Temporary targeted renal blood flow interruption using a reverse thermosensitive polymer to facilitate bloodless partial nephrectomy: a swine survival study.

UNLABELLED: What's known on the subject? and What does the study add? Lumagel™ is a reverse thermosensitive polymer (RTP) that has previously been described in the literature as providing temporary vascular occlusion to allow for bloodless partial nephrectomy (PN) while maintaining blood flow to the untargeted portion of the kidney. At body temperature, Lumagel™ has the consistency of a viscous gel but upon cooling rapidly converts to a liquid state and does not reconstitute thereafter. This property has allowed for it to be used in situations requiring temporary vascular occlusion. Previous experience with similar RTPs in coronary arteries proved successful, with no detectable adverse events. We have previously described our technique for temporary vascular occlusion of the main renal artery, as well as segmental and sub-segmental renal branches, to allow for bloodless PN in either an open or minimally invasive approach. These experiments were performed in the acute setting. This study is a two-armed survival trial to assess whether this RTP is as safe as hilar clamping for bloodless PN. Surviving animals showed normal growth after using the RTP, absence of toxicity, no organ dysfunction, and no pathological changes attributable to the RTP. We conclude that Lumagel™ is as safe as conventional PN with hilar clamping, while adding the advantage of uninterrupted perfusion during renal resection. OBJECTIVE: To examine whether randomly selected regions of the kidney could undergo temporary flow interruption with a reverse thermosensitive polymer (RTP), Lumagel™ (Pluromed, Inc., Woburn, MA, USA), followed by partial nephrectomy (PN), without adding risks beyond those encountered in the same procedure with the use of hilar clamping. MATERIALS AND METHODS: A two-armed (RTP vs hilar clamp), 6-week swine survival study was performed. Four swine underwent PN using hilar clamps, while six underwent PN with flow interruption using the RTP. The RTP, administered angiographically, was used for intraluminal occlusion of segmental or subsegmental arteries and was compared with main renal artery clamping with hilar clamps. The resection site was randomized for each swine. Laboratory studies were performed preoperatively, and at weeks 1, 3 and 6. Before killing the swine, repeat angiography was performed with emphasis on the site of previous flow interruption. Gross and microscopic examination of kidney, liver, lung, heart, skeletal muscle was later performed, and the vessel that had supported the previous plug was examined. RESULTS: All animals survived. No abnormal chemistry or haematology results were encountered over the 6 weeks. There were no surgical complications in either group. Using angiography we found 100% patency of vessels that had been occluded with the polymer 6 weeks previously for PN. The only gross or microscopic abnormalities were related to the renal resection and scar formation, and were similar in the two groups. CONCLUSION: Targeted flow interruption with the RTP added no additional risk to PN while allowing bloodless resection and uninterrupted flow to untargeted renal tissue.

Targeted endovascular temporary vessel occlusion with a reverse thermosensitive polymer for near-bloodless partial nephrectomy: comparison to standard surgical clamping techniques.

PURPOSE: To determine whether reversible blood flow interruption to a randomly chosen target region of the kidney may be achieved with the injection of a reverse thermoplastic polymer through an angiographic catheter, thereby facilitating partial nephrectomy without compromising blood flow to the remaining kidney or adding risks beyond those encountered by the use of hilar clamping. METHODS: Fifteen pigs underwent partial nephrectomy after blood flow interruption by vascular cross-clamping or injection of polymer (Lumagel™) into a segmental artery. Five animals were euthanized after surgery (three open and two laparoscopic resection, cross-clamping n = 2), and 10 (open resection, cross-clamping n = 4) were euthanized after 6 weeks' survival. Blood specimens were obtained periodically, and angiogram and necropsy were performed at 6 weeks. RESULTS: Selective renal ischemia was achieved in all cases. Surgical resection time averaged 9 and 24.5 min in the open and laparoscopic groups, respectively. Estimated blood loss was negligible with the exception of one case where an accessory renal artery was originally overlooked. Reversal of the polymer to a liquid state was consistent angiographically and visually in all cases. Time to complete flow return averaged 7.4 and 2 min for polymer and clamping, respectively. Angiography at 6 weeks revealed no evidence of vascular injury. Laboratory data and necropsies revealed no differences between animals undergoing vascular clamping or polymer injection. CONCLUSION: Lumagel was as effective as vascular clamping in producing a near bloodless operative field for partial nephrectomy while maintaining flow to the uninvolved portion of the affected kidney.

Temporary targeted hemostasis to facilitate bloodless partial nephrectomy.

OBJECTIVE: To extend previous robotic-assisted techniques developed in the swine model to studies of laparoscopic and open partial nephrectomy conducted in pigs and calves, designed to encompass vessel diameters similar to those encountered in humans. Lumagel (Pluromed, Woburn, MA), a nontoxic polymer, can be administered intra-arterially under fluoroscopic guidance to obtain a bloodless operative field during partial nephrectomy while maintaining normal circulation to uninvolved renal tissue. METHODS: A total of 10 animals (7 pigs and 3 calves) underwent flow interruption to the kidney, 2 with cross-clamping of the main renal artery, the remaining with Lumagel. Other than the first pig and calf, all the animals then underwent partial nephrectomy. RESULTS: Using Lumagel, targeted blood flow interruption was achieved and circulation to the uninvolved renal tissue was maintained. Hemostasis lasted for ≥30 minutes. The surgical resection time averaged 11 minutes (range 10-13) and 23.3 minutes (range 9-40) in the open and laparoscopic groups, respectively. The estimated blood loss was negligible, with the exception of 2 cases, 1 in which an error in angiographic assessment led to an unoccluded vessel near the resection site and a second case in which a guidewire was inadvertently passed through a vessel. The interval to complete flow return, as determined by direct visualization of the kidney and its corresponding angiogram, averaged 7 and 2.5 minutes for Lumagel and arterial clamping, respectively. CONCLUSION: Lumagel provides reliable and reproducible intraluminal blood flow interruption and flow restoration in both main and segmental renal arteries. By providing blood-free resection, the techniques described could facilitate partial nephrectomy without global renal ischemia.

Comparative modeling and analysis of microfluidic and conventional DNA microarrays.

A theoretical analysis was developed to predict molecular hybridization rates for microarrays where samples flow through microfluidic channels and for conventional microarrays where samples remain stationary during hybridization. The theory was validated by using a multiplexed microfluidic microarray where eight samples were hybridized simultaneously against eight probes using 60-mer DNA strands. Mass transfer coefficients ranged over three orders of magnitude where either kinetic reaction rates or molecular diffusion rates controlled overall hybridization rates. Probes were printed using microfluidic channels and also conventional spotting techniques. Consistent with the theoretical model, the microfluidic microarray demonstrated the ability to print DNA probes in less than 1 min and to detect 10-pM target concentrations with hybridization times in less than 5 min.