Search

Background: The accurate delineation of ablation zones (AZs) is crucial for assessing radiofrequency ablation (RFA) therapy's efficacy. Manual measurement, the current standard, is subject to variability and potential inaccuracies., Aim: This study aims to assess the effectiveness of Artificial Intelligence (AI) in automating AZ measurements in ultrasound images and compare its accuracy with manual measurements in ultrasound images., Methods: An in vitro study was conducted using chicken breast and liver samples subjected to bipolar RFA. Ultrasound images were captured every 15 s, with the AI model Mask2Former trained for AZ segmentation. The measurements were compared across all methods, focusing on short-axis (SA) metrics., Results: We performed 308 RFA procedures, generating 7275 ultrasound images across liver and chicken breast tissues. Manual and AI measurement comparisons for ablation zone diameters revealed no significant differences, with correlation coefficients exceeding 0.96 in both tissues ( p < 0.001). Bland-Altman plots and a Deming regression analysis demonstrated a very close alignment between AI predictions and manual measurements, with the average difference between the two methods being -0.259 and -0.243 mm, for bovine liver and chicken breast tissue, respectively., Conclusion: The study validates the Mask2Former model as a promising tool for automating AZ measurement in RFA research, offering a significant step towards reducing manual measurement variability.

Endoscopic submucosal dissection (ESD) was developed for the removal of benign and early malignant lesions in the gastrointestinal tract. We aimed to evaluate the performance and safety of a novel high-pressure waterjet-assisted ESD knife in colorectal applications. Six female German Landrace pigs with an average weight of 62 kg (range 60-65 kg) were used in this prospective, randomized, and controlled study. Twenty-four ESDs were performed by three endoscopists: Twelve each with the new Erbe HYBRIDknife ® flex T-Type (HK-T) and the Olympus DualKnife ® J (DK-J), including six rectal and six colonic ESDs per instrument. The order of performance was randomized regarding anatomic position and instrument. As the primary endpoint, ESD knife performance characteristics were combined and rated on a 5-point Likert scale, with 5 Likert points (LP) representing the best response (5 = very good). The HK-T was rated significantly better than the DK-J (4.7 LP versus 4.4 LP, p = 0.0295), mainly because of HK-T injection ability (5 LP versus 3 LP, p < 0.0001) and hemostasis (5 LP versus 4 LP, p = 0.0452). There was no difference in procedure time (HK-T: 35 min versus DK-J: 34 min, p = 0.8005), resection diameter (3.1 cm versus 2.8 cm, p = 0.3492), injection volume (41 mL versus 46 mL, p = 0.5633), and complication rates. HK-T is as effective as DK-J in colorectal ESD in terms of dissection quality but has better injection and hemostatic properties. The impact of these technical advantages on the ESD treatment of patients with large superficial colorectal lesions remains to be clinically verified.

Immunological consequences of endoscopic ultrasound (EUS)-local thermal ablation (LTA) for pancreatic ductal adenocarcinoma (PDAC) have not been extensively assessed. We aimed to explore EUS-LTA effects on the systemic immune response in PDAC. Peripheral blood was collected from 10 treatment-naïve patients with borderline resectable and locally advanced PDAC, randomly allocated to Nab-paclitaxel plus Gemcitabine chemotherapy (CT-arm, n = 5) or EUS-LTA with HybridTherm Probe plus CT (HTP + CT-arm, n = 5). Twenty healthy donors were included as controls. Flow-cytometry and multiplex assays were used to profile immune cell subsets and measure serum cytokines/chemokines, respectively. At baseline, PDAC patients showed increased circulating monocytes and lower circulating lymphocytes and CD19+ B cells counts compared to healthy controls. After 4 months, CT induced decrease of B regulatory cells, CD4+ cytotoxic T cells and IL-1β. The addition of EUS-HTP to CT selectively decreased the serum levels of APRIL/TNFSF13 as well as T regulatory cells, total, classic and inflammatory monocytes. Serum levels of APRIL/TNFSF13 and total, classic and inflammatory monocytes counts at baseline were associated with worse overall survival. EUS-HTP has the potential to selectively impact on immune cells and cytokines associated with poor outcomes in PDAC.

Video 1Case description and video in cholangioscopic view demonstrating bile duct tissue acquisition by cholangioscopy-guided cryobiopsy technique., (Copyright © 2023 American Society for Gastrointestinal Endoscopy.)

Introduction: A novel multipurpose bipolar radiofrequency instrument, the Erbe Dissector (EDS), which simultaneously seals and cuts tissue, was developed. Ex vivo sealing rate and time, burst pressure, jaw temperature and thermal spread were studied in porcine renal arteries., Material and Methods: In vivo , 13 surgical tasks were performed in two pigs: beside sealing rate and time, overall performance in sharp and blunt dissection, tissue sticking, hemostasis, precision, etc., were evaluated by four surgeons compared with ENSEAL G2 (EG2) using surveys on a Likert scale (1 = very poor; 5 = very good)., Results: Ex vivo , the EDS sealing rate was 91.7% (33/36 arteries) at an average sealing time of 2.1 s (range 1.7-2.8) and a burst pressure of 1040 ± 350 mmHg. The maximum jaw temperature was 87 ± 4 °C and the mean lateral thermal spread was 0.8 ± 0.2 mm. In vivo , the sealing rate for arteries and veins was 92.6% (50/54) and the median seal and cut time was 1.6 s (range: 1.3-2.9). The average EDS performance score across all tasks was 4.4 ± 0.6 Likert points. For five shared tasks, EDS was better than EG2 (4.4 ± 0.5 versus 3.4 ± 0.6 Likert points; p  = 0.016)., Conclusions: EDS seals and cuts arteries and veins rapidly with good safety and user-friendliness.

Background and Objectives: Data on the clinical efficacy of EUS-guided ablation using the HybridTherm-Probe (EUS-HTP) in locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) are lacking. The aim of the study was to assess the impact of EUS-HTP added to chemotherapy (CT) on overall survival (OS) and progression-free survival (PFS) of LA-PDAC patients with local disease progression (DP) after first-line therapy, compared to CT alone in controls., Methods: LA-PDAC cases, prospectively treated by EUS-HTP, were retrospectively compared to matched controls (1:2) receiving standard treatment. Study endpoints were the OS and PFS from local DP after first-line therapy, compared through log-rank test calculating hazard ratios and differences in restricted mean OS/PFS time (RMOST/RMPFST) within prespecified time points (4, 6, and 12 months)., Results: Thirteen cases and 26 controls were included. Clinical, tumor, and therapy features before and after first-line therapy were case-control balanced. The median OS and PFS were not significantly improved in cases over controls (months: 7 vs. 5 and 5 vs. 3, respectively). At 4 and 6 months, the RMPFST difference was in favor of cases (P = 0.0001 and P = 0.003, respectively). In cases and controls not candidate to further CT (N = 5 and N = 9), the median OS and PFS were not significantly improved in cases over controls (months: 6 vs. 3 and 4 vs. 2, respectively), but the RMPFST difference was in favor of cases at 4 months (P = 0.002)., Conclusions: In locally progressive PDAC patients experiencing failure of first-line therapy, EUS-HTP achieves a significantly better RMPFST up to 6 months compared to standard treatment, although without a significant impact on OS., Competing Interests: None

Background and study aims  Indeterminate biliary strictures represent a major challenge in clinical diagnostics. Diagnostic yield of radiological, endoscopic imaging and histopathological diagnosis is insufficient. The cryobiopsy technique is a new method for tissue extraction already used in different clinical settings. The aim of this ex vivo clinical study was to investigate feasibility and tissue quality of cryobiopsy in the bile duct. Patients and methods  We included 14 patients who underwent pancreaticoduodenectomy. Bile duct samples were taken with either a new prototype cryoprobe or one of two forceps types. Results were analyzed for general feasibility, specimen size, histological assessability as well as representativity of retrieved tissue. Results  Feasibility of cholangioscopic forceps was poor compared to gastric biopsy forceps or cryobiopsy. Significantly larger tissue samples were obtained with cryobiopsy (5.6 ± 4.5 mm 2 ) compared to gastric biopsy forceps (3.3 ± 5.1 mm 2 , P  = 0.006). Furthermore, cryobiopsy was superior in histological assessment quality ( P  = 0.02) and concerning representativity ( P  = 0.03). Conclusions  Cryobiopsy in the bile duct is feasible and the quality of the obtained tissue is high. Further investigation of bile duct cryobiopsy in vivo is warranted., Competing Interests: Competing interests The co-authors Walter Linzenbold and Markus Enderle are employees of ERBE Elektromedizin GmbH, Tuebingen, Germany. Cryoprobes were provided by ERBE Elektromedizin GmbH, Tuebingen, Germany. All other authors have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

(1) Development of radiofrequency ablation (RFA) systems for pulmonary lesions is restricted by availability of human tumor specimens and limited comparability of animal tissue. We aimed to develop a new surrogate tissue overcoming these drawbacks. (2) Reference values for electrical impedance in lung tumor tissue were collected during routine lung tumor RFA (n = 10). Subsequently, a tissue-mimicking surrogate with comparable electrical impedance and facilitating detection of the ablation margins was developed. (3) The mean electrical impedance for all patients was 103.5 ± 14.7 Ω. In the optimized surrogate tissue model consisting of 68% agar solution, 23% egg yolk, 9% thermochromic ink, and variable amounts of sodium chloride, the mean electrical impedance was adjustable from 74.3 ± 0.4 Ω to 183.2 ± 5.6 Ω and was a function (y = 368.4x + 175.2; R2 = 0.96; p < 0.001) of sodium chloride concentration (between 0 and 0.3%). The surrogate tissue achieved sufficient dimensional stability, and sample cuts revealed clear margins of color change for temperatures higher 60 °C. (4) The tissue-mimicking surrogate can be adapted to lung tumor with respect to its electrical properties. As the surrogate tissue allows for simple and cost-effective manufacturing, it is suitable for extensive laboratory testing of RFA systems for pulmonary ablation.

Objective: The quality of histopathological specimens obtained from the upper urinary tract with conventional flexible ureterorenoscopic biopsy needs to be improved. We investigated the feasibility and biopsy quality of specimens obtained by cryobiopsy, compared with standard ureterorenoscopic biopsy techniques in a human ex vivo model., Materials and Methods: Human ureters obtained from nephrectomy specimens (N=12) were dissected and canulated with an ureteral access sheath. Ureterorenoscopic biopsies were randomly obtained from different sites of the renal pelvic caliceal system using different types of instruments. The performance of two newly developed flexible cryoprobes with outer diameters of 1.1 mm (CB11) and 0.9 mm (CB09) was compared with that of the biopsy forceps(FB) and Bigopsy®(BiG) and two different Dormia baskets N-Gage (NG) and Zero-Tip (ZT). We assessed the feasibility of the various biopsy techniques based on the number of biopsy attempts needed to obtain macroscopically discernible biopsies. The specimens were examined histopathologically for size, biopsy quality, presence of various artifact types, and representativeness., Results: Biopsies taken with the cryoprobes showed a higher biopsy quality than biopsies taken with the comparative instruments. The CB11 provided significantly larger biopsies than forceps biopsies and also than biopsies with ZT. The CB09 was able to collect larger samples when compared with the FB and BiG biopsy forceps. There were no significant differences in artifact area, except for the CB11 cryoprobe compared with the NG. To clarify the results a subdivision of larger or smaller than 20% artifact area was performed. A significant difference was found between CB11 and the forceps biopsies, as well as between CB11 and NG and ZT in favor of the cryoprobe. The representation of the histopathological sample was also determined. Biopsies taken with CB11 were more representative compared with forceps biopsies BiG and FB and basket biopsies NG and ZT., Conclusions: In a standardized comparative ex vivo setting, larger biopsies were obtained by using the cryobiopsy technique with the CB11 probe. Qualitatively, cryobiopsy specimens were overlaid by fewer artifacts and a higher biopsy quality was achieved in histopathologic examination compared with standard instrumentation. Further stepwise development will transfer the promising cryobiopsy technique into the clinical setting., Competing Interests: ME and WL are employed by Erbe Elektromedizin GmbH, Tuebingen Germany. The remaining 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 © 2022 Klein, John, Bohnert, Enderle, Linzenbold and Bolenz.)

Current regimen to treat patients suffering from stress urinary incontinence often seems not to yield satisfactory improvement or may come with severe side effects. To overcome these hurdles, preclinical studies and clinical feasibility studies explored the potential of cell therapies successfully and raised high hopes for better outcome. However, other studies were rather disappointing. We therefore developed a novel cell injection technology to deliver viable cells in the urethral sphincter complex by waterjet instead of using injection needles. We hypothesized that the risk of tissue injury and loss of cells could be reduced by a needle-free injection technology. Muscle-derived cells were obtained from young male piglets and characterized. Upon expansion and fluorescent labeling, cells were injected into cadaveric tissue samples by either waterjet or injection needle. In other experiments, labeled cells were injected by waterjet in the urethra of living pigs and incubated for up to 7 days of follow-up. The analyses documented that the cells injected by waterjet in vitro were viable and proliferated well. Upon injection in live animals, cells appeared undamaged, showed defined cellular somata with distinct nuclei, and contained intact chromosomal DNA. Most importantly, by in vivo waterjet injections, a significantly wider cell distribution was observed when compared with needle injections ( P < .05, n ≥ 12 samples). The success rates of waterjet cell application in living animals were significantly higher (≥95%, n = 24) when compared with needle injections, and the injection depth of cells in the urethra could be adapted to the need by adjusting waterjet pressures. We conclude that the novel waterjet technology injects viable muscle cells in tissues at distinct and predetermined depth depending on the injection pressure employed. After waterjet injection, loss of cells by full penetration or injury of the tissue targeted was reduced significantly in comparison with our previous studies employing needle injections.

Urinary incontinence (UI) is a highly prevalent condition characterized by the deficiency of the urethral sphincter muscle. Regenerative medicine branches, particularly cell therapy, are novel approaches to improve and restore the urethral sphincter function. Even though injection of active functional cells is routinely performed in clinical settings by needle and syringe, these approaches have significant disadvantages and limitations. In this context, needle-free waterjet (WJ) technology is a feasible and innovative method that can inject viable cells by visual guided cystoscopy in the urethral sphincter. In the present study, we used WJ to deliver porcine adipose tissue-derived stromal cells (pADSCs) into cadaveric urethral tissue and subsequently investigated the effect of WJ delivery on cell yield and viability. We also assessed the biomechanical features (i.e., elasticity) by atomic force microscopy (AFM) measurements. We showed that WJ delivered pADSCs were significantly reduced in their cellular elasticity. The viability was significantly lower compared to controls but is still above 80%.

Endoscopic ultrasound-ablation with HybridTherm-Probe (EUS-HTP) significantly reduces tumour volume (TV) in locally-advanced pancreatic ductal adenocarcinoma (LA-PDAC). We aimed at investigating the clinical efficacy of EUS-HTP plus chemotherapy versus chemotherapy (HTP-CT and CT arms) in LA- and borderline-resectable (BR) PDAC, with 6-months progression-free survival (6-PFS) rate as primary endpoint. In a phase-II randomized-controlled-trial, 33 LA/BR-PDAC patients per-arm were planned to verify 20% improved 6-PFS rate. Radiological response (Choi criteria), TV and serum CA19.9 were assessed up to 6-months. Seventeen and 20 LA/BR-PDAC patients were randomized to HTP-CT or CT. Baseline and CT-related features were balanced. At 6-months, 6-PFS rate was 41.2% and 30% in HTP-CT and CT arms ( p = 0.48), respectively. A decrease ≥50% of serum CA19.9 was achieved in 75% and 64.3% of HTP-CT and CT patients ( p = 0.53), respectively. TV reduced up to 6-months in 64.3% and 47.1% of HTP-CT and CT patients ( p = 0.35), respectively. Resection rate, PFS-time and overall survival (OS-time) were similar. HTP-CT achieves a non-significant 11.2%, 10.7% and 17.2% improved 6-PFS, CA19.9 decrease ≥50% and TV reduction rates over CT, without any impact on resection rate, PFS-time and OS-time. As the study was underpowered, these results suggest further investigation of EUS-local ablation in selected patients with localized disease after induction CT.

We noted recently that the injection of cells with a needle through a cystoscope in the urethral sphincter muscle of pigs failed to deposit them nearby or at the intended target position in about 50% of all animals investigated ( n > 100). Increasing the chance for precise cell injection by shotgun approaches employing several circumferential injections into the sphincter muscle bears the risk of tissue injury. In this study, we developed and tested a novel needle-free technique to precisely inject cells in the urethral sphincter tissue, or other tissues, using a water-jet system. This system was designed to fit in the working channels of endoscopes and cystoscopes, allowing a wide range of minimally invasive applications. We analyze key features, including the physical parameters of the injector design, pressure ranges applicable for tissue penetration and cell injections and biochemical parameters, such as different compositions of injection media. Our results present settings that enable the high viability of cells post-injection. Lastly, the method is suitable to inject cells in the superficial tissue layer and in deeper layers, required when the submucosa or the sphincter muscle of the urethra is targeted.

Previously, we developed a novel, needle-free waterjet (WJ) technology capable of injecting viable cells by visual guided cystoscopy in the urethral sphincter. In the present study, we aimed to investigate the effect of WJ technology on cell viability, surface markers, differentiation and attachment capabilities, and biomechanical features. Porcine adipose tissue-derived stromal cells (pADSCs) were isolated, expanded, and injected by WJ technology. Cell attachment assays were employed to investigate cell-matrix interactions. Cell surface molecules were analyzed by flow cytometry. Cells injected by Williams Needle (WN), normal cannula, or not injected cells served as controls. Biomechanical properties were assessed by atomic force microscopy (AFM). pADSCs injected by the WJ were viable (85.9%), proliferated well, and maintained their in vitro adipogenic and osteogenic differentiation capacities. The attachment of pADSCs was not affected by WJ injection and no major changes were noted for cell surface markers. AFM measurements yielded a significant reduction of cellular stiffness after WJ injections ( p < 0.001). WJ cell delivery satisfies several key considerations required in a clinical context, including the fast, simple, and reproducible delivery of viable cells. However, the optimization of the WJ device may be necessary to further reduce the effects on the biomechanical properties of cells.

Objectives: To investigate the therapy of stress urinary incontinence in a preclinical setting cells were injected into the urethrae of minipigs; however, cells injected by William's needle were frequently misplaced or lost; thus, we investigated if needle-free cell injections using a novel waterjet technology facilitates precise injections in the urethral sphincter complex., Materials and Methods: Porcine adipose tissue-derived stromal cells (pADSCs) were isolated from boars, expanded, labelled, and injected in the sphincter of female pigs by waterjet employing two different protocols. After incubation for 15 min or 3 days, the urethrae of the pigs were examined. Injected cells were visualised by imaging and fluorescence microscopy of tissue sections. DNA of injected male cells was verified by polymerase chain reaction (PCR) of the sex-determining region (SRY) gene. Cell injections by William's needle served as controls., Results: The new waterjet technology delivered pADSCs faster and with better on-site precision than the needle injections. Bleeding during or after waterjet injection or other adverse effects, such as swelling or urinary retention, were not observed. Morphologically intact pADSCs were detected in the urethrae of all pigs treated by waterjet. SRY-PCR of chromosomal DNA and detection of recombinant green fluorescent protein verified the injection of viable cells. In contrast, three of four pigs injected by William's needle displayed no or misplaced cells., Conclusion: Transurethral injection of viable pADSCs by waterjet is a simple, fast, precise, and yet gentle new technology. This is the first proof-of-principle concept study providing evidence that a waterjet injects intact cells exactly in the tissue targeted in a preclinical in vivo situation. To further explore the clinical potential of the waterjet technology longer follow-up, as well as incontinence models have to be studied., (© 2020 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

The reprogramming of patient´s somatic cells into induced pluripotent stem cells (iPSCs) and the consecutive differentiation into cardiomyocytes enables new options for the treatment of infarcted myocardium. In this study, the applicability of a hydrojet-based method to deliver footprint-free iPSC-derived cardiomyocytes into the myocardium was analyzed. A new hydrojet system enabling a rapid and accurate change between high tissue penetration pressures and low cell injection pressures was developed. Iron oxide-coated microparticles were ex vivo injected into porcine hearts to establish the application parameters and the distribution was analyzed using magnetic resonance imaging. The influence of different hydrojet pressure settings on the viability of cardiomyocytes was analyzed. Subsequently, cardiomyocytes were delivered into the porcine myocardium and analyzed by an in vivo imaging system. The delivery of microparticles or cardiomyocytes into porcine myocardium resulted in a widespread three-dimensional distribution. In vitro, 7 days post-injection, only cardiomyocytes applied with a hydrojet pressure setting of E20 (79.57 ± 1.44%) showed a significantly reduced cell viability in comparison to the cells applied with 27G needle (98.35 ± 5.15%). Furthermore, significantly less undesired distribution of the cells via blood vessels was detected compared to 27G needle injection. This study demonstrated the applicability of the hydrojet-based method for the intramyocardial delivery of iPSC-derived cardiomyocytes. The efficient delivery of cardiomyocytes into infarcted myocardium could significantly improve the regeneration.

Background and study aims  Endoscopic ultrasound (EUS)-guided ablation of pancreatic ductal adenocarcinoma (PDAC) with HybridTherm-Probe (EUS-HTP) is feasible and safe, but the radiological response and ideal tool to measure it have not been investigated yet. The aims of this study were to: 1) assess the radiological response to EUS-HTP evaluating the vital tumor volume reduction rate, Response Evaluation Criteria in Solid Tumors (RECIST1.1) and Choi criteria; 2) determine the prognostic predictive yield of these criteria. Patients and methods  A retrospective analysis was performed of patients with locally advanced PDAC after primary treatment or unfit for chemotherapy prospectively treated by EUS-HTP. Computed tomography scan was performed 1 month after EUS-HTP to evaluate: 1) vital tumor volume reduction rate (VTVRR) by measuring necrosis and tumor volumes through a computer-aided detection system; and 2) RECIST1.1 and Choi criteria. Results  EUS-HTP was feasible in 22 of 31 patients (71 %), with no severe adverse events. Median post-HTP survival was 7 months (1 - 35). Compared to pre-HTP tumor volume, a significant 1-month VTVRR (mean 21.4 %) was observed after EUS-HTP ( P  = 0.005). We identified through ROC analysis a VTVRR > 11.46 % as the best cut-off to determine post-HTP 6-month survival outcome (AUC = 0.733; sensitivity = 70.0 %, specificity = 83.3 %). This cut-off was significantly associated with longer overall survival (HR = 0.372; P  = 0.039). According to RECIST1.1 and Choi criteria, good responders to EUS-HTP were 60 % and 46.7 %, respectively. Good responders according to Choi, but not to RECIST1.1, had longer survival (HR = 0.407; P  = 0.04). Conclusions  EUS-HTP induces a significant 1-month VTVRR. This effect is assessed accurately by evaluation of necrosis and tumor volumes. Use of VTVRR and Choi criteria, but not RECIST 1.1 criteria, might identify patients who could benefit clinically from EUS-HTP., Competing Interests: Competing interests Prof. M. Enderle and Dr. W. Linzenbold are employees of the research department of Erbe Elektromedizin GmbH, Tubingen, Germany., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Aims: In a recent preclinical study, we noticed that injection of cells in the urethral sphincter by needle through a cystoscope under visual control frequently yielded in misplacement or loss of cells. We, therefore, investigated if a needle-free waterjet device delivers viable cells under defined settings, including injection volume and pressure, fluid velocity and transportation media, precisely through the urothelium and connective tissue close to the sphincter muscle without full penetration of the sphincter apparatus., Methods: Mesenchymal stromal cells (MSCs) were prepared for needle-free waterjet injections. Upon injections into liquids cell viability and yield were investigated by trypan blue dye exclusion. Upon injection into cadaveric urethral tissue samples, cells were isolated from the urethrae and expanded to prove that this novel method delivered viable cells into the tissue. MSC injections by William's needle served as controls., Results: Waterjet injections of MSCs into isotonic cell culture medium resulted in equal or better yields of viable cells when compared with needle injections. Upon injection in urethral tissue samples, the waterjet technology facilitated fast and precise injections of viable cells through urothelial, mucosal and submucosal layers to reach the sphincter muscle. By controlling the injection pressure, loss of cells due to insufficient thrust or unintended full penetration was avoided., Conclusions: Needle-free waterjet injections deliver cells in the urethra faster and more precisely when compared with needle injections without compromising their viability. This is the first proof-of-concept study providing evidence that a waterjet transports viable cells precisely into the targeted tissue., (© 2109 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.)

Background: Forceps biopsy (FB) is still the most popular procedure for the bronchoscopic sampling of lung tissue. However, it has limitations like inadequate sample size and crush artifacts. Cryobiopsy (CB) has been introduced to obtain bronchoscopic biopsies with improved diagnostic yield compared to FB. Limitations of CB are the need to retract the cryoprobe en bloc with bronchoscope because samples are larger than the working channel and the variations of the freezing power of the reusable CB (rCB). Therefore, 3 new disposable cryoprobes (dCB) have been developed with different outer diameters: 1.1 mm (CB11-S) that can be retracted through the working channel of the bronchoscope, 1.7 mm (CB17) and 2.4 mm (CB24n), respectively., Objectives: The aim was to evaluate the new cryoprobes with regard to feasibility, specimen area, specimen quality and complications., Methods: We compared biopsy samples of the new probes with those obtained by FB and by rCB in an in vivo (porcine) model. A flexible bronchoscope was used to perform biopsy at 4 different locations at the upper and lower lobes of the right and left lung, respectively. The biopsies were taken under fluoroscopic control. The biopsy tool and activation times were allocated randomly. Altogether 204 biopsy procedures were performed., Results: The sample quality of the dCB was superior to that of FB (all p < 0.05) and not significantly different to the rCB sample quality. Mean specimen sample area of all CB was significantly larger compared to FB (p < 0.05). The sample area of the small cryoprobe (CB11-S) was significantly smaller compared to the other CB probes (p < 0.05). No severe bleedings occurred. Pneumothoraces were detected in 3 of the 7 pigs., Conclusion: We conclude that CB with the new single-use instruments are feasible and represent a viable option to improve the diagnostic accuracy of histopathological evaluation compared to FB., (© 2020 S. Karger AG, Basel.)

Objective: To develop a novel device for cryobiopsy of the upper urinary tract (UUT) and to evaluate its feasibility in a standardized preclinical setting., Materials and Methods: Flexible cryoprobes (diameter 0.9 mm; cooling agent CO2) were developed and used to extract biopsies in porcine UUTs. Cryosamples obtained by ureterorenoscopy were systematically compared with biopsy specimens obtained with standard of care devices in terms of physical characteristics (deflection angle and irrigation flow rates) and histologic criteria (assessability)., Results: Irrigation flow rates were significantly higher with introduced BIGopsy (2.8 ± 0.1) compared with standard forceps (0.94 ± 0.06; P < .001) and cryoprobe (1.1 ± 0.1; P < .001). Angular deflection was significantly reduced by the inserted cryoprobe (130.7° ± 1.2° vs 166.9° ± 1.1° [BIGopsy] or 161.4° ± 1.9° [standard forceps]; both P < .001). Significantly larger UUT tissue samples were obtained by the cryoprobe (mean specimen area 7.5 ± 2.5 vs 4.6 ± 2.5 mm² [BIGopsy] or 1.4 ± 1.4 mm² [standard forceps]; both P < .001). No crush artifacts were observed in cryosamples. Superior histologic assessability scores were achieved in samples obtained by the cryoprobe (mean 2.8 ± 0.8) and BIGopsy (2.3 ± 1.9) when compared with standard forceps (0.4 ± 0.9; P < .001)., Conclusion: Cryobiopsy in the UUT is feasible and represents a viable new option to improve the diagnostic accuracy of histopathologic evaluation. Larger and more representative tissue samples can be obtained using a cryoprobe and artifacts may be avoided. Further optimization of the probe will reduce possible restrictions of ureterorenoscopy handling when the device is inserted., (Copyright © 2018. Published by Elsevier Inc.)

Background: Bipolar vessel sealing has been successfully introduced in a variety of procedures like prostatectomy, hysterectomy, and nephrectomy. In this study, we evaluated a new sealing mode-the thermoSEAL ® mode (TSM)-operated with the VIO3 generator in an ex vivo and in vivo animal study and compared the results with the commercially available BiClamp mode (BCM), operated with the VIO300D generator. Two different instruments were used in combination with both modes, BiCision ® and BiClamp ® 201T (Erbe Elektromedizin GmbH)., Methods: In the ex vivo experiment, the sealing of renal arteries was evaluated using both instruments and modes. For the in vivo study, different types of arteries and veins were sealed using both modes and instruments in a side-by-side comparison for acute complications in a total of four animals., Results: Mean burst pressure was in all cases significantly above 360 mmHg (p < 0.001). Sealing time during the ex vivo setting was significantly shorter for TSM compared to BCM: BiCision ® (3.7 ± 0.4 vs. 7.1 ± 0.3 s; p < 0.0001); BiClamp ® 201T (3.9 ± 0.3 vs. 5.1 ± 1.1 s; p < 0.0015). Lateral thermal damage was more pronounced for BCM: BiCision ® (TSM 1.4 ± 0.3 mm vs. BCM 1.9 ± 0.2 mm; p < 0.0001); BiClamp ® 201T (TSM 1.9 ± 0.6 mm vs. BCM 3.1 ± 0.6 mm; p < 0.0001). The sealing time during the in vivo study was significantly shorter for TSM in combination with BiCision ® for arteries [TSM 3.0 ± 0.7 s vs. BCM 6.5 ± 1.3 s, (p < 0.0001) and veins 3.2 ± 1.1 vs. 5.8 ± 1.8 s, (p < 0.0001)]. No significant differences were seen for the two modes used with BiClamp ® 201T [artery: TSM 3.3 ± 0.7 s vs. BCM 3.4 ± 0.9 s, (p = 0.891)]. High sealing rates for arteries (100%) and veins (>90%) were noted for both instruments and modes., Conclusions: While both modes used with two different instruments reveal high safety characterized by a high burst pressure, low thermal damage (ex vivo) zones, and high sealing rates (in vivo), the thermoSEAL ® mode convinces by its fast sealing speed probably helping to reduce operation time.

Background: Transbronchial cryobiopsy (TBCB) is a minimally invasive procedure to establish a diagnosis of interstitial lung disease though with the disadvantage that samples have to be extracted together with the bronchoscope., Objectives: The aim of the present study was to evaluate the feasibility of a new cryoprobe with which biopsy samples can be obtained through the working channel of the flexible bronchoscope., Methods: The feasibility of obtaining transbronchial specimens with TBCB was tested and the technique was compared to transbronchial forceps biopsy (TBFB) in a prospectively randomized ex vivo animal study using a standard flexible bronchoscopy technique. The rate of successful biopsies and the duration of the sampling procedure were recorded for both methods. Size and quality of the biopsies were histologically evaluated and measured., Results: Biopsy samples could be obtained in 93.3% of TBCB and in 79.0% of TBFB procedures (p = 0.182). Sampling procedure time did not differ in any clinically relevant manner between the two methods. The mean specimen area of TBCB samples was significantly higher compared to that of TBFB samples (8.08 ± 5.80 vs. 2.61 ± 2.14 mm2; p < 0.0001). TBCB specimens showed less artifacts and a significantly higher percentage of alveolar tissue (53.57 vs. 25.42%; p = 0.0285) than TBFB specimens., Conclusions: It is feasible to retrieve TBCB samples of good quality and size with the new mini cryoprobe through the working channel of the bronchoscope, while the bronchoscope remains within the central airways throughout the whole procedure. Further studies are necessary to evaluate the safety and efficacy in an in vivo setting., (© 2016 S. Karger AG, Basel.)

Purpose: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard procedure for intrathoracic lymph node biopsies. The newly developed cryo-needle operates in a similar way to the EBUS-TBNA but is able to obtain specimens for histological evaluation. The purpose of this animal study was to evaluate the feasibility, effect, and safety of the cryo-needle biopsies., Methods: Four EBUS-guided cryo-needle biopsies were obtained from a mediastinal lymph node of a healthy pig. In an open surgery approach, cryo-needle biopsies using activation times of 1, 2, and 3 s (A1/A2/A3) and needle biopsies using a 21-gauge EBUS-TBNA needle were obtained from mesenteric lymph nodes. Cryo-needle biopsies A2 were performed with (A2+) and without (A2-) an oversheath. The size, weight, percentage of lymphatic tissue and artefact-free area of each cryobiopsy were evaluated. Smears were made with the TBNA-needle aspirates to determine the number of lymphocytes per high-power field (HPF). The bleeding duration was measured., Results: We successfully obtained EBUS-guided cryo-needle biopsies. The area and weight of the biopsies A3 and A2+ were significantly larger compared with A1 (1.7 ± 0.8 and 1.4 ± 0.3 vs. 0.9 ± 0.4 mm(2); 5.2 ± 2.4 and 3.4 ± 1.8 vs. 1.5 ± 0.7 mg). The percentage of lymphatic tissue of the cryobiopsies was 90 ± 25 and 98 % of samples were artefact-free. The number of lymphocytes/HPF of TBNA-needle smears was 128 ± 54.3. There was no difference in bleeding duration between the techniques., Conclusions: The cryo-needle yields large histological specimens of high quality.

Electrophysiological and micro-stimulation studies in non-human animal species indicated that the superior colliculus (SC) plays a role in the control of upper limb movements. In our previous work we found reach-related signals in the deep superior colliculus in humans. Here we show that also signals in more dorsal locations are correlated with the execution of arm movements. We instructed healthy participants to reach for visual targets either presented in the left or in the right visual hemifield during an fMRI measurement. Visual stimulation was dissociated from movement execution using a pro- and anti-reaching task. Thereby, we successfully differentiated between signals at these locations induced by the visual input of target presentations on the one hand and by the execution of arm movements on the other hand. Extending our previous report, the results of this study are in good agreement with the observed anatomical distribution of reach-related neurons in macaques. Obviously, reach-related signals can be found across a considerable depth range also in humans., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The cortical systems involved in eye movement control in humans have been investigated extensively using fMRI. In contrast, there is virtually no data concerning the functional status of the human oculomotor brainstem nuclei. This lack of evidence has usually been explained by technical constraints of EPI based imaging and anatomical characteristics of the brainstem. Against this assumption, we successfully localised nuclei of the oculomotor system using high-resolution fMRI based on standard EPI sequences in a group of healthy subjects executing reflexive horizontal saccades. A random-effects group analysis revealed task-related BOLD increases in the superior colliculus, the oculomotor nucleus, the abducens nucleus and in the paramedian pontine reticular formation. This group analysis was complemented by individual positive findings in up to 94% of single subject analyses. A visual control paradigm led to increased signal levels in the superior colliculus consistent with its visual properties but no corresponding signal changes in other brainstem nuclei. These results are consistent with findings in animal studies and demonstrate the feasibility to detect BOLD signal increases associated with oculomotor tasks even in the human brainstem using conventional EPI imaging techniques., (Copyright © 2011 Elsevier Inc. All rights reserved.)