Strategies in the management of renal tumors amenable to partial nephrectomy.

PURPOSE: The laparoscopic approach to radical and partial nephrectomy is becoming the standard of care for treating patients with renal tumors. Hand-assisted laparoscopic partial nephrectomy (HALPN) provides some advantages over the pure laparoscopic approach which include manual manipulation of the kidney, tactile feedback, and timely specimen removal. MATERIALS AND METHODS: We describe our technique for HALPN and emphasize the implementation of an in-room pathologist to examine gross margins during the period of renal arterial occlusion. Between 2004 and 2007, 46 patients underwent HALPN performed by the same surgeons. Mean patient age was 59.5 years and mean tumor size was 2.55 cm. Twelve of these patients underwent significant concomitant procedures. RESULTS: Our mean operating time was 173.26 min (range 90-306 min) and our mean warm ischemic time was 28.32 min (range 14-54 min). Average estimated blood loss was 116.82 ml (range 10-1000 ml) with no transfusions. Thirty-six (78%) tumors were renal cell carcinoma, seven (15%) were oncocytomas, and three (7%) were angiomyolipomas. The average length of stay was 5.17 days (range 3-9 days) and there were no positive margins. There was one postoperative bleed (2%) and two postoperative urine leaks (4.3%). DISCUSSION: In our institution, the hand-assist approach to laparoscopic partial nephrectomy has resulted in favorable perioperative outcomes. The use of an in-room pathologist to provide real-time assessment of gross tumor margins has allowed us to achieve a 0% positive final margin rate. We believe that the use of an in-room pathologist during the timely extraction of the specimen made possible by the hand-assisted approach provides a great advantage over pure laparoscopic partial nephrectomy. This low positive margin rate is also the result of maintaining a bloodless field of resection with temporary renal arterial occlusion as well as the avoidance of visual tissue distortion with cold, sharp scissor dissection.

Social and environmental influences on opioid sensitivity in rats: importance of an opioid's relative efficacy at the mu-receptor.

RATIONALE: Evidence indicates that social and environmental enrichment can influence the functional maturation of the central nervous system and may affect an organism's sensitivity to centrally acting drugs. OBJECTIVE: The purpose of the present study was to examine the effects of social and environmental enrichment on sensitivity to mu-opioids possessing a range of relative efficacies at the mu-receptor. METHODS: Rats were obtained at weaning (21 days) and divided into two groups immediately upon arrival. Isolated rats were housed individually in opaque laboratory cages with no visual or tactile contact with other rats; enriched rats were housed socially in groups of four in large cages and given various novel objects on a daily basis. After 6 weeks under these conditions, the effects of morphine, levorphanol, buprenorphine, butorphanol, and nalbuphine were examined in the warm-water, tail-withdrawal procedure and the place-conditioning procedure. RESULTS: In the tail-withdrawal procedure, isolated and enriched rats did not differ in sensitivity to morphine (1.0-30 mg/kg) and levorphanol (0.3-10 mg/kg), but enriched rats were more sensitive to buprenorphine (0.03-3.0 mg/kg), butorphanol (0.3-30 mg/kg), and nalbuphine (0.3-30 mg/kg). In drug combination tests, butorphanol and nalbuphine antagonized the effects of morphine in isolated rats under conditions in which they produced high levels of antinociception in enriched rats. In the place-conditioning procedure, doses of 10 morphine and 3.0 levorphanol established a place preference in both groups of rats, whereas doses of 0.3 buprenorphine, 3.0 butorphanol, and 10 nalbuphine established a place preference only in enriched rats. CONCLUSIONS: These findings may be taken as evidence that enriched rats are more sensitive than isolated rats to the effects of lower-efficacy mu-opioids and that social and environmental enrichment leads to functional alterations in opioid receptor populations.

Sensitivity to the effects of a kappa opioid in rats with free access to exercise wheels: differential effects across behavioral measures.

It is well established that chronic exercise decreases sensitivity to mu opioid agonists; however, it is less clear what effects it has on kappa opioids. The purpose of the present study was to examine sensitivity to the effects of the selective, kappa opioid spiradoline in rats with free access to exercise wheels. Rats were obtained at weaning and randomly assigned to either standard polycarbonate cages (sedentary) or modified cages equipped with exercise wheels (exercise). After approximately 7 weeks under these conditions, sensitivity to the effects of spiradoline on tests of antinociception, locomotor activity, conditioned place preference, and diuresis were examined in both groups of rats. Sedentary rats were more sensitive than exercising rats to the antinociceptive effects of spiradoline, and this effect was observed at both low and high nociceptive intensities. In contrast, exercising rats were more sensitive than sedentary rats to the diuretic effects of spiradoline, and slightly more sensitive to spiradoline's effects in the conditioned place preference procedure. No differences in sensitivity were observed to the effects of spiradoline on locomotor activity. Sensitivity to the antinociceptive effects of spiradoline nonsignificantly increased in exercising rats that were reassigned to sedentary housing conditions, and changes in spiradoline sensitivity were correlated with exercise output in individual subjects. Collectively, these data suggest that exercise alters sensitivity to the behavioral effects of kappa opioids, but that the direction and magnitude of this effect depends on the behavioral measure examined.

Social and environmental enrichment enhances sensitivity to the effects of kappa opioids: studies on antinociception, diuresis and conditioned place preference.

Previous studies have reported that social and environmental enrichment can have a marked impact on the functional maturation of the central nervous system and may influence an organism's sensitivity to psychotropic drugs. The purpose of the present study was to examine the effects of social and environmental enrichment on sensitivity to drugs possessing activity at the kappa opioid receptor. Rats were obtained at weaning and randomly assigned to one of two housing conditions: isolated rats were housed individually with no visual or tactile contact with other rats; enriched rats were housed in groups of four in large cages and given various novel objects on a regular basis. After 7 weeks under these conditions, the effects of spiradoline, U69,593 and nalorphine were examined in the warm water, tail-withdrawal procedure. The effects of spiradoline were also examined on urine output and in the conditioned place preference procedure. Enriched rats were more sensitive to the antinociceptive effects of all the opioids examined in the tail-withdrawal procedure, and were more sensitive to the effects of spiradoline on urine output and in the conditioned place preference procedure. Following the conclusion of these tests, housing conditions were reassigned, such that isolated rats were transferred to enrichment cages, and enriched rats were transferred to isolation cages. After 7 weeks under these new conditions, the two groups were equally sensitive to the antinociceptive effects of spiradoline, indicating that the effects of the initial housing conditions were, in part, reversible. Collectively, these data suggest that enriched rats are more sensitive than isolated rats to the effects of kappa opioids, and that the kappa opioid receptor system is sensitive to social and environmental manipulations after weaning.

Interactions between opioids and cocaine on locomotor activity in rats: influence of an opioid's relative efficacy at the mu receptor.

RATIONALE: Cocaine and mu opioid agonists increase central dopamine concentrations and produce robust interactions at both neurochemical and behavioral levels. Although the interactions between cocaine and high-efficacy mu opioids have been well characterized, the interactions between cocaine and lower efficacy opioids have not been as extensively examined. OBJECTIVE: The purpose of this study was to examine the interactions between cocaine and opioids possessing a range of relative efficacy at the mu receptor. METHODS: Male, Long-Evans rats were habituated to an open-field, locomotor activity chamber, and the effects of cocaine and various opioids were tested under a cumulative dosing procedure. In this procedure, a selected dose of an opioid was administered during the first component of a session, with increasing doses of cocaine administered during subsequent components. RESULTS: When administered alone, cocaine produced dose-dependent increases in locomotor activity that was stable across 5 weeks of behavioral testing. The high-efficacy mu opioid levorphanol, and the low-efficacy opioids buprenorphine, butorphanol, nalbuphine and (-)-pentazocine, dose-dependently enhanced the effects of cocaine at doses that did not alter locomotor activity when administered alone. In contrast, the opioid antagonist naloxone, and to a lesser extent, the kappa opioid spiradoline attenuated the effects of cocaine at doses that did not alter locomotor activity when administered alone. Across an extensive dose range, the low-efficacy opioid nalorphine failed to alter cocaine's locomotor-activating effects. CONCLUSIONS: These data suggest that low-efficacy opioids possessing significant mu-agonist activity (e.g. buprenorphine, butorphanol, nalbuphine, (-)-pentazocine) may potentiate the effects of cocaine in a manner similar to that typically observed with high-efficacy mu opioids.