Search

PurposeWhile several biopsy techniques and platforms for magnetic resonance imaging (MRI)-guided targeted biopsy of the prostate have been established, none of them has proven definite superiority. Augmented and virtual reality (mixed reality) smartglasses have emerged as an innovative technology to support image-guidance and optimize accuracy during medical interventions. We aimed to investigate the benefits of smartglasses for MRI-guided mixed reality-assisted cognitive targeted biopsy of the prostate.MethodsFor prospectively collected patients with suspect prostate PIRADS lesions, multiparametric MRI was uploaded to a smartglass (Microsoft® Hololens I), and smartglass-assisted targeted biopsy (SMART TB) of the prostate was executed by generation of a cognitive fusion technology at the point-of-care. Detection rates of prostate cancer (PCA) were compared between SMART TB and 12-core systematic biopsy. Assessment of SMART-TB was executed by the two performing surgeons based on 10 domains on a 10-point scale ranging from bad (1) to excellent (10).ResultsSMART TB and systematic biopsy of the prostate were performed for 10 patients with a total of 17 suspect PIRADS lesions (PIRADS 3, n = 6; PIRADS 4, n = 6; PIRADS 5, n = 5). PCA detection rate per core was significant (p

Abstract Background Simultaneous urothelial cancer manifestation in the lower and upper urinary tract affects approximately 2% of patients. Data on the surgical benchmarks and mid-term oncological outcomes of enbloc robot-assisted radical cystectomy and nephro-ureterectomy are scarce. Methods After written informed consent was obtained, we prospectively enrolled consecutive patients undergoing enbloc radical cystectomy and nephro-ureterectomy with robotic assistance from the DaVinci Si-HD® system in a prospective institutional database and collected surgical benchmarks and oncological outcomes. Furthermore, as one console surgeon conducted all the procedures, whereas the team providing bedside assistance was composed ad hoc, we assessed the impact of this approach on the operative duration. Results Nineteen patients (9 women), with a mean age of 73 (SD: 7.5) years, underwent simultaneous enbloc robot-assisted radical cystectomy and nephro-ureterectomy. There were no cases of conversion to open surgery. In the postoperative period, we registered 2 Clavien-Dindo class 2 complications (transfusions) and 1 Clavien-Dindo class 3b complication (port hernia). After a median follow-up of 23 months, there were 3 cases of mortality and 1 case of metachronous urothelial cancer (contralateral kidney).The total operative duration did not decrease with increasing experience (r = 0.174, p = 0.534). In contrast, there was a significant, inverse, strong correlation between the console time relative to the total operative duration and the number of conducted procedures after adjusting for the degree of adhesions and the type of urinary diversion(r = -0.593, p = 0.02). Conclusions These data suggest that en bloc simultaneous robot-assisted radical cystectomy and nephro-ureterectomy can be safely conducted with satisfactory mid-term oncological outcomes. With increasing experience, improved performance was detectable for the console surgeon but not in terms of the total operative duration. Simulation training of all team members for highly complex procedures might be a suitable approach for improving team performance. Trial registration: Not applicable. Video Abstract

Abstract Background Coronary artery disease (CAD) is the leading cause of death worldwide. Chromosome locus 9p21 was the first to be associated with increased risk of CAD and coronary artery calcification (CAC). Vascular calcification increases the risk for CAD. Vascular smooth muscle cells (VSMCs) are one of the major cell types involved in the development of vascular calcification. Methods So far, mainly animal models or primary SMCs have been used to model human vascular calcification. In this study, a human in vitro assay using iPSC-derived VSMCs was developed to examine vascular calcification. Human iPSCs were derived from a healthy non-risk (NR) and risk (R) donor carrying SNPs in the 9p21 locus. Additionally, 9p21 locus knockouts of each donor iPSC line (NR and R) were used. Following differentiation, the iPSC-derived VSMCs were characterized based on cell type, proliferation, and migration rate, along with calcium phosphate (CaP) deposits. CaP deposits were confirmed using Calcein and Alizarin Red S staining and then quantified. Results The data demonstrated significantly more proliferation, migration, and CaP deposition in VSMCs derived from the R and both KO iPSC lines than in those derived from the NR line. Molecular analyses confirmed upregulation of calcification markers. These results are consistent with recent data demonstrating increased calcification when the 9p21 murine ortholog is knocked-out. Conclusion Therefore, in conclusion, genetic variation or deletion of the CAD risk locus leads to an increased risk of vascular calcification. This in vitro human iPSC model of calcification could be used to develop new drug screening strategies to combat CAC.

Checkpoint blocking therapies are used to treat metastatic melanoma, but can have adverse immune-mediated effects, including liver pathology. Here the authors identify an expanded pool of CD4+ effector memory T cells resulting from prior CMV exposure as a risk factor for this adverse effect in these patients.

(1) Background: Keratinocyte cancer (KC) is associated with exposure to ultraviolet (UV) radiation. However, data are controversial as to whether chronic UV exposure or high intermittent UV exposure are key drivers of carcinogenesis in cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC). Prolonged sun exposure of the skin causes photo-aging, which is associated with actinic elastosis, a condition characterized by the degeneration of elastin in the upper dermis, which is assessable via conventional histology. In this study, we aimed to compare the degree of actinic elastosis in different types of KC with regard to various patient characteristics. (2) Methods: We defined a semiquantitative score for the degree of actinic elastosis ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration). The extent was measured histometrically by two independent dermatohistopathologists in the immediate vicinity of 353 KC. The scores were merged and matched with tumor types (cSCC and BCC with subtypes), and clinical variables such as body site, sex and age. (3) Results: As expected, the degree of actinic elastosis correlated with age. However, it was significantly higher in cSCC compared to BCC irrespective of age, sex, body site and tumor subtypes. (4): Conclusions: Lifetime sun exposure may be estimated via routine histology using this scoring technique for actinic elastosis as a surrogate marker. cSCCs are more strongly associated with chronic UV exposure than BCCs, even in sun-exposed localizations such as the face.

We have recently shown that cancer cells of various origins take up extracellular citrate through the plasma membrane citrate carrier (pmCiC), a specific plasma membrane citrate transporter. Extracellular citrate is required to support cancer cell metabolism, in particular fatty acid synthesis, mitochondrial activity, protein synthesis and histone acetylation. In addition, cancer cells tend to acquire a metastatic phenotype in the presence of extracellular citrate. Our recent study also showed that cancer-associated stromal cells synthesise and release citrate and that this process is controlled by cancer cells. In the present study, we evaluated the expression of pmCiC, fibroblast activation protein-a (FAP) and the angiogenesis marker cluster of differentiation 31 (CD31) in human cancer tissues of different origins. In the cohort studied, we found no correlation between disease stage and the expression of FAP or CD31. However, we have identified a clear correlation between pmCiC expression in cancer cells and cancer-associated stroma with tumour stage. It can be concluded that pmCiC is increased in cancer cells and in cancersupporting cells in the tumour microenvironment at the later stages of cancer development, particularly at the metastatic sites. Therefore, pmCiC expression has the potential to serve as a prognostic marker, although further studies are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: While sun exposure and associated tissue changes stemming from ultraviolet radiation are closely associated with the most common forms of skin cancer, far less is known regarding rare types of skin cancer. In this study, for the first time, we used a light microscopy technique to evaluate connective tissue changes in samples from patients with six different types of rare skin cancers, assessing the relationship between these changes, patient age, and whether tumors arose on sun-exposed parts of the body. We found that these tissue changes were most pronounced for patients with specific cancers known to be linked to chronic sun damage and tumors arising on sun-exposed parts of the body. We also noted tumor type-specific trends in terms of sex ratios, sites of tumor presentation, and the relationship between the development of particular tumors and patient immunosuppression. Our results are important and novel as they expand the available data associated with these rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic, and/or therapeutic approaches. (1) Background: Rare skin cancers include epithelial, neuroendocrine, and hematopoietic neoplasias as well as cutaneous sarcomas. Ultraviolet (UV) radiation and sunburns are important drivers for the incidence of certain cutaneous sarcomas; however, the pathogenetic role of UV light is less clear in rare skin cancers compared to keratinocyte cancer and melanoma. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure among selected rare skin cancers (atypical fibroxanthoma [AFX], pleomorphic dermal sarcoma [PDS], dermatofibrosarcoma protuberans [DFSP], Kaposi sarcoma [KS], Merkel cell carcinoma [MCC], and leiomyosarcoma [LMS]) while taking into account relevant clinical variables (age, sex, and body site). (2) Methods: We newly established a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 210 rare skin cancers from 210 patients with their clinical variables. (3) Results: TEG values were correlated with age and whether tumors arose on UV-exposed body sites. TEG values were significantly higher in AFX and PDS cases compared to all other analyzed rare skin cancer types. As expected, TEG values were low in DFSP and KS, while MCC cases exhibited intermediate TEG values. (4) Conclusions: High cumulative UV exposure is more strongly associated with AFX/PDS and MCC than with other rare skin cancers. These important results expand the available data associated with rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic and/or therapeutic approaches. [ABSTRACT FROM AUTHOR]

Amygdalin is purported to exhibit anti-cancer properties when hydrolyzed to hydrogen cyanide (HCN). However, knowledge about amygdalin efficacy is limited. A questionnaire evaluating the efficacy, treatment, and dosing protocols, reasons for use, HCN levels, and toxicity was distributed to physicians and healers in Germany, providing amygdalin as an anti-cancer drug. Physicians (20) and healers (18) provided amygdalin over 8 (average) years to nearly 80 annually treated patients/providers. Information about amygdalin was predominantly obtained from colleagues (55%). Amygdalin was administered both intravenously (100%) and orally (32%). Intravenous application was considered to maximally delay disease progression (90%) and relieve symptoms (55%). Dosing was based on recommendations from colleagues (71%) or personal experience (47%). If limited success became apparent after an initial 3g/infusion, infusions were increased to 27g/infusion. Treatment response was primarily monitored with established (26%) and non-established tumor markers (19%). 90% did not monitor HCN levels. Negative effects were restricted to a few dizzy spells and nausea. Only 58% were willing to participate in clinical trials or contribute data for analysis (34%). Amygdalin infusions are commonly administered by healers and physicians with few side effects. The absence of standardized treatment calls for guidelines. Since intravenous application bypasses metabolization, re-evaluation of its mode of action is required. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) promises to be the next revolutionary step in modern society. Yet, its role in all fields of industry and science need to be determined. One very promising field is represented by AI‐based decision‐making tools in clinical oncology leading to more comprehensive, personalized therapy approaches. In this review, the authors provide an overview on all relevant technical applications of AI in oncology, which are required to understand the future challenges and realistic perspectives for decision‐making tools. In recent years, various applications of AI in medicine have been developed focusing on the analysis of radiological and pathological images. AI applications encompass large amounts of complex data supporting clinical decision‐making and reducing errors by objectively quantifying all aspects of the data collected. In clinical oncology, almost all patients receive a treatment recommendation in a multidisciplinary cancer conference at the beginning and during their treatment periods. These highly complex decisions are based on a large amount of information (of the patients and of the various treatment options), which need to be analyzed and correctly classified in a short time. In this review, the authors describe the technical and medical requirements of AI to address these scientific challenges in a multidisciplinary manner. Major challenges in the use of AI in oncology and decision‐making tools are data security, data representation, and explainability of AI‐based outcome predictions, in particular for decision‐making processes in multidisciplinary cancer conferences. Finally, limitations and potential solutions are described and compared for current and future research attempts. [ABSTRACT FROM AUTHOR]

BackgroundRenal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort.MethodsThe records of 413 patients collected by the International Renal Cell Carcinoma-Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan-Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors.ResultsVTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasion, and higher Fuhrman grade. Survival analysis and Cox regression rejected TC as prognostic marker for CSS.ConclusionsIn the largest cohort published so far, TC seems not to be independently associated with survival in RCC patients and should therefore not be included in risk stratification models. J. Surg. Oncol. 2016;114:764-768. © 2016 Wiley Periodicals, Inc.

Novel therapeutic strategies are urgently needed for advanced metastatic prostate cancer (PCa). Phytochemicals used in Traditional Chinese Medicine seem to exhibit tumor suppressive properties. Therefore, the therapeutic potential of artesunate (ART) on the progressive growth of therapy-sensitive (parental) and docetaxel (DX)-resistant PCa cells was investigated. Parental and DX-resistant PCa cell lines DU145, PC3, and LNCaP were incubated with artesunate (ART) [1-100 µM]. ART-untreated and ‘non-cancerous’ cells served as controls. Cell growth, proliferation, cell cycle progression, cell death and the expression of involved proteins were evaluated. ART, dose- and time-dependently, significantly restricted cell growth and proliferation of parental and DX-resistant PCa cells, but not of ‘normal, non-cancerous’ cells. ART-induced growth and proliferation inhibition was accompanied by G0/G1 phase arrest and down-regulation of cell cycle activating proteins in all DX-resistant PCa cells and parental LNCaP. In the parental and DX-resistant PC3 and LNCaP cell lines, ART also promoted apoptotic cell death. Ferroptosis was exclusively induced by ART in parental and DX-resistant DU145 cells by increasing reactive oxygen species (ROS). The anti-cancer activity displayed by ART took effect in all three PCa cell lines, but through different mechanisms of action. Thus, in advanced PCa, ART may hold promise as a complementary treatment together with conventional therapy.