Brain metastases in patients under 50?years of age: retrospective analysis

Several previous publications suggested that younger patients with brain metastases have longer survival than older patients. However, detailed studies of younger patient groups are scarce. Therefore, a multi-institutional analysis of younger patients with brain metastases was performed (defined as adults with age <50?years). Prognostic factors for survival were examined by uni- and multivariate analyses and compared to those obtained in patients with age ??50?years. Multivariate analysis of 106 patients (median age 44?years, range 23?C49?years) revealed three independent prognostic factors for survival: performance status, extracranial metastases and primary tumor control. Survival was significantly better in patients treated after the year 2000 (median 9.4?months) as compared to those treated before the year 2000 (median 5.1?months, p?=?0.04). This improvement appeared to be related to an increased use of surgery or radiosurgery (SRS) and decreasing numbers of patients with uncontrolled primary tumor. Irrespective of management approach, survival beyond 5?years was uncommon (actuarial rate 6?%; 17?% in patients treated with upfront surgery or SRS). In conclusion, more intense multidisciplinary approaches aiming at control both in the brain, extracranial metastatic sites, and primary tumor site might have contributed to gradual survival improvements in recent years. Nevertheless, further efforts are necessary to improve long-term survival.     

WAITING TIMES AND SOCIOECONOMIC STATUS. EVIDENCE FROM NORWAY

We investigate whether socioeconomic status, measured by income and education, affects waiting time when controls for severity and hospital‐specific conditions are included. We also examine which aspects of the hospital supply (attachment to local hospital, traveling time, or choice of hospital) matter most for unequal treatment of different socioeconomic groups. The study uses administrative data from all elective inpatient and outpatient stays in somatic hospitals in Norway. The main results are that we find very little indication of discrimination with regard to income and education when both severity and aspects of hospital supply are controlled for. This result holds for both men and women. Copyright © 2013 John Wiley & Sons, Ltd.     

Presentation,patterns of care,and survival in patients with brain metastases

BACKGROUND:

It is largely unknown to what extent new oncologic treatment options have improved survival of patients with brain metastasis in recent decades. Therefore, a multi‐institutional time‐staggered analysis was performed.

METHODS:

Two cohorts of 103 patients each were analyzed, one treated between 2005 and 2009 and the other between 1983 and 1989, ie, approximately 20 years earlier. Stratified analyses by prognostic groups were also performed (graded prognostic assessment [GPA] and Radiation Therapy Oncology Group recursive partitioning analysis [RTOG‐RPA]).

RESULTS:

Patterns of care have changed significantly. Contemporary patients received focal treatments such as stereotactic radiosurgery and surgical resection far more frequently. Furthermore, systemic treatment was used more often in contemporary patients, both before and after diagnosis of brain metastasis. Improved survival was observed in the contemporary cohort (P = .03). The 1‐year survival rate increased from 15% (95% confidence interval [CI], 7%‐25%) to 34% (95% CI, 25%‐44%). However, this improvement was largely driven by patients with favorable prognostic features. More than 40% of the patients still belong to unfavorable prognostic groups with limited median survival and little improvement.

CONCLUSIONS:

Contemporary patients were managed on a much more individualized basis, requiring multidisciplinary case discussion and thorough assessment of prognostic features. Progress has been made, but the overall outcome needs to be improved further. Avoiding overtreatment in patients with poor prognosis is as important as aggressive treatment in patients who might survive for several years. Cancer 2011. © 2010 American Cancer Society.     

Cytologic features of ductal carcinoma in situ in fine-needle aspiration of the breast mirror the histopathologic growth pattern heterogeneity and grading

BACKGROUND: Approximately 20% of the breast carcinoma cases detected on mammography screening represent ductal carcinoma in situ (DCIS). Cytopathologists are exposed to cytologic material from DCIS when nonpalpable, mammographic lesions are aspirated during the workup of organized and opportunistic mammography screening. METHODS: The material in the current study was comprised of 225 representative fine-needle aspiration cytology (FNAC) smears from histologically confirmed DCIS of the breast that were diagnosed between 1990-2003. Smears were rescreened to search for the following features: nuclear size (grading), monolayer sheets, solid and cribriform epithelial aggregates, micropapillary and true papillary structures, comedo-type necrosis, microcalcifications, myoepithelial cells, and discohesion. RESULTS: There were 174 high-grade lesions (77% were Grade 3) and 51 nonhigh-grade lesions (Grades 1 and 2). The concordance between the cytologic and histologic grading was 97% in the Grade 3 lesions and 94% in the Grade 1/2 lesions. Smears from Grade 3 DCIS contained solid and/or cribriform epithelial aggregates in > 93%% of the cases, whereas smears from Grade 1/2 lesions were found to contain cribriform aggregates in 94% of the cases. Pure subtypes were virtually nonexistent. Monolayer sheets were found in 49% of nonhigh-grade DCIS and in 16% of high-grade DCIS. Myoepithelial cells were demonstrated in 51% of the nonhigh-grade DCIS lesions and 27% of the Grade 3 lesions. Microcalcifications were found on the smears from 96% of nonhigh-grade lesions and 84% of high-grade lesions. Approximately 47% of high-grade DCIS and 31% of nonhigh-grade DCIS were found to harbor a distinct single cell population. CONCLUSIONS: The findings on FNAC from DCIS of the breast completely mirror the histologic heterogeneity of growth pattern subtypes. Primary cytologic grading can effectively separate the high-grade lesions from the nonhigh-grade lesions.     

Effects of conventional and aggressive statin treatment on markers of endothelial function and inflammation

BACKGROUND: Atherosclerosis is considered to be a chronic inflammatory disorder. Several large-scale clinical studies demonstrate that markers of inflammation, such as high-sensitivity C-reactive protein (hsCRP), fibrinogen, and soluble CD40 ligand, are potent and independent predictors of vascular risk. HYPOTHESIS: The study was undertaken to investigate the effect of increasing the statin dose from conventional to aggressive treatment on lipids levels, inflammation, and endothelial function in patients with coronary artery disease (CAD). METHODS: We randomized 97 patients to either 20 mg simvastatin or 80 mg atorvastatin. Plasma levels of lipids, hsCRP, fibrinogen, soluble adhesion molecules, and nitric oxide-total were analyzed at baseline and after 6 months of treatment. RESULTS: Lipid values were significantly reduced in both treatment groups, but with significantly greater reduction in the aggressively treated group. Furthermore, aggressive statin treatment significantly decreased hsCRP and fibrinogen, while only small reductions were seen in the conventionally treated group, resulting in significant differences between the two treatment groups (p < 0.001). Nitric oxide-total increased significantly in both treatment groups, although the increase was more pronounced in the aggressively treated group (22.6 vs. 15.6%). CONCLUSION: Aggressive statin treatment significantly improved lipid status and reduced markers of inflammation and improved endothelial function compared with conventional treatment in patients with CAD. No interaction was observed, and high-dose treatment did not offer additional benefit compared with standard-dose treatment with respect to soluble adhesion molecules.     

Alternating mitomycin C and BCG instillations versus BCG alone in treatment of carcinoma in situ of the urinary bladder: a nordic study

OBJECTIVES: To evaluate whether, in patients with carcinoma in situ (CIS) of the urinary bladder, alternating instillation therapy with mitomycin C (MMC) and bacillus Calmette-Guerin (BCG) was more effective and less toxic than conventional BCG monotherapy. METHODS: Patients were stratified prospectively for primary, secondary, and concomitant CIS and randomized to one of two regimens. Patients in the alternating group received six weekly intravesical instillations of MMC 40 mg, followed by alternating monthly instillations of BCG 120 mg and MMC for one year. In the monotherapy group, only BCG was instilled on the same schedule. RESULTS: Of 323 enrolled patients, 304 were eligible for analysis. After an overall median follow-up of 56 months, the Kaplan-Meier disease-free estimate for BCG monotherapy was significantly better than that for alternating therapy (p=0.03; log rank test). Risk for progression appeared lower in the BCG monotherapy group (p=0.07), but no differences existed in survival. Besides the regimen, CIS category also predicted outcome to some extent. BCG monotherapy caused significantly more local side-effects and premature cessation of instillation treatment than did the alternating therapy. However, no differences were observed in the number of serious side-effects. CONCLUSION: One-year BCG monotherapy was more effective than the alternating therapy for reducing recurrence and compared well with the best regimens reported from substantially smaller series. The alternating therapy was better tolerated.     

Involvement of the extracellular signal regulated kinase pathway in hydrocarbon-induced reactive oxygen species formation in human neutrophil granulocytes

In the present study we have examined the effects of hydrocarbons on the formation of reactive oxygen species (ROS) in human neutrophil granulocytes in vitro. We found that hydrocarbons induce ROS formation in a concentration-dependent manner and that the ROS-inducing potency increases with increasing number of carbon atoms in the structure. In general, aromatic hydrocarbons were less potent inducers of ROS than aliphatic and cyclic hydrocarbons. The most potent compound in each group, t-butylcyclohexane, n-decane, and n-butylbenzene, were chosen for mechanistic studies. ROS formation was inhibited by the MEK1/2 inhibitor U0126, the tyrosine kinase inhibitor erbstatin-A, and the phosphatidylinositol-3 kinase inhibitor wortmannin. The involvement of the ERK1/2 pathway was confirmed by Western blot analysis of phosphorylated ERK1/2. The study revealed only small differences in the mechanisms involved for the three compounds. The responses were not affected by Pertussis toxin, indicating that Gi-protein coupled receptors are not involved in neutrophil activation after hydrocarbon exposure. Based on these findings we propose a mechanism involving tyrosine kinases, PI3 kinase, and the ERK1/2 pathway, leading to activation of the NADPH oxidase and production of ROS in neutrophils stimulated by organic solvents.