Improving detection of carcinoma in situ in bladder cancer: urinary cytology vs the Xpert® BC Monitor.

OBJECTIVE: To investigate and compare the performance of urinary cytology and the Xpert BC Monitor test in the detection of bladder cancer in various clinically significant patient cohorts, including patients with carcinoma in situ (CIS), in a prospective multicentre setting, aiming to identify potential applications in clinical practice. PATIENTS AND METHODS: A total of 756 patients scheduled for transurethral resection of bladder tumour (TURBT) were prospectively screened between July 2018 and December 2020 at six German University Centres. Central urinary cytology and Xpert BC Monitor tests were performed prior to TURBT. The diagnostic performance of urinary cytology and the Xpert BC Monitor was evaluated according to sensitivity (SN), specificity (SC), negative predictive value (NPV) and positive predictive value (PPV). Statistical comparison of urinary cytology and the Xpert BC Monitor was conducted using the McNemar test. RESULTS: Of 756 screened patients, 733 (568 male [78%]; median [interquartile range] age 72 [62-79] years) were included. Bladder cancer was present in 482 patients (65.8%) with 258 (53.5%) high-grade tumours. Overall SN, SC, NPV and PPV were 39%, 93%, 44% and 92% for urinary cytology, and 75%, 69%, 59% and 82% for the Xpert BC Monitor. In patients with CIS (concomitant or solitary), SN, SC, NPV and PPV were 59%, 93%, 87% and 50% for urinary cytology, and 90%, 69%, 95% and 50% for the Xpert BC Monitor. The Xpert BC Monitor missed four tumours (NPV = 98%) in patients with solitary CIS, while potentially avoiding 63.3% of TURBTs in inconclusive or negative cystoscopy and a negative Xpert result. CONCLUSION: Positive urinary cytology may indicate bladder cancer and should be taken seriously. The Xpert BC Monitor may represent a useful diagnostic tool for correctly identifying patients with solitary CIS and unsuspicious or inconclusive cystoscopy.

Ureteroplasty with buccal mucosa graft without omental wrap: an effective method to treat ureteral strictures.

PURPOSE: Successful treatment options for ureteral strictures are limited. Surgical options such as ileal interposition and kidney autotransplantation are difficult and associated with morbidity and complications. Techniques such as Boari flap and psoas hitch are limited to distal strictures. Only limited case studies on the success of open buccal mucosa graft (BMG) ureteroplasty exist to this date. The purpose of this study was to evaluate the success of open BMG ureteroplasty without omental wrap. METHODS: In this single-center retrospective study between July 2020 and January 2023, we included 14 consecutive patients with ureteric strictures who were treated with open BMG ureteroplasty without omental wrap. The primary outcome was the success of open BMG ureteroplasty. Further endpoints were complications and hospital readmission. Outcome variables were assessed by clinical examination, kidney sonography, and patient anamnesis. RESULTS: Out of 14 patients, 13 were stricture and ectasia-free without a double-J stent at a median follow-up of 15 months (success rate 93%). No complications were observed at the donor site, and the complication rate overall was low with 3 out of 14 patients (21%) having mild-to-medium complications. CONCLUSIONS: Open BMG ureteroplasty without omental wrap is a successful and feasible technique for ureteric stricture repair.

A novel grading approach predicts worse outcomes in stage pT1 non-muscle-invasive bladder cancer.

OBJECTIVE: To develop a prognostically relevant scoring system for stage pT1 non-muscle-invasive bladder cancer (NMIBC) incorporating tumour budding, growth pattern and invasion pattern because the World Health Organisation grading system shows limited prognostic value in such patients. PATIENTS AND METHODS: The tissue specimens and clinical data of 113 patients with stage pT1 NMIBC who underwent transurethral resection of bladder tumour were retrospectively investigated. Tumour budding, and growth and invasion patterns were evaluated and categorised into two grade groups (GGs). GGs and other clinical and histopathological variables were investigated regarding recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS) using univariable and multivariable Cox regression analyses. RESULTS: The integration of two tumour budding groups, two growth patterns, and two invasion patterns yielded an unfavourable GG (n = 28; 24.7%) that had a high impact on oncological outcomes. The unfavourable GG was identified as an independent RFS and OS predictor (P = 0.004 and P = 0.046, respectively) and linked to worse PFS (P = 0.001) and CSS (P = 0.001), irrespective of the European Association of Urology risk group. The unfavourable GG was associated with higher rates of BCG-unresponsive tumours (P = 0.006). Study limitations include the retrospective, single-centre design, diverse therapies and small cohort. CONCLUSIONS: We present a morphology-based grading system for stage pT1 NMIBC that correlates with disease aggressiveness and oncological patient outcomes. It therefore identifies a highest risk group of stage pT1 NMIBC patients, who should be followed up more intensively or receive immediate radical cystectomy. The grading incorporates objective variables assessable on haematoxylin and eosin slides and immunohistochemistry, enabling an easy-to-use low-cost approach that is applicable in daily routine. Further studies are needed to validate and confirm these results.

Xpert bladder cancer monitor to predict the need for a second TURB (MoniTURB trial).

To determine whether Xpert bladder cancer monitor, a noninvasive PCR-based biomarker test, can predict the need for 2nd transurethral resection of the bladder (TURB) better than clinical assessment. Patients scheduled for TURB were prospectively screened. After initial TURB, patients were assigned to 2nd TURB or follow-up cystoscopy at 3 months (FU) by clinicians' discretion. Central urine cytology and Xpert monitor tests were performed prior to the 1st TURB and 2nd TURB or FU, respectively. Statistical analysis to compare clinical assessment and Xpert monitor comprised sensitivity (SENS), specificity (SPEC), NPV and PPV. Of 756 screened patients, 171 were included (114 with 2nd TURB, 57 with FU). Residual tumors were detected in 34 patients who underwent 2nd TURB, and recurrent tumors were detected in 2 patients with FU. SENS and SPEC of Xpert monitor were 83.3% and 53.0%, respectively, PPV was 32.6% and NPV was 92.1%. Clinical risk assessment outperformed Xpert monitor. In patients with pTa disease at initial TURB, Xpert monitor revealed a NPV of 96%. Xpert monitor was not superior than clinical assessment in predicting the need for 2nd TURB. It might be an option to omit 2nd TURB for selected patients with pTa disease.

The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension.

Human WIPI ß-propellers function as PI3P effectors in autophagy, with WIPI4 and WIPI3 being able to link autophagy control by AMPK and TORC1 to the formation of autophagosomes. WIPI1, instead, assists WIPI2 in efficiently recruiting the ATG16L1 complex at the nascent autophagosome, which in turn promotes lipidation of LC3/GABARAP and autophagosome maturation. However, the specific role of WIPI1 and its regulation are unknown. Here, we discovered the ABL-ERK-MYC signalling axis controlling WIPI1. As a result of this signalling, MYC binds to the WIPI1 promoter and represses WIPI1 gene expression. When ABL-ERK-MYC signalling is counteracted, increased WIPI1 gene expression enhances the formation of autophagic membranes capable of migrating through tunnelling nanotubes to neighbouring cells with low autophagic activity. ABL-regulated WIPI1 function is relevant to lifespan control, as ABL deficiency in C. elegans increased gene expression of the WIPI1 orthologue ATG-18 and prolonged lifespan in a manner dependent on ATG-18. We propose that WIPI1 acts as an enhancer of autophagy that is physiologically relevant for regulating the level of autophagic activity over the lifespan.

Risk factors for bladder neck contracture after transurethral resection of the prostate.

INTRODUCTION: Transurethral resection of the prostate (TURP) is the most frequently used treatment of benign prostate hyperplasia with a prostate volume of <80 mL. A long-term complication is bladder neck contracture (BNC). The aim of the present study was to identify the risk factors for BNC formation after TURP. METHODS: We conducted a retrospective analysis of all TURP primary procedures which were performed at one academic institution between 2013 and 2018. All patients were analyzed and compared with regard to postoperative formation of a BNC requiring further therapy. Uni- and multivariable logistic regression analyses (MVAs) were performed to identify possible risk factors for BNC development. RESULTS: We included 1368 patients in this analysis. Out of these, 88 patients (6.4%) developed BNC requiring further surgical therapy. The following factors showed a statistically significant association with BNC development: smaller preoperative prostate volume (p = 0.001), lower resected prostate weight (p = 0.004), lower preoperative levels of prostate-specific antigen (PSA, p < 0.001), shorter duration of the surgery (p = 0.027), secondary transurethral intervention (due to urinary retention or gross hematuria) during inpatient stay (p = 0.018), positive (≥100 CFU/mL) preoperative urine culture (p = 0.010), and urethral stricture (US) formation requiring direct visual internal urethrotomy (DVIU) postoperatively after TURP (p < 0.001), in particular membranous (p = 0.046) and bulbar (p < 0.001) strictures. Preoperative antibiotic treatment showed a protective effect (p = 0.042). Histopathological findings of prostate cancer (PCA) in the resected prostate tissue were more frequent among patients who did not develop BNC (p = 0.049). On MVA, smaller preoperative prostate volume (p = 0.046), positive preoperative urine culture (p = 0.021), and US requiring DVIU after TURP (p < 0.001) were identified as independent predictors for BNC development. CONCLUSION: BNC is a relevant long-term complication after TURP. In particular, patients with a smaller prostate should be thoroughly informed about this complication.

Body Composition of Patients Undergoing Radical Cystectomy for Bladder Cancer: Sarcopenia, Low Psoas Muscle Index, and Myosteatosis Are Independent Risk Factors for Mortality.

BACKGROUND: We assessed a wide array of body composition parameters to identify those most relevant as prognostic tools for patients undergoing radical cystectomy (RC) due to bladder cancer (BC). METHODS: In this retrospective, single-center study, preoperative computed tomography (CT) scans of 657 patients were measured at the level of the 3rd lumbar vertebra (L3) to determine common body composition indices including sarcopenia, myosteatosis, psoas muscle index (PMI), subcutaneous and visceral fat index (SFI and VFI), visceral-to-subcutaneous fat ratio (VSR), and visceral obesity. Predictors of overall survival (OS) and cancer-specific survival (CSS) were identified in univariate and multivariate survival analysis. RESULTS: Sarcopenia and a low PMI were independently associated with shorter OS (Sarcopenia: HR 1.30; 95% CI 1.02-1.66; p = 0.04 and a low PMI: HR 1.32; 95% CI 1.02-1.70; p = 0.03) and CSS (Sarcopenia: HR 1.64; 95% CI 1.19-2.25; p < 0.01 and a low PMI: HR 1.41; 95% CI 1.02-1.96; p = 0.04). Myosteatosis, measured as decreasing average Hounsfield units of skeletal muscle, was an independent risk factor for OS (HR 0.98; 95% CI 0.97-1.00; p = 0.01) and CSS (HR 0.98; 95% CI 0.96-1.00; p < 0.05). The assessed adipose tissue indices were not significant predictors for OS and CSS. CONCLUSIONS: Sarcopenia, a low PMI, and myosteatosis are independent predictors for OS and CSS in patients undergoing radical cystectomy for bladder cancer.

Body Composition as a Comorbidity-Independent Predictor of Survival following Nephroureterectomy for Urothelial Cancer of the Upper Urinary Tract.

Radical nephroureterectomy (NUE) is the gold standard treatment for high-risk urothelial cancer of the upper urinary tract (UTUC). Besides sarcopenia and frailty, fat distribution is moving increasingly into focus. Components of body composition were assessed in patients undergoing NUE due to UTUC. The study cohort included 142 patients. By using CT-based measurements, the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured at the height of the third lumbar vertebra. Overall survival (OS) and cancer-specific survival (CSS) were estimated using univariable und multivariable Cox regression models. The prevalence of sarcopenia in the study population (n = 142) was 37%. OS and CSS were significantly reduced in sarcopenic patients. In the multivariable cox regression analysis, including age, ACE-27, T-stage, R-stage, LVI and necrosis, sarcopenia remained a significant risk factor of OS (HR, 1.77; 95% CI 1.02-3.07; p = 0.042) and CSS (HR, 2.17; 95% CI 1.18-3.99; p = 0.012). High visceral adipose tissue seems to be protective, although not statistically significant. Sarcopenia is a comorbidity-independent risk factor in patients who underwent NUE due to UTUC. Visceral fat represents a potentially protective factor. These results suggest that specific factors of body composition can be used for better risk stratification.

Short-Term and Long-Term Morbidity after Radical Cystectomy in Patients with NMIBC and Comparison with MIBC: Identifying Risk Factors for Severe Short-Term Complications.

INTRODUCTION: RC represents a viable treatment option for certain NMIBC patients. However, studies investigating morbidity in the context of RC for NMIBC are scarce. The goal of the current study was to assess and compare morbidity after RC performed in patients with NMIBC and patients with MIBC and to identify risk factors for severe short-term complications. METHODS: Medical records of 521 patients who underwent RC for bladder cancer were retrospectively reviewed. Patients were divided into patients with NMIBC and patients with MIBC. The groups were compared and risk factors for severe complications were identified. RESULTS: RC for NMIBC was performed in 123 patients (23.6%). Histological upstaging was seen in 47 NMIBC patients (38.2%) and in 231 MIBC patients (58%, p < 0.001). OS was 29.8% and CSS was 15.5%. Both endpoints were higher for RC for MIBC (p < 0.001). More complications affecting the urinary diversion were seen with RC for NMIBC (p = 0.033) and more continent urinary diversions (p = 0.040) were performed in those patients. Obesity (p = 0.008), a higher ASA score (p = 0.004), and preoperative medical drug anticoagulation (p = 0.025) were risk factors for severe short-term morbidity after both, RC for NMIBC and for MIBC. CONCLUSION: Patients who underwent RC for NMIBC are exposed to a comparably high perioperative risk than patients with MIBC. RC seems to be a viable treatment option for certain NMIBC patients with a significant histological upstaging in both groups. In patients with obesity, a high ASA score, and with medical drug anticoagulation, the indication for surgery should be confirmed especially strict and possible treatment alternatives should be considered particularly thorough.

The comprehensive complication index is associated with a significant increase in complication severity between 30 and 90 days after radical cystectomy for bladder cancer.

OBJECTIVE: To assess the true cumulative morbidity after RC by implementing the Comprehensive Complication Index (CCI) over a 90-day period, since recent evidence suggests underreporting of the cumulative morbidity after radical cystectomy (RC) with inconsistent complication rates when reported with conventional reporting systems. PATIENTS AND METHODS: Medical records of 433 patients with bladder cancer who underwent RC were retrospectively reviewed over a 90-day period. Clinical variables were assessed and complications were graded by the Clavien-Dindo Classification (CDC). The resulting 30- and 90-day CCI-scores were calculated and compared for each patient. Multivariable regression models for developing at least one severe (≥CDC IIIb) complication were designed. RESULTS: Overall, 848 complications were recorded in 371 patients (85.7%). Severe complications occurred in 130 patients (30%) and the cumulative morbidity corresponded to the level of a severe complication in 159 patients (36.7%), meaning an upgrade in 6.7% of patients compared to the CDC. The 90-day CCI (24.2 (median, IQR 20.9-39.7)) was higher than the 30-day CCI (22.6 (median, IQR 8.7-39.7)), (p < 0.001). Comorbidity indices (ASA, ACE 27), BMI, and incontinent urinary diversions were independent risk factors for suffering a severe complication within 90 days post-surgery. CONCLUSION: The cumulative morbidity (CCI) after RC seems to be higher than previously reported with CDC, especially over a 90-day period. The CCI is an appropriate assessment-tool with an upgrade in morbidity in a significant proportion of patients when compared to the CDC. BMI, several comorbidity indices, and incontinent urinary diversions are independent risk factors for suffering a severe complication after RC.

ΔN-Tp63 Mediates Wnt/ß-Catenin-Induced Inhibition of Differentiation in Basal Stem Cells of Mucociliary Epithelia.

Mucociliary epithelia provide a first line of defense against pathogens. Impaired regeneration and remodeling of mucociliary epithelia are associated with dysregulated Wnt/ß-catenin signaling in chronic airway diseases, but underlying mechanisms remain elusive, and studies yield seemingly contradicting results. Employing the Xenopus mucociliary epidermis, the mouse airway, and human airway Basal cells, we characterize the evolutionarily conserved roles of Wnt/ß-catenin signaling in vertebrates. In multiciliated cells, Wnt is required for cilia formation during differentiation. In Basal cells, Wnt prevents specification of epithelial cell types by activating ΔN-TP63, a master transcription factor, which is necessary and sufficient to mediate the Wnt-induced inhibition of specification and is required to retain Basal cells during development. Chronic Wnt activation leads to remodeling and Basal cell hyperplasia, which are reversible in vivo and in vitro, suggesting Wnt inhibition as a treatment option in chronic lung diseases. Our work provides important insights into mucociliary signaling, development, and disease.

Glenoid morphology is associated with the development of instability arthropathy.

BACKGROUND: Instability arthropathy (IA) is a major long-term concern in patients with anterior shoulder instability. This study investigated the association of glenoid morphology with the development of IA. METHODS: The study included 118 patients with unilateral anterior shoulder instability and available bilateral computed tomography scans. Instability-specific information was obtained from all patients. The glenoid morphology of the affected shoulder was compared with the nonaffected contralateral side resembling the constitutional preinjury glenoid shape. Both shoulders were evaluated independently by 3 observers to assess the grade of IA according to a Comprehensive Arthropathy Rating (CAR) system. Associations between IA and the glenoid morphology parameters were investigated. RESULTS: The average glenoid retroversion (P < .001), glenoid depth (P < .001), glenoid diameter (P < .001), and the bony shoulder stability ratio (P < .001) of the affected shoulder were significantly reduced compared with the contralateral side due to bony defects in 79.6% of the patients. The CAR of the affected side was significantly higher (P < .001), with more osteophytes (P = .001) and more sclerosis and cysts (P < .001). Differences in CAR (Δ-CAR) correlated positively with the age at the time of the computed tomography scan (P < .001), age at the initial dislocation (P = .001), size of the glenoid defect (P = .005), and the contralateral glenoid depth (P = .011), glenoid diameter (P = .016), and bony shoulder stability (P = .029), and negatively with glenoid retroversion of the affected side (P = .027). CONCLUSION: Development of IA arthropathy is associated not only with the age of the patients but also with morphologic parameters of the glenoid, including glenoid defect size and the constitutional glenoid concavity shape.

Na+/H+ Exchangers Are Required for the Development and Function of Vertebrate Mucociliary Epithelia.

Na+/H+ exchangers (NHEs) represent a highly conserved family of ion transporters that regulate pH homeostasis. NHEs as well as other proton transporters were previously linked to the regulation of the Wnt signaling pathway, cell polarity signaling, and mucociliary function. Furthermore, mutations in the gene SLC9A3 (encoding NHE3) were detected as additional risk factors for airway infections in cystic fibrosis patients. Here, we used the Xenopus embryonic mucociliary epidermis as well as human airway epithelial cells (HAECs) as models to investigate the functional roles of NHEs in mucociliary development and regeneration. In Xenopus embryos, NHEs 1-3 were expressed during epidermal development, and loss of NHE function impaired mucociliary clearance in tadpoles. Clearance defects were caused by reduced cilia formation, disrupted alignment of basal bodies in multiciliated cells (MCCs), and dysregulated mucociliary gene expression. These data also suggested that NHEs may contribute to the activation of Wnt signaling in mucociliary epithelia. In HAECs, pharmacological inhibition of NHE function also caused defective ciliation and regeneration in airway MCCs. Collectively, our data revealed a requirement for NHEs in vertebrate mucociliary epithelia and linked NHE activity to cilia formation and function in differentiating MCCs. Our results provide an entry point for the understanding of the contribution of NHEs to signaling, development, and pathogenesis in the human respiratory tract.

Clinical and Radiological Long-term Results After Implant-Free, Autologous, Iliac Crest Bone Graft Procedure for the Treatment of Anterior Shoulder Instability.

BACKGROUND: The implant-free, autologous, iliac crest bone graft procedure (J-bone graft) for the treatment of anterior shoulder instability shows low rates of recurrent dislocations and moderate progression of instability arthropathy in the midterm follow-up. PURPOSE: To analyze the clinical and radiological long-term results of the J-bone graft procedure. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 46 patients (47 shoulders) with anterior shoulder instability and a relevant bony glenoid defect who received a J-bone graft between 1993 and 2000 and who were previously subjected to a midterm follow-up (mean, 8 years) were included. In total, 34 patients and 35 shoulders (74%) were clinically and radiologically assessed after a mean follow-up of 18 years (range, 15-23 years). Patients were assessed in terms of pain, bilateral active range of motion, and strength; in addition, the Western Ontario Shoulder Instability Index (WOSI), the Rowe Score, and the Subjective Shoulder Value (SSV) were obtained. Both an apprehension test and a relocation test were performed. Radiological imaging included bilateral radiographs (true anteroposterior and axillary view) to determine the grade of instability arthropathy. RESULTS: At final follow-up, a mean WOSI score of 295 (range, 0-1765), Rowe Score of 94 (range, 55-100), SSV of 90% (range, 20%-100%), and pain level of 0.5 (range, 0-4) were noted. Slight differences were detected in active range of motion between the affected and the contralateral side: flexion 178° vs 179° ( P = .325), abduction 177° vs 179° ( P = .225), external rotation 63° vs 67° ( P = .048), high external rotation 77° vs 82° ( P = .007), internal rotation 8.8 vs 9.4 points ( P = .017), and high internal rotation 70° vs 74° ( P = .026). No significant strength deficit of the affected side was noticed. In 1 patient, a traumatic redislocation with fracture of the bone graft was observed 6 weeks after index surgery. No further recurrences were found during the follow-up period. Negative apprehension and relocation tests were confirmed in 77% of the shoulders, while 23% were positive. At final follow-up, 9 shoulders showed no signs of instability arthropathy (26%), mild arthropathy was revealed in 22 shoulders (63%), moderate arthropathy was noted in 3 shoulders (9%), and signs of severe arthropathy were found in 1 shoulder (3%) (collective instability arthropathy score, 0.9). The collective instability arthropathy score on the contralateral side was 0.4 ± 0.8 with no instability arthropathy in 24 shoulders (69%), mild arthropathy in 8 shoulders (23%), moderate signs of arthropathy in 2 shoulders (6%), and severe arthropathy in 1 shoulder (3%) at the time of follow-up examination (collective instability arthropathy score, 0.4). The overall difference between affected shoulders and contralateral shoulders was significant ( P = .005). CONCLUSION: The J-bone graft procedure for the treatment of recurrent anterior shoulder instability shows excellent results regarding stability and function after a mean follow-up period of 18 years. However, the development of instability arthropathy of the affected shoulder is not prevented by this procedure.

A prospective injury surveillance study in canyoning.

INTRODUCTION: Little is known about injuries in canyoning. It was the purpose of this study to determine injury rates, patterns, causes and risk factors in canyoning; and to identify targets for future injury prevention strategies. METHODS: From May to October 2015, 109 participants from 17 different countries were prospectively followed via a monthly e-mail-based questionnaire. RESULTS: During 13,690 h of canyoning, 57 injury-events occurred. The overall injury-rate was 4.2 injuries/1000 h of canyoning. The hand (23%) and lower leg and foot (25%) were most frequently involved. Most of the injuries were mild (n = 27, 49%) and limited to the soft-tissue. There were seven severe injuries (12%) with two lateral malleolar fractures, both necessitating surgery. The majority of injuries were due to material failure (44%) and significantly more injury-events were reported when the tour included rappelling (p = 0.037). Canyoning guides suffered from significantly less injuries compared to beginners and advanced canyoneers (p < 0.001). CONCLUSIONS: The majority of canyoning injuries are mild. On the other side, roughly one-tenth suffered from severe injury. Canyoning guides are less prone to injury-events and beginners should consider performing tours with experienced guides. Notwithstanding, rappelling was the most common activity associated with an injury and the material used was deemed causative for an injury-event in almost half of all cases. Further improvement in canyoning equipment, frequent equipment service, and instructional courses to ensure adequate employment of equipment might minimize the risk of getting injured.

Correlated MRI and Ultramicroscopy (MR-UM) of Brain Tumors Reveals Vast Heterogeneity of Tumor Infiltration and Neoangiogenesis in Preclinical Models and Human Disease.

Diffuse tumor infiltration into the adjacent parenchyma is an effective dissemination mechanism of brain tumors. We have previously developed correlated high field magnetic resonance imaging and ultramicroscopy (MR-UM) to study neonangiogenesis in a glioma model. In the present study we used MR-UM to investigate tumor infiltration and neoangiogenesis in a translational approach. We compare infiltration and neoangiogenesis patterns in four brain tumor models and the human disease: whereas the U87MG glioma model resembles brain metastases with an encapsulated growth and extensive neoangiogenesis, S24 experimental gliomas mimic IDH1 wildtype glioblastomas, exhibiting infiltration into the adjacent parenchyma and along white matter tracts to the contralateral hemisphere. MR-UM resolves tumor infiltration and neoangiogenesis longitudinally based on the expression of fluorescent proteins, intravital dyes or endogenous contrasts. Our study demonstrates the huge morphological diversity of brain tumor models regarding their infiltrative and neoangiogenic capacities and further establishes MR-UM as a platform for translational neuroimaging.

Distribution Pattern of the Superior and Inferior Labial Arteries: Impact for Safe Upper and Lower Lip Augmentation Procedures.

BACKGROUND: Understanding the precise position and course of the superior and inferior labial arteries within the upper lip and the lower lip is crucial for safe and complication-free applications of volumizing materials. METHODS: One hundred ninety-three anatomical head specimens (56.5 percent female cadavers) of Caucasian ethnicity were investigated in this large multicenter anatomical study. In total, six 3-cm-long vertical incisions were performed on each lip (midline and 1 cm medial to the angles of the mouth) to identify the position of the superior and inferior labial arteries in relation to the orbicularis oris muscle. RESULTS: Three different positions of the superior and inferior labial arteries were identified: submucosal (i.e., between the oral mucosa and the orbicularis oris muscle in 78.1 percent of the cases), intramuscular (i.e., between the superficial and deep layers of the orbicularis oris muscle in 17.5 percent of the cases), and subcutaneous (i.e., between the skin and the orbicularis oris muscle in 2.1 percent of the cases). The variability in changing the respective position along the labial course was 29 percent for the total upper and 32 percent for the total lower lip. The midline location was identified in both the upper and lower lips to be the most variable. CONCLUSIONS: Based on the results of this investigation, a safer location for the application of volumizing material is the subcutaneous plane in the paramedian location of both the upper lip and the lower lip. Care has to be taken when aiming to inject in the midline, as the artery can be identified more frequently in superficial positions.