Temperature assessment study of ex vivo holmium laser enucleation of the prostate model.

PURPOSE: There isscarce evidence to date on how temperature develops during holmium laser enucleation of the prostate (HoLEP). We aimed to determine the potential heat generation during HoLEP under ex vivo conditions. METHODS: We developed two experimental setups. Firstly, we simulated HoLEP ex vivo using narrow-neck laboratory bottles mimicking enucleation cavities and a prostate resection trainer. Seven temperature probes were placed at different locations in the experimental setup, and the heat generation was measured separately during laser application. Secondly, we simulated high-frequency current-based coagulation of the vessels using a roller probe. RESULTS: We observed that the larger the enucleated cavity, the higher the temperature rises, regardless of the irrigation flow rate. The highest temperature difference with an irrigation flow was approximately + 4.5 K for a cavity measuring 100ccm and a 300 ml/min irrigation flow rate. The higher flow rate generates faster removal of the generated heat, thus cooling down the artificial cavity. Furthermore, the temperature differences at different irrigation flow rates (except at 0 ml/min) were consistently below 5 K. Within the resection trainer, the temperature increase with and without irrigation flow was approximately 0.5 K and 3.0 K, respectively. The mean depth of necrosis (1084 ± 176 µm) achieved by the roller probe was significantly greater when using 144 W energy. CONCLUSION: Carefully adjusted irrigation and monitoring during HoLEP are crucial when evacuating the thermal energy generated during the procedure. We believe this study of ours provides evidence with the potential to facilitate clinical studies on patient safety.

Proteomic analyses identify HK1 and ATP5A to be overexpressed in distant metastases of lung adenocarcinomas compared to matched primary tumors.

Lung cancer is the leading cause of cancer-related deaths worldwide with lung adenocarcinoma (LUAD) being the most common type. Genomic studies of LUAD have advanced our understanding of its tumor biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD are still insufficiently explored. The prognosis for lung cancer patients is still mostly determined by the stage of disease at the time of diagnosis. Focusing on late-stage metastatic LUAD with poor prognosis, we compared the proteomic profiles of primary tumors and matched distant metastases to identify relevant and potentially druggable differences. We performed high-performance liquid chromatography (HPLC) and electrospray ionization tandem mass spectrometry (ESI-MS/MS) on a total of 38 FFPE (formalin-fixed and paraffin-embedded) samples. Using differential expression analysis and unsupervised clustering we identified several proteins that were differentially regulated in metastases compared to matched primary tumors. Selected proteins (HK1, ATP5A, SRI and ARHGDIB) were subjected to validation by immunoblotting. Thereby, significant differential expression could be confirmed for HK1 and ATP5A, both upregulated in metastases compared to matched primary tumors. Our findings give a better understanding of tumor progression and metastatic spreads in LUAD but also demonstrate considerable inter-individual heterogeneity on the proteomic level.

Ex-vivo evaluation of miniaturized probes for endoscopic optical coherence tomography in urothelial cancer diagnostics.

Background: The gold standard for detecting bladder cancer is white light cystoscopy (WLC) and resection of suspicious lesions. In this study, we evaluate two miniaturized Optical Coherence Tomography (OCT) probes for endoscopic use, regarding their applicability in diagnosing urothelial cancer. Materials and methods: In total, 33 patients who underwent a radical cystectomy were included. Preoperative oncological staging and determining the indication for the surgical intervention were done following the latest European Association of Urology (EAU) guidelines. Samples were taken from bladder tissue after bladder removal and prepared for OCT measurement. Additionally, porcine bladder samples were used as reference tissue. We took measurements using two miniaturized probes: a bimodal probe and a single modality OCT probe. A non-miniaturized standard OCT scanner was used as a reference. Results: Histopathological examination revealed urothelial cancer in all but three patients. Measurements on porcine tissue revealed a clear distinction between the urothelial layers for all probes. Furthermore, we detected improved image quality thanks to the stretching of the tissue. We took 271 measurements in human samples. While the urothelial layers were well delineated in healthy tissue, all the probes revealed a loss of these structures in cancerous regions. While the single-modality probe delivered an image quality equaling the reference images, it was possible to detect cancerous areas with the bimodal probe. Conclusion: We demonstrate that endoscopic probes for OCT imaging are technologically feasible and deliver acceptable image quality. A distinction between healthy and abnormal tissue is possible. We propose combining different endoscopic imaging modalities as a promising approach for urothelial cancer diagnostics.

Evaluation of functional parameters, patient-reported outcomes and workload related to continuous urinary bladder irrigation after transurethral surgery.

BACKGROUND: Continuous saline bladder irrigation (CBI) is a common procedure after transurethral surgery and to treat gross hematuria. We conducted this study to gather data on parameters of CBI, medical staff's work load associated with CBI monitoring, patients' feeling of safety and of patients' impairments during CBI. METHODS: We observed CBI taking place after transurethral surgery for a 2-9-hour period. Patients were asked to rank how safe they felt, general impairments and impaired mobility. Irrigation parameters and complications were documented at least every 30 minutes. The staff's workload was evaluated through the frequency of visits and presence time. RESULTS: The patients' mobility was notably reduced with an average of 10.5%±16.7% of time spent outside of bed, pain was low (mean 0.60±1.15). Patients felt very safe with CBI (8.8±1.9), hardly impaired overall (3.8±3.0), but restricted in mobility (5.9±2.8). Pain was associated with general impairment and impaired mobility. Clot retention occurred in 5 patients. Average irrigation speed was 9.46±8.69 mL/min (0 to 86.7 mL/min). Urine bags were emptied on average every 2.2±1.2 hours. Patients were visited by medical personnel 1 to 11 times. CONCLUSIONS: CBI remains an improvable procedure in terms of the irrigation process itself to prevent complications, the patients' feeling of safety and comfort during CBI and the amount of work associated with its monitoring. We have provided parameters for the implementation of more individualized CBI monitoring. TRIAL REGISTRATION: German Clinical Trial Registry; DRKS00023707; Registered retrospectively November 25 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00023707.

Epidermal Growth Factor Based Targeted Toxin for the Treatment of Bladder Cancer.

BACKGROUND/AIM: Reports on over-expression of the epidermal growth factor receptor (EGFR) in bladder cancer and its function in tumorigenesis have suggested to target this antigen. MATERIALS AND METHODS: We generated the targeted toxin EGF-PE40 consisting of the human epidermal growth factor (EGF) as the binding domain and PE40, a truncated version of Pseudomonas Exotoxin A, as the toxin domain. EGF-PE40 was tested on EGFR-expressing bladder cancer cells in view of binding via flow cytometry, and cytotoxicity via WST viability assay. Induction of apoptosis was examined by western blot. RESULTS: The targeted toxin specifically triggered cytotoxicity in the bladder cancer cells with 50% inhibitory concentration (IC50) values in the low nanomolar or picomolar range, and was about 1,250- to 1,500-fold more cytotoxic than the EGFR inhibitor erlotinib. Cytotoxicity of EGF-PE40 was based on the induction of apoptosis. CONCLUSION: EGF-PE40 represents a promising candidate for the future treatment of bladder cancer.

Use of Artificial Intelligence for Medical Literature Search: Randomized Controlled Trial Using the Hackathon Format.

BACKGROUND: Mapping out the research landscape around a project is often time consuming and difficult. OBJECTIVE: This study evaluates a commercial artificial intelligence (AI) search engine (IRIS.AI) for its applicability in an automated literature search on a specific medical topic. METHODS: To evaluate the AI search engine in a standardized manner, the concept of a science hackathon was applied. Three groups of researchers were tasked with performing a literature search on a clearly defined scientific project. All participants had a high level of expertise for this specific field of research. Two groups were given access to the AI search engine IRIS.AI. All groups were given the same amount of time for their search and were instructed to document their results. Search results were summarized and ranked according to a predetermined scoring system. RESULTS: The final scoring awarded 49 and 39 points out of 60 to AI groups 1 and 2, respectively, and the control group received 46 points. A total of 20 scientific studies with high relevance were identified, and 5 highly relevant studies ("spot on") were reported by each group. CONCLUSIONS: AI technology is a promising approach to facilitate literature searches and the management of medical libraries. In this study, however, the application of AI technology lead to a more focused literature search without a significant improvement in the number of results.

In Vitro Effects of a Novel Coating Agent on Bacterial Biofilm Development on Ureteral Stents.

OBJECTIVES: Ureteral stenting is a widely used method for noninvasive urinary drainage in ureteral obstruction. However, biofilm development due to transient bacteriuria can cause severe complications such as incrustation with subsequent obstruction as well as recurrent urinary tract infection. Apart from local ailment such as dysuria, this increases both stent replacement frequency and incidence of complications. In this work, we investigated in vitro the bacterial adhesion to a surface-attached and cross-linked poly(N,N-dimethylacrylamide) (PDMAA) hydrogel network, which is known for its nonfouling and protein-repellent characteristics. MATERIALS AND METHODS: To mimic the conditions encountered in vivo, PDMAA-coated and uncoated cyclic olefin polymer (COP) slides as well as polyurethane (PU)-coated glass slides were incubated in sterile human urine for 48 hours. Colonization was then simulated by adding known uropathogens, cultivated from clinical urine samples (such as Escherichia coli). After further incubation for 24 and 48 hours, slides were washed, and the remaining adherent bacteria were solubilized by ultrasound. CFUs were counted after plating and incubation for 48 hours of the resulting solution. RESULTS: PDMAA reduced adherent E. coli about fivefold on coated PU glass slides as well as in PDMAA-coated COP slides. With adherent Enterococcus faecalis and Klebsiella pneumoniae there was a tendency to decreased biofilm formation, but the difference was not statistically significant. CONCLUSIONS: PDMAA reduces surface adherence of the most common uropathogen significantly. Assessment of clinical relevance and of the effect on further uropathogens needs further experimental and clinical evaluations. German Clinical Trial Register ID: DRKS00013264 (approved WHO primary register).