A novel less-traumatic needle for kidney puncture: first clinical experience.

INTRODUCTION: To decrease complication rate, we developed a novel MG needle for kidney puncture consisting of a pointed cannula, an atraumatic mandrin-bulb and a spring mechanism pushing the mandrin-bulb forward. AIM OF THE STUDY: To assess efficacy and safety of kidney puncture during percutaneous nephrolithotomy (PCNL) using a novel less-traumatic MG needle within a clinical trial. MATERIALS AND METHODS: We conducted a prospective randomized single-center study. In the experimental group, kidney puncture was performed with a novel MG needle while in the control group, standard Trocar or Chiba puncture needles were used. PRIMARY ENDPOINT: hemoglobin drop. RESULTS: A total of 67 patients were enrolled. Patients who underwent standard puncture (n = 33) had higher hemoglobin drop in the early postoperative period (p = 0.024). Although there was no statistical difference in overall complication rate between the two groups (p = 0.351), two severe Clavien-Dindo IIIa complications with urinoma occurred in patients from the control group. CONCLUSION: Less-traumatic needle for kidney puncture may reduce hemoglobin drop and prevent the development of severe complications. At the same time, in terms of stone-free rate (SFR), the efficacy of PCNL remains the same regardless of the needle used for renal access.

Ex vivo organotypic cultures for synergistic therapy prioritization identify patient-specific responses to combined MEK and Src inhibition in colorectal cancer.

Translating preclinical studies to effective treatment protocols and identifying specific therapeutic responses in individuals with cancer is challenging. This may arise due to the complex genetic makeup of tumor cells and the impact of their multifaceted tumor microenvironment on drug response. To find new clinically relevant drug combinations for colorectal cancer (CRC), we prioritized the top five synergistic combinations from a large in vitro screen for ex vivo testing on 29 freshly resected human CRC tumors and found that only the combination of mitogen-activated protein kinase kinase (MEK) and proto-oncogene tyrosine-protein kinase Src (Src) inhibition was effective when tested ex vivo. Pretreatment phosphorylated Src (pSrc) was identified as a predictive biomarker for MEK and Src inhibition only in the absence of KRASG12 mutations. Overall, we demonstrate the potential of using ex vivo platforms to identify drug combinations and discover MEK and Src dual inhibition as an effective drug combination in a predefined subset of individuals with CRC.