Prognostic factors and outcome in patients with T1 high‐grade bladder cancer: can we identify patients for early cystectomy?

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Although several papers have attempted to identify individual risk factors for T1 high‐grade (T1HG) urothelial carcinoma of the bladder for disease recurrence or progression, and nomograms have been generated to aid in the prediction of disease progression, there has been a lack of systematic examination of which factors predict clinically important outcomes. Treatment of T1HG remains controversial, particularly with regards to timing of radical cystectomy. Patients with T1HG bladder cancer are at a significant risk of progression and death from disease. Primary tumours, sessile architecture, and trigonal location are factors associated with worse outcome and may be used to counsel patients towards early cystectomy.

OBJECTIVE

• ? To assess outcome in patients with T1 high‐grade (T1HG) bladder cancer treated at a single academic institution and to determine the prognostic factors that can help in counselling patients towards early cystectomy.

PATIENTS AND METHODS

• ? Records of 2570 patients with bladder cancer treated from 1995 to 2005 were reviewed. Only patients diagnosed with T1HG disease were included in the analysis.
• ? Collected variables included various clinicopathological parameters, use of statins, smoking, as well as dates of recurrence, progression, radical cystectomy and death.
• ? Recurrence‐free survival (RFS) and worsening‐free survival (WFS) were analyzed.
• ? Multivariate Cox proportional regression analysis was employed to verify the prognostic significance of various variables.

RESULTS

• ? In total, 278 (10.8%) patients were identified as having T1HG disease on transurethral resection.
• ? 66% of patients who recurred, and 36.3% developed stage progression after a median (range) follow‐up of 3 (0.1–15.4) years.
• ? 30% patients who underwent radical cystectomy, and 9% were dead of disease.
• ? The 5‐year RFS and WFS rates were 26.6% and 49.4%, respectively.
• ? On multivariate analysis, only non‐trigonal tumour location, restaging transurethral resection, history of previous carcinoma not invading bladder muscle and adjuvant bacille Calmette‐Guérin (BCG) therapy were significantly associated with prolonged RFS, whereas papillary tumour architecture, history of previous carcinoma not invading bladder muscle and adjuvant BCG therapy were significantly associated with prolonged WFS.

CONCLUSIONS

• ? Patients with T1HG bladder cancer are at a significant risk of progression and death from disease.
• ? Primary tumours, sessile architecture and trigonal location are factors associated with a worse outcome and may be used to counsel patients towards early cystectomy.

     

Hematopoietic Stem Cells with High Proliferative Potential: ASSAY OF THEIR CONCENTRATION IN MARROW BY THE FREQUENCY AND DURATION OF CURE OF W/Wv MICE

This study was designed to approach two primary questions concerning hematopoietic stem cells (HSC) in mice: what is the concentration of HSC with extensive proliferative potential in marrow, and how long can an HSC continue to function in an intact animal? The assay system was the W/W^v mouse, a mouse with an inherited HSC defect, reflected in a reduction in all myeloid tissue and most particularly in a macrocytic anemia.A single chromosomally marked HSC will reconstitute the defective hematopoietic system of the W/W^v. The concentration of HSC in normal littermate (+/+) marrow was assayed by limiting dilution calculation using cure of W/W^v as an end point (correction of anemia and erythrocytes'' macrocytosis) and found to be ∼10/10⁵. This is significantly less than spleen colony forming cell (CFU-S) concentration: ∼220/10⁵ in +/+ and ranging from 50 to 270/10⁵ in various other studies. Blood values were studied at selected intervals for as long as 26 mo. Of 24 initially cured mice, which were observed for at least 2 yr, 75% remained cured. However, of all cured mice, 17 lost the cure, returning to a macrocytic anemic state. Cured mice had normal numbers of nucleated and granulocytic cells per humerus and a normal concentration of CFU-S. However, cure of secondary W/W^v recipients by this marrow was inefficient compared with the original +/+ marrow. These studies suggest the CFU-S assay over-estimates extensively proliferating HSC or perhaps does not assay such a cell. A single such HSC can not only cure a W/W^v, but can sustain the cure for 2 yr or more, despite a relative deficit of cells capable of curing other W/W^v. However, the duration of sustained cure may be finite.     

Resuscitation in the hospital: relationship of year and rhythm to outcome

OBJECTIVE: determine the frequency of initial rhythms in in-hospital resuscitation and examine its relationship to survival. Assess changes in outcome over time. METHODS: retrospective cohort (registry) including all admissions to the Medical Center of Central Georgia in which a resuscitation was attempted between 1 January, 1987 and 31 December, 1996. RESULTS: the registry includes 3327 admissions in which 3926 resuscitations were attempted. Only the first event is reported. There were 961 hospital survivors. Survival increased from 24.2% in 1987 to 33.4% in 1996 (chi(2)=39.0, df=1, P<0.0001). Survival was affected strongly by initial rhythm (chi(2)=420.0, df=1, P<0.0001) and decreased from 63.2% for supraventricular tachycardia (SVT) to 55.3% for ventricular tachycardia (VT), 51.0% for perfusing rhythms (PER), 34.8% for ventricular fibrillation (VF), 14.3% for pulseless electrical activity (PEA) and 10.0% for asystole (ASYS). PEA was the most frequent rhythm (1180 cases) followed by perfusing (963), asystole (580), VF (459), VT (94) and SVT (38). DISCUSSION: the powerful effect of initial rhythm on survival has been reported in pre-hospital and in-hospital resuscitation. VF is considered the dominant rhythm and generally accounts for the most survivors. We report good outcome for each; however, VF represents only 13.8% of events and 16.7% of survivors. PEA accounts for more survivors (169) than does VF (160). Our improved outcome is partially explained by changes in rhythms, but other institutional variables need to be identified to fully explain the results. Further studies are needed to see if our findings can be sustained or replicated.     

Physical activity patterns and multimorbidity burden of older adults with different levels of functional status: NHANES 2003–2006

BackgroundPhysical function and physical activity decrease with age, but differences in physical activity patterns within different physical functioning groups are unknown.ObjectivesTo describe physical activity patterns and multimorbidity burden by physical function group and age.MethodsActigraph accelerometer-derived physical activity patterns were compared by physical function (high functioning, activity limitations, activity of daily living disabled) determined by questionnaire and age among 2174 older adults (mean age = 70.9, sd = 0.2 years) from the cross-sectional 2003–2006 National Health and Nutrition Examination Survey. Associations between physical function, physical activity, and multimorbidity were examined.ResultsReduced physical function and increased age were associated with lower physical activity, increased sedentary time and a compressed activity profile. During the most active hour of the day (11:00 a.m.), the oldest, lowest physical functioning group was 82% less active than the youngest, highest physical functioning group. High functioning had over 30% more total activity counts, over 56% more time in moderate-to-vigorous activity, about 8% less time sedentary and took approximately one more sedentary break/hour than lower physical functioning groups. Gender differences in physical activity variables were prevalent for high functioning, but limited within reduced physical functioning groups. Physical function, age, total activity counts/day, and breaks in sedentary time/day were independently associated with multimorbidity (p < 0.005).ConclusionsReduced physical function and increased age are associated with physical activity levels, and all three are associated with multimorbidity. Understanding physical activity differences by physical function is important for designing interventions for older individuals at increased risk for mobility disability.     

Markers of bone turnover in patients with lung cancer

INTRODUCTION: Bone metastases may change the primary treatment modality, especially if the bone is the only site of metastasis in patients considered to be in the early stage of lung cancer. It is usually diagnosed by imaging techniques. However, the diagnostic yields of imaging methods are limited. Some bone markers such as propeptides of type-1 collagen, pyridinoline cross-links and deoxypyridinoline (D-PYD) cross-links, serum osteocalcin, alkaline phosphatase are thought to be useful in the detection of bone metastasis in lung cancer. Thus, we aimed to determine the clinical usefulness of bone turnover markers in the assessment of bone metastases in patients with lung cancer. MATERIAL AND METHODS: Urinary D-PYD, calcium, and serum osteocalcin, calcium and total alkaline phosphatase (T-ALP) were measured in 60 lung cancer patients. Patients were evaluated by technetium 99 (99Tc) bone scintigraphy. The comparisons of measured values in patients with and without bone metastasis were done by using appropriate statistical methods. RESULTS: Fifty-four males and six females were included into study. Twenty-two patients had bone metastases, while 38 did not. Forty-two patients were nonsmall-cell lung cancer, whereas 18 were small-cell carcinoma. Urinary D-PYD level was the unique value that was statistically significantly higher in patients with bone metastases than that level in patients without bone metastasis (p < 0.05). CONCLUSION: Our study suggests that urinary measurement of D-PYD might be helpful in detecting bone metastasis in lung cancer. The high urinary D-PYD level may be an early sign of occult metastases in patients with no bone metastasis assessed by scintigraphic techniques.