patients with biochemically recurrent PCa. PSA value and PSA velocity were significant predictors of scan positivity as well as of the presence and number of bone and soft tissue lesions and the number of LN lesions. Our findings can guide clinicians in optimal patient selection for [18F]PSMA-1007-PET/CT and support further research leading to the development of a prediction nomogram.

Molecular Subtypes and Gene Expression Signatures as Prognostic Features in Fully Resected Clear Cell Renal Cell Carcinoma: A Tailored Approach to Adjuvant Trials.

BACKGROUND: Trials with adjuvant vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) failed to demonstrate meaningful benefit in clinically high-risk, fully resected clear cell renal cell carcinoma (ccRCC). We evaluated whether the ccrcc1-4 molecular subtypes and gene expression signatures (GES) are associated with outcomes in this setting. MATERIALS AND METHODS: We determined molecular subtypes as well as angiogenesis- and immune-related GES through RNA sequencing of 75 fresh frozen (FF) and 62 formalin-fixed, paraffin-embedded (FFPE) tumor samples. We studied disease-free (DFS) and overall survival (OS) and determined correlations among GES and Leibovich score. RESULTS: Angiogenesis-related GES and molecular subtypes were associated with longer DFS and OS across both cohorts, whereas immune-related GES were not. In the FF cohort, molecular subtypes (ccrcc2 & 3 vs. ccrcc1 & 4) were associated with DFS and OS, on bivariable analysis with Leibovich score (HR 0.62, 95%CI 0.39-0.98, P = .04 and HR 0.35, 95%CI 0.19-0.64, P < .001). In the FFPE cohort, molecular subtypes (ccrcc2 & 3 vs. ccrcc1&4) were also associated with DFS (HR 0.53, 95%CI 0.31-0.93, P = .03), but not OS (HR 0.59, 95%CI 0.31-1.13, P = .11) on bivariable analysis with Leibovich score. Leibovich score was significantly inversely correlated with all angiogenesis-related GES (all P < .01), but not correlated with immune-related GES. CONCLUSIONS: Molecular subtypes and angiogenesis-related GES are prognostic for DFS and OS in fully resected, localized ccRCC. Favorable ccrcc2 & 3 molecular subtypes with high angiogenesis-related GES, which respond best to VEGFR-TKIs, are at lower risk of relapse but were probably underrepresented in the adjuvant VEGFR-TKI trials since they inversely correlate with Leibovich score. Conversely, immune-related GES are not correlated with Leibovich score and clinically high-risk tumors can display both high and low immune-related GES. Therefore, molecular characterization could guide patient selection for adjuvant treatment.

Laparoscopic inguinal hernia repair in men with lightweight meshes may significantly impair sperm motility: a randomized controlled trial.

OBJECTIVE: To compare quality of life and fertility aspects after laparoscopic inguinal hernia repair in men using a heavyweight or lightweight mesh. SUMMARY BACKGROUND DATA: The use of lightweight meshes in laparoscopic inguinal hernia repair could have beneficial effects on quality of life and preservation of the spermatic structures due to a decreased foreign-body reaction. METHODS: A total of 59 male patients planned for primary, unilateral or bilateral inguinal hernia repair were randomized between a standard polypropylene (Marlex) or lightweight mesh (Vypro II, TiMesh). Main outcome measures were fertility aspects, assessed preoperatively and at 1-year follow-up by semen analysis and scrotal ultrasonography. Secondary outcomes were quality of life (SF-36 and McGill Pain Questionnaire) and recurrence up to 1 year postoperatively. RESULTS: Patients operated on with a VyproII or TiMesh mesh exhibited a decreased sperm motility (vs. preoperatively) compared with Marlex patients, respectively -9.5% and -5.5% versus +2% (P = 0.013). When the results after uni- and bilateral hernia repair were analyzed separately, this difference only remained significant in the bilateral hernia subgroup: -10% for VyproII and -17% for TiMesh versus +1% for Marlex (P = 0.037). Other fertility parameters (sperm concentration, morphology, and alpha-glucosidase level) were unchanged. There were no differences at any study point between the 3 groups regarding quality of life. Only for resumption of sport activities was a small advantage noted for VyproII versus Marlex patients (P = 0.045). After 1 year, no recurrences were observed; 3 patients (6%) complained of chronic disabling pain. CONCLUSIONS: Our data suggest that the use of lightweight meshes for laparoscopic inguinal hernia repair in male patients negatively influences sperm motility, without any benefit on quality of life. These alterations might be important in a subgroup of young male patients operated on laparoscopically for a bilateral hernia. This study was registered in the clinicaltrials.gov database (ID number NCT00925067).