Risk of Cancer-specific Mortality following Recurrence After Radical Nephroureterectomy

Purpose

To describe the natural history and identify predictors of cancer-specific survival in patients who experience disease recurrence after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).

Methods

Of 2,494 UTUC patients treated with RNU without neoadjuvant chemotherapy, 597 patients experienced disease recurrence. A total of 148 patients (25?%) received adjuvant chemotherapy before disease recurrence. Multivariable Cox regression model addressed time to cancer-specific mortality after disease recurrence.

Results

The median time from RNU to disease recurrence was 12?months (interquartile range 5?C22). A total of 491 (82?%) of 597 patients died from UTUC, and 8 patients (1.3?%) died from other causes. The median time from disease recurrence to death of UTUC was 10?months. Actuarial cancer-specific survival estimate at 12?months after disease recurrence was 35?%. On multivariable analysis that adjusted for the effects of standard clinicopathologic characteristics, higher tumor stages [hazard ratio (HR) pT3 vs. pT0?CT1: 1.66, p?=?0.001; HR pT4 vs. pT0?CT1: 1.90, p?=?0.002], absence of lymph node dissection (HR 1.28, p?=?0.041), ureteral tumor location (HR 1.44, p?<?0.0005) and a shorter interval from surgery to disease recurrence (p?<?0.0005) were significantly associated with cancer-specific mortality. The adjusted 6-, 12- and 24-month postrecurrence cancer-specific mortality was 73, 60 and 57?%, respectively.

Conclusions

Approximately 80?% of patients who experience disease recurrence after RNU die within 2?years after recurrence. Patients with non-organ-confined stage, absence of lymph node dissection, ureteral tumor location and/or shorter time to disease recurrence died of their tumor more quickly than their counterparts. These factors should be considered in patient counseling and risk stratification for salvage treatment decision making.     

Comparison of rates and risk factors for development of anaemia and erythropoiesis-stimulating agent utilization after radical or partial nephrectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The consequences and significance of iatrogenically‐induced CKD are poorly understood. Most data regarding risk of CKD and its complications are inferred from the medical literature. This is the first study to examine impact of surgical management of renal masses on development of anaemia. Patients who underwent radical nephrectomy had a significantly higher incidence of anaemia and ESA utilization than a contemporary well‐matched cohort that underwent partial nephrectomy. The results obtained add to the growing body of data supporting the use of partial nephrectomy in the management of clinically appropriate renal masses.

OBJECTIVE

• ? To examine the incidence of and risk factors for the development of anaemia and erythropoiesis‐stimulation agent (ESA) treatment in patients undergoing radical nephrectomy (RN) and partial nephrectomy (PN) because anaemia is a significant cause of morbidity in chronic kidney disease.

PATIENTS AND METHODS

• ? The study comprised a retrospective review of 905 patients (610 RN/295 PN; mean age, 57.5 years; mean follow‐up, 6.4 years) who underwent surgery for renal tumours at two institutions from July 1987 to June 2007.
• ? Demographics, disease characteristics and pre‐ and postoperative (i.e. renal function, metabolic parameters, anaemia and ESA treatment) were recorded.
• ? Data were analyzed within subgroups based on treatment (RN vs PN).
• ? Multivariate analysis was conducted to determine the risk factors for developing anaemia after surgery.

RESULTS

• ? Tumour size (cm) was significantly larger for RN (RN 7.0 vs PN 3.7; P < 0.001). No significant differences were noted with respect to demographics and preoperative anaemia (RN 16.4% vs PN 18.6%; P= 0.454) and ESA‐treatment (RN 0.7% vs PN 1.4%; P= 0.499).
• ? After surgery, significantly less de novo anaemia (PN 4.1% vs RN 17.5%; P < 0.001) and ESA utilization (PN 2.7% vs RN 13.4%; P < 0.001) occurred in the PN cohort.
• ? Multivariate analysis showed that age ≥60 years (odds ratio, OR, 1.62; P= 0.008), African American ethnicity (OR, 2.30; P < 0.001), smoking (OR, 1.60; P= 0.013), glomerular filtration rate (GFR) <60 mL/min/1.73 m² (OR, 4.09; P < 0.001), ≥1+ proteinuria (OR, 2.19; P < 0.03), metabolic acidosis (OR, 4.08; P= 0.007) and RN (OR, 2.58; P < 0.001) were significantly associated with de novo anaemia.

CONCLUSIONS

• ? Patients who underwent RN had a significantly higher prevalence of anaemia and ESA‐treatment compared to a well‐matched cohort that underwent PN.
• ? In addition to RN, age ≥60 years, African American ethnicity, history of smoking, GFR < 60 mL/min/1.73 m², proteinuria and metabolic acidosis were associated with developing anaemia.

     

Effect of exercise training on respiratory muscle oxygenation in children with congenital heart disease.

BACKGROUND: Diminished aerobic capacity and weakness of both respiratory and peripheral muscles have been observed in cardiac patients and may contribute to exercise limitation. The aim of this study was to evaluate the effects of a home-based training programme on aerobic fitness and oxygenation of the respiratory muscles in children with congenital heart disease (CHD). METHODS AND RESULTS: Eighteen patients with CHD aged 12-15 years participated in this study. Ten patients (training group, TG) underwent a training programme for 12 weeks and eight patients served as a non-training control group (CG). All subjects performed a cardiopulmonary exercise test before and after the study period. Oxygenation of the respiratory muscles was assessed using near-infrared spectroscopy. No significant differences were observed, at baseline and after the completion of the study, between the CG and TG in peak exercise workload, oxygen uptake (VO2), carbon dioxide output (VCO2), pulmonary ventilation (VE), and heart rate (HR). However, a significant improvement in exercise performance was found in the TG versus the CG when results were compared at the ventilatory threshold (Vth): workload (45.2+/-8.0 versus 58.5+/-7.4%; P<0.05), VO2 (62.3+/-7.5 versus 69.8+/-5.1%; P<0.05), VCO2 (49.8+/-5.7 versus 60.0+/-5.8%; P<0.05), VE (42.8+/-9.9 versus 50.1+/-9.5%; P<0.05), and HR (69.5+/-6.1 versus 76.0+/-3.5%; P<0.05). After training, an improvement in oxygenation of the respiratory muscles was found in the TG from 60% of VO2max until the end of exercise. At the Vth, the TG showed greater oxygenation after training (55.1+/-6.6 versus 43.0+/-6.9%, P<0.01, respectively). Furthermore, we showed a significant correlation of the change in respiratory muscle oxygenation and VO2 in the TG (r=0.90, P<0.01). CONCLUSION: It is concluded that general physical training at submaximal intensity induces better aerobic fitness and improves respiratory muscle oxygenation in children with CHD.     

Management of acute decompensated heart failure in an evidence-based era: what is the evidence behind the current standard of care?

Despite the increased mortality and morbidity in patients with acute decompensated heart failure (ADHF), its management has been based primarily on anecdotal experiences and physiologic assumptions rather than on prospective randomized controlled trials. The data on diuretics have been conflicting. Routine use of inotropes in ADHF has been clearly associated with increased mortality and morbidity, although inotropes seem to cause short-term clinical improvement. The safety of the different vasoactive medications has never been adequately confirmed in prospective trials despite their use for a long time in heart failure. Good evidence that supports the safety and efficacy of the different medications that are routinely used in ADHF is lacking. Unless properly designed prospective clinical trials are done to evaluate the safety of the various ADHF regimens, clinicians might continue to be misguided by the beneficial short-term effects at the expense of long-term mortality and morbidity.     

Determinants of exercise blood pressure response in normotensive and hypertensive women: role of cardiorespiratory fitness

PURPOSE: Exaggerated blood pressure (BP) response during physical exertion is associated with increased risk for cardiovascular events. Furthermore, it may be the predisposing factor for myocardial infarction triggered by physical exertion. The authors have shown that systolic BP achieved after 6 minutes of exercise is the strongest predictor of left ventricular hypertrophy. Furthermore, a 37 mm Hg increase in systolic BP above resting BP at 6 minutes of exercise was the threshold for left ventricular hypertrophy. The purpose of this study was to determine predictors of exercise BP response in normotensive and hypertensive women. METHODS: An exercise tolerance test (Bruce) was performed by 1411 normotensive (resting BP < 140/90 mm Hg) and hypertensive (resting BP > or = 140/90 mm Hg) women. These women were faculty, students, and staff at the University of Maryland, College Park, Maryland, and the George Washington University Medical Center, as well as patients undergoing a routine exercise tolerance test at West Coast Cardiology, Pinellas Park, Florida. Two fitness categories (low-fit and high-fit) were established on the basis of treadmill time to exhaustion adjusted for age. RESULTS: Significant associations were observed among the 6-minute exercise BP and age, body mass index, resting systolic and diastolic BP, heart rate, and exercise time to exhaustion. In a stepwise multiple-regression analysis, the determinants of BP after 6 minutes of exercise were resting systolic BP and treadmill time to exhaustion (R2 = 0.36) for normotensive women and treadmill time to exhaustion and resting systolic BP (R2 = 0.30) for hypertensive women. When fitness categories were contrasted, low-fit women in both the normotensive and hypertensive categories had higher BP and rate-pressure product after 6 minutes of exercise than the high-fit women (P <.05). CONCLUSIONS: Resting systolic BP and cardiorespiratory fitness are determinants of a submaximal exercise BP response for both hypertensive and normotensive women. Low cardiorespiratory fitness is associated with a higher BP response during submaximal exercise, suggesting that increased fitness may attenuate this abnormal rise in BP. Thus, low- to moderate-intensity physical activities for most days of the week should be encouraged for all women to increase cardiorespiratory fitness. This is likely to attenuate an abnormal rise in systolic BP that may occur during routine daily activities and protect against the associated health consequences.     

Stage-Specific Impact of Tumor Location on Oncologic Outcomes in Patients With Upper and Lower Tract Urothelial Carcinoma Following Radical Surgery

BACKGROUND: Dissimilarities in management and outcomes exist between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB). OBJECTIVE: The aim of this study was to analyze the stage-specific impact of upper or lower urinary tract tumor location on oncologic outcomes. DESIGN, SETTING, AND PARTICIPANTS: Data were collected from 4335 patients with UCB treated with radical cystectomy (RC) and bilateral pelvic lymphadenectomy (PLND), 877 patients with ureteral UTUC, and 1615 with pelvicalyceal UTUC treated with radical nephroureterectomy (RNU). No patient received preoperative chemotherapy or radiation therapy. INTERVENTIONS: Patients were treated with RC and bilateral PLND or RNU. MEASUREMENTS: Outcomes were assessed according to primary tumor location. RESULTS AND LIMITATIONS: Compared to UTUC patients, UCB patients had more advanced tumor stage and higher grade, and they were more likely to harbor lymphovascular invasion (LVI) and lymph node metastasis (p<0.001). In non-muscle-invasive tumor stages, UCB patients were more likely to experience disease recurrence and mortality compared to renal pelvicalyceal tumor patients (p<0.002) but not ureteral tumors (p>0.05). In pT2 and pT3 tumors, there was no difference in outcomes between the three tumor locations. In pT4 tumors, patients with ureteral and pelvicalyceal tumors were more likely to experience disease recurrence and mortality compared to UCB patients (p<0.004). These stage-specific findings were unchanged after adjustment for the effects of age, gender, tumor grade, LVI, lymph node status, and adjuvant chemotherapy. This study is limited by its retrospective and multicenter nature. CONCLUSIONS: Stage-specific differences in outcomes exist between UCB and UTUC. The differentially worse outcomes by stage between UCB and UTUC patients underline the differences between both cancer entities and the need for individualized stage-specific management for each patient.     

Subclassification of pT3 urothelial carcinoma of the renal pelvicalyceal system is associated with recurrence-free and cancer-specific survival: proposal for a revision of the current TNM classification

Background

The clinical course of pT3 upper tract urothelial carcinoma (UTUC) is highly variable.

Objectives

The aim of the current study was to validate the clinical and prognostic importance of pT3 subclassification in the renal pelvicalyceal system in a large international cohort of patients.

Design, setting, and participants

From a multi-institutional international database, 858 renal pelvicalyceal tumors treated with radical nephroureterectomy (RNU) were systematically reevaluated by genitourinary pathologists. Category pT3 pelvic tumors were categorized as pT3a (infiltration of the renal parenchyma on a microscopic level only) versus pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue).

Intervention

RNU.

Measurements

Associations of pT3 subclassifications with clinicopathologic features were assessed with the chi-square test. Prognostic impact was assessed with the log-rank test and multivariable Cox regression analyses.

Results and limitations

Of 858 patients with renal pelvicalyceal tumors, 266 (31%) had pT3 disease. Of these, 146 (54.9%) were classified as pT3a and 120 (45.1%) as pT3b. Compared with pT3a, pT3b cancers were associated with higher tumor grade, nodal disease, and tumor necrosis. Ten-year recurrence-free (pT3a 58% vs pT3b 38%; p < 0.001) and cancer-specific (pT3a 60% vs pT3b 39%; p = 0.002) survival rates were lower for patients with pT3b disease. In multivariable analyses, classification pT3b was an independent predictor of both disease recurrence (hazard ratio [HR]: 1.8, p = 0.003) and cancer-specific mortality (HR: 1.7; p = 0.02). The major limitation is the retrospective character of the study.

Conclusions

Subclassification of pT3 renal pelvicalyceal UTUC helps identify patients who are at increased risk of disease progression and cancer-related death. Further research may help assess the value of subclassification and its inclusion in future editions of the American Joint Committee on Cancer–International Union Against Cancer TNM classification system.