Michael Kerger - Academia.edu (original) (raw)

Papers by Michael Kerger

2016 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS), 2016

This paper introduces the CableRobot simulator, which was developed at the Max Planck Institute f... more This paper introduces the CableRobot simulator, which was developed at the Max Planck Institute for Biological Cybernetics in cooperation with the Fraunhofer Institute for Manufacturing Engineering and Automation IPA. The simulator is a completely novel approach to the design of motion simulation platforms in so far as it uses cables and winches for actuation instead of rigid links known from hexapod simulators. This approach allows to reduce the actuated mass, scale up the workspace significantly, and provides great flexibility to switch between system configurations in which the robot can be operated. The simulator will be used for studies in the field of human perception research and virtual reality applications. The paper discusses some of the issues arising from the usage of cables and provides a system overview regarding kinematics and system dynamics as well as giving a brief introduction into possible application use cases.

Endocrine connections, May 1, 2019

Prostate cancer is a leading cause of morbidity and cancer-related death worldwide. Androgen depr... more Prostate cancer is a leading cause of morbidity and cancer-related death worldwide. Androgen deprivation therapy (ADT) is the cornerstone of management for advanced disease. The use of these therapies is associated with multiple side effects, including metabolic syndrome and truncal obesity. At the same time, obesity has been associated with both prostate cancer development and disease progression, linked to its effects on chronic inflammation at a tissue level. The connection between ADT, obesity, inflammation and prostate cancer progression is well established in clinical settings; however, an understanding of the changes in adipose tissue at the molecular level induced by castration therapies is missing. Here, we investigated the transcriptional changes in periprostatic fat tissue induced by profound ADT in a group of patients with high-risk tumours compared to a matching untreated cohort. We find that the deprivation of androgen is associated with a pro-inflammatory and obesity-like adipose tissue microenvironment. This study suggests that the beneficial effect of therapies based on androgen deprivation may be partially counteracted by metabolic and inflammatory side effects in the adipose tissue surrounding the prostate.

European Urology, Jun 1, 2009

Background: Robotic-assisted laparoscopic radical prostatectomy (RALP) using the da Vinci 1 surgi... more Background: Robotic-assisted laparoscopic radical prostatectomy (RALP) using the da Vinci 1 surgical system (Intuitive Surgical, Sunnyvale, CA) is increasingly used for the management of localised prostate cancer. Objective: We report the operative details and short-term oncological and functional outcome of the first 400 RALPs performed at our unit. Design, setting and participants: From December 2003 to August 2006, 400 consecutive patients underwent RALP at our institution. A prospective database was established to record the relevant details of all RALP cases. Surgical procedure: A six port transperitoneal approach using a 4-arm da Vinci 1 system was used to perform RALP. This database was reviewed to establish the operative details and oncological and functional outcome of all patients with a minimum of 12 months follow-up. Measurements: Perioperative characteristics and outcomes are reported. Functional outcome was assessed using continence and erectile function questionnaires. Biochemical recurrence (prostate-specific antigen (PSA) !0.2 ng/mL) is used as a surrogate for cancer control. Results and limitations: The mean age AE standard deviation (SD) was 60.2 AE 6 years. Median PSA level was 7.0 (interquartile range (IQR) 5.3-9.6) ng/mL. The mean operating time AE SD was 186 AE 49 mins. The complication rate was 15.75% comprising Clavien grade I-II and Clavien grade III complications in 10.5% and 5.25% of patients respectively. The overall positive surgical margin rate was 19.2% with T2 and T3 positive margin rates of 9.6% and 42.3% respectively. The biochemical recurrence-free survival was 86.6% at a median follow-up of 22 (IQR = 15-30) months. At 12 months follow-up, 91.4% of patients were pad-free or used a security liner. Of those men previously potent (defined as Sexual Health Inventory for Men [SHIM] score !21) who underwent nerve-sparing RALP, 62% were potent at 12 months. Conclusions: The safety and feasibility of RALP has already been established. Our initial experience with this procedure shows promising short-term outcomes.

Piloting peer-delivered hepatitis C testing and counselling at a needle and syringe program Micha... more Piloting peer-delivered hepatitis C testing and counselling at a needle and syringe program Michael Kerger, Campbell Aitken and Nick Crofts Centre for Harm Reduction, Macfarlane Burnet Centre for Medical Research, Fairfield Between August 1999 and January 2000 the authors piloted the provision of a free peer-based hepatitis C testing and counselling/education service at Western Region AIDS and Hepatitis Prevention (WRAP) Footscray’s primary needle & syringe program (NSP). The project was funded by NH&MRC grant #983608. This service (which as far as we know has never been established or trialled elsewhere) proved popular among WRAP clients, who requested and received more than 300 counselling episodes in six months. In addition, it provided support for busy NSP workers, who often did not have the time or specialised knowledge to respond to such requests. Forty-seven IDUs who had not had a hepatitis C antibody test in the previous 12 months including 29 never-tested were given tests and pre and posttest counselling. They were interviewed about reasons for not getting tested, knowledge of hepatitis C, and risk behaviour as well as barriers to safe use. Most people were attracted by the convenience and suitability of testing in the pilot program. The most common reason for never previously being tested was “didn’t think I was at risk”, but reported risk behaviour and test results showed otherwise. The effect testing and counselling had on risk practices was evaluated and found to be beneficial in several important respects. Our results suggest that NSPs are practical locations for hepatitis C testing, counselling and education (and potentially other primary health care services), and are more acceptable and appropriate to IDUs than traditional health services.

Clinical Genitourinary Cancer, Oct 1, 2022

BMC Cancer, Jul 22, 2021

Background: Prostate cancer is caused by genomic aberrations in normal epithelial cells, however ... more Background: Prostate cancer is caused by genomic aberrations in normal epithelial cells, however clinical translation of findings from analyses of cancer cells alone has been very limited. A deeper understanding of the tumour microenvironment is needed to identify the key drivers of disease progression and reveal novel therapeutic opportunities. Results: In this study, the experimental enrichment of selected cell-types, the development of a Bayesian inference model for continuous differential transcript abundance, and multiplex immunohistochemistry permitted us to define the transcriptional landscape of the prostate cancer microenvironment along the disease progression axis. An important role of monocytes and macrophages in prostate cancer progression and disease recurrence was uncovered, supported by both transcriptional landscape findings and by differential tissue composition analyses. These findings were corroborated and validated by spatial analyses at the single-cell level using multiplex immunohistochemistry. Conclusions: This study advances our knowledge concerning the role of monocyte-derived recruitment in primary prostate cancer, and supports their key role in disease progression, patient survival and prostate microenvironment immune modulation.

Social Science Research Network, 2018

Patients with defects in the mismatch repair (MMR) pathway driven by either MSH2 or MSH6 loss exp... more Patients with defects in the mismatch repair (MMR) pathway driven by either MSH2 or MSH6 loss experience a significant increase in the incidence of prostate cancer, whilst germline MMR defects in either MLH1 or PMS2, exhibit no such increase. Prostatic carcinogenesis is driven by androgen signalling. Here we show that androgen-receptor activation can disrupt the MSH2 gene in prostate cancer model systems. We screened tumors from two contrasting risk cohorts of prostate cancer patients to confirm loss of MSH2 protein expression and surprisingly found a small but significant fraction of high risk cases exhibited reduced expression of MSH2. Stratifying a large independent TCGA prostate cancer cohort for MSH2 expression levels revealed that patients whose tumors exhibited either complete loss or aberrant levels of MSH2 had equally significant worse survival outcomes and accelerated clinical progression. In contrast, colorectal cancer patients with aberrant MSH2 levels had improved clinical survival. We show that reduced expression of MSH2 can also occur through androgen-induced miRNA regulatory mechanisms. Aberrant MSH2 expression in prostate tumors does not induce enhanced immune cell mobilisation seen in colorectal tumors suggesting that the prostate is an immune privileged site that is less likely to benefit from immunotherapies.

Journal of Clinical Oncology, Mar 1, 2015

71 Background: Androgen receptor splice variants (ARvs) are upregulated in response to castration... more 71 Background: Androgen receptor splice variants (ARvs) are upregulated in response to castration, and can activate transcription in the absence of ligand. Recent evidence indicates that CTC ARv7 expression is an accurate predictor of absence of response to abiraterone and enzalutamide, providing strong clinical support for ARv7 upregulation as potential overarching mechanism of castration resistance. There is however limited data regarding the expression of ARv7 in clinically localized prostate cancer (CaP), and it is unknown if expression in the primary tumor is similarly predictive. We were therefore interested to determine the expression of ARv7 in high-risk disease, and correlate this with response to an abiraterone-containing castrating regimen. Methods: We performed an open label non-randomized Phase II neoadjuvant study of ‘supercastration’ in men with high-risk clinically localized CaP using an optimal 2-stage design (ACTRN12612000772842). Treatment consisted of degarelix 240/80mg q 1/12, abiraterone 1000mg OD, bicalutamide 50mg OD and prednisolone 5mg OD for 24 weeks. The primary endpoints were safety/tolerability and pT0 response rate. ARv7 expression was determined by immunohistochemistry and qRT-PCR in both pre- and post treatment tumor specimens, and correlated with pathological response. Fresh specimens from resistant tumors are currently being profiled by RNA-seq. Results: 17 patients were recruited to the study. The combination treatment was well tolerated, with hot flushes and fatigue being the most commonly reported side effects, and all patients completed six months of treatment. Six patients with asymptomatic elevation of liver transaminases required Abiraterone dose reductions, and there were no unexpected toxicities. 16 patients proceeded to prostatectomy, and a pT0 response observed in one patient, with minimal residual disease present in a further three patients. ARv7 expression was uniformly present in all pre-treatment specimens, and neither level nor localization of expression predicted tumor response. Conclusions: ARv7 expression in primary CaP does not predict response to abiraterone-based castration. Clinical trial information: ACTRN12612000772842.

Clinical Genitourinary Cancer

Cell, Jan 5, 2015

There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of mol... more There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as poten...