Percutaneous bladder cryoablation in porcine model

PURPOSE: To demonstrate the morphologic changes of full-thickness bladder cryoablation utilizing contemporary percutaneous technology. MATERIALS AND METHODS: Cryoablation of the bladder wall was conducted in 24 pigs. The bladders were exposed laparoscopically and inspected cystoscopically. The animals underwent either extravesical (serosal) or transvesical (mucosal) approaches for the creation of the cryoablation lesion. Single or double freeze/thaw cycles were applied, and no bladder drainage was used. The bladder was evaluated for perforation, and histologic examination was undertaken to assess the extent of acute, subacute (2 weeks), or chronic (1 month) lesions. RESULTS: Cryoablation reliably produced a controlled transmural area of necrosis (both serosa and mucosa) by both techniques. The size and extent of the lesion were directly proportional to the duration of freezing and the type of cryoprobe used. The pathology report confirmed the full-thickness coagulative necrosis of muscle. Bladder perforation was not detected clinically or at autopsy. CONCLUSION: Cryoablation produces reliable zones of tissue destruction without bladder perforation. These preliminary data show the safety and feasibility for trials in the treatment of bladder tumors by laparoscopic, cystoscopic, or image-guided techniques.     

Management of ureteral stenoses and urinary fistulas following kidney transplantation]

The treatment of strictures and fistulas at the lower ureter after kidney transplantation was simple and could be achieved by reimplantation into the bladder. Proximal urinary fistulas caused early abdominal symptoms. The i.v. urogram showed a dilated renal pelvis without drainage into the ureter. The anatomical findings were in all cases strictures or total obstruction of the ureter beneath the pelvic junction and a rupture of the renal pelvis or calix. Adequate therapy consisted of ureteroureterostomy with the recipient ureter and nephrostomy splintage.     

Treatment of ureteral obstruction and urinary fistulas after kidney transplantation]

In 285 renal transplantations, performed during the years 1967-1978, 6 ureteral obstructions (2,1%) and 15 urinary fistulas (5,3%) were observed. Ureteral obstructions occurred in the late phase after transplantation and were caused by strictures at the uretero-vesical anastomosis (two patients), compression of the ureter by enlarged kidney during rejection (one patient) resp. lymphocele (one patient) and strictures at the pyelo-ureteral junction (two patients). Satisfactory results were achieved by surgical treatment in all patients. Urinary fistulas occurred in the early postoperative phase. Two vesical, 12 vesico-ureteral and one calyceal fistula were observed. 7 fistulas (1 vesical, 6 vesico-ureteral) closed spontaneously after temporary drainage of the bladder. 8 fistulas were repaired surgically. While satisfactory results were obtained in 13 patients, two patients died due to infection and sepsis after reoccurrence of fistulas.     

Hemothorax after percutaneous cryoablation of the kidney

Pleural effusions have not been reported after percutaneous cryoablation of the kidney. In our initial experience, we identified and treated two patients who had the complication of hemothorax after percutaneous cryoablation for renal malignancy. The occurrence of pleural effusions is frequently related to technical aspects of the procedure. The pathogenesis of this serious complication is discussed and preventive measures are highlighted.     

Effect of urinary transport function on the development of kidney calculi]

The formation of renal calculus is, according to the currently accepted view, a polyetiological process whose most important components are the composition of the urine and urinary stasis. The second of these factors is discussed. The importance of anatomical lesions is indicated by the finding of a hindrance of flow in 66 of the 100 patients operated for renal calculus. The stasis may, however, have some functional cause, too. X-rays revealed two types of hypomotility: a temporary, or in certain parts constant, lack of contractions and sluggish contractions of normal frequency. Temporary lack or sluggishness of contraction promotes calculus formation because the physiological pyelo-calicous reflux which occurs in three quarters of the intact cases is lacking. These refluxes counteract sedimentation and together with the orthostatic emptying are the most effective factors preventing the retention of calculus nuclei.     

Irreversible electroporation of the porcine kidney: Temperature development and distribution

ObjectiveAlthough 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.MethodsThe animal procedures were conducted following an approved Institutional Animal Ethics Committee protocol. IRE ablation was performed in 8 porcine kidneys. Of them, 4 kidneys were treated with a 3-needle configuration and the remaining 4 with a 4-needle configuration. All IRE ablations consisted of 70 pulses with a length 90 µs. The pulse frequency was set at 90 pulses/min, and the pulse intensity at 1,500 V/cm with a spacing of 15 mm between the needles. The temperature was measured internally using 4 fiber-optic temperature probes and at the surface using a thermal camera.ResultsFor the 3-needle configuration, a peak temperature of 57°C (mean = 49±10°C, n = 3) was measured in the core of the ablation zone and 40°C (mean = 36±3°C, n = 3) at 1 cm outside of the ablation zone, from a baseline temperature of 33±1°C. For the 4-needle configuration, a peak temperature of 79°C (mean = 62±16°C, n = 3) was measured in the core of the ablation zone and 42°C (mean = 39±3°C, n = 3) at 1 cm outside of the ablation zone, from a baseline of 35±1°C. The thermal camera recorded the peak surface temperatures in the center of the ablation zone, reaching 31°C and 35°C for the 3- and 4-needle configuration IRE (baseline 22°C).ConclusionsThe application of repetitive high-intensity electric pulses during IRE ablation in porcine kidney causes a lethal rise in temperature within the ablation zone. Temperature monitoring should be considered when performing IRE ablation near vital structures.     

Ultrashort intracorporeally maneuverable cryoprobes for laparoscopic renal cryoablation in the porcine model

AIM: To determine the feasibility and efficacy of laparoscopic renal cryosurgery using a novel ultrathin ultrashort intracorporeal cryoprobe in a porcine model. MATERIAL AND METHODS: Novel cryoprobes 4 cm in length and 1.5 mm in diameter were manipulated intracorporeally after insertion via a designated 15 mm laparoscopic port. Renal cryoablative lesions were induced laparoscopically in four 40 kg female piglets. We correlated between intraoperative temperature, ice ball geometry, intraoperative ultrasonographic properties, and histology. RESULTS: Laparoscopic manipulation of the cryoprobes was straightforward. No port site bleeding occurred during insertion, freezing, thawing or upon removal of the probes. The 0 degrees C, -20 degrees C, and -40 degrees C isotherms were measured at 6, 8, and 12 mm from the probe circumferentially. Ice-ball volume stabilization as determined by ultrasound occurred after 10 min of activation. Lower temperatures were reached after 10 min of probe activation as compared with 5 min (ice ball diameter 30 mm, DeltaT = 13-21 degrees C). Using a second 10-min-long freeze cycle resulted in a 14-22 degrees C lower temperature within the ice ball compared to a single cycle. Full coagulative necrosis was noted in the areas between the inserted probes with an additional 1-2 mm circumferential rim of severe tubular damage and apoptosis. CONCLUSIONS: Our novel cryoprobe can be used effectively and conveniently in laparoscopic renal cryosurgery. Considering the size of the cryogenic lesion, using a cluster of probes may be advisable.     

Cortical blood-flow in the porcine kidney

Summary Renal cortical blood-flow distribution was measured by means of radiolabeled microscopheres in eight kidneys from 4 pigs of mixed Yorkshire and Danisk landrace. We found a pronounced intracortical variation in the perfusion pattern of 28 sections of outer cortex. Three consequetive flow determinations with an interval of 45 minutes showd that the heterologous perfusion pattern was plastic, changing between the flow-determinations. In addition, we found a significantly reduced perfusion in the renal poles, compared to the rest of the outer cortex. It is speculated that the reduced polar perfusion is a contributing aetiological factor to the increased incidence of polar scar formation secondary to reflux nephropathy.     

Effects of an acute protein load on urinary albumin excretion in kidney donors

In six kidney donors with normal baseline urinary albumin excretion (UAE) we studied the behavior of the UAE after 150 g of a meat protein meal and after a carbohydrate meal of equal caloric (1,370 kcal), water (1 liter) and sodium content (51 mEq). The mean creatinine clearance (Ccr) increased significantly after a protein load at the first (p less than 0.01) and second hour (p less than 0.05), while it did not change after the carbohydrate meal. The mean UAE increased significantly after the protein meal at the first (p less than 0.05) and second hour (p less than 0.05), while after the carbohydrate meal the mean values were increased at the first (p less than 0.05), second (p less than 0.05) and third hour (p less than 0.05). Furthermore, the mean values of UAE after the protein meal were significantly higher (p less than 0.05) than those found at the same time after the carbohydrate meal. Diuresis and natriuresis increased significantly after both meals. These findings show that the increased UAE after the protein meal may be due to a further increase in Ccr in the hyperfiltering remaining kidney, while the smaller increase in the UAE observed after the carbohydrate meal may be due to water load and increased urine flow, which impairs albumin tubular reabsorption. The prognostic importance of microalbuminuria after either meal is therefore uncertain.     

Effects of missense mutations on rat aquaporin-2 in LLC-PK1 porcine kidney cells.

BACKGROUND: Mutations in the aquaporin-2 (AQP2) gene have been found in families with nephrogenic diabetes insipidus (NDI), but the pathophysiological mechanisms of how mutant AQP2 causes the disease are still not clear. METHODS: Wild-type (WT) AQP2 and four mutants-T126M, A147T, R187C, and S216P-were transiently expressed in LLC-PK1 cells. The osmotic water permeability of LLC-PK1 cells expressing AQP2 mutants was determined by stopped-flow light-scattering microphotometry. Cell surface expression, subcellular localization, and effects of vasopressin stimulation were examined by surface biotin labeling and confocal immunohistochemistry. RESULTS: The osmotic water permeability (Pf) of cells expressing WT increased significantly after vasopressin treatment, whereas the Pf of cells expressing T126M A147T, R187C, and S216P was not significantly different from that of the control even after vasopressin stimulation. Confocal immunohistochemistry demonstrated distribution of WT and A147T in early/recycling endosomal compartments and vasopressin-responsive translocation and surface expression. In contrast, stainings of T126M, R187C, and S216P were similar to that of Grp78, indicating that these mutants were misassembled and retarded in the endoplasmic reticulum. CONCLUSION: Our results indicated that the intracellular distribution and vasopressin-regulated trafficking of A147T is intact, in contrast to the other three mutants, of which both were impaired. Thus, it is conceivable that the disruption of the AQP2 channel function accounts for the pathogenesis of A147T NDI, whereas trafficking defects account for that of the other types, suggesting that the pathophysiology of AQP2-related NDI is heterogeneous.     

Fibroblast growth factor receptor signaling in kidney and lower urinary tract development

Fibroblast growth factor receptors (FGFRs) and FGF ligands are highly expressed in the developing kidney and lower urinary tract. Several classic studies showed many effects of exogenous FGF ligands on embryonic renal tissues in vitro and in vivo. Another older landmark publication showed that mice with a dominant negative Fgfr fragment had severe renal dysplasia. Together, these studies revealed the importance of FGFR signaling in kidney and lower urinary tract development. With the advent of modern gene targeting techniques, including conditional knockout approaches, several publications have revealed critical roles for FGFR signaling in many lineages of the kidney and lower urinary tract at different stages of development. FGFR signaling has been shown to be critical for early metanephric mesenchymal patterning, Wolffian duct patterning including induction of the ureteric bud, ureteric bud branching morphogenesis, nephron progenitor survival and nephrogenesis, and bladder mesenchyme patterning. FGFRs pattern these tissues by interacting with many other growth factor signaling pathways. Moreover, the many genetic Fgfr and Fgf animal models have structural defects mimicking numerous congenital anomalies of the kidney and urinary tract seen in humans. Finally, many studies have shown how FGFR signaling is critical for kidney and lower urinary tract patterning in humans.     

Endoscopic ureteral occlusion for urinary diversion in patients with lower urinary tract fistulas

Endoscopic ureteral occlusion and nephrostomy drainage is a simple, nonsurgical procedure that can control urine leakage from an intractable lower urinary tract fistula and improve the quality of life for a patient with a short life expectancy.     

The effect of short-term obstruction on urinary bladder function in the rabbit

The effect of short term partial obstruction on urinary bladder function was studied in rabbits. After 1 week of partial bladder obstruction, the bladders were significantly hypertrophied with a mass over 9 times that of control bladders. The obstruction resulted in a marked decrease in both intracellular ATP and muscarinic receptor density. In vitro response of isolated smooth muscle strips from the obstructed bladder body to cholinergic stimulation was only 50 per cent of the response of control bladders. The obstructed bladder was able to expel only 28 per cent of its volume whereas control bladders expelled 100 per cent of their volume. The results of these studies demonstrate the rapid nature of the response of the bladder to chronic obstruction. Within 1 week frank hypertrophy and significant defects in the contractile ability of the bladder were evident.     

Effects of arterial pressure in an experimental isolated haemoperfused porcine kidney preservation system

BACKGROUND: Normothermic preservation provides metabolic support to an ischaemically damaged organ before use as a kidney transplant. Optimal conditions for ex vivo preservation have not yet been established. This study examined the effects of arterial pressure on renal preservation using isolated haemoperfused kidneys. METHODS: An isolated organ preservation system, developed using cardiopulmonary bypass technology, was used to perfuse porcine kidneys with normothermic oxygenated blood. Groups of kidneys (n = 6) were perfused at a mean arterial pressure of 95, 75 or 55 mmHg. RESULTS: Kidneys perfused at the higher mean arterial pressures of 95 and 75 mmHg demonstrated improved renal function: mean(s.d.) area under the curve (AUC) for creatinine clearance 71(19) and 55(30) respectively versus 14(12) in the 55-mmHg group, P = 0.002; AUC for serum creatinine 938(140) and 1290(394) versus 2404(595), P = 0.003. The higher perfusion pressures were also associated with better acid-base homeostasis and improved renal haemodynamics. CONCLUSION: Mean arterial pressures of either 95 or 75 mmHg were capable of sustaining physiological renal function, but kidneys in the 95-mmHg group demonstrated superior renal function overall.