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Background: We examined differences in DNA methylation patterns in the NR3C1 and FKBP5 genes in relation to personality vulnerability to depression, resilience, and perinatal depressive symptoms, whilst also considering possible moderating effects of childhood traumatic events. Methods: N = 160 perinatal women were assessed at late pregnancy and 1 year postpartum for personality vulnerability to depression, resilience, depressive symptoms, and childhood traumatic events with self-reported questionnaires. NR3C1 and FKBP5 methylation markers were analyzed via sodium bisulfite sequencing. Associations of methylation markers with the above mentioned variables were tested using multivariable regressions. Results: NR3C1 methylation at CpGs 1, 4 and average methylation sites were negatively associated with resilience; NR3C1 methylation at CpG 2 was positively associated with postpartum depressive symptoms; methylation at CpG 4 was positively associated with prenatal depressive symptoms. The interaction between current distress due to interpersonal traumatic events and NR3C1 CpG sites in relation to personality vulnerability was significant on CpG sites 3 and 4, whereas the interaction between current distress due to total traumatic events and NR3C1 in relation to personality vulnerability was significant on CpG site 2. FKBP5 showed no significant associations with the outcomes. Conclusions: This study identified associations between NR3C1 methylation and resilience as well as perinatal depressive symptoms. Interestingly, an interaction between early trauma and personality vulnerability was noted. Our findings on these specific DNA methylation markers may, if replicated and integrated into risk prediction models, contribute to early diagnosis of mothers at risk, targeted health promotion, and early interventions.

Objectives It is important to be able to detect symptoms of common mental disorders (CMDs) in pregnant women. However, the expression of these disorders can differ across cultures and depend on the specific scale used. This study aimed to (a) compare Gambian pregnant women’s responses to the Edinburgh Postnatal Depression Scale (EPDS) and Self-reporting Questionnaire (SRQ-20) and (b) compare responses to the EPDS in pregnant women in The Gambia and UK.Design This cross-sectional comparison study investigates Gambian EPDS and SRQ-20 scores through correlation between the two scales, score distributions, proportion of women with high levels of symptoms, and descriptive item analysis. Comparisons between the UK and Gambian EPDS scores were made by investigating score distributions, proportion of women with high levels of symptoms, and descriptive item analysis.Setting This study took place in The Gambia, West Africa and London, UK.Participants 221 pregnant women from The Gambia completed both the SRQ-20 and the EPDS; 368 pregnant women from the UK completed the EPDS.Results Gambian participants’ EPDS and SRQ-20 scores were significantly moderately correlated (rs=0.6, p

Highlights • There is a lack of studies on health professionals’ views about women’s utilisation of internet-based interventions in the perinatal period. • Our findings suggest that midwives have a positive perception of internet-based interventions, despite identifying disadvantages and having concerns about their use. • These findings are encouraging and contribute to the continued efforts to develop internet-based mental health interventions as a way to support perinatal women screened or diagnosed with anxiety and/or depressive symptoms.

QUESTIONS UNDER STUDY: The epidemiology of maternal perinatal-psychiatric disorders as well as their effect on the baby is well recognised. Increasingly well researched specialised treatment methods can reduce maternal morbidity, positively affect mother-baby bonding and empower women’s confidence as a mother. Here, we aimed to compare guidelines and the structure of perinatal-psychiatric service delivery in the United Kingdom and in Switzerland from the government’s perspective. METHODS: Swiss cantons provided information regarding guidelines and structure of service delivery in 2000. A subsequent survey using the same questionnaire was carried out in 2007. In the UK, similar information was accessed through published reports from 2000–2012. RESULTS: Guidelines for perinatal psychiatry exist in the UK, whereas in Switzerland in 2000 none of the 26 cantons had guidelines, and in 2007 only one canton did. Joint mother-baby admissions on general psychiatric wards were offered by 92% of the Swiss cantons. In the UK, pregnant women and joint mother-baby admissions are only advised onto specialised perinatal-psychiatric units. In Switzerland, in 2007, three specialised units (max. 24 beds) were in place corresponding to 1 unit per 2.5 million people, while in the UK there were 22 mother-baby units (168 beds) in 2012 (1 unit per 2.8 million). In the UK, less than 50% of trusts provided specialised perinatal-psychiatric health care. CONCLUSIONS: The main difference between the UK and Switzerland was the absence of guidelines, regular assessment and plans for future development of perinatal psychiatry in Switzerland. There are still geographical differences in the provision of perinatal-psychiatric services in the UK.

The primary objective of urolithiasis therapy is complete stone removal and highest stone-clearance rates possible to minimize recurrence. A novel approach that employs a magnetic suspension and a magnetic probe for the passive collection and removal of small residual fragments was developed. This study assessed the feasibility of this system in porcine models. Five female domestic pigs underwent retrograde intrarenal surgery under general anaesthesia to assess the new magnetic system. Pre-analysed human calculi were endoscopically inserted and comminuted using lithotripsy. The magnetic suspension was applied, and the magnetic-stone fragment complex was extracted. After nephrectomy, independent blinded pathologists evaluated all the kidneys. Safety and tolerance assessments revealed no adverse events (i.e. no complications on the Clavien-Dindo scale > 1) or complications associated with treatment. This study revealed superficial urothelial damage in all animals, characterized by desquamation and inflammation, caused primarily by the insertion of access sheaths and laser lithotripsy. Residual magnetic particles were observed in the renal pelvis but did not show signs of toxicity even though this study is limited to the acute treatment. No pathological indicators were observed in the hemogram and urinalysis. Overall, the treatment did not cause any significant pathological changes. Preclinical in vivo evaluation of magnetic extraction of small rest fragments in porcine kidneys presents a promising, atraumatic approach for fragments removal. It demonstrated safety, tolerance, and feasibility that warrants clinical investigation. This method has the potential to increase stone-clearance rates with shorter extraction times, offering a possibility for addressing the challenge of urolithiasis in clinical practice., Competing Interests: Declarations. Conflict of interest: Shyam Srinivasan, Chiara Turrina, Florian Ebel, Sebastian P. Schwaminger: founded the company Dymium GmbH. In addition, Shyam Srinivasan and Sebastian Schwaminger hold the patents AU2021229560A1, CA3168407A1, CN115243671A, EP3875075B1, EP3875075A1, KR20220143098A, JP2023516703A, US2023149450A1, and WO2021175660A1 all issued by the Technical University of Munich. Shyam Srinivasan also holds the patents EP4144308A1 and WO2023036817A1 filed by the Dymium GmbH. None of the other authors has any other conflict of interest or financial ties to disclose. Ethical approval: Animal studies were approved by the local governmental review board for animal studies and performed in accordance with current EU regulations and were performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Stone models were anonymized to prevent traceability. Ethical approval was obtained from the Landesamt für Arbeitsschutz, Verbraucherschutz und Gesundheit of the Land Brandenburg (2347-06-2022-25-G) and Ethics Committee of the Technical University of Munich (2023-227-S-KH)., (© 2024. The Author(s).)

Cone-Beam Computed Tomography-Sialography (Sialo-CBCT) is used to demonstrate salivary ductal structure. This study aimed to conduct a volumetric analysis of the anatomical morphology of Normal-Appearing Glands (NAGs) in parotid sialo-CBCT. Our retrospective study included 14 parotid sialo-CBCT scans interpreted as NAGs in 11 patients with salivary gland impairment. The main duct length and width, as well as number and width of secondary and tertiary ducts were manually evaluated. We found that the main parotid duct showed an average width of 1.39 mm, 1.15 mm, and 0.98 mm, for the proximal, middle and distal thirds, respectively. The arborization pattern showed approximately 20% more tertiary (average number 11.1 ± 2.7) than secondary ducts (average number 9.0 ± 2.4) and approximately 8% narrower tertiary ducts (average width 0.65 ± 0.11 mm) compared to the secondary ducts (average width 0.77 ± 0.14 mm). Our anatomical analysis of NAGs in parotid sialo-CBCT demonstrated progressive narrowing of the main duct and increasing arborization and decreasing lumen size starting from the primary to the tertiary ducts. This is the most updated study regarding the anatomy of the parotid glands as demonstrated in sialo-CBCT. Our results may provide clinicians with the basic information for understanding aberration from normal morphology, as seen in salivary gland pathologies as well facilitate planning of treatment strategies, such as minimally invasive sialo-endoscopies, commonly practiced today., (© 2024 The Authors. Clinical Anatomy published by Wiley Periodicals LLC on behalf of American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Background: We examined differences in DNA methylation patterns in the NR3C1 and FKBP5 genes in relation to personality vulnerability to depression, resilience, and perinatal depressive symptoms, whilst also considering possible moderating effects of childhood traumatic events., Methods: N = 160 perinatal women were assessed at late pregnancy and 1 year postpartum for personality vulnerability to depression, resilience, depressive symptoms, and childhood traumatic events with self-reported questionnaires. NR3C1 and FKBP5 methylation markers were analyzed via sodium bisulfite sequencing. Associations of methylation markers with the above mentioned variables were tested using multivariable regressions., Results: NR3C1 methylation at CpGs 1, 4 and average methylation sites were negatively associated with resilience; NR3C1 methylation at CpG 2 was positively associated with postpartum depressive symptoms; methylation at CpG 4 was positively associated with prenatal depressive symptoms. The interaction between current distress due to interpersonal traumatic events and NR3C1 CpG sites in relation to personality vulnerability was significant on CpG sites 3 and 4, whereas the interaction between current distress due to total traumatic events and NR3C1 in relation to personality vulnerability was significant on CpG site 2. FKBP5 showed no significant associations with the outcomes., Conclusions: This study identified associations between NR3C1 methylation and resilience as well as perinatal depressive symptoms. Interestingly, an interaction between early trauma and personality vulnerability was noted. Our findings on these specific DNA methylation markers may, if replicated and integrated into risk prediction models, contribute to early diagnosis of mothers at risk, targeted health promotion, and early interventions., Competing Interests: All authors confirm they have no conflicts of interests to declare. This work was funded by the University of Zurich Foundation for Research in Science and the Humanities (RAC and UE: STWF-18-019), the Swedish Research Council (AS: 523-2014-2342, 523-2014-07605, and 521-2013-2339), the Swedish Brain Foundation (AS: FO2022-0098), and the Marianne and Marcus Wallenberg Foundation (AS: MMW2011.0115)., (© 2024 The Author(s). Published by Upsala Medical Society.)

Purpose: This study addressed the challenge of detecting and classifying the severity of ductopenia in parotid glands, a structural abnormality characterized by a reduced number of salivary ducts, previously shown to be associated with salivary gland impairment. The aim of the study was to develop an automatic algorithm designed to improve diagnostic accuracy and efficiency in analyzing ductopenic parotid glands using sialo cone-beam CT (sialo-CBCT) images., Methods: We developed an end-to-end automatic pipeline consisting of three main steps: (1) region of interest (ROI) computation, (2) parotid gland segmentation using the Frangi filter, and (3) ductopenia case classification with a residual neural network (RNN) augmented by multidirectional maximum intensity projection (MIP) images. To explore the impact of the first two steps, the RNN was trained on three datasets: (1) original MIP images, (2) MIP images with predefined ROIs, and (3) MIP images after segmentation., Results: Evaluation was conducted on 126 parotid sialo-CBCT scans of normal, moderate, and severe ductopenic cases, yielding a high performance of 100% for the ROI computation and 89% for the gland segmentation. Improvements in accuracy and F1 score were noted among the original MIP images (accuracy: 0.73, F1 score: 0.53), ROI-predefined images (accuracy: 0.78, F1 score: 0.56), and segmented images (accuracy: 0.95, F1 score: 0.90). Notably, ductopenic detection sensitivity was 0.99 in the segmented dataset, highlighting the capabilities of the algorithm in detecting ductopenic cases., Conclusions: Our method, which combines classical image processing and deep learning techniques, offers a promising solution for automatic detection of parotid glands ductopenia in sialo-CBCT scans. This may be used for further research aimed at understanding the role of presence and severity of ductopenia in salivary gland dysfunction., (© 2024. CARS.)

Purpose: The recent restriction on the use of fluoroquinolones for prophylaxis by the European Commission has left a gap in clear recommendations for practical antibiotic prophylaxis (PAP) for transrectal prostate biopsy (TRPB). This analysis investigated the viability of cotrimoxazole for PAP in TRPB., Methods: This analysis included n = 697 patients who underwent TRPB for suspected prostate cancer (PCa). All patients received either empiric PAP with four doses of cotrimoxazole 960 mg or targeted antibiotic prophylaxis in case of a positive rectal or urine screening for multiresistant gram-negatives. Infectious complications after TRPB, microbiological findings, and clinical characteristics were evaluated. A multivariable logistic regression model was calculated to identify variables associated with infectious complications., Results: Of the cohort, 86% (600/697) received PAP with cotrimoxazole, 1% (8/697) received cotrimoxazole plus an additional antibiotic, 4% (28/697) received amoxicillin + clavulanic acid, 4% (28/697) received fluoroquinolones, and 5% (33/697) received a single shot intravenous antibiotic prophylaxis with meropenem or piperacillin + tazobactam due to multiresistant microbiological findings in either pre-interventional urine culture or rectal swab. Infectious complications occurred in 2.6% (18/697) of patients. Fever was noted in 89% (16/18) of cases. Inpatient treatment was given to 67% (12/18) of affected patients, with 38% (7/18) having positive blood cultures, identifying cotrimoxazole-resistant E. coli strains in six out of seven cases. Multivariable logistic regression analysis revealed no clinically significant variables, including PAP with cotrimoxazole, as independent risk factors for an infectious complication., Conclusions: Using cotrimoxazole as PAP for TRPB in cases without multiresistant gram-negatives in pre-interventional urine cultures or rectal swabs seems feasible and practical., (© 2024. The Author(s).)

Purpose: To determine the role of biopsy experience regarding a potential benefit of additional systematic biopsies and fusion failures during MRI-targeted biopsy of the prostate., Subjects/patients and Methods: We retrospectively evaluated 576 men undergoing transrectal (MRI)-targeted biopsy of the prostate by seven residents in urology between November 2019 and March 2022. Benefit of systematic biopsies (detection of ISUP ≥ 2 PCa (clinically significant PCa (csPCa)) solely in systematic biopsies) and fusion failure (detection of csPCa during systematic biopsies in the area of a reported MRI-lesion and no detection of csPCa in targeted biopsy) were compared by growing biopsy experience levels. Multivariable regression analyses were calculated to investigate the association with benefit of systematic biopsies and fusion failure., Results: The overall PCa detection rate was 72% (413/576). A benefit of systematic biopsies was observed in 11% (63/576); of those, fusion failure was seen in 76% (48/63). Benefit of systematic biopsies and fusion failure were more common among residents with very low experience compared to highly experienced residents (18% versus 4%, p = 0.026; 13% versus 3%, p = 0.015, respectively). Increasing biopsy experience was associated with less benefit from systematic biopsies (OR: 0.98, 95% CI 0.97-0.99) and less fusion failure (OR: 0.98, 95% CI 0.97-0.99)., Conclusions: The benefit of systematic biopsies following targeted biopsy decreases with growing biopsy experience. The higher risk of fusion failure among inexperienced residents necessitates systematic biopsies to ensure the detection of csPCa. Further prospective trials are warranted before a targeted only approach can be recommended in routine clinical practice., (© 2023. The Author(s).)

Purpose: We hypothesized that two-tier re-classification of the "M" (metastasis) domain of the Tumor-Node-Metastasis (TNM) staging of Renal Cell Carcinoma (RCC) may improve staging accuracy than the current monolithic classification, as advancements in the understanding of tumor biology have led to increased recognition of the heterogeneous potential of metastatic RCC (mRCC)., Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. Patients were stratified by number of metastases into two groups, M1 (≤3, "Oligometastatic") and M2 (>3, "Polymetastatic"). Primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS). Cox-regression and Kaplan-Meier (KMA) analysis were utilized for outcomes, and receiver operating characteristic analysis (ROC) was utilized to assess diagnostic accuracy compared to current "M" staging., Results: 429 patients were stratified into proposed M1 and M2 groups (M1 = 286/M2 = 143; median follow-up 19.2 months). Cox-regression revealed M2 classification as an independent risk factor for worsened all-cause mortality (HR=1.67, p=0.001) and cancer-specific mortality (HR=1.74, p<0.001). Comparing M1-oligometastatic vs. M2-polymetastatic groups, KMA revealed significantly higher 5-year OS (36% vs. 21%, p<0.001) and 5-year CSS (39% vs. 17%, p<0.001). ROC analyses comparing OS and CSS, for M1/M2 reclassification versus unitary M designation currently in use demonstrated improved c-index for OS (M1/M2 0.635 vs. unitary M 0.500) and CSS (M1/M2 0.627 vs. unitary M 0.500)., Conclusion: Subclassification of Stage "M" domain of mRCC into two clinical substage categories based on metastatic burden corresponds to distinctive tumor groups whose oncological potential varies significantly and result in improved predictive capability compared to current staging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Meagher, Mir, Minervini, Kriegmair, Heck, Porpiglia, Van Bruwaene, Linares, Hevia, D’Anna, Veccia, Roussel, Claps, Palumbo, Marchioni, Afari, Saitta, Liu, Rubio, Campi, Mari, Amiel, Checcucci, Musquera, Guruli, Pavan, Albersen, Antonelli, Klatte, Autorino, McKay and Derweesh.)

Background: To assess the performance of prospectively accelerated and deep learning (DL) reconstructed T2-weighted (T2w) imaging in volunteers and patients with histologically proven prostate cancer (PCa)., Methods: Prospectively undersampled T2w datasets were acquired with acceleration factors of 1.7 (reference), 3.4 and 4.8 in 10 healthy volunteers and 23 patients with histologically proven PCa. Image reconstructions using compressed SENSE (C-SENSE) and a combination of C-SENSE and DL-based artificial intelligence (C-SENSE AI) were analyzed. Qualitative image comparison was performed using a 6-point Likert scale (overall image quality, noise, motion artifacts, lesion detection, diagnostic certainty); the T2 and PI-RADS scores were compared between the two reconstructions. Additionally, quantitative image parameters were assessed (apparent SNR, apparent CNR, lesion size, line profiles)., Results: All C-SENSE AI-reconstructed images received a significantly higher qualitative rating compared to the C-SENSE standard images. Analysis of the quantitative parameters supported this finding, with significantly higher aSNR and aCNR. The line profiles demonstrated a significantly steeper signal change at the border of the prostatic lesion and the adjacent normal tissue in the C-SENSE AI-reconstructed images, whereas the T2 and PI-RADS scores as well as the lesion size did not differ., Conclusion: In this prospective study, we demonstrated the clinical feasibility of a novel C-SENSE AI reconstruction enabling a 58% acceleration in T2w imaging of the prostate while obtaining significantly better image quality.

Specialist care following (nephron-sparing) kidney surgery serves to detect postoperative complications and to monitor kidney function and cardiovascular health. From an oncological point of view, the early detection of local and contralateral recurrences as well as (single) distant metastases in the early disease stages is paramount. This enables the option of metastasis-directed surgery to delay systemic therapies. On the other hand, the early detection of distant metastases can facilitate the initiation of necessary systemic therapies. In general, nephron-sparing surgery is recommended as the first-line treatment of choice for localized renal tumors. Current guidelines recommend a risk-adapted follow-up based on histopathological criteria (pT, pN or R status). For patients with intermediate and high-risk findings, aftercare should be intensified. In addition to routine blood tests, cross-sectional imaging using contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) remain the method of choice. Recently presented results of the phase III KEYNOTE-564 study on the adjuvant therapy with the programmed cell death 1 (PD1) inhibitor pembrolizumab in clear cell, locally advanced renal cell carcinoma (≥ pT1 GII and or ≥ N+) or oligometastatic renal cell carcinoma without evidence of distant metastases (e.g., after metastasis surgery < 1 year after nephrectomy) demonstrated an advantage in terms of disease-free survival compared to follow-up alone. However, overall survival results are pending. Other potentially effective adjuvant concepts including atezolizumab, nivolumab/ipilimumab, everolimus or pembrolizumab/belzutifan are currently being investigated in clinical trials., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: Cytoreductive radical prostatectomy (cRP) has been proposed as local treatment option in metastatic hormone-sensitive prostate cancer (mHSPC) to prevent local complications and potentially improve oncological outcomes. In this study, we examined the feasibility of a multimodal concept with primary chemohormonal therapy followed by cRP and analyzed prostate size reduction under systemic treatment, postoperative complication rates, as well as early postoperative continence., Methods: In this retrospective study, 38 patients with mHSPC underwent cRP after primary chemohormonal therapy (3-monthly luteinising hormone-releasing hormone-analogue + six cycles 3-weekly docetaxel 75 mg/m 2 ) at two centers between September 2015 and December 2018., Results: Overall, 10 (26%) patients had high volume and 28 (74%) patients had low volume disease at diagnosis, according to CHAARTED definition. Median prostate-specific antigen (PSA) decreased from 65 ng/mL (interquartile range [IQR] 35.0-124.5 ng/mL) pre-chemotherapy to 1 ng/mL (IQR 0.3-1.7 ng/mL) post-chemotherapy. Prostate gland volume was significantly reduced by a median of 50% (IQR 29%-56%) under chemohormonal therapy ( p  = 0.003). Postoperative histopathology showed seminal vesicle invasion in 33 (87%) patients and negative surgical margins in 17 (45%) patients. Severe complications (Grade 3 according to Clavien-Dindo) were observed in 4 (11%) patients within 30 days. Continence was reached in 87% of patients after 1 month and in 92% of patients after 6 months. Median time to castration-resistance from begin of chemohormonal therapy was 41.1 months and from cRP was 35.9 months. Postoperative PSA-nadir ≤1 ng/mL versus >1 ng/mL was a significant predictor of time to castration-resistance after cRP (median not reached versus 5.3 months; p <0.0001)., Conclusion: We observed a reduction of prostate volume under chemohormonal therapy going along with a low postoperative complication and high early continence rate. However, the oncologic benefit from cRP is still under evaluation., Competing Interests: The authors declare no conflict of interest., (© 2022 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.)

Purpose: To evaluate the performance of combined PET and multiparametric MRI (mpMRI) radiomics for the group-wise prediction of postsurgical Gleason scores (psGSs) in primary prostate cancer (PCa) patients., Methods: Patients with PCa, who underwent [ 68  Ga]Ga-PSMA-11 PET/MRI followed by radical prostatectomy, were included in this retrospective analysis (n = 101). Patients were grouped by psGS in three categories: ISUP grades 1-3, ISUP grade 4, and ISUP grade 5. mpMRI images included T1-weighted, T2-weighted, and apparent diffusion coefficient (ADC) map. Whole-prostate segmentations were performed on each modality, and image biomarker standardization initiative (IBSI)-compliant radiomic features were extracted. Nine support vector machine (SVM) models were trained: four single-modality radiomic models (PET, T1w, T2w, ADC); three PET + MRI double-modality models (PET + T1w, PET + T2w, PET + ADC), and two baseline models (one with patient data, one image-based) for comparison. A sixfold stratified cross-validation was performed, and balanced accuracies (bAcc) of the predictions of the best-performing models were reported and compared through Student's t-tests. The predictions of the best-performing model were compared against biopsy GS (bGS)., Results: All radiomic models outperformed the baseline models. The best-performing (mean ± stdv [%]) single-modality model was the ADC model (76 ± 6%), although not significantly better (p > 0.05) than other single-modality models (T1w: 72 ± 3%, T2w: 73 ± 2%; PET: 75 ± 5%). The overall best-performing model combined PET + ADC radiomics (82 ± 5%). It significantly outperformed most other double-modality (PET + T1w: 74 ± 5%, p = 0.026; PET + T2w: 71 ± 4%, p = 0.003) and single-modality models (PET: p = 0.042; T1w: p = 0.002; T2w: p = 0.003), except the ADC-only model (p = 0.138). In this initial cohort, the PET + ADC model outperformed bGS overall (82.5% vs 72.4%) in the prediction of psGS., Conclusion: All single- and double-modality models outperformed the baseline models, showing their potential in the prediction of GS, even with an unbalanced cohort. The best-performing model included PET + ADC radiomics, suggesting a complementary value of PSMA-PET and ADC radiomics., (© 2021. The Author(s).)

Background: The prostate-specific membrane antigen (PSMA) is a relevant target in prostate cancer, and immunohistochemistry studies showed associations with outcome. PSMA-ligand positron emission tomography (PET) is increasingly used for primary prostate cancer staging, and the molecular imaging TNM classification (miTNM) standardizes its reporting. We aimed to investigate the potential of PET-imaging to serve as a noninvasive imaging biomarker to predict disease outcome in primary prostate cancer after radical prostatectomy (RP)., Methods: In this retrospective analysis, 186 primary prostate cancer patients treated with RP who had undergone a 68 Ga-PSMA-11 PET up to three months prior to the surgery were included. Maximum standardized uptake value (SUV max ), SUV mean , tumor volume (TV) and total lesion (TL) were collected from PET-imaging. Moreover, clinicopathological information, including age, serum prostate-specific antigen (PSA) level, and pathological characteristics, was assessed for disease outcome prediction. A stage group system for PET-imaging findings based on the miTNM framework was developed., Results: At a median follow-up after RP of 38 months (interquartile range (IQR) 22-53), biochemical recurrence (BCR) was observed in 58 patients during the follow-up period. A significant association between a positive surgical margin and miN status (miN1 vs. miN0, odds ratio (OR): 5.428, p = 0.004) was detected. miT status (miT ≥ 3a vs. miT < 3, OR: 2.696, p = 0.003) was identified as an independent predictor for Gleason score (GS) ≥ 8. Multivariate Cox regression analysis indicated that PSA level (hazard ratio (HR): 1.024, p = 0.014), advanced GS (GS ≥ 8 vs. GS < 8, HR: 3.253, p < 0.001) and miT status (miT ≥ 3a vs. miT < 3, HR: 1.941, p = 0.035) were independent predictors for BCR. For stage I disease as determined by PET-imaging, a shorter BCR-free survival was observed in the patients with higher SUV max (IA vs. IB stage, log-rank, p = 0.022)., Conclusion: Preoperative miTNM classification from 68 Ga-PSMA-11 PET correlates with postoperative GS, surgical margin status and time to BCR. The association between miTNM staging and outcome proposes 68 Ga-PSMA-11 PET as a novel non-invasive imaging biomarker and potentially serves for ancillary pre-treatment stratification., (© 2021. The Author(s).)

Purpose: We sought to address the impact of preoperative prostate specific membrane antigen (PSMA) positron emission tomography (PET) findings prior to radical prostatectomy and pelvic lymph node dissection on biochemical recurrence and time to adjuvant or salvage treatment., Materials and Methods: Between 2013 and 2017, 64 intermediate and 166 high risk (230) prostate cancer patients received 68 Ga-PSMA-11 PET followed by radical prostatectomy and pelvic lymph node dissection. Biochemical recurrence-free and therapy-free survivalwere determined. For all time-to-event analyses, univariable and multivariable Cox proportional hazards models and univariable Kaplan-Meier analyses were applied, with a significance threshold of p <0.05., Results: The overall sensitivity, specificity, positive predictive value and negative predictive value of PSMA PET for pN1 disease was 48.5%, 95.7%, 82.1% and 82.2%, respectively. Median followup was 30.2 months. Biochemical recurrence occurred in 50.4% (116) of patients and adjuvant or salvage treatment was performed in 46.5% (107). Worst biochemical recurrence-free and therapy-free survival was observed in pN1 patients who also exhibited PSMA PET positive lymph node, followed by pN1 patients without PSMA PET positive lymph node and patients without evidence of lymph node metastasis on histology and PSMA PET (median biochemical recurrence-free survival 1.7 vs. 7.5 vs. >36 months, median therapy-free survival 2.6 vs. 8.9 vs. >36 months)., Conclusions: Patients with positive lymph node on PSMA PET prior to radical prostatectomy have to expect early biochemical recurrence and adjuvant/salvage therapy, despite thorough pelvic lymph node dissection. Therefore, results from PSMA PET can be used for patients' consultation and more stringent followup as well as for planning of neoadjuvant/adjuvant therapy.

Background: Selection of patients for upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has to be improved., Objective: To evaluate a new scoring system for the prediction of overall mortality (OM) in mRCC patients undergoing CN., Design, Setting, and Participants: We identified a total of 519 patients with synchronous mRCC undergoing CN between 2005 and 2019 from a multi-institutional registry (Registry for Metastatic RCC [REMARCC])., Outcome Measurements and Statistical Analysis: Cox proportional hazard regression was used to test the main predictors of OM. Restricted mean survival time was estimated as a measure of the average overall survival time up to 36 mo of follow-up. The concordance index (C-index) was used to determine the model's discrimination. Decision curve analyses were used to compare the net benefit from the REMARCC model with International mRCC Database Consortium (IMDC) or Memorial Sloan Kettering Cancer Center (MSKCC) risk scores., Results and Limitations: The median follow-up period was 18 mo (interquartile range: 5.9-39.7). Our models showed lower mortality rates in obese patients (p = 0.007). Higher OM rates were recorded in those with bone (p = 0.010), liver (p = 0.002), and lung metastases (p < 0.001). Those with poor performance status (<80%) and those with more than three metastases had also higher OM rates (p = 0.026 and 0.040, respectively). The C-index of the REMARCC model was higher than that of the MSKCC and IMDC models (66.4% vs 60.4% vs 60.3%). After stratification, 113 (22.0%) patients were classified to have a favorable (no risk factors), 202 (39.5%) an intermediate (one or two risk factors), and 197 (38.5%) a poor (more than two risk factors) prognosis. Moreover, 72 (17.2%) and 51 (13.9%) patients classified as having an intermediate and a poor prognosis according to MSKCC and IMDC categories, respectively, would be reclassified as having a good prognosis according to the REMARCC score., Conclusions: Our findings confirm the relevance of tumor and patient features for the risk stratification of mRCC patients and clinical decision-making regarding CN. Further prospective external validations are required for the scoring system proposed herein., Patient Summary: Current stratification systems for selecting patients for kidney removal when metastatic disease is shown are controversial. We suggest a system that includes tumor and patient features besides the systems already in use, which are based on blood tests., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Partial nephrectomy (PN) in elderly patients is underutilized with concerns regarding risk of complications and potential for poor outcomes., Objective: To evaluate quality and functional outcomes of PN in patients >75 yr using trifecta as a composite outcome of surgical quality., Design, Setting, and Participants: Multicenter retrospective analysis of 653 patients aged >75 yr who underwent PN (REnal SURGery in Elderly [RESURGE] Group)., Intervention: PN., Outcome Measurements and Statistical Analysis: Primary outcome was achievement of trifecta (negative margin, no major [Clavien ≥3] urological complications, and ≥90% estimated glomerular filtration rate [eGFR] recovery). Secondary outcomes included chronic kidney disease (CKD) stage III and CKD upstaging. Multivariable analysis (MVA) was used to assess variables for achieving trifecta and functional outcomes. Kaplan-Meier survival analysis (KMA) was used to calculate renal functional outcomes., Results and Limitations: We analyzed 653 patients (mean age 78.4 yr, median follow-up 33 mo; 382 open, 157 laparoscopic, and 114 robotic). Trifecta rate was 40.4% (n=264). Trifecta patients had less transfusion (p<0.001), lower intraoperative (5.3% vs 27%, p<0.001) and postoperative (25.4% vs 37.8%, p=0.001) complications, shorter hospital stay (p=0.045), and lower ΔeGFR (p <0.001). MVA for predictive factors for trifecta revealed decreasing RENAL nephrometry score (odds ratio [OR] 1.26, 95% confidence interval 1.07-1.51, p=0.007) as being associated with increased likelihood to achieve trifecta. Achievement of trifecta was associated with decreased risk of CKD upstaging (OR 0.47, 95% confidence interval 0.32-0.62, p<0.001). KMA showed that trifecta patients had improved 5-yr freedom from CKD stage 3 (93.5% vs 57.7%, p<0.001) and CKD upstaging (84.3% vs 8.2%, p<0.001). Limitations include retrospective design., Conclusions: PN in elderly patients can be performed with acceptable quality outcomes. Trifecta was associated with decreased tumor complexity and improved functional preservation., Patient Summary: We looked at quality outcomes after partial nephrectomy in elderly patients. Acceptable quality outcomes were achieved, measured by a composite outcome called trifecta, whose achievement was associated with improved kidney functional preservation., (Copyright © 2019. Published by Elsevier B.V.)

Background: Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients., Objective: We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes., Design, Setting, and Participants: Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC)., Outcome Measurements and Statistical Analysis: Logistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates., Results and Limitations: Intraoperative complications were observed in 69 patients (10.9%). Thrombectomy (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08-1.75, p = 0.009) and adjacent organ removal (OR 2.7, 95% CI 1.38-5.30) were significant predictors of intraoperative complications at multivariable analysis. Two hundred seventeen patients (29.5%) encountered AGCs, while 45 (6.1%) encountered an HGC, of whom 10 (1.4%) died. Twenty-four (3.3%) patients had multiple postoperative complications. Estimated blood loss (EBL; OR 1.49, 95% CI 1.08-2.05, p = 0.01) was a significant predictor of AGCs at multivariable analysis. CN case load (OR 0.13, 95% CI 0.03-0.59, p = 0.009) and EBL (OR 2.93, 95% CI 1.20-7.15, p = 0.02) were significant predictors solely for HGCs at multivariable analysis. Forty-one patients (11.5%) were readmitted within 30 d of surgery. No significant predictors were identified. Results were confirmed in a subanalysis focusing solely on patients treated in the contemporary targeted therapy era., Conclusions: Morbidity associated with CN is not negligible. Predictors of high-grade postoperative morbidity are predominantly indicators of complex surgery. EBL is a strong predictor of postoperative complications. CN case load correlates with lower high-grade morbidity and highlights the benefit of centralization of complex surgery. However, risks and benefits should be balanced when considering CN in mRCC patients., Patient Summary: We studied patients with metastatic renal cancer to evaluate the outcomes associated with the surgical removal of the primary kidney tumor. We found that this procedure is often complex and adverse events are not uncommon. High intraoperative blood loss and a small number of cases performed at the treating center are associated with a higher rate of postoperative complications., (Copyright © 2020. Published by Elsevier B.V.)

The aim of the study was to perform a comprehensive investigation of clinical outcomes of robot-assisted partial nephrectomy (RAPN) or laparoscopic partial nephrectomy (LPN) in elderly patients presenting with a renal mass. The REnal SURGery in Elderly (RESURGE) collaborative database was queried to identify patients aged 75 or older diagnosed with cT1-2 renal mass and treated with RAPN or LPN. Study outcomes were: overall complications (OC); warm ischemia time (WIT) and 6-month estimated glomerular filtration rate (eGFR); positive surgical margins (PSM), disease recurrence (REC), cancer-specific mortality (CSM) and other-cause mortality (OCM). Descriptive statistics, Kaplan-Meier, smoothed Poisson plots and logistic and linear regression models (MVA) were used. Overall, 216 patients were included in this analysis. OC rate was 34%, most of them being of low Clavien grade. Median WIT was 17 minutes and median 6-month eGFR was 54 ml/min/1.73 m 2 . PSM rate was 5%. After a median follow-up of 20 months, the 5-year rates of REC, CSM and OCM were 4, 4 and 5%, respectively. At MVA predicting perioperative morbidity, RAPN relative to LPN (odds ratio [OR] 0.33; p <0.0001) was associated with lower OC rate. At MVA predicting functional outcomes, RAPN relative to LPN was associated with shorter WIT (estimate [EST] -4.09; p <0.0001), and with higher 6-month eGFR (EST 6.03; p = 0.01). In appropriately selected patients with small renal masses, minimally-invasive PN is associated with acceptable perioperative outcomes. The use of a robotic approach over a standard laparoscopic approach can be advantageous with respect to clinically relevant outcomes, and it should be preferred when available., Competing Interests: The authors declare no conflicts of interest., (Copyright by Polish Urological Association.)

Purpose: To compare the outcomes of PN to those of RN in very elderly patients treated for clinically localized renal tumor., Patients and Methods: A purpose-built multi-institutional international database (RESURGE project) was used for this retrospective analysis. Patients over 75 years old and surgically treated for a suspicious of localized renal with either PN or RN were included in this database. Surgical, renal function and oncological outcomes were analyzed. Propensity scores for the predicted probability to receive PN in each patient were estimated by logistic regression models. Cox proportional hazard models were estimated to determine the relative change in hazard associated with PN vs RN on overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM)., Results: A total of 613 patients who underwent RN were successfully matched with 613 controls who underwent PN. Higher overall complication rate was recorded in the PN group (33% vs 25%; p = 0.01). Median follow-up for the entire cohort was 35 months (interquartile range [IQR] 13-63 months). There was a significant difference between RN and PN in median decline of eGFR (39% vs 17%; p < 0.01). PN was not correlated with OM (HR = 0.71; p = 0.56), OCM (HR = 0.74; p = 0.5), and showed a protective trend for CSM (HR = 0.19; p = 0.05). PN was found to be a protective factor for surgical CKD (HR = 0.28; p < 0.01) and worsening of eGFR in patients with baseline CKD. Retrospective design represents a limitation of this analysis., Conclusions: Adoption of PN in very elderly patients with localized renal tumor does not compromise oncological outcomes, and it allows better functional preservation at mid-term (3-year) follow-up, relative to RN. Whether this functional benefit translates into a survival benefit remains to be determined.

Telomeres are TTAGGG repetitions at the ends of chromosomes. Functioning telomeres are essential for normal segregation and maintenance of chromosomes during mitotic and meiotic divisions. Dysfunctional telomeres support the survival of aneuploid cells, a characteristic of many human malignancies. In contrast to the non-overlapping nature of telomeres in normal nuclei, telomeres of tumor nuclei tend to form aggregates. In this study, our objective was to evaluate the number of telomere aggregates (TAs) in karyotype-balanced structural rearrangements. This is an additional parameter of genetic instability, which might suggest a possible increased risk for diseases related to genomic instability, such as cancer. Twenty-six amniotic fluid cell cultures were established following genetic amniocentesis. Telomere FISH protocol was applied to the samples. Telomere aggregates were counted using a 2D microscope. The results were statistically tested by analysis of variance (ANOVA) and Kruskal-Wallis tests. More telomere aggregates in the structural balanced rearrangements were found in both study groups (balanced translocations and inversions) compared to the control group (P < 0.05). The persistence of TAs in cells is probably related to Breakage-Bridge-Fusion (BBF) cycles, a mechanism of TAs described by Muller and McClintock, resulting in end-to-end fusion that contributes to the onset of genomic instability. BBF cycles contribute to deletions, gene amplification, non-reciprocal translocations, and overall genetic changes associated with tumor genesis. According to our studies, the individuals who are carriers of balanced structural chromosomal rearrangements show some of the genetic instability parameters that appear in other circumstances, such as premalignant and malignant conditions.

Recent work has shown that DNA sequences related to the mammalian ras proto-oncogenes are highly conserved in eucaryotic evolution. A monoclonal antibody (Y13-259) to mammalian p21ras specifically precipitated a 23,000-molecular-weight protein (p23) from lysates of Dictyostelium discoideum amoebae. Tryptic peptide analysis indicated that D. discoideum p23 was closely related in its primary structure to mammalian p21ras. p23 was apparently derived by post-translational modification of a 24,000-molecular-weight primary gene product. The amount of p23 was highest in growing amoebae, but declined markedly with the onset of differentiation such that by fruiting body formation there was less than 10% of the amoeboid level. The rate of p23 synthesis dropped rapidly during aggregation, rose transiently during pseudoplasmodial formation, and then declined during the terminal stages of differentiation. There was, therefore, a strong correlation between the expression of the ras-related protein p23 and cell proliferation of D. discoideum.