Trends of lymphadenectomy in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy

Introduction

To evaluate temporal trends in the delivery and extent of lymphadenectomy (LND) in radical nephroureterectomy (RNU) performed in upper tract urothelial carcinoma (UTUC) patients.

Methods

We evaluated a multi institutional collaborative database composed by 1512 consecutive patients diagnosed with UTUC treated with RNU between 1990 and 2016. Year of surgery were grouped in five periods: 1990–1996, 1997–2002, 2003–2007, 2008–2012 and 2013–2016. Data about LND were available for all patients and numbers of nodes removed and positive were reported by dedicate uropathologists. The Mann–Whitney and Chi square tests were used to compare the statistical significance of differences in medians and proportions, respectively.

Results

Five hundred forty-five patients (36.0%) received a concomitant LND while 967 (64.0%) did not; 41.9% of open RNU patients received a concomitant LND compared to 24.4% of laparoscopic RNU patients. The rate of concomitant LND increased with time in the overall, laparoscopic and open RNU patients (all p?<?0.03). Patients treated with open RNU also had an increasing likelihood to receive an adequate concomitant LND (p?<?0.001) while those undergoing a laparoscopic approach did not (p?=?0.1). Patients treated with concomitant LND had a median longer operative time of 20 min (p?=?0.01). There were no differences in perioperative outcomes and complications between patients who received a concomitant LND and those who did not (p?>?0.1).

Conclusion

Although an increased trend was observed, most patients treated with RNU did not receive LND. Surgeons using a laparoscopic RNU were less likely to perform a concomitant LND, and when done, they remove less nodes.

     

Halothane enhances dopamine metabolism at presynaptic sites in a calcium-independent manner in rat striatum

Background. We have previously reported that halothane anaesthesiaincreases the extracellular concentration of dopamine (DA) metabolitesin the rat striatum with no change in DA. Although the metabolismof catecholamines is a source of oxidative stress, there islittle information about DA metabolism and anaesthesia. We assessedthe mechanism(s) of enhanced DA metabolism induced by halothane. Methods. Microdialysis probes were implanted into male Sprague–Dawleyrats and perfused with artificial cerebrospinal fluid (CSF).The dialysate was injected directly into an HPLC every 20 min.Each group of rats (n=5–7) was administered saline, apomorphine100 µg kg^–1, pargyline 7.5 or 75 mg kg^–1,reserpine 2 mg kg^–1 or -methyl-p-tyrosine (AMPT) 250 mgkg^–1. Another set of rats was perfused with artificialCSF containing tetrodotoxin (TTX) 1 µM or calcium-freeCSF containing 10 mM EGTA. Rats were anaesthetized with halothane0.5 or 1.5% 1 h after pharmacological treatments. Results. In rats pretreated with apomorphine, despite a decreasein DA concentration, halothane induced a increase in DA metabolites.Pargyline (high dose) and reserpine completely and AMPT partiallyantagonized the increase in DA metabolites induced by halothaneanaesthesia. TTX perfusion reduced the increase in DA, whereascalcium-free CSF perfusion did not. Conclusions. Our data suggest that halothane accelerates DAmetabolism at presynaptic sites by releasing DA from reserpine-sensitivestorage vesicles to the cytoplasm in a calcium-independent manner.The metabolic oxidative stress of inhalation anaesthesia requiresfuture investigation.     

Antifracture Efficacy and Reduction of Mortality in Relation to Timing of the First Dose of Zoledronic Acid After Hip Fracture

Annual infusions of zoledronic acid (5 mg) significantly reduced the risk of vertebral, hip, and nonvertebral fractures in a study of postmenopausal women with osteoporosis and significantly reduced clinical fractures and all‐cause mortality in another study of women and men who had recently undergone surgical repair of hip fracture. In this analysis, we examined whether timing of the first infusion of zoledronic acid study drug after hip fracture repair influenced the antifracture efficacy and mortality benefit observed in the study. A total of 2127 patients (1065 on active treatment and 1062 on placebo; mean age, 75 yr; 76% women and 24% men) were administered zoledronic acid or placebo within 90 days after surgical repair of an osteoporotic hip fracture and annually thereafter, with a median follow‐up time of 1.9 yr. Median time to first dose after the incident hip fracture surgery was ～6 wk. Posthoc analyses were performed by dividing the study population into 2‐wk intervals (calculated from time of first infusion in relation to surgical repair) to examine effects on BMD, fracture, and mortality. Analysis by 2‐wk intervals showed a significant total hip BMD response and a consistent reduction of overall clinical fractures and mortality in patients receiving the first dose 2‐wk or later after surgical repair. Clinical fracture subgroups (vertebral, nonvertebral, and hip) were also reduced, albeit with more variation and 95% CIs crossing 1 at most time points. We concluded that administration of zoledronic acid to patients suffering a low‐trauma hip fracture 2 wk or later after surgical repair increases hip BMD, induces significant reductions in the risk of subsequent clinical vertebral, nonvertebral, and hip fractures, and reduces mortality.     

Repeat Low‐Trauma Fractures Occur Frequently Among Men and Women Who Have Osteopenic BMD

Fracture risk assessment based solely on BMD has limitations. Additional risk factors include the presence of a previous low‐trauma fracture. We sought to quantify the fracture burden attributable to first versus repeat fracture. We studied 2179 men and 5269 women, 50–90 yr of age, participating in the Canadian Multicentre Osteoporosis Study (CaMos). We included all low‐trauma fractures that occurred over 8 yr of follow‐up and classified these as either first or repeat clinical low‐trauma fracture based on lifetime fracture history. Analyses were further stratified by sex, age, BMD risk categories (normal, osteopenia, osteoporosis), and vertebral deformity status. There were 128 fractures in men and 577 fractures in women. About 25% of fractures in men and 40% in women were repeat fractures. Just over one half of first fractures occurred in those with osteopenic BMD (58% in men, 54% in women). Just under one half of repeat fractures also occurred in those with osteopenic BMD (42% in men, 47% in women). The incidence of repeat fracture was, in most cases, nearly double, but sometimes nearly quadruple, the incidence of first fracture within a given BMD risk category in both men and women. Repeat fractures contribute substantially to overall fracture burden, and the contribution is independent of BMD. Furthermore, those with a combination of prior low‐trauma fracture and another risk factor were at especially high risk of future fracture.     

Repeat biopsy of the suspicious prostate cancer: especially the usefulness of MRI

Among patients with negative initial biopsies of the prostate, 51 patients underwent total 59 repeat biopsies at the Department of Urology of Ikeda Municipal Hospital between January 1998 and April 2004. Overall 26 patients (44.1%) were confirmed to have cancer, 22 patients by second repeat biopsy (22/51), four patients by third biopsy (4/7) and none by fourth biopsy (0/1). Clinical parameters (age, PSA, PSA density, PSA velocity) were analyzed for the possibility to predict the pathological outcome. Significant differences between the positive biopsy group and the negative biopsy group were obtained in age, PSA level and prostatic volume. Of the diagnostic evaluations including palpation and imaging studies (DRE, TRUS, MRI), the most powerful predictor for prostate cancer seemed to be the MRI findings, especially in the cases of short-interval repeat biopsy. Biopsies directed at the positive lesion on MRI in addition to systematic prostate biopsies should be useful.     

Living-Donor Liver Transplantation for Hepatoblastoma

Hepatoblastoma is the most common malignant liver tumor in children. Recently, liver transplantation has been indicated for unresectable hepatoblastoma. We retrospectively reviewed 14 children with a diagnosis of hepatoblastoma who had undergone living-donor liver transplantation (LDLT) at Kyoto University Hospital. During the period from June 1990 to December 2004, 607 children underwent LDLT. Of these interventions, 2.3% were performed for hepatoblastoma. Based on radiological findings, the pre-treatment extent of disease (PRETEXT) grouping was used for pre-treatment staging of the tumor. There were grade III in seven patients and grade IV in seven patients. Thirteen patients received chemotherapy, and seven underwent hepatectomy 11 times. Immunosuppressive treatment consisted of tacrolimus monotherapy in 11 patients. Actuarial 1- and 5-year graft and patient survival rates were 78.6% and 65.5%. The poor prognostic factors were macroscopic venous invasion and extrahepatic involvement with 1-year and 5-year survival rates of 33.0% and 0%. Pediatric patients without these factors showed an acceptable 5-year survival rate of 90.9%. LDLT provides a valuable alternative with excellent results in children with hepatoblastoma because it allows optimal timing of the liver transplantation, given the absence of delay between the completion of chemotherapy and planned liver transplantation.     

alpha1-Adrenergic mechanism in diabetic urethral dysfunction in rats

PURPOSE: We investigated the contribution of alpha1-adrenoceptor mechanisms to urethral dysfunction associated with diabetes mellitus (DM) in rats. MATERIALS AND METHODS: Eight weeks after streptozotocin injection (65 mg/kg intraperitoneally) the effects of DM on urethral relaxation mechanisms were evaluated with subjects under urethane anesthesia by simultaneous recordings of intravesical pressure in isovolumetric conditions and urethral perfusion pressure (UPP). RESULTS: In diabetic rats the intravesical pressure thresholds for inducing urethral relaxation and the lowest urethral pressure (UPP nadir) during urethral relaxation were significantly higher by 142% and 86%, respectively, than in normal rats, while baseline UPPs were not significantly different. The mean rate of high frequency oscillations of urethral striated muscle in diabetic rats was also significantly lower by 23% than in normal rats. After alpha-bungarotoxin treatment (333 mug/kg intravenously) to eliminate striated muscle sphincter contractions the SD of baseline UPPs was significantly larger by 93% than in normal rats. Intravenous administration of terazosin (0.4 mg/kg), an alpha1-adrenoceptor antagonist, significantly decreased the UPP nadir, intravesical pressure thresholds inducing urethral relaxation and the SD by 41%, 87% and 138%, respectively, in diabetic rats but not in normal rats. In the 2 groups of animals after alpha-bungarotoxin treatment urethral relaxation during a reflex bladder contraction was inhibited by Nomega-nitro-L-arginine (40 mg/kg intravenously), a nitric oxide synthase inhibitor. CONCLUSIONS: During reflex bladder contractions streptozotocin induced diabetic rats showed smooth and striated muscle dysfunctions of the urethra. The inhibition of alpha1-adrenoceptors, which decreased the UPP nadir and UPP fluctuation, may be useful for treating urethral dysfunction in DM.     

Suppression of energy requirement by lidocaine in the ischemic mouse brain

Effects of lidocaine on parameters of membrane functional integrity were investigated in the mouse brain. Changes in the direct-current potential shift in the cerebral cortex provoked by decapitation ischemia were compared in animals given lidocaine (0.05, 0.25, or 1.0 micromol, intracerebroventricular) or saline 15 minutes before ischemia. The brain content of adenosine 5'-triphosphate (ATP) was measured in animals subjected to 0, 0.5, 1, and 2 minutes of decapitation ischemia, and the effect of preischemic administration of lidocaine (0.25 micromol, intracerebroventricular) was evaluated. Na+, K+-ATPase, and Ca2+-ATPase activity was evaluated in brains pretreated with lidocaine (0.25 micromol, intracerebroventricular) or saline 15 minutes before decapitation. Changes in the intracellular Ca concentration ([Ca2+]i) were evaluated in hippocampal slices and the effects of lidocaine (50, 100, or 400 microM) were assessed in the hippocampal CA1 field and dentate gyrus at pH 7.4 and pH 6.8 every 60s for a duration of 50 min. The preischemic administration of lidocaine (1.0 and 0.25 micromol) delayed the onset of anoxic depolarization to 49 seconds and 44 seconds, respectively, as compared with that in the saline group at 27 seconds. Lidocaine maintained ATP levels higher than those in corresponding saline groups, values being 165% after 1 minute of ischemia and 212% after 2 minutes, respectively. Lidocaine did not affect Na+, K+-ATPase, and Ca2+-ATPase activity. Lidocaine did not affect changes in the [Ca2+]i in either area at either pH. The findings may suggest that lidocaine maintains the energy level by delaying depolarization in neurons, which may contribute to removal of cytosolic Ca2+ in ischemic states.     

Facilitation of Serotonergic Activity and Amnesia in Rats Caused by Intravenous Anesthetics

Background: Midazolam and propofol often provoke retrograde amnesia after recovery from anesthesia in humans. Because an increase in central serotonergic activity impairs learning and memory, the authors examined the relation between changes in the serotonergic activity caused by intravenous anesthetics and memory.

Methods: Changes in extracellular concentrations of monoamines and their metabolites were investigated in rat striatum by a microdialysis procedure, and the effects of intraperitoneal injections of midazolam (5 mg/kg), propofol (60 mg/kg), and pentobarbital (15 mg/kg) were then examined. To evaluate the behavioral alteration with these agents, the authors used a step-through passive avoidance test.

Results: Midazolam and propofol slightly increased the extracellular concentration of 5-hydroxytryptamine in the striatum, although pentobarbital did not produce any changes. Midazolam and propofol increased the extracellular concentration of 5-hydroxyindoleacetic acid, a metabolite of 5-hydroxytryptamine, with the peak values each 138% and 138% of that in saline-injected animals, respectively. However, pentobarbital decreased the 5-hydroxyindoleacetic acid concentration to 61% of that in the saline group. Administration of midazolam or propofol immediately after the completing the passive avoidance learning reduced step-through latencies after 24 h, although pentobarbital-injected animals maintained a consistent performance. The effects of midazolam and propofol on step-through latencies were completely antagonized by intracerebroventricular administration of spiroxatrine (5 [mu]g), a 5-hydroxytryptamine 1A antagonist, 30 min before training.