For clear cell renal cell carcinoma (ccRCC) risk-dependent diagnostic and therapeutic algorithms are routinely implemented in clinical practice. Artificial intelligence-based image analysis has the ...potential to improve outcome prediction and thereby risk stratification. Thus, we investigated whether a convolutional neural network (CNN) can extract relevant image features from a representative hematoxylin and eosin-stained slide to predict 5-year overall survival (5y-OS) in ccRCC. The CNN was trained to predict 5y-OS in a binary manner using slides from TCGA and validated using an independent in-house cohort. Multivariable logistic regression was used to combine of the CNNs prediction and clinicopathological parameters. A mean balanced accuracy of 72.0% (standard deviation SD = 7.9%), sensitivity of 72.4% (SD = 10.6%), specificity of 71.7% (SD = 11.9%) and area under receiver operating characteristics curve (AUROC) of 0.75 (SD = 0.07) was achieved on the TCGA training set (n = 254 patients / WSIs) using 10-fold cross-validation. On the external validation cohort (n = 99 patients / WSIs), mean accuracy, sensitivity, specificity and AUROC were 65.5% (95%-confidence interval CI: 62.9–68.1%), 86.2% (95%-CI: 81.8–90.5%), 44.9% (95%-CI: 40.2–49.6%), and 0.70 (95%-CI: 0.69–0.71). A multivariable model including age, tumor stage and metastasis yielded an AUROC of 0.75 on the TCGA cohort. The inclusion of the CNN-based classification (Odds ratio = 4.86, 95%-CI: 2.70–8.75, p < 0.01) raised the AUROC to 0.81. On the validation cohort, both models showed an AUROC of 0.88. In univariable Cox regression, the CNN showed a hazard ratio of 3.69 (95%-CI: 2.60–5.23, p < 0.01) on TCGA and 2.13 (95%-CI: 0.92–4.94, p = 0.08) on external validation. The results demonstrate that the CNN’s image-based prediction of survival is promising and thus this widely applicable technique should be further investigated with the aim of improving existing risk stratification in ccRCC.
Objective
To evaluate the nationwide online decision aid ‘Entscheidungshilfe Prostatakrebs’ (established in 2016, >11.000 users and 60 new users/week) for patients with non‐metastatic prostate cancer ...(PCa), from the perspective of patients and urologists.
Patients and Methods
To provide personalised information, the tool collects most of the International Consortium for Health Outcomes Measurement standard set, personal preferences, psychological features, and a validated rating of the tool. To evaluate urologists’ opinions, we developed a structured two‐page questionnaire. All data were collected anonymously.
Results
From June 2016 to December 2020, 11 290 patients used the PCa decision aid. Their median (interquartile range IQR) age was 67 (61–72) years. The median (IQR) time from initial diagnosis to using the tool was 4 (3–7) weeks. In all, 87.7% of users reported high satisfaction. In a multivariable model, predictors for considering observation were higher knowledge, using the decision aid alone, lower oncological risk, normal erectile function, and respective personal preferences. Of 194 urologists, 91 (47%) had implemented the decision aid in their clinical practice. The urologists’ mean (SD) satisfaction score (1 ‘very good’; 6 ‘unsatisfactory’) with it was 1.45 (0.55), and 92% recommended it. Half of the urologists reported time savings.
Conclusion
Patients and urologists report a very high level of acceptance and satisfaction with this online tool. It offers advantages in shared decision‐making and time efficiency. The usage of the decision aid might improve the adoption of active surveillance and watchful waiting when indicated.
Ureteral stenting is a common procedure in urology. The cystoscopic removal of Double-J stents (DJ) causes unpleasant side effects with a negative impact on patient's quality of life. The aim of our ...study was to evaluate this newly developed magnetic DJ and compare it with a standard DJ regarding quality of life with indwelling DJs as well as discomfort during the removal.
The magnetic DJ (Blackstar, Urotech Achenmühle, Germany) is a standard 7F ureteral stent with a small magnetic cube fixed through a string on the loop of the distal part of the stent. For DJ removal, a special catheter-like retrieval instrument with a magnetic tip is inserted, the two magnets connect and the retrieval instrument is removed with the DJ. We first tested this DJ in 20 cases. Afterward we evaluated 40 consecutive cases that required a DJ placement after ureterorenoscopy in a prospective randomized manner. The quality of life was assessed by the ureteral stent symptom questionnaire. A visual analogue scale was used to document the pain by DJ removal.
There was a significant difference regarding the pain location with the indwelling DJ (p = 0.038). The maximum pain was located in the lower abdomen and/or around the bladder (48%) with the magnetic DJ, whereas the standard DJ caused flank pain in 54% of the patients. The mean time for the magnetic DJ removal including preparation and cleaning as for a transurethral catheter insertion was 9.55 7-14 minutes, whereas the mean time for the cystoscopic DJ removal was 21.35 18-30 minutes. The pain caused by the removal of the magnetic DJ was significantly less than that caused by the cystoscopic DJ removal (p = 0.019).
The discomfort caused by the indwelling magnetic DJ is comparable with that caused by the standard DJ. However, the magnetic DJ removal is less painful and faster.
In prostate cancer and other malignancies sensitive and robust biomarkers are lacking or have relevant limitations. Prostate specific antigen (PSA), the only biomarker widely used in prostate cancer, ...is suffering from low specificity. Exosomes offer new perspectives in the discovery of blood-based biomarkers. Here we present a proof-of principle study for a proteomics-based identification pipeline, implementing existing data sources, to exemplarily identify exosome-based biomarker candidates in prostate cancer.
Exosomes from malignant PC3 and benign PNT1A cells and from FBS-containing medium were isolated using sequential ultracentrifugation. Exosome and control samples were analyzed on an LTQ-Orbitrap XL mass spectrometer. Proteomic data is available via ProteomeXchange with identifier PXD003651. We developed a scoring scheme to rank 64 proteins exclusively found in PC3 exosomes, integrating data from four public databases and published mass spectrometry data sets. Among the top candidates, we focused on the tight junction protein claudin 3. Retests under serum-free conditions using immunoblotting and immunogold labeling confirmed the presence of claudin 3 on PC3 exosomes. Claudin 3 levels were determined in the blood plasma of patients with localized (n = 58; 42 with Gleason score 6–7, 16 with Gleason score ≥8) and metastatic prostate cancer (n = 11) compared with patients with benign prostatic hyperplasia (n = 15) and healthy individuals (n = 15) using ELISA, without prior laborious exosome isolation. ANOVA showed different CLDN3 plasma levels in these groups (p = 0.004). CLDN3 levels were higher in patients with Gleason ≥8 tumors compared with patients with benign prostatic hyperplasia (p = 0.012) and Gleason 6–7 tumors (p = 0.029). In patients with localized tumors CLDN3 levels predicted a Gleason score ≥ 8 (AUC = 0.705; p = 0.016) and did not correlate with serum PSA.
By using the described workflow claudin 3 was identified and validated as a potential blood-based biomarker in prostate cancer. Furthermore this workflow could serve as a template to be used in other cancer entities.
Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide. The carcinogenesis of CRC is based on a stepwise accumulation of mutations, leading either to an activation of oncogenes ...or a deactivation of suppressor genes. The loss of genetic stability triggers activation of proto-oncogenes (e.g.,
) and inactivation of tumor suppression genes, namely
and
, which together drive the transition from adenoma to adenocarcinoma. On the one hand, p53 mutations confer resistance to classical chemotherapy but, on the other hand, they open the door for immunotherapy, as p53-mutated tumors are rich in neoantigens. Aberrant function of the
gene product, p53, also affects stromal and non-stromal cells in the tumor microenvironment. Cancer-associated fibroblasts together with other immunosuppressive cells become valuable assets for the tumor by p53-mediated tumor signaling. In this review, we address the manifold implications of p53 mutations in CRC regarding therapy, treatment response and personalized medicine.
Objective
To develop a new digital biomarker based on the analysis of primary tumour tissue by a convolutional neural network (CNN) to predict lymph node metastasis (LNM) in a cohort matched for ...already established risk factors.
Patients and Methods
Haematoxylin and eosin (H&E) stained primary tumour slides from 218 patients (102 N+; 116 N0), matched for Gleason score, tumour size, venous invasion, perineural invasion and age, who underwent radical prostatectomy were selected to train a CNN and evaluate its ability to predict LN status.
Results
With 10 models trained with the same data, a mean area under the receiver operating characteristic curve (AUROC) of 0.68 (95% confidence interval CI 0.678–0.682) and a mean balanced accuracy of 61.37% (95% CI 60.05–62.69%) was achieved. The mean sensitivity and specificity was 53.09% (95% CI 49.77–56.41%) and 69.65% (95% CI 68.21–71.1%), respectively. These results were confirmed via cross‐validation. The probability score for LNM prediction was significantly higher on image sections from N+ samples (mean SD N+ probability score 0.58 0.17 vs 0.47 0.15 N0 probability score, P = 0.002). In multivariable analysis, the probability score of the CNN (odds ratio OR 1.04 per percentage probability, 95% CI 1.02–1.08; P = 0.04) and lymphovascular invasion (OR 11.73, 95% CI 3.96–35.7; P < 0.001) proved to be independent predictors for LNM.
Conclusion
In our present study, CNN‐based image analyses showed promising results as a potential novel low‐cost method to extract relevant prognostic information directly from H&E histology to predict the LN status of patients with prostate cancer. Our ubiquitously available technique might contribute to an improved LN status prediction.
Abstract Objective This review focuses on a step-by-step approach to percutaneous nephrolithotomy (PNL) and its complications and management. Methods Based on institutional and personal experience ...with >1000 patients treated by PNL, we reviewed the literature (Pubmed search) focusing on technique, type, and incidence of complications of the procedure. Results Complications during or after PNL may be present with an overall complication rate of up to 83%, including extravasation (7.2%), transfusion (11.2 – 17.5%), and fever (21.0 – 32.1%), whereas major complications, such as septicaemia (0.3 – 4.7%) and colonic (0.2 – 0.8%) or pleural injury (0.0 – 3.1%) are rare. Comorbidity (i.e., renal insufficiency, diabetes, gross obesity, pulmonary disease) increases the risk of complications. Most complications (i.e., bleeding, extravasation, fever) can be managed conservatively or minimally invasively (i.e., pleural drain, superselective renal embolisation) if recognised early. Conclusions The most important consideration for achieving consistently successful outcomes in PNL with minimal major complications is the correct selection of patients. A well-standardised technique and postoperative follow-up are mandatory for early detection of complications.
•We assessed anxiety and depression before a medical consultation.•A quarter of urology patients reported clinically relevant emotional distress.•Anxiety and depression significantly predicted higher ...decisional conflict.•We recommend systematic assessment of emotional distress in clinical consultation.•Ultimately, this may result in better outcomes of shared decision making.
Emotional distress can be a potential barrier to shared decision making (SDM), yet affect is typically not systematically assessed in medical consultation. We examined whether urological patients report anxiety or depression prior to a consultation and if emotional distress predicts decisional conflict thereafter.
We recruited a large sample of urological outpatients (N = 397) with a range of different diagnoses (42 % oncological). Prior to a medical consultation, patients filled in questionnaires, including the Hospital Anxiety and Depression Scale. After the consultation, patients completed the Decisional Conflict Scale. We scored the rate of anxiety and depression in our sample and conducted multiple regression analysis to examine if emotional distress before the consultation predicts decisional conflict thereafter.
About a quarter of patients reported values at or above cut-off for clinically relevant emotional distress. Emotional distress significantly predicted a higher degree of decisional conflict. There were no differences in emotional distress between patients with and without uro-oncological diagnosis.
Emotional distress is common in urology patients – oncological as well as non-oncological. It predicts decisional conflict after physician consultation.
Emotional distress should be systematically assessed in clinical consultations. This may improve the process and outcome of SDM.
To comprehensively compare quality-of-life (QoL) outcomes between open partial nephrectomy (OPN) and robot-assisted PN (RAPN) from the randomised ROBOtic-assisted versus Conventional Open Partial ...nephrectomy (ROBOCOP) II trial, as QoL data comparing OPN and RAPN are virtually non-existent, especially not from randomised controlled trials (RCTs).
The ROBOCOP II was a single-centre, open-label RCT between OPN and RAPN. The pre-planned analyses of QoL outcomes are presented. Data were analysed descriptively in a modified intention-to-treat population.
A total of 50 patients underwent surgery. At postoperative Day 90 (POD90), there was no significant difference for the Kidney Disease Quality of Life-Short Form questionnaire score (mean sd OPN 72 20 vs RAPN 76 15, P = 0.850), while there were advantages for RAPN in the subdomains of 'Pain' (P = 0.006) and 'Physical functioning' (P = 0.011) immediately after surgery. For the European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core there were overall advantages directly after surgery (mean sd score OPN 63 20 vs RAPN 75 17, P = 0.031), as well as for the subdomains 'Fatigue' (P = 0.026), 'Pain' (P = 0.002) and 'Constipation' (P = 0.045) but no differences at POD90. There were no differences for the EuroQoL five Dimensions five Levels questionnaire at POD90 (mean sd score OPN 70 22 vs RAPN 72 17, P = 1.0) or at any other time point. Finally, no significant differences were found for the overall Convalescence and Recovery Evaluation questionnaire score at POD90 (mean sd OPN 84 13 vs RAPN 86 10, P = 0.818) but less pain in the RAPN group (P = 0.017) directly after surgery.
Pain and physical functioning as subdomains of QoL are improved after RAPN compared to OPN in the early postoperative course, while there are no differences anymore after 3 months.
Abstract Background Understanding how to sequence targeted therapies for metastatic renal cell carcinoma (mRCC) is important for maximisation of clinical benefit. Objectives To prospectively evaluate ...sequential use of the multikinase inhibitors sorafenib followed by sunitinib (So-Su) versus sunitinib followed by sorafenib (Su-So) in patients with mRCC. Design, setting, and participants The multicentre, randomised, open-label, phase 3 SWITCH study assessed So-Su versus Su-So in patients with mRCC without prior systemic therapy, and stratified by Memorial Sloan Kettering Cancer Center risk score (favourable or intermediate). Intervention Patients were randomised to sorafenib 400 mg twice daily followed, on progression or intolerable toxicity, by sunitinib 50 mg once daily (4 wk on, 2 wk off) (So-Su), or vice versa (Su-So). Outcome measurements and statistical analysis The primary endpoint was improvement in progression-free survival (PFS) with So-Su versus Su-So, assessed from randomisation to progression or death during second-line therapy. Secondary endpoints included overall survival (OS) and safety. Results and limitations In total, 365 patients were randomised (So-Su, n = 182; Su-So, n = 183). There was no significant difference in total PFS between So-Su and Su-So (median 12.5 vs 14.9 mo; hazard ratio HR 1.01; 90% confidence interval CI 0.81–1.27; p = 0.5 for superiority). OS was similar for So-Su and Su-So (median 31.5 and 30.2 mo; HR 1.00, 90% CI 0.77–1.30; p = 0.5 for superiority). More So-Su patients than Su-So patients reached protocol-defined second-line therapy (57% vs 42%). Overall, adverse event rates were generally similar between the treatment arms. The most frequent any-grade treatment-emergent first-line adverse events were diarrhoea (54%) and hand-foot skin reaction (39%) for sorafenib; and diarrhoea (40%) and fatigue (40%) for sunitinib. Conclusions Total PFS was not superior with So-Su versus Su-So. These results demonstrate that sorafenib followed by sunitinib and vice versa provide similar clinical benefit in mRCC. Patient summary We investigated if total progression-free survival (PFS) is improved in patients with advanced/metastatic kidney cancer who are treated with sorafenib and then with sunitinib (So-Su), compared with sunitinib and then sorafenib (Su-So). We found that total PFS was not improved with So-Su compared with Su-So, but both treatment options were similarly effective in patients with advanced/metastatic kidney cancer. Trial registration ClinicalTrials.gov identifier NCT00732914 , www.clinicaltrials.gov
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