Uncertainty-aware temporal self-learning (UATS): Semi-supervised learning for segmentation of prostate zones and beyond.

Various convolutional neural network (CNN) based concepts have been introduced for the prostate's automatic segmentation and its coarse subdivision into transition zone (TZ) and peripheral zone (PZ). However, when targeting a fine-grained segmentation of TZ, PZ, distal prostatic urethra (DPU) and the anterior fibromuscular stroma (AFS), the task becomes more challenging and has not yet been solved at the level of human performance. One reason might be the insufficient amount of labeled data for supervised training. Therefore, we propose to apply a semi-supervised learning (SSL) technique named uncertainty-aware temporal self-learning (UATS) to overcome the expensive and time-consuming manual ground truth labeling. We combine the SSL techniques temporal ensembling and uncertainty-guided self-learning to benefit from unlabeled images, which are often readily available. Our method significantly outperforms the supervised baseline and obtained a Dice coefficient (DC) of up to 78.9%, 87.3%, 75.3%, 50.6% for TZ, PZ, DPU and AFS, respectively. The obtained results are in the range of human inter-rater performance for all structures. Moreover, we investigate the method's robustness against noise and demonstrate the generalization capability for varying ratios of labeled data and on other challenging tasks, namely the hippocampus and skin lesion segmentation. UATS achieved superiority segmentation quality compared to the supervised baseline, particularly for minimal amounts of labeled data.

Triggers and oncologic outcome of salvage radical prostatectomy, salvage radiotherapy and active surveillance after focal therapy of prostate cancer.

PURPOSE: Due to the tissue preserving approach of focal therapy (FT), local cancer relapse can occur. Uncertainty exists regarding triggers and outcome of salvage strategies. METHODS: Patients with biopsy-proven prostate cancer (PCa) after FT for localized PCa from 2011 to 2020 at eight tertiary referral hospitals in Germany that underwent salvage radical prostatectomy (S-RP), salvage radiotherapy (S-RT) or active surveillance (AS) were reported. Prostate specific antigen (PSA) changes, suspicious lesions on mpMRI and histopathological findings on biopsy were analyzed. A multivariable regression model was created for adverse pathological findings (APF) at S-RP specimen. Kaplan-Meier curves were generated to determine oncological outcomes. RESULTS: A total of 90 men were included. Cancer relapse after FT was detected at a median of 12 months (IQR 9-16). Of 50 men initially under AS 13 received S-RP or S-RT. In total, 44 men underwent S-RP and 13 S-RT. At cancer relapse 17 men (38.6%) in the S-RP group [S-RT n = 4 (30.8%); AS n = 3 (6%)] had ISUP > 2. APF (pT ≥ 3, ISUP ≥ 3, pN + or R1) were observed in 23 men (52.3%). A higher ISUP on biopsy was associated with APF [p = 0.006 (HR 2.32, 97.5% CI 1.35-4.59)] on univariable analysis. Progression-free survival was 80.4% after S-RP and 100% after S-RT at 3 years. Secondary therapy-free survival was 41.7% at 3 years in men undergoing AS. Metastasis-free survival was 80% at 5 years for the whole cohort. CONCLUSION: With early detection of cancer relapse after FT S-RP and S-RT provide sufficient oncologic control at short to intermediate follow-up. After AS, a high secondary-therapy rate was observed.

Anisotropic 3D Multi-Stream CNN for Accurate Prostate Segmentation from Multi-Planar MRI.

BACKGROUND AND OBJECTIVE: Accurate and reliable segmentation of the prostate gland in MR images can support the clinical assessment of prostate cancer, as well as the planning and monitoring of focal and loco-regional therapeutic interventions. Despite the availability of multi-planar MR scans due to standardized protocols, the majority of segmentation approaches presented in the literature consider the axial scans only. In this work, we investigate whether a neural network processing anisotropic multi-planar images could work in the context of a semantic segmentation task, and if so, how this additional information would improve the segmentation quality. METHODS: We propose an anisotropic 3D multi-stream CNN architecture, which processes additional scan directions to produce a high-resolution isotropic prostate segmentation. We investigate two variants of our architecture, which work on two (dual-plane) and three (triple-plane) image orientations, respectively. The influence of additional information used by these models is evaluated by comparing them with a single-plane baseline processing only axial images. To realize a fair comparison, we employ a hyperparameter optimization strategy to select optimal configurations for the individual approaches. RESULTS: Training and evaluation on two datasets spanning multiple sites show statistical significant improvement over the plain axial segmentation (p<0.05 on the Dice similarity coefficient). The improvement can be observed especially at the base (0.898 single-plane vs. 0.906 triple-plane) and apex (0.888 single-plane vs. 0.901 dual-plane). CONCLUSION: This study indicates that models employing two or three scan directions are superior to plain axial segmentation. The knowledge of precise boundaries of the prostate is crucial for the conservation of risk structures. Thus, the proposed models have the potential to improve the outcome of prostate cancer diagnosis and therapies.

MRI targeted single fraction HDR Brachytherapy for localized Prostate Carcinoma: a feasibility study of focal radiation therapy (ProFocAL).

OBJECTIVES: The aim of the study was to establish the setup and workflow for delivering focal MRI-guided high-dose-rate (HDR) brachytherapy for prostate cancer (PCA) and to assess patient comfort and safety aspects of MRI-guided single-fraction HDR. METHODS: Patients with histologically proven focal low- to intermediate-risk PCA with a single PIRADS 4/5 lesion were treated with percutaneous interstitial HDR brachytherapy in a single fraction with a minimum dose for the gross tumor volume of 20 Gy while sparing the organ at risk (OAR). Using a 3T-MRI, brachytherapy catheters were placed transgluteal in freehand technique. No antibiotic therapy or general analgesics were administered. Patient data, procedure time, patient discomfort, and complications were recorded. Quarterly PSA controls, biannual follow-up imaging, and annual re-biopsy were planned. RESULTS: So far, 9 patients were successfully treated and followed for 6 months. Mean intervention time was 34 min. Using the VAS scale, the pain reported for the intervention ranged from 2 to 3. Short-term follow-up showed no acute genitourinary or gastrointestinal toxicity so far. None of the patients displayed signs of infection. PSA levels in all patients decreased significantly. On follow up no residual PCA was detected treated region so far. PSA levels in all patients decreased significantly. On follow-up, no residual PCA was detected so far. CONCLUSIONS: MR-guided single-fraction focal HDR brachytherapy for localized PCA is feasible as well as safe for the individual patient. Catheters can be placed accurately and maximum therapeutic dose distribution can be restricted to the tumor. Countersigning the minimally invasive character of the procedure, no general anesthesia or antibiosis is necessary. KEY POINTS: • MR-guided focal HDR brachytherapy allows an accurate placement of catheters with maximum therapeutic dose distribution restricted to the tumor. • No major anesthesia or antibiosis is necessary emphasizing the minimal invasive character of the procedure. • Patients with low- and intermediate-risk prostate carcinoma in particular may benefit to halt disease progression whereas treatment-related morbidity is reduced compared with radical therapy.

How well do software assistants for minimally invasive partial nephrectomy meet surgeon information needs? A cognitive task analysis and literature review study.

INTRODUCTION: Intraoperative software assistance is gaining increasing importance in laparoscopic and robot-assisted surgery. Within the user-centred development process of such systems, the first question to be asked is: What information does the surgeon need and when does he or she need it? In this article, we present an approach to investigate these surgeon information needs for minimally invasive partial nephrectomy and compare these needs to the relevant surgical computer assistance literature. MATERIALS AND METHODS: First, we conducted a literature-based hierarchical task analysis of the surgical procedure. This task analysis was taken as a basis for a qualitative in-depth interview study with nine experienced surgical urologists. The study employed a cognitive task analysis method to elicit surgeons' information needs during minimally invasive partial nephrectomy. Finally, a systematic literature search was conducted to review proposed software assistance solutions for minimally invasive partial nephrectomy. The review focused on what information the solutions present to the surgeon and what phase of the surgery they aim to support. RESULTS: The task analysis yielded a workflow description for minimally invasive partial nephrectomy. During the subsequent interview study, we identified three challenging phases of the procedure, which may particularly benefit from software assistance. These phases are I. Hilar and vascular management, II. Tumour excision, and III. Repair of the renal defects. Between these phases, 25 individual challenges were found which define the surgeon information needs. The literature review identified 34 relevant publications, all of which aim to support the surgeon in hilar and vascular management (phase I) or tumour excision (phase II). CONCLUSION: The work presented in this article identified unmet surgeon information needs in minimally invasive partial nephrectomy. Namely, our results suggest that future solutions should address the repair of renal defects (phase III) or put more focus on the renal collecting system as a critical anatomical structure.

Crosstalk between Akt signaling and cold shock proteins in mediating invasive cell phenotypes.

Cold shock proteins are up-regulated by cellular stress and orchestrate inflammatory responses, cell proliferation, and differentiation. Enhanced cold shock protein expression promotes malignant cell transformation; up-regulation is detected in most cancers and associated with poor prognosis. Akt1, a serine/threonine kinase, is a potent oncogene, which activates pro-proliferative and anti-apoptotic signaling pathways, and phosphorylates the cold shock domain. Unexpectedly, chicken-YB-1 abrogates PI3K-Akt-dependent oncogenic cell transformation in embryonic fibroblasts. Here, we addressed the question whether chicken and human Y-box binding protein-1 (YB-1) act differently on cell transformation, and how a related protein, DNA-binding protein-A (DbpA) behaves in comparison. NIH3T3 cells were transduced with lentiviral vectors encoding for myristoylated (constitutive active) Akt1, YB-1, DbpA, or shRNA targeting YB-1 expression. Colony formation assays showed that human YB-1 acts similar to chicken on Akt-dependent cell transformation. This activity was not titratable. Given the correlation of nuclear YB-1 and upregulated DbpA expression in a series of clear cell renal cell carcinomas (n = 40) the colony formation assay was extended to include ectopic DbpA expression. DbpA alone prominently induced cell transformation, which was enhanced when constitutive active Akt1 or concomitant YB-1 expression was present. Notably, co-expression of DbpA together with YB-1 abrogated the repressive effect on Akt1 signaling observed with YB-1 alone. Macroscopically, some colonies yielded a remarkable "invasive" phenotype. Thus, cold shock proteins may convey profound anti- and pro-oncogenic effects on Akt-dependent cell transformation. DbpA is able to overcome the anti-oncogenic effects seen with combined YB-1 and Akt signaling in an in vitro model of colonial growth.

Initial Assessment of the Efficacy of Irreversible Electroporation in the Focal Treatment of Localized Renal Cell Carcinoma With Delayed-interval Kidney Tumor Resection (Irreversible Electroporation of Kidney Tumors Before Partial Nephrectomy [IRENE] Trial-An Ablate-and-Resect Pilot Study).

OBJECTIVE: To assess the efficacy of irreversible electroporation (IRE) ablation of pT1a renal cell carcinoma (RCC) in the first prospective, monocentric phase 2a pilot ablate-and-resect study (Irreversible Electroporation of Kidney Tumors Before Partial Nephrectomy [IRENE] trial). It has been postulated that focal IRE can bring about complete ablation of soft-tissue tumors with protection of healthy peritumoral tissue and anatomic structures. PATIENTS AND METHODS: The first 7 study patients with biopsy-proven pT1a RCC (15-39 mm) underwent IRE. Percutaneous computed tomography-guided IRE was performed with electrocardiographic triggering under general anesthesia and deep muscle paralysis with 3-6 monopolar electrodes positioned within the renal tumor. Twenty-eight days later, the tumor region was completely resected to confirm tumor destruction pathologically. Individual results for these patients are displayed, described, and discussed. RESULTS: Technical feasibility was attained in all patients, but electrode placement and ablation were complex, with a mean overall procedure time of 129 minutes. There were no major complications. Partial kidney resection was performed in 5 patients, and radical nephrectomy was performed in 2 patients because of central tumor location and ablation areas. Resections revealed by tumor, node, and metastasis classification of the International Union for Cancer Control 2017 no residual tumor as complete ablation in 4 cases (ypT0V0N0Pn0R0) and microscopic residual tumor cells as incomplete ablation in the other 3 cases (ypT1aV0N0Pn0R1). CONCLUSION: Renal percutaneous IRE appears to be a safe treatment for pT1a RCC but requires substantial procedural effort. Resection specimens of the ablation zone revealed a high rate of microscopic incomplete ablation 4 weeks after IRE. According to these initial study results, curative, kidney-sparing ablation of T1a RCC appears possible but needs technical improvement to ensure complete ablation.

Virtual and Augmented Reality Systems for Renal Interventions: A Systematic Review.

PURPOSE: Many virtual and augmented reality systems have been proposed to support renal interventions. This paper reviews such systems employed in the treatment of renal cell carcinoma and renal stones. METHODS: A systematic literature search was performed. Inclusion criteria were virtual and augmented reality systems for radical or partial nephrectomy and renal stone treatment, excluding systems solely developed or evaluated for training purposes. RESULTS: In total, 52 research papers were identified and analyzed. Most of the identified literature (87%) deals with systems for renal cell carcinoma treatment. About 44% of the systems have already been employed in clinical practice, but only 20% in studies with ten or more patients. Main challenges remaining for future research include the consideration of organ movement and deformation, human factor issues, and the conduction of large clinical studies. CONCLUSION: Augmented and virtual reality systems have the potential to improve safety and outcomes of renal interventions. In the last ten years, many technical advances have led to more sophisticated systems, which are already applied in clinical practice. Further research is required to cope with current limitations of virtual and augmented reality assistance in clinical environments.

Circular Abscess Formation of the Inner Preputial Leaf as a Complication of a Penile Mondor's Disease: The First Case Report.

Introduction. Mondor's disease of the penis is an uncommon condition characterized by thrombosis or thrombophlebitis involving the superficial dorsal veins. An accompanied lymphangitis is discussed. There is typical self-limiting clinical course. Case Presentation. This paper firstly reports a secondary abscess formation of the preputial leaf two weeks after penile Mondor's disease and subcutaneous lymphangitis as complication of excessive sexual intercourse of a 44-year-old man. Sexual transmitted diseases could be excluded. Lesions healed up completely under abscess drainage, antibiotic, and anti-inflammatory medication. Conclusion. Previous reports in the literature include several entities of the penile Mondor's disease. Our patient is very unusual in that he presented with a secondary preputial abscess formation due to superficial thrombophlebitis, subcutaneous lymphangitis, and local bacterial colonisation. Abscess drainage plus antiphlogistic and antibiotic medication is the treatment of choice.

A Randomised Phase II Trial Comparing Docetaxel Plus Prednisone with Docetaxel Plus Prednisone Plus Low-Dose Cyclophosphamide in Castration-Resistant Prostate Cancer.

BACKGROUND: Docetaxel plus prednisone is a standard treatment for castration-resistant prostate cancer. Cyclophosphamide may be an effective combination partner. METHODS: This randomised, multicentre, phase II trial compared the combination therapy of docetaxel plus prednisone plus cyclophosphamide with the standard therapy of docetaxel plus prednisone. RESULTS: Thirty-three patients received six 3-week treatment cycles (in total 171 cycles). During treatment, an adequate decline in prostate-specific antigen was seen in both groups (p = 0.068) without between-group differences (p = 0.683). No relevant differences between within-group changes were observed for blood pressure, weight, pain score, laboratory variables or quality of life. There were no serious side effects apart from leucopenia requiring treatment (docetaxel + prednisone + cyclophosphamide arm) and no drug-related withdrawals; all three fatalities were considered to be cancer related. CONCLUSIONS: The oncological effectiveness and tolerability of docetaxel plus prednisone were supported; an additional effect of cyclophosphamide was not detected. However, the small number of patients and short observation period restrict the generalisability of the results.

Mucosal Progranulin expression is induced by H. pylori, but independent of Secretory Leukocyte Protease Inhibitor (SLPI) expression.

BACKGROUND: Mucosal levels of Secretory Leukocyte Protease Inhibitor (SLPI) are specifically reduced in relation to H. pylori-induced gastritis. Progranulin is an epithelial growth factor that is proteolytically degraded into fragments by elastase (the main target of SLPI). Considering the role of SLPI for regulating the activity of elastase, we studied whether the H. pylori-induced reduction of SLPI and the resulting increase of elastase-derived activity would reduce the Progranulin protein levels both ex vivo and in vitro. METHODS: The expression of Progranulin was studied in biopsies of H. pylori-positive, -negative and -eradicated subjects as well as in the gastric tumor cell line AGS by ELISA, immunohistochemistry and real-time RT-PCR. RESULTS: H. pylori-infected subjects had about 2-fold increased antral Progranulin expression compared to H. pylori-negative and -eradicated subjects (P < 0.05). Overall, no correlations between mucosal Progranulin and SLPI levels were identified. Immunohistochemical analysis confirmed the upregulation of Progranulin in relation to H. pylori infection; both epithelial and infiltrating immune cells contributed to the higher Progranulin expression levels. The H. pylori-induced upregulation of Progranulin was verified in AGS cells infected by H. pylori. The down-regulation of endogenous SLPI expression in AGS cells by siRNA methodology did not affect the Progranulin expression independent of the infection by H. pylori. CONCLUSIONS: Taken together, Progranulin was identified as novel molecule that is upregulated in context to H. pylori infection. In contrast to other diseases, SLPI seems not to have a regulatory role for Progranulin in H. pylori-mediated gastritis.