Citations

Although HER2‐positive breast cancers demonstrate a propensity for central nervous system (CNS) metastasis, it is unknown whether other HER2‐positive tumors, including adenocarcinomas of the esophagus/gastroesophageal junction (EAC), share this characteristic. Insight into this association may inform the development of HER2‐targeted therapies that penetrate the blood‐brain barrier. We examined HER2 overexpression and gene amplification in 708 patients with EAC who underwent curative‐intent surgery during a time period (1980–1997) when no patient received HER2‐targeted therapy. We identified patients whose site of first cancer recurrence was CNS and those who had a CNS relapse at any time. After a median follow‐up of 61.2 months, 3.4% (24/708) of patients developed CNS relapse (all involved the brain). Patients with HER2‐positive (vs ‐negative) primary tumors showed a higher 5‐year cumulative incidence of CNS relapse as first recurrence (5.8% vs. 1.2%; p = 0.0058) and at any time (8.3% vs. 2.4%; p = 0.0062). In a multivariable model that included covariates previously associated with HER2 or with CNS relapse in breast cancer, HER2 positivity was the only variable that was statistically significantly associated with shorter time to CNS relapse as first recurrence (p = 0.0026) or at any time (hazard ratio 4.3 [95% confidence interval 1.8 to 10.3]; p = 0.001). These are the first data in a non‐breast cancer to demonstrate an association between HER2 positivity and higher CNS relapse risk after surgery, and suggest that HER2‐positive EACs have a predilection for CNS metastases.

Introduction Parenteral anticoagulants may improve outcomes in patients with cancer by reducing risk of venous thromboembolic disease and through a direct antitumour effect. Study-level systematic reviews indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. It remains unclear if any patient subgroups experience potential benefits. Methods and analysis First, we will perform a comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library, hand search scientific conference abstracts and check clinical trials registries for randomised control trials of participants with solid cancers who are administered parenteral anticoagulants. We anticipate identifying at least 15 trials, exceeding 9000 participants. Second, we will perform an individual participant data meta-analysis to explore the magnitude of survival benefit and address whether subgroups of patients are more likely to benefit from parenteral anticoagulants. All analyses will follow the intention-to-treat principle. For our primary outcome, mortality, we will use multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We will adjust analysis for important prognostic characteristics. To investigate whether intervention effects vary by predefined subgroups of patients, we will test interaction terms in the statistical model. Furthermore, we will develop a risk-prediction model for venous thromboembolism, with a focus on control patients of randomised trials. Ethics and dissemination Aside from maintaining participant anonymity, there are no major ethical concerns. This will be the first individual participant data meta-analysis addressing heparin use among patients with cancer and will directly influence recommendations in clinical practice guidelines. Major cancer guideline development organisations will use eventual results to inform their guideline recommendations. Several knowledge users will disseminate results through presentations at clinical rounds as well as national and international conferences. We will prepare an evidence brief and facilitate dialogue to engage policymakers and stakeholders in acting on findings. Trial registration number PROSPERO CRD42013003526.

Introduction Vertebral artery injury is a rare but serious complication of cervical spine surgery with an overall incidence rate of 1.4% (Rampersaud, 2006). Iatrogenic injury of the vertebral artery can lead to serious complications including lateral medullary (Wallenberg) syndrome, quadriparesis, and mortality. The high rate of vertebral artery anomalies in the general population mandates assessment via advanced imaging modalities in the preoperative period (Schroeder, 2013). The rarity of this complication makes it difficult to set expectations after an injury is encountered. This study utilized a multi-center database to compile outcomes data after vertebral artery injury during a cervical spine procedure. Materials and Methods A multi-center retrospective case series was compiled involving 23 medical institutions. Inclusion criteria included patients who underwent cervical spine surgery between 2005–2011 and who sustained a vertebral artery injury. IRBs were obtained from all institutions and data was sent to a private research organization that collected and collated all of the data. Patients were evaluated on the basis of condition-specific functional status using the Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA) score, the Nurick scale, and the 36-Item Short-Form Health Survey (SF-36). Results Vertebral artery injuries were identified in a total of 14 of 16,582 total patients screened (8.4 per 10,000). The mean age of patients with vertebral artery injury was 59 years (+/− 10) with a female predominance (78.6%). Diagnoses of affected patients included 7 with myelopathy, 3 with radiculopathy, 1 with cervical instability, and 2 with metastatic disease. The mean duration of operative time for cases was 4.7 hours (+/− 1.8). Vertebral artery injury was also associated with substantial blood loss (770 mL), although only 3 cases required transfusion. Of the 14 cases, 7 occurred with an anterior only approach, 3 cases with posterior only approach, and 4 during circumferential approach. Average length of hospital stay for these patients was 10 days (+/− 8). Notably, 13 of the 14 (92.86%) cases reportedly resolved without residual deficits. Compared with preoperative baseline NDI, Nurick, and SF-36 physical and mental component scores for these patients, there were no observed changes after surgery ( p = 0.20 Ð 0.94). Conclusion Vertebral artery injuries are potentially catastrophic complications that can be sustained from either anterior or posterior cervical spine approaches. This adverse event is associated with an increase in hospital stay and functional disability measured on NDI score. However, the data from this study suggests that with proper steps to ensure hemostasis, patients recover function at a high rate and do not exhibit residual deficits (13 out of 14). Preoperative imaging studies may provide insight into VA anomalies and anatomic variations and are vital to the preoperative assessment. Furthermore, although surgeons should expect increased blood loss once a vertebral artery injury is encountered, patients do not often require a blood transfusion.

Background: This study examines the efficacy of hypobaric oxygenation as it relates to the elimination of gaseous microemboli (GME) at designated flow, pressure and temperature combinations. Methods: Hypobaric oxygenation was employed for experimental trials (n=60), but not for control trials (n=60), while circuit design, data measurements and testing conditions were maintained for both settings. Hypobaric oxygenation conditions were created by applying 100% oxygen at sub-atmospheric sweep gas pressures of 0.67 atmospheres to the gas phase of an integrated hollow-fiber microporous membrane oxygenator. GME were quantified using an Emboli Detection and Classification system (EDAC), while a continuous air infusion, at a rate of 100 ml/min, was applied to the circuit. Trials were conducted at 37°C, 28°C, and 18°C and at two flow and line pressure combinations of: 3.5 L/min & 150 mmHg and 5 L/min & 200 mmHg. Results: Sub-atmospheric sweep gas pressures allowed adequate oxygenation independent of carbon dioxide removal while significantly reducing the potential entrance of nitrogen into the blood. GME was reduced significantly across all temperatures and flows when compared to control trials; GME counts were reduced by 99.7% post-oxygenator and 99.99% at the arterial cannula. Conclusion: Correlation between the use of hypobaric oxygenation and GME counts suggests hypobaric oxygenation could play a significant role in the reduction of GME.

Osteosarcoma is an aggressive primary bone tumor. It is currently treated with multimodality therapy including en bloc resection, which has been demonstrated to confer a survival benefit over intralesional resection. The authors present the case of an 8-year-old girl with a C-1 lateral mass osteosarcoma, which was treated with a 4-stage en bloc resection and spinal reconstruction. While technically complex, the feasibility of en bloc resection for spinal osteosarcoma should be explored in the pediatric population.

ABSTRACT Protective antigen (PA)-specific antibody and cell-mediated immune (CMI) responses to annual and alternate booster schedules of anthrax vaccine adsorbed (AVA; BioThrax) were characterized in humans over 43 months. Study participants received 1 of 6 vaccination schedules: a 3-dose intramuscular (IM) priming series (0, 1, and 6 months) with a single booster at 42 months (4-IM); 3-dose IM priming with boosters at 18 and 42 months (5-IM); 3-dose IM priming with boosters at 12, 18, 30, and 42 months (7-IM); the 1970 licensed priming series of 6 doses (0, 0.5, 1, 6, 12, and 18 months) and two annual boosters (30 and 42 months) administered either subcutaneously (SQ) (8-SQ) or IM (8-IM); or saline placebo control at all eight time points. Antibody response profiles included serum anti-PA IgG levels, subclass distributions, avidity, and lethal toxin neutralization activity (TNA). CMI profiles included frequencies of gamma interferon (IFN-γ)- and interleukin 4 (IL-4)-secreting cells and memory B cells (MBCs), lymphocyte stimulation indices (SI), and induction of IFN-γ, IL-2, IL-4, IL-6, IL-1β, and tumor necrosis factor alpha (TNF-α) mRNA. All active schedules elicited high-avidity PA-specific IgG, TNA, MBCs, and T cell responses with a mixed Th1-Th2 profile and Th2 dominance. Anti-PA IgG and TNA were highly correlated (e.g., month 7, r 2 = 0.86, P < 0.0001, log 10 transformed) and declined in the absence of boosters. Boosters administered IM generated the highest antibody responses. Increasing time intervals between boosters generated antibody responses that were faster than and superior to those obtained with the final month 42 vaccination. CMI responses to the 3-dose IM priming remained elevated up to 43 months. (This study has been registered at ClinicalTrials.gov under registration no. NCT00119067.)

Background Although rare, spinal arteriovenous malformations (AVMs) are thought to be more prevalent in the hereditary Hereditary Hemorrhagic Telangiectasia (HHT) population. Methods We report a case of a spinal AVM in a 37-year-old female with HHT treated with endovascular embolization. In addition, we report findings from a systematic review of the literature on the clinical characteristics, angioarchitecture, and clinical outcomes of HHT patients with spinal AVMs. Results The patient is a 37 year-old female with definite HHT who presented with a one-year history of progressive gait difficulty. The spinal fistula was incidentally detected on chest computed tomography (CT). Spinal angiography demonstrated a large perimedullary arteriovenous fistula was supplied by a posterolateral spinal artery. The fistula was treated with detachable coils. The patient made a complete neurological recovery. Our systematic review yielded 25 additional cases of spinal AVMs in HHT patients. All fistulae were perimedullary (100.0%). Treatments were described in 24 of the 26 lesions. Endovascular-only treatment was performed in 16 cases (66.6%) and surgical-only treatment was performed in five cases (20.8%). Complete or near-complete occlusion rates were 86.7% (13/15) for endovascular treated cases, 100.0% (4/4) for surgery and 66.6% (2/3) for combined treatments. Overall, 80.0% of patients (16/20) reported improvement in function following treatment, 100.0% (5/5) in the surgery group and 84.6% (11/13) reported improvement in the endovascular group. Conclusions Spinal fistulae in HHT patients are usually type IV perimedullary fistulae. Both endovascular and surgical treatments appeared to be effective in treating these lesions. However, it is clear that endovascular therapy has become the preferred treatment modality.