[Enhanced imaging in urological endoscopy]. / Erweiterte Bildgebung in der urologischen Endoskopie.

White light cystoscopy and the concise documentation of pathological findings are standard diagnostic procedures in urology. Additional imaging modalities and technical innovations may support clinicians in the detection of bladder tumors. Modern endoscopy systems provide ultra-high-resolution imaging and the option of digital contrast enhancement. Photodynamic diagnostics and narrow band imaging are well-established in clinical routine and have shown significant benefits in the detection of bladder cancer. By means of multispectral imaging, different modalities can now be combined in real-time. Probe-based procedures such as optical coherence tomography (OCT) or Raman spectroscopy can further contribute to advanced imaging through an "optical biopsy" which may primarily improve diagnostics in the upper urinary tract. The aim of all techniques is to optimize the detection rate in order to achieve a more accurate diagnosis, resection and lower recurrence rates. Current research projects aim to digitalize the documentation of endoscopy and also make it more patient- and user-friendly. In the future, the use of image processing and artificial intelligence may automatically support the surgeon during endoscopy.

Mixed reality for teaching catheter placement to medical students: a randomized single-blinded, prospective trial.

BACKGROUND: Cost-effective methods to facilitate practical medical education are in high demand and the "mixed-reality" (MR) technology seems suitable to provide students with instructions when learning a new practical task. To evaluate a step-by-step mixed reality (MR) guidance system for instructing a practical medical procedure, we conducted a randomized, single-blinded prospective trial on medical students learning bladder catheter placement. METHODS: We enrolled 164 medical students. Students were randomized into 2 groups and received instructions on how to perform bladder catheter placement on a male catheterization training model. One group (107 students) were given their instructions by an instructor, while the other group (57 students) were instructed via an MR guidance system using a Microsoft HoloLens. Both groups did hands on training. A standardized questionnaire covering previous knowledge, interest in modern technologies and a self-evaluation was filled out. In addition, students were asked to evaluate the system's usability. We assessed both groups's learning outcome via a standardized OSCE (objective structured clinical examination). RESULTS: Our evaluation of the learning outcome revealed an average point value of 19.96 ± 2,42 for the control group and 21.49 ± 2.27 for the MR group - the MR group's result was significantly better (p = 0.00). The self-evaluations revealed no difference between groups, however, the control group gave higher ratings when evaluating the quality of instructions. The MR system's assessment showed less usability, with a cumulative SUS (system usability scale) score of 56.6 (lower half) as well as a cumulative score of 24.2 ± 7.3 (n = 52) out of 100 in the NASA task load index. CONCLUSIONS: MR is a promising tool for instructing practical skills, and has the potential to enable superior learning outcomes. Advances in MR technology are necessary to improve the usability of current systems. TRIAL REGISTRATION: German Clinical Trial Register ID: DRKS00013186.

Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study.

PURPOSE: HER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction. METHODS: Patients with stage I-IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40-49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%. RESULTS: Of 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%. CONCLUSION: This study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population.

Magnetic Ureteral Stents Are Feasible in Kidney Transplant Recipients: A Single-Center Experience.

BACKGROUND: Insertion of ureteral catheters is a common procedure in kidney transplantation. The stent is usually removed by cystoscope. Magnetic ureteral stents may be an alternative to conventional stents. OBJECTIVE: To assess the functional efficacy and feasibility of magnetic double J (DJ) stents in kidney transplant recipients. METHODS: We used 6 Fr (diameter), 22 cm (length) magnetic DJs. We examined 7 cases of exclusively AB0-identical living donations. Stent were removed 10-12 days after transplantation. Ureteral Stent Symptoms Questionnaire (USSQ) and visual analog scale (VAS) were used to determine quality of life and pain of the recipients. The total removal time was recorded and cost reduction was calculated. RESULTS: Removal of the magnetic DJ was successful in all cases. The mean±SD duration of the removal was 3.4±1.6 min. The mean±SD overall pain score on the VAS during the procedure was 2.6±1.1. Using this technique was associated with a cost reduction of € 130. CONCLUSION: Using magnetic ureteral stents is a feasible option for living donation AB0-identical kidney transplant recipients.

Isolevuglandins as a gauge of lipid peroxidation in human tumors.

The cellular production of free radicals or reactive oxygen species (ROS) can lead to protein, lipid or DNA modifications and tumor formation. The cellular lipids undergo structural changes through the actions of enzymes (e.g. cyclooxygenases) or free radicals to form a class of compounds called Isolevuglandins (IsoLGs). The recruitment and continued exposure of tissue to ROS and IsoLGs causes increased cell proliferation, mutagenesis, loss of normal cell function and angiogenesis. The elevated concentration of ROS in cancerous tissues suggests that these mediators play an important role in cancer development. We hypothesized that tumors with elevated ROS levels would similarly possess an increased concentration of IsoLGs when compared with normal tissue. Using D11, an ScFv recombinant antibody specific for IsoLGs, we utilized immunohistochemistry to visualize the presence of IsoLG in human tumors compared to normal adjacent tissue (NAT) to the same tumor. We found that IsoLG concentrations were elevated in human breast, colon, kidney, liver, lung, pancreatic and tongue tumor cells when compared to NAT and believe that IsoLGs can be used as a gauge indicative of lipid peroxidation in tumors.

A phase I trial of the bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC3095 in patients with advanced solid malignancies.

Bombesin/gastrin-releasing peptides (BN/GRP) were shown to bind selectively to cell surface receptors, stimulating the growth of various types of malignancies in murine and human models. The novel BN/GRP synthetic receptor antagonist, RC-3095, was able to produce long-lasting tumor regressions in murine and human tumor models in vitro and in vivo. Animal toxicology studies showed no detectable organ toxicity apart from local irritation at the injection site. The purpose of this study was to determine the safety and feasibility of the administration of RC-3095 by daily subcutaneous injections in patients with advanced and refractory solid malignancies. Twenty-five patients received RC-3095 once or twice-daily at doses ranging from 8 to 96 ug/kg. Dose was escalated in groups of 3-5 patients per dose level. The only toxicity observed was local discomfort in the injection site at the highest doses. A single dose administration of RC-3095 at the highest dose level (96 ug/kg) was tested in a clearly hypergastrinemic individual with the Zollingen-Ellison syndrome and produced a decrease in plasma gastrin down to 50% of basal levels in 6 h. There was no objective tumor responses in patients included in the study. A short-lasting minor tumor response was observed in a patient with a GRP-expressing progressive medullary carcinoma of the thyroid. Due to problems with the analytical method, plasma pharmacokinetic data was obtained only from two patients included at the highest dose level. In these patients, RC-3095 reached plasma concentrations >100 ng/mL for about 8 h, which were within therapeutic levels on the basis of prior data obtained in mice and rats. The plasma elimination half-life was between 8.6-10.9 h. Due to the occurrence of local toxicity at the injection site, the dose escalation procedure could not be fully evaluated up to a maximum tolerated dose. Thus, a recommended dose of RC-3095 for Phase II trials could not be clearly established. Considering the novelty of its mechanism of action and impressive preclinical anti-tumor activity, further studies exploiting new formulations of RC-3095 for human use, such as slow-release preparations, and analogues with a more favorable pharmacokinetics are warranted.

CXCL8 secretion by dendritic cells predicts contact allergens from irritants.

Monocyte-derived dendritic cell functions have been explored for identification of contact allergens in vitro. Current methods, including measurement of changes in cell surface marker expression (e.g. CD83, CD86) do not provide a sensitive method for detecting the sensitising potential of a chemical. In this study, we investigated whether chemokine production by monocyte-derived dendritic cells is increased upon maturation and whether chemokine production can provide methodology for the detection of allergens. Monocyte-derived dendritic cells were exposed to allergens (nickel sulphate, cobalt chloride, palladium chloride, copper sulphate, chrome-(III)-chloride, potassium dichromate, p-phenylenediamine and dinitrochlorobenzene) and irritants (sodium dodecyl sulphate, dimethylsulphoxide, benzalkoniumchloride and propane-1-ol). CD83 and CD86 expression was analysed by flow cytometry and chemokine production (CXCL8, CCL5, CCL17, CCL18, CCL19, CCL20, CCL22) was determined by ELISA. Significant up regulation of CD83 and CD86 expression could only be induced by three out of seven and five out of seven allergens, respectively. In contrast, CXCL8 production was significantly increased after stimulation with all allergens tested, whereas irritant exposure led to decreased CXCL8 production. All other chemokines tested, failed in identifying contact allergens. In conclusion, CXCL8 production, next to CD83 and CD86 up regulation, by monocyte-derived dendritic cells provides a promising in vitro tool for discrimination between allergens and irritants.

Accuracy of frozen-section analysis in the diagnosis of ovarian tumors: a systematic quantitative review.

A quantitative systematic review was performed to estimate the diagnostic accuracy of frozen sections in ovarian tumors. Studies that compared frozen sections and paraffin sections within subjects for diagnosis of ovarian tumors were included. Fourteen primary studies were analyzed, which included 3 659 women. For benign ovarian vs borderline/malignant tumor cases, the occurrence of a positive frozen-section result for benignity (pooled likelihood ratio [LR], 8.7; 95% confidence interval [CI], 7.3-10.4) and posttest probability for benign diagnosis was 95% (95% CI, 94-96%). A positive frozen-section result for malignant vs benign diagnosis (pooled LR, 303; 95% CI, 101-605) increased the probability of ovarian cancer to 98% (95% CI, 97-99%). In borderline vs benign ovarian tumor cases, a positive frozen-section result (pooled LR, 69; 95% CI, 45-106) increased the probability of borderline tumors to 79% (95% CI, 71-85%). In borderline vs malignant ovarian tumor cases, a positive frozen-section result (pooled LR, 18; 95% CI, 13-26) increased the probability of borderline tumors to 51% (95% CI, 42-60%). We conclude that diagnostic accuracy rates for frozen-section analysis is high for malignant and benign ovarian tumors, but the accuracy rates in borderline tumors remain relatively low.

Extended neoadjuvant chemotherapy in locally advanced breast cancer combined with GM-CSF: effect on tumour-draining lymph node dendritic cells.

The effect of long-term administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) on dendritic cell (DC) activation and survival in patients with locally advanced breast cancer (LABC) was studied. To this end, the number of activated DC (i.e. positive for the marker S100) in tumour-draining lymph nodes (TDLN) was determined and compared between LABC patients receiving neoadjuvant chemotherapy with GM-CSF (n=52) or without GM-CSF (n=11), and a control group of chemonaïve breast cancer patients (n=10). A significantly higher mean percentage of S100+ DC in the TDLN of the GM-CSF-treated patients (9.9%) was found compared with each of the respective control groups (5.3 and 5.1%, P=0.002). Moreover, intrapatient comparison before and after treatment showed that the percentage of S100+ DC significantly increased over the course of the GM-CSF treatment (P=0.018). In a univariate survival analysis with a median follow-up of 64 months, relatively high percentages of S100+ DC (> or =8%) were associated with a longer disease-free survival (DFS) (P=0.078). In patients with a high tumour load, where immunosuppressed conditions generally prevail, long-term administration of GM-CSF may thus contribute to survival through enhanced DC activation and consequently improved chances of effective antitumour immunity.

Mortalidade por câncer de colo uterino no Rio Grande do Sul / Mortality from uterine cervix neoplasm in Rio Grande do Sul

O objetivo deste estudo refere-se a mortalidade por câncer do colo uterino (Cid 180), através da verificaçäo dos coeficientes de mortalidade no Rio Grande os Sul e nas 24 microrregiöes que compöem o referido Estado, com estudo das tendências (regressäo linear simples), período de 1970 a 1989. Como objetivos secundários foram abordados a feqüência relativa desta neoplasia em relaçäo ao total de óbitos por neoplasias malignas, estudo comparativo com outras localidades e correlaçäo com fatores de risco. Os dados que permitiram este estudo foram obtidos na Secretaria de Saúde e Meio Ambiente do Rio Grande do Sul, Instituto Brasileiro de Geografia e Estatística IBGE), Ministério de Saúde e Organizaçäo Mundial de Saúde. A média dos coeficientes de mortalidade/100.000 mulheres no Rio Grande do Sul (1970-1989) foi de 3,8, com tendência ascendente. Observaram-se diferenças importantes na distribuiçäo dos coeficientes de mortalidade nas 24 microrregiöes do Estado, com médias oscilando entre 2,5 e 6,7. O câncer de colo uterino ocupou o 4§ lugar na mortalidade por neoplasias entre as mulheres do Rio Grande do Sul, em 1989. Vírus de papiloma humano e tabagismo säo importantes fatores de risco nesta neoplasia

[Mortality from uterine cervix cancer in Rio Grande do Sul]. / Mortalidade por câncer de colo uterino no Rio Grande do Sul.

The mortality from cervical cancer was studied by checking the death rates in Rio Grande do Sul (RS) and in its 24 microregions. Each tendency (linear regression), in the period from 1970 to 1989, was also investigated. We have also studied the relative rates of this kind of cancer, the comparison with the rate in other places and the risk factors. The data were obtained at the Office of Health in Rio Grande do Sul as well as in the Statistics and Geography Brazilian Institute and World Health Organization. The average mortality rates/100,000 women in RS (1970-1989) was 3.8, with ascending tendency. Important differences in the death rates in the 24 microregions in RS were observed and they ranged from 2.5 to 6.7. The cervical cancer was the fourth cause of death in women from RS (mortality by cancer), in 1989. Papillomaviruses and smoking were important factors in the development of cervical cancer.

[Smoking in Porto Alegre: prevalence and the role of health professionals in its prevention]. / Tabagismo em Porto Alegre: prevalência e o papel dos profissionais da saúde na prevenção.

This study was undertaken in 1988 in order to evaluate the prevalence of smoking, the degree of awareness of smokers and ex-smokers to risks of smoking, and the role of health professionals in the control of smoking in Porto Alegre. A total of 407 persons between 15 and 64 years were interviewed in a population-based survey. Of these, 170 (41.8%) smoked. Among ex-smokers, 85.7% stopped due to awareness of the harm that cigarettes can cause. Only 16.5% of smokers and ex-smokers were warned to the risks of smoking by health professionals before acquiring the habit. After becoming smokers, only 51.4% were warned. These indices are a cause for concern as we believe that prevention is the best approach to control of the smoking epidemic.