Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial.

Background: The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy. Patients and methods: In a phase III, randomized, double-blind trial, patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease [independent review committee (IRC) confirmed]. The intent-to-treat population included all randomized patients [≥pT2 and/or N+, any Fuhrman grade (FG), Eastern Cooperative Oncology Group status 0/1]. Patients (stratified by risk group/country) received (1 : 1) oral twice-daily axitinib 5 mg or placebo for ≤3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG ≥ 3 or pT4 and/or N+, any T, any FG) was conducted. Results: A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from 8 May 2012, to 1 July 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC [hazard ratio (HR) = 0.870; 95% confidence interval (CI) : 0.660-1.147; P = 0.3211). In the highest-risk subpopulation, a 36% and 27% reduction in risk of a DFS event (HR; 95% CI) was observed per investigator (0.641; 0.468-0.879; P = 0.0051), and by IRC (0.735; 0.525-1.028; P = 0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99% versus 92%) and serious AEs (19% versus 14%), but more grade 3/4 AEs (61% versus 30%) were reported for axitinib versus placebo. Conclusions: ATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported. Trial registration number: NCT01599754.

Evaluation of treatment pattern and symptom control in patients with gastroesophageal reflux disease: multihospital questionnaire survey on the current situation in Korea.

Proton pump inhibitors (PPIs) are the most effective treatment for gastroesophageal reflux disease (GERD); however, a considerable number of patients fail to respond to PPI therapy and complain of nocturnal heartburn and sleep disturbance. The aims of this study are to evaluate the treatment pattern of GERD-related medications and their efficacy in relieving nocturnal heartburn. A total of 334 patients with GERD receiving PPI therapy within 6 months were enrolled in a multihospital questionnaire survey from January, 2014 to March, 2015. GERD symptoms and patients' satisfaction were assessed by patient questionnaires, and treatment patterns of GERD-related medications were assessed by investigators. Among the 334 patients, 95.8% used PPI once daily and 58.6% used a half-dose of PPI. The PPI treatment pattern was changed in 26.6% of all patients, of those, 54% of the patients doubled the PPI dose, and 29.2% of the patients switched to another PPI. Approximately 60.3% of all patients were prescribed more than three GERD-related medications. The overall satisfaction rate was 61.8%, and 32.2% of patients experienced nocturnal heartburn and sleep disturbance. In the extended-release PPI group, there were fewer nocturnal symptoms compared with the conventional PPI group (10% vs. 33.7%, respectively, P = 0.027). The use of more than three medications was inversely associated with patients' satisfaction (OR = 0.355, 95% CI; 0.197-0.642, P = 0.001). Most patients were prescribed adjunctive medications other than PPIs; however, patients' satisfaction was inversely associated with multiple drugs. Patients' satisfaction was superior in extended-release PPIs than conventional PPIs for the relief of nocturnal heartburn in Korean patients.

Compensatory structural and functional adaptation after radical nephrectomy for renal cell carcinoma according to preoperative stage of chronic kidney disease. Choi DK, Jung SB, Park BH, Jeong BC, Seo SI, Jeon SS, Lee HM, Choi HY, Jeon HG.J Urol. 2015 Oct;194(4):910-5. [Epub 2015 Apr 28]. doi: 10.1016/j.juro.2015.04.093.

PURPOSE: We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. MATERIALS AND METHODS: We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease-glomerular filtration rate 90ml/min/1.73m2 or greater (230, 42.4%), chronic kidney disease stage II-glomerular filtration rate 60 to less than 90ml/min/1.73m2 (227, 41.8%), and chronic kidney disease stage III-glomerular filtration rate 30 to less than 60ml/min/1.73m2 (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. RESULTS: Among all patients (mean age = 56.0y) mean preoperative glomerular filtration rate, functional renal volume, and glomerular filtration rate/functional renal volume were 83.2ml/min/1.73m2, 340.6cm3, and 0.25ml/min/1.73m2/cm3, respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs. stage II 26.5% vs. stage III 12.8%, P<0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs. stage II 17.3% vs. stage III 16.5%, P = 0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs. stage II 20.1% vs. stage III 45.9%, P<0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (P = 0.012), diabetes mellitus (P = 0.023), hypertension (P = 0.015), and chronic kidney disease stage (P<0.001). CONCLUSIONS: Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration.

Erythrocyte sedimentation rate and anaemia are independent predictors of survival in patients with clear cell renal cell carcinoma.

BACKGROUND: The 1997 international consensus conference on renal cell cancer (RCC) prognosis suggested erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), and anaemia as prognostic biomarkers, but most studies reviewed were limited by small sample sizes. METHODS: The Cox proportional hazards model was used to evaluate whether ESR, ALP, haemoglobin (Hb), and haematocrit (Hct) could predict survival outcomes in 1307 patients with clear cell RCC (ccRCC) who underwent nephrectomy during 1994-2008. RESULTS: During a median follow-up of 43 months, we found that the patients with preoperative high levels of ESR, had a 2.10-fold (95% confidence interval (CI): 1.21-3.67) greater risk of dying from RCC compared with patients with low levels (normal range). Patients with preoperative anaemia, assessed by Hb and Hct, had a 3.11-fold (95% CI: 1.17-8.25) and 6.20-fold (95% CI: 2.30-16.72) greater risk of dying from other illnesses, respectively, compared with patients without anaemia. ALP levels were not associated with ccRCC patients' survival. These associations for ESR and anaemia were more pronounced in patients with body mass index (BMI) <25 compared with patients with BMI ≥ 25 kg m(-2). CONCLUSION: Preoperative high ESR, but not ALP, was a significant predictor for cancer-specific survival among ccRCC patients. Anaemia increases the risk of death from other illness.

Mechanically-induced proximal arterial occlusion and stent-within-a-stent technique for the treatment of bilateral vertebral artery dissecting aneurysms.

Several endovascular approaches have been used in the treatment of dissecting aneurysms of the vertebrobasilar system. We present a case of a bilateral spontaneous vertebral artery (VA) dissecting aneurysms presenting with a subarachnoid haemorrhage. The dominant left VA aneurysm was treated with a stent-within-a-stent construct and the contralateral VA aneurysm was proximally occluded, with no complications, by an unintentional mechanically-induced arterial occlusion.

N-butyl 2-cyanoacrylate embolization of spinal dural arteriovenous fistula. Presenting with subarachnoid haemorrhage.

SUMMARY: We report an unusual case of spinal dural arteriovenous fistula (SDAVF) presenting with subarachnoid haemorrhage (SAH). Cure was achieved with endovascular treatment with n-butyl 2- cyanoacrylate (NBCA). A review of the literature revealed five cases of cervical SDAVF that presented with SAH. None of these cases were treated with NBCA.

Effects of partial bladder outlet obstruction and its relief on types I and III collagen and detrusor contractility in the rat.

Bladder outlet obstruction induces a rapid hypertrophy characterized by increased bladder mass and collagen deposition. An increase in collagen is likely to reduce the contractility and compliance of bladder wall. This study was undertaken to investigate the effects of partial bladder outlet obstruction and its relief on types I and III collagen, and the relationship between detrusor contractility and collagen types. A total of 40 female rats was used for experiment and divided into one control, one obstruction, and three recovery groups. The contractility to field stimulation was recorded; total collagen and collagen concentration were quantified. The localization of types I and III collagen and the expression of pro-alpha1(I) and alpha1(III) collagen mRNA were determined by immunohistochemical staining and Northern blot hybridization, respectively. Contractile response to field stimulation was reduced after obstruction and recovered following relief. The total amount of collagen increased after obstruction and decreased after relief; however, collagen concentration decreased after obstruction and increased following relief. Contractility correlated negatively with total collagen but positively with collagen concentration. The protein deposition of types I and III collagen was localized in lamina propria and muscle bundles in all groups. The expression of types I and III collagen gene was up regulated after obstruction, but down regulated after relief. Negative correlation between contractility and gene expressions of collagen types was significant. These data suggest that the change in localization and quantity of collagen types leads to morphologic changes of bladder and can have an impact on the contractility of detrusor. Neurourol. Urodynam. 19:29-42, 2000.

Long-term results of percutaneous endourologic management of renal infundibular stricture.

PURPOSE: The long-term result of percutaneous endourologic management in the relief of infundibular stricture is not clear. We reviewed the long-term efficacy in our series of patients. PATIENTS AND METHODS: Twenty-seven patients underwent percutaneous endourologic management between August 1990 and February 1996. This study included the 21 who could be followed for more than 2 years (mean 4.8 years). The causes of stricture were tuberculosis (N = 18; 86%) and stone (N = 3; 14%). We made a cold-knife incision in eight patients; the others underwent only dilation with fascial dilators from 20F to 30F. Success was defined as symptomatic improvement and radiographic resolution of obstruction. RESULTS: The overall success rate was 76% (16 of 21). Seven of the eleven patients (64%) with concomitant ureteral stricture had a successful result. In the nine patients with multiple infundibular strictures, five procedure (56%) were successful. The success rates of the cold-knife or fascial dilator were 88% (7 of 8) and 69% (8 of 13), respectively. In the five patients in whom the procedure failed, ureteral stricture was associated in four and multiple infundibular strictures in four. All of them had tuberculous infundibular strictures. No significant difference in the success rate was observed according to the duration of indwelling catheter. There was no significant complication except pyelonephritis in four patients, which was controlled with conservative treatment. CONCLUSIONS: Percutaneous endourologic management is an effective and safe procedure to treat renal infundibular stricture. Risk factors for failure are multiple infundibular strictures and concomitant ureteral stricture. If the procedure does fail, other treatments have not been compromised. Cold-knife incision seems to be more effective than dilation.

The effects of androgen on penile reflex, erectile response to electrical stimulation and penile NOS activity in the rat.

AIM: To investigate the effects of androgen on penile erection through the reflex arc and penile corpus cavernosum, and study the respective roles of testosterone (T) and dihydrotestosterone (DHT) in penile erection in rats. METHODS: Male Sprague-Dawley rats were castrated and implanted with silastic brand silicone tube containing T or DHT, with or without daily injections of a 5alpha-reductase inhibitor, MK-434. The penile reflex, erectile response to electrical stimulation (ES) of the cavernous nerves and penile nitric-oxide synthase (NOS) activity were observed under varying androgenic status. RESULTS: Penile reflex erection in the rat was, on the whole, related to serum T levels though the number of glans engorgements was not. The number of cups and flips was significantly decreased by castration, and restored to the control level by T supplementation. Erectile response to ES and NOS activity in penile tissue was also related to serum T level. T administered together with a 5alpha-reductase inhibitor no longer restored the number of reflex erection, erectile responses to ES and NOS activity in the corpus caveenosum. CONCLUSION: Androgen influenced the penile reflex arc, corpus cavernosum, and the perineal striated muscles. In reflex erection, erectile response to ES and penile NOS activity in the rat, T seems to be first converted to DHT, the more active androgen modality.