Ischaemia-reperfusion injury (IRI) during various surgical procedures, including partial nephrectomy for kidney cancer or renal transplantation, is a major cause of acute kidney injury and chronic kidney disease. Currently there are no drugs or methods for protecting human organs, including the kidneys, against the peril of IRI. The aim of this study was therefore to investigate the reno-protective effect of Zn preconditioning in a clinically relevant large animal sheep model of IRI. Further the reno-protective effectiveness of Zn preconditioning was tested on normal human kidney cell lines HK-2 and HEK293. Anaesthetised sheep were subjected to uninephrectomy and 60 min of renal ischaemia followed by reperfusion. Sheep were preconditioned with intravenous injection of zinc chloride prior to occlusion. Serum creatinine and urea were measured before ischaemia and for 7 days after reperfusion. HK-2 and HEK293 cells were subjected to in vitro IRI using the oxygen- and glucose-deprivation model. Zn preconditioning reduced ischaemic burden determined by creatinine and urea rise over time by ~ 70% in sheep. Zn preconditioning also increased the survival of normal human kidney cells subjected to cellular stress such as hypoxia, hydrogen peroxide injury, and serum starvation. Overall, our protocol incorporating specific Zn dosage, number of dosages (two), time of injection (24 and 4 h prior), mode of Zn delivery (IV) and testing of efficacy in a rat model, a large preclinical sheep model of IRI and cells of human origin has laid the foundation for assessment of the benefit of Zn preconditioning for human applications.

SUMMARYNeuroendocrine carcinoma (NEC) of the head and neck is rare. We report a case of a 56-year-old man with a 6-week history of dysphagia, a neck mass and weight loss. He was diagnosed with a hypopharyngeal large cell NEC (LCNEC) with metastases to multiple sites. He received two cycles of cisplatin and etoposide. Subsequent restaging scan revealed progressive disease. The patient declined further chemotherapy and died shortly after. This is the third case of LCNEC of hypopharynx reported in the English literature and the first to progress on platinum-based chemotherapy. Although LCNEC of the head and neck is still classified as an atypical carcinoid, there is increasing evidence it is a distinct clinicohistopathological entity that carries an especially poor prognosis. Currently, there is a paucity of data to guide treatment of this rare malignancy. BACKGROUND

ObjectiveTo document the histological changes observed in renal units subjected to elevated intrarenal pressures (IRPs) and postulate the possible mechanisms of infectious complications after ureteroscopy.Materials and MethodsEx vivo studies were performed on porcine renal models. Each ureter was cannulated with a 10‐F dual‐lumen ureteric catheter. A pressure‐sensing wire was inserted through one lumen and with the sensor positioned in the renal pelvis for IRP measurement. Undiluted India ink stain was irrigated through the second lumen. Each renal unit was subjected to ink irrigation at target IRPs of 5 (control), 30, 60, 90, 120, 150, and 200 mmHg. Three renal units were subjected to each target IRP. After irrigation, each renal unit was processed by a uropathologist. Macroscopically, the amount of renal cortex stained by ink was calculated as a percentage of the total perimeter. Microscopically, presence of ink reflux into collecting ducts or distal convoluted tubules, and pressure‐related features, was noted at each IRP.ResultsSigns of pressure, as represented by collecting duct dilatation, was first observed at 60 mmHg. Ink staining was consistently observed in the distal convoluted tubules at IRPs ≥60 mmHg, and all renal units above this pressure showed renal cortex involvement. At ≥90 mmHg, ink staining was observed in venous structures. At 200 mmHg, ink staining was observed in supportive tissue, venous tributaries in the sinus fat, peritubular capillaries, and glomerular capillaries.ConclusionUsing an ex vivo porcine model, pyelovenous backflow occurred at IRPs of ≥90 mmHg. Pyelotubular backflow occurred when irrigation IRPs were ≥60 mmHg. These findings have implications for the development of complications after flexible intrarenal surgery.

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