in-vivo-percutaneous-needle-based-optical-coherence-tomography-renal

<em>In Vivo</em>, Percutaneous, Needle Based, Optical Coherence Tomography of Renal Masses

Optical coherence tomography (OCT) is the optical equivalent of ultrasound imaging, based on the backscattering of near infrared light. OCT provides real ...

Academic Medical Center

High-risk prostate cancer (PCa), established according to the d’Amico criteria or other prognostic tools, remains very heterogeneous, including a third of patients with excellent prognosis in whom surgical treatment can result in long-term progression-free survival. In contrast, a substantial proportion of high risk will not be cured by local treatment alone and might benefit from a more aggressive multimodal adjuvant treatment strategy. However, to date, except in one adjuvant radiotherapy series, no neoadjuvant or adjuvant therapy has shown a survival improvement after radical prostatectomy for high-risk PCa. Recent observational studies tend to prove that radical prostatectomy may offer benefits over radiotherapy in disease-free and overall survival. However, good Level 1 evidence is lacking and further prospective studies are warranted to directly compare the outcomes of radical prostatectomy to combined radiation and hormonal therapy in high-risk patients.

Radical prostatectomy as primary treatment of high-risk prostate cancer.

Patients with clinical stage I testicular seminoma have historically been treated with adjuvant radiotherapy in the United States. However, nearly 80% of patients on surveillance will not experience relapse and even with relapse, salvage rates approach 100%. It remains unclear how practice patterns have changed with recently accumulating evidence and changes in guidelines. In a population based setting we evaluated contemporary trends and factors that may affect the use of adjuvant radiotherapy.

Stage I testicular seminoma: a SEER analysis of contemporary adjuvant radiotherapy trends.

We report 2 cases of mixed epithelial and stromal tumours revealed by flank pain in a 56-year-old woman and by a renal biopsy in another asymptomatic woman. A greater awareness among urologists and radiologists of the features of mixed epithelial and stromal tumours could help evoke this diagnosis preoperatively leading to needle biopsy and to the most appropriate type of renal surgery.

Advocacy for renal biopsy based on two cases of mixed epithelial and stromal tumour.

Discovery of curative therapies for renal cell carcinoma (RCC) is hampered by lack of authentic preclinical models. Tumorgrafts, generated by direct implantation of patient-derived tissues into mice, have demonstrated superior ability to predict therapeutic response. We evaluated "tissue slice grafts" (TSGs) as an improved tumorgraft model of RCC.

Tissue slice grafts of human renal cell carcinoma: an authentic preclinical model with high engraftment rate and metastatic potential.

To assess correlations between concomitant high-grade prostatic intraepithelial neoplasia (HGPIN), pathological features and oncologic outcomes after radical prostatectomy (RP).

Concomitant high-grade prostatic intraepithelial neoplasia is associated with good prognosis factors and oncologic outcome after radical prostatectomy.

Effective eradication of high-risk primary prostate cancer (HRPCa) could significantly decrease mortality from prostate cancer. However, the discovery of curative therapies for HRPCa is hampered by the lack of authentic preclinical models.

Patient-derived tissue slice grafts accurately depict response of high-risk primary prostate cancer to androgen deprivation therapy.

mTOR is a rational target in renal cell carcinoma (RCC) because of its role in disease progression. However, the effects of temsirolimus, the only first-generation mTOR inhibitor approved by the FDA for first-line treatment of metastatic RCC, on tumor reduction and progression-free survival are minimal. Second-generation mTOR inhibitors have not been evaluated on RCC. We compared the effects of temsirolimus and MLN0128, a potent second-generation mTOR inhibitor, on RCC growth and metastasis using a realistic patient-derived tissue slice graft (TSG) model. TSGs were derived from three fresh primary RCC specimens by subrenal implantation of precision-cut tissue slices into immunodeficient mice that were randomized and treated with MLN0128, temsirolimus, or placebo. MLN0128 consistently suppressed primary RCC growth, monitored by magnetic resonance imaging (MRI), in three TSG cohorts for up to 2 months. Temsirolimus, in contrast, only transiently inhibited the growth of TSGs in one of two cohorts before resistance developed. In addition, MLN0128 reduced liver metastases, determined by human-specific quantitative polymerase chain reaction, in two TSG cohorts, whereas temsirolimus failed to have any significant impact. Moreover, MLN0128 decreased levels of key components of the two mTOR subpathways including TORC1 targets 4EBP1, p-S6K1, HIF1α and MTA1 and the TORC2 target c-Myc, consistent with dual inhibition. Our results demonstrated that MLN0128 is superior to temsirolimus in inhibiting primary RCC growth as well as metastases, lending strong support for further clinical development of dual mTOR inhibitors for RCC treatment.

Preclinical trial of a new dual mTOR inhibitor, MLN0128, using renal cell carcinoma tumorgrafts.

About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastases. The incidence of RCC is increasing and bone metastatic RCC merits greater focus. Realistic preclinical bone metastasis models of RCC are lacking, hampering the development of effective therapies. We developed a realistic in vivo bone metastasis model of human RCC by implanting precision-cut tissue slices under the renal capsule of immunodeficient mice. The presence of disseminated cells in bone marrow of tissue slice graft (TSG)-bearing mice was screened by human-specific polymerase chain reaction and confirmed by immunohistology using human-specific antibody. Disseminated tumor cells in bone marrow of TSG-bearing mice derived from three of seven RCC patients were detected as early as 1 month after tissue implantation at a high frequency with close resemblance to parent tumors (e.g., CAIX expression and high vascularity). The metastatic patterns of TSGs correlated with disease progression in patients. In addition, TSGs retained capacity to metastasize to bone at high frequency after serial passaging and cryopreservation. Moreover, bone metastases in mice responded to Temsirolimus treatment. Intratibial injections of single cells generated from TSGs showed 100 % engraftment and produced X-ray-visible tumors as early as 3 weeks after cancer cell inoculation. Micro-computed tomography (μCT) and histological analysis revealed osteolytic characteristics of these lesions. Our results demonstrated that orthotopic RCC TSGs have potential to develop bone metastases that respond to standard therapy. This first reported primary RCC bone metastasis model provides a realistic setting to test therapeutics to prevent or treat bone metastases in RCC.

Development of a realistic in vivo bone metastasis model of human renal cell carcinoma.

This article provides an overview of recent developments in the field of thermal ablation for renal cell carcinoma and focuses on current standard techniques, new technologies, imaging for ablation guidance and evaluation, and future perspectives.

Thermal ablation in renal cell carcinoma management: a comprehensive review.

To define immunoscore in bladder cancer studying T helper 1 (Th1) immunoreaction. To define a cancer-specific survival model based on Th1 cells infiltration.

T-helper 1 immunoreaction influences survival in muscle-invasive bladder cancer: proof of concept.

Although tissue ablation by irreversible electroporation (IRE) has been characterized as nonthermal, the application of frequent repetitive high-intensity electric pulses has the potential of substantially heating the targeted tissue and causing thermal damage. This study evaluates the risk of possible thermal damage by measuring temperature development and distribution during IRE of porcine kidney tissue.

Article	Year
Radical prostatectomy as primary treatment of high-risk prostate cancer. Current urology reports\| PubMed ID: 22314881	2012
Stage I testicular seminoma: a SEER analysis of contemporary adjuvant radiotherapy trends. The Journal of urology\| PubMed ID: 23567749	2013
Advocacy for renal biopsy based on two cases of mixed epithelial and stromal tumour. Urologia internationalis\| PubMed ID: 23711728	2014
Tissue slice grafts of human renal cell carcinoma: an authentic preclinical model with high engraftment rate and metastatic potential. Urologic oncology\| PubMed ID: 23911681	2014
Concomitant high-grade prostatic intraepithelial neoplasia is associated with good prognosis factors and oncologic outcome after radical prostatectomy. Urologia internationalis\| PubMed ID: 23919964	2014
Patient-derived tissue slice grafts accurately depict response of high-risk primary prostate cancer to androgen deprivation therapy. Journal of translational medicine\| PubMed ID: 23985008	2013
Preclinical trial of a new dual mTOR inhibitor, MLN0128, using renal cell carcinoma tumorgrafts. International journal of cancer. Journal international du cancer\| PubMed ID: 24243565	2014
Development of a realistic in vivo bone metastasis model of human renal cell carcinoma. Clinical & experimental metastasis\| PubMed ID: 24715498	2014
Thermal ablation in renal cell carcinoma management: a comprehensive review. Current opinion in urology\| PubMed ID: 25051022	2014
T-helper 1 immunoreaction influences survival in muscle-invasive bladder cancer: proof of concept. Ecancermedicalscience\| PubMed ID: 25525464	2014
Irreversible electroporation of the porcine kidney: Temperature development and distribution. Urologic oncology\| PubMed ID: 25557146	2014

Alexandre Ingels

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