Best practices in near-infrared fluorescence imaging with indocyanine green (NIRF/ICG)-guided robotic urologic surgery: a systematic review-based expert consensus.

PURPOSE: The aim of the present study is to investigate the impact of the near-infrared (NIRF) technology with indocyanine green (ICG) in robotic urologic surgery by performing a systematic literature review and to provide evidence-based expert recommendations on best practices in this field. METHODS: All English language publications on NIRF/ICG-guided robotic urologic procedures were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement to evaluate PubMed®, Scopus® and Web of Science™ databases (up to April 2019). Experts in the field provided detailed pictures and intraoperative video-clips of different NIRF/ICG-guided robotic surgeries with recommendations for each procedure. A unique QRcode was generated and linked to each underlying video-clip. This new exclusive feature makes the present the first "dynamic paper" that merges text and figure description with their own video providing readers an innovative, immersive, high-quality and user-friendly experience. RESULTS: Our electronic search identified a total of 576 papers. Of these, 36 studies included in the present systematic review reporting the use of NIRF/ICG in robotic partial nephrectomy (n = 13), robotic radical prostatectomy and lymphadenectomy (n = 7), robotic ureteral re-implantation and reconstruction (n = 5), robotic adrenalectomy (n = 4), robotic radical cystectomy (n = 3), penectomy and robotic inguinal lymphadenectomy (n = 2), robotic simple prostatectomy (n = 1), robotic kidney transplantation (n = 1) and robotic sacrocolpopexy (n = 1). CONCLUSION: NIRF/ICG technology has now emerged as a safe, feasible and useful tool that may facilitate urologic robotic surgery. It has been shown to improve the identification of key anatomical landmarks and pathological structures for oncological and non-oncological procedures. Level of evidence is predominantly low. Larger series with longer follow-up are needed, especially in assessing the quality of the nodal dissection and the feasibility of the identification of sentinel nodes and the impact of these novel technologies on long-term oncological and functional outcomes.

PAX2 inactivation enhances cisplatin-induced apoptosis in renal carcinoma cells.

Renal cell carcinoma (RCC) is the most common kidney malignancy and has a poor prognosis owing to its resistance to chemotherapy. RCC cells overexpress the transcription factor, PAX2, normally expressed in fetal kidney but downregulated at birth. Since Pax2 suppresses apoptosis during renal development, we reasoned that PAX2 may confer resistance to cisplatin-induced apoptosis in RCC. Here, we show that PAX2 confers resistance to cisplatin-induced apoptosis in normal kidney cells and fetal kidney explants. Human embryonic kidney 293 cells transfected with a PAX2 expression vector and exposed to cisplatin (40 microM) exhibited 45 +/- 15% as much caspase-3 cleavage compared to control cells. Conversely, murine collecting duct cells stably transfected with PAX2 antisense cDNA had twofold increase in cisplatin-induced apoptosis. Murine fetal (embryonic day 15) kidney explants from PAX2(1Neu)+/- mice exposed to cisplatin (25 microM x 24 h) had 50% increased apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining). We then show that RCC cells (CAKI-1 (human, Caucasian, kidney, carcinoma) and ACHN (human, Caucasian, kidney, adenocarcinoma)) express PAX2 protein. PAX2-small interfering RNA (100 nM) reduces endogenous PAX2 protein (10% of baseline) and induces apoptosis (Annexin-V staining). Pax2 knockdown sensitized RCC cells to cisplatin-induced apoptosis, killing 50-60% of cisplatin-resistant ACHN and CAKI-1 cells. These findings suggest that PAX2 confers resistance to cisplatin-induced apoptosis in non-transformed kidney cells and fetal kidney explants. Similarly, Pax2 overexpression in RCC cells contributes to cisplatin resistance. Conceivably, a therapeutic strategy that inactivates Pax2 in vivo might enhance the efficacy of conventional cytotoxic drugs against RCC.

CLCN5 chloride-channel mutations in six new North American families with X-linked nephrolithiasis.

BACKGROUND: X-linked nephrolithiasis, or Dent's disease, encompasses several clinical syndromes of low molecular weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal failure, and is associated with mutations in the CLCN5 gene encoding a kidney-specific voltage-gated chloride channel. Some patients from Europe have rickets, and all symptomatic patients confirmed by mutation analysis have been male. METHODS: We analyzed the CLCN5 DNA sequence in six new families with this disease. RESULTS: In three probands, a single-base substitution yielded a nonsense triplet at codons 28, 34, and 343, respectively, and in two families, one of which was Hispanic, we found single-base deletions at codons 40 and 44, leading to premature termination of translation. In the sixth family, a single-base change from C to T predicted substitution of leucine for serine at codon 244, previously reported in two European families with prominent rickets, though this patient of Ashkenazi origin did not have rickets. Each of these mutations was confirmed by restriction endonuclease analysis, or repeat sequencing and CFLP. The R34X mutation occurred in a Canadian infant with severe rickets. The family with the R28X nonsense mutation included one woman with recurrent kidney stones and another woman with glomerular sclerosis. In another family, a woman heterozygous for the W343X mutation also had nephrolithiasis. CONCLUSIONS: These studies expand the range of mutations identified in this disease, and broaden the phenotypic range to include clinically affected women and the first North American case with severe rickets.