Intracranial hemorrhage (ICH) in cancer patients treated with bevacizumab : the Memorial Sloan-Kettering experience

Background: Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor approved for recurrent glioblastoma (GBM), metastatic breast, colorectal and non-small-cell lung cancers (NSCLC). There has been a potentially increased risk of intracranial hemorrhage (ICH) in patients receiving bevacizumab.

Methods: We retrospectively identified patients with ICH who received bevacizumab between 1 January 2001 and 10 January 2009.

Results: We identified 1024 patients with ICH, 4191 patients who received bevacizumab and 12 (0.3%) who met both our criteria. There were eight women and four men with a median age of 66 years. Primary cancers were ovarian (n = 3), NSCLC (n = 3), colon (n = 1), angiosarcoma (n = 1) and GBM (n = 4). Intracranial tumors were present in 9 of the 12 patients; the remaining three (25%) had no evidence of intracranial pathology. Two hundred and fifty-seven patients with these same primary pathologies and brain tumors were treated with bevacizumab; ICH was seen in nine (3.7%), which was comparable to the 3.6% frequency seen in comparable patients not receiving bevacizumab.

Conclusions: ICH with bevacizumab treatment in this population is rare and does not appear to increase its frequency over the baseline rate of ICH in a comparable population. Most bevacizumab-related ICH occurs into central nervous system tumors but spontaneous hemorrhages were seen.

The health loss from ischemic stroke and intracerebral hemorrhage : evidence from the North East Melbourne Stroke Incidence Study (NEMESIS)

Background People suffering different types of stroke have differing demographic characteristics and survival. However, current estimates of disease burden are based on the same underlying assumptions irrespective of stroke type. We hypothesized that average Quality Adjusted Life Years (QALYs) lost from stroke would be different for ischemic stroke and intracerebral hemorrhage (ICH).

Methods We used 1 and 5-year data collected from patients with first-ever stroke participating in the North East Melbourne Stroke Incidence Study (NEMESIS). We calculated case fatality rates, health-adjusted life expectancy, and quality-of-life (QoL) weights specific to each age and gender category. Lifetime 'health loss' for first-ever ischemic stroke and ICH surviving 28-days for the 2004 Australian population cohort was then estimated. Multivariable uncertainty analyses and sensitivity analyses (SA) were used to assess the impact of varying input parameters e.g. case fatality and QoL weights.

Results Paired QoL data at 1 and 5 years were available for 237 NEMESIS participants. Extrapolating NEMESIS rates, 31,539 first-ever strokes were expected for Australia in 2004. Average discounted (3%) QALYs lost per first-ever stroke were estimated to be 5.09 (SD 0.20; SA 5.49) for ischemic stroke (n = 27,660) and 6.17 (SD 0.26; SA 6.45) for ICH (n = 4,291; p < 0.001). QALYs lost also differed according to gender for both subtypes (ischemic stroke: males 4.69 SD 0.38, females 5.51 SD 0.46; ICH: males 5.82 SD 0.67, females 6.50 SD 0.40).

Discussion People with ICH incurred greater loss of health over a lifetime than people with ischemic stroke. This is explained by greater stroke related case fatality at a younger age, but longer life expectancy with disability after the first 12 months for people with ICH. Thus, studies of disease burden in stroke should account for these differences between subtype and gender. Otherwise, in countries where ICH is more common, health loss for stroke may be underestimated. Similar to other studies of this type, the generalisability of the results may be limited. Sensitivity and uncertainty analyses were used to provide a plausible range of variation for Australia. In countries with demographic and life expectancy characteristics comparable to Australia, our QoL weights may be reasonably applicable.

Fish oil diet associated with acute reperfusion related hemorrhage, and with reduced stroke-related sickness behaviors and motor impairment

Ischemic stroke is associated with motor impairment and increased incidence of affective disorders such as anxiety/clinical depression. In non-stroke populations, successful management of such disorders and symptoms has been reported following diet supplementation with long chain omega-3-polyunsaturated-fatty-acids (PUFAs). However, the potential protective effects of PUFA supplementation on affective behaviors after experimentally induced stroke and sham surgery have not been examined previously. This study investigated the behavioral effects of PUFA supplementation over a 6-week period following either middle cerebral artery occlusion or sham surgery in the hooded-Wistar rat. The PUFA diet supplied during the acclimation period prior to surgery was found to be associated with an increased risk of acute hemorrhage following the reperfusion component of the surgery. In surviving animals, PUFA supplementation did not influence infarct size as determined 6 weeks after surgery, but did decrease omega-6-fatty-acid levels, moderate sickness behaviors, acute motor impairment, and longer-term locomotor hyperactivity and depression/anxiety-like behavior.

Lifetime cost of stroke subtypes in Australia: findings from the North East Melbourne stroke incidence study (NEMESIS)

Background and Purpose-: Little is known about any variations in resource use and costs of care between stroke subtypes, especially nonhospital costs. The purpose of this study was to describe the patterns of resource use and to estimate the first-year and lifetime costs for stroke subtypes.

Methods-: A cost-of-illness model was used to estimate the total first-year costs and lifetime costs of stroke subtypes for all strokes (subarachnoid hemorrhages excluded) that occurred in Australia during 1997. For each subtype, average cost per case during the first year and the present value of average cost per case over a lifetime were calculated. Resource use data obtained in the North East Melbourne Stroke Incidence Study (NEMESIS) were used.

Results-: The present value of total lifetime costs for all strokes was Aus $1.3 billion (US $985 million). Total lifetime costs were greatest for ischemic stroke (72%; Aus $936.8 million; US $709.7 million), followed by intracerebral hemorrhage (26%; Aus $334.5 million; US $253.4 million) and unclassified stroke (2%; Aus $30 million; US $22.7 million). The average cost per case during the first year was greatest for total anterior circulation infarction (Aus $28 266). Over a lifetime, the present value of average costs was greatest for intracerebral hemorrhage (Aus $73 542), followed by total anterior circulation infarction (Aus $53 020), partial anterior circulation infarction (Aus $50 692), posterior circulation infarction (Aus $37 270), lacunar infarction (Aus $34 470), and unclassified stroke (Aus $12 031).

Conclusions-: First-year and lifetime costs vary considerably between stroke subtypes. Variation in average length of total hospital stay is the main explanation for differences in first-year costs.

The frontotemporal-orbitozygomatic approach : reconstructive technique and outcome

Background The frontotemporal-orbitozygomatic (FTOZ) approach, also known as "the workhorse of skull base surgery," has captured the interest of many researchers throughout the years. Most of the studies published have focused on the surgical technique and the gained exposure. However, few studies have described reconstructive techniques or functional and cosmetic outcomes. The goal of this study was to describe the surgical reconstruction after the FTOZ approach and analyze the functional and cosmetic outcomes. Methods Seventy-five consecutive patients who had undergone FTOZ craniotomy for different reasons were selected. The same surgical (one-piece FTOZ) and reconstructive techniques were applied in all patients. The functional outcome was measured by complications related to the surgical approach: retro-orbital pain, exophthalmos, enophthalmos, ocular movement restriction, cranial nerve injuries, pseudomeningocele (PMC) and secondary surgeries required to attain a reconstructive closure. The cosmetic outcome was evaluated by analyzing the satisfaction of the patients and their families. Questionnaires were conducted later in the postoperative period. A statistical analysis of the data obtained from the charts and questions was performed. Results Of the 75 patients studied, 59 had no complications whatsoever. Ocular movement restriction was found in two patients (2.4 %). Cranial nerve injury was documented in seven patients (8.5 %). One patient (1.2 %) underwent surgical repair of a cerebrospinal fluid (CSF) leak from the initial surgery. Two patients (2.4 %) developed delayed postoperative pseudomenigocele. One patient (1.2 %) developed intraparenchymal hemorrhage (IPH). Full responses to the questionnaires were collected from 28 patients giving an overall response rate of 34 %. Overall, 22 patients (78.5 %) were satisfied with the cosmetic outcome of surgery. Conclusion The reconstruction after FTOZ approach is as important as the performance of the surgical technique. Attention to anatomical details and the stepwise reconstruction are a prerequisite to the successful preservation of function and cosmesis. In our series, the orbitozygomatic osteotomy did not increase surgical complications or alter cosmetic outcomes.