Citations

SummaryObjectivesIn pediatric patients vascular access is often more difficult than in adults because of the smaller size of the vessels and the inability of the patient to cooperate without deep sedation or general anesthesia. Therefore Ultrasound has already become an invaluable tool for vascular access, but the full potential of ultrasound has yet to be fully realized. Improvements in image quality and a better understanding of optimal insertion techniques continue to help clinicians safely and efficiently place catheters with fewer complications.Methods and TechniqueThe probes used for the vascular access are mainly linear and convex type. Higher‐ frequency ultrasound provides a vivid image; however, the signals are remarkably attenuated. Therefore, the choice of the probe with appropriate frequency is essential. As blood vessels are relatively easily identified with ultrasound, ultrasound‐guided vascular access does not require as sharp images as ultrasound‐guided nerve block. For pediatric vascular access, the linear probe with 5–15 MHz, 2–5 cm depth is ideal and adequate for almost all cases. Ultrasound‐guided vascular access has two main approaches: ‘long‐axis’ or ‘in‐plane approach’ and ‘short‐axis’ or ‘transverse approach’. The long‐axis approach visualizes the vessel along the insertion pathway and is commonly used to monitor the entire approach of the needle into the vessel. The short‐axis approach is easier to show the positional relationship and depth of target vessels, but it is much harder to follow the needle tip within the tissues.ConclusionThe use of ‘real‐time’ ultrasound has been shown to increase first insertion success, reduce access time, have a higher overall success, and reduce arterial puncture. As the technology continues to improve the use of ultrasound will become as ubiquitous as the lines themselves.

Abstract Background and Aims: Cholangiocarcinomas (CCA) are highly desmoplastic tumors containing abundant cancer associated myofibroblasts (CAF). An inverse association between the abundance of CAF and survival has been demonstrated in CCA, suggesting that CAF play a pivotal role in CCA development and progression. The CAF phenotype represents an ‘activated cell state’ and as such may be uniquely susceptible to apoptosis. BH3 mimetics induce apoptosis in cells ‘primed’ for cell death, representing a therapeutic strategy for cancer. Herein we examine whether CAF display a selective sensitivity to the BH3 mimetic ABT-263 and whether ABT-263 induced ablation of CAF reduces tumor growth and progression. Methods: We employed human and rat CAF, myofibroblastic human LX2 cells, human and rat control fibroblasts, the rat cholangiocarcinoma cell line BDEneu and human CCA cell lines for these studies. In-vivo experiments were conducted using a syngeneic, orthotopic rat CCA model. Results: We observed a significant and dose dependent induction of apoptosis by ABT-263 in human and rat primary CAF as well as activated LX2 cells as compared to rat BDEneu and human CCA cell lines. Comparison of Bcl-2 protein expression in quiescent fibroblasts versus CAF demonstrated a consistent upregulation of Bax in the CAF, likely explaining their enhanced sensitivity to pro-death stimuli. Indeed, ABT-263 treatment of CAF was associated with Bax activation as compared to human CCA cell lines. Finally, administration of ABT-263 decreased tumor size and metastasis in a human-like in-vivo rat model of CCA. Analysis of the rat tumors revealed a decrease in Tenascin C positive tumor stroma and an increase of TUNEL-positive apoptotic stromal cells. Conclusions: CCA associated CAF appear to be ‘primed’ for cell death, possibly due to overexpression of the pro-apoptotic Bcl-2 protein Bax. Consequently CAF display increased sensitivity to the BH3 mimetic ABT-263, which selectively depletes them from a rat in-vivo model of CCA, thereby reducing tumor growth and metastasis. Thus targeting CCA tumor stroma by inducing apoptosis in CAF may represent a new therapeutic approach in human CCA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4905. doi:1538-7445.AM2012-4905

Abstract Previous epidemiological studies have suggested that African Americans (AA) are twice as likely to be diagnosed with and to die from Multiple Myeloma (MM) as compared to European Americans (EA). In recent years, however, mortality rates have become more comparable between these groups. Although socioeconomic factors could play a major role to this potential disparity, biological factors may also be responsible for influencing these differences in either incidence and/or mortality. Here we examined a multi-ethnic cohort of MM tumors to assess potential differences in the frequency of molecular events in tumors derived from either African American (AA) or European American (EA) patients. First, we compared the frequency of 14q32 translocation breakpoints at the IgH locus among a series of data from 115 AA MM patients from three studies and EA MM from the Eastern Cooperative Oncology Group (ECOG). Furthermore, we analyzed matching genome-wide copy number and transcriptional data among 47 AA MM tumors and 196 EA MM tumors to determine differences in the frequency of molecular events in tumors from these populations. Univariate analyses were conducted using the Fisher's Exact Test and p-values were calculated to measure statistical significance. We observed statistically significant differences in the frequency of IgH translocations and somatic copy number alterations. Although we did not detect differences for specific translocation subtypes, we saw a statistically significant difference in the overall frequency of IgH translocations between the two groups, which occurred more frequently in EA patients (p = 0.032). When assessing genomic copy number events previously shown to be associated with poor outcome in MM, chromosome 13 monosomy was more frequent in hyperdiploid MM from AA patients and significant after correcting for multiple testing using the Bonferoni correction method (p = 0.001). Moreover, when using the Benjamini-Hochberg multiple testing correction method, chromosome 13 monosomy remained significantly different among hyperdiploid AA patients (p = 0.0121). Chromosome 1q amplification was also significant among hyperdiploid tumors from EA patients when using this correction method (p = 0.036). No differences in the frequency of hyperdiploid status or gene expression-based subtypes were detected when comparing tumors from AA and EA patients. Our study represents the first comprehensive assessment of the frequency and distribution of molecular alterations in MM tumors from both AA and EA patients and could help shed light on possible biological features associated with population differences in incidence and outcome in MM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5064. doi:1538-7445.AM2012-5064

Cyclosporine induces hypertension and wide-spread vasoconstriction after transplantation in addition to reducing kidney function. We studied hemodynamic, renal, and hormonal effects of monotherapy with nifedipine XL (n = 37) in liver transplant recipients within a year after transplant (median, 4.4 months). Systemic hemodynamics were determined with thoracic electrical bioimpedance. Blood pressure before therapy was 172 +/- 4/108 +/- 2 mm Hg. Sixty-four percent of recipients achieved blood pressures less than 140/90 mm Hg mediated by a fall in systemic vascular resistance index (2427 +/- 245 dyne.s.cm-5.m-2 in responders versus 2905 +/- 281 in nonresponders, P < .01). Despite the fall in systemic vascular resistance, glomerular filtration rates were not changed during nifedipine therapy, as measured by both creatinine and iothalamate clearances. Urinary prostacyclin (6-ketoprostaglandin F1 alpha) was suppressed below normal from 2468 +/- 323 ng/d before transplant to 1103 +/- 99 ng/d (P < .01) after transplant and did not change during nifedipine therapy. Urinary thromboxane B2 and plasma renin activity also fell after transplant and remained low during nifedipine. These data demonstrate that nifedipine can reverse systemic vasoconstriction associated with hypertension after transplantation. Systemic effects were not transmitted to the kidney sufficiently to improve glomerular filtration rate or reverse hormonal changes within the kidney. Hence, vascular and functional regulation of the kidney was dissociated from the systemic circulation during nifedipine administration after transplantation.

AbstractBackgroundCancer‐specific anxiety (CSA) can affect treatment decisions and is common in men following surgery for prostate cancer (PCa). We hypothesized that CSA is also associated with factors affecting quality of life. Herein, we examine the association of CSA with psychosocial factors and PCa aggressiveness in a cohort of men 1 year after prostatectomy for localized PCa.MethodsFrom our prospective PCa Registry, we identified 365 men who underwent prostatectomy for localized PCa who completed the Memorial Anxiety Scale for Prostate Cancer (MAX‐PC) and Expanded Prostate Cancer Index Composite at 1‐year follow‐up. We evaluated the association of scores on the MAX‐PC with demographics, clinicopathologic features, sexual function, and depression scores using Wilcoxon Rank Sum and Kendall's tau correlation tests.ResultsHigher scores on the MAX‐PC (i.e., higher anxiety) are associated with younger age (p < 0.01) and non‐Caucasian race (p < 0.01). Men with higher MAX‐PC scores also reported poor sexual satisfaction/function (p < 0.01) and increasing depressive symptoms (p < 0.01). Finally, although higher anxiety is associated with several pathologic features of aggressiveness (stage, positive margins, PSA at 1 year; all p‐values < 0.01), we noted several men with clinically indolent disease who reported significant anxiety.ConclusionsOur data suggest that higher levels of CSA are associated with poor sexual function and increased depressive symptoms 1 year after prostatectomy. Moreover, we noted demographic and pathologic features associated with higher CSA as well. If confirmed, our data support development of models to predict men at high risk of CSA following PCa surgery and targeted referral for additional counseling. Copyright © 2012 John Wiley & Sons, Ltd.

Purpose. To investigate EEG and SPECT in the surgical outcome of patients with normal MRI (nonlesional) and extratemporal lobe epilepsy. Methods. We retrospectively identified 41 consecutive patients with nonlesional extratemporal epilepsy who underwent epilepsy surgery between 1997 and 2007. The history, noninvasive diagnostic studies (scalp EEG, MRI, and SPECT) and intracranial EEG (iEEG) monitoring was reviewed. Scalp and iEEG ictal onset patterns were defined. The association of preoperative studies and postoperative seizure freedom was analyzed using Kaplan-Meier analysis, log-rank test, and Cox proportional hazard. Results. Thirty-six of 41 patients had adequate information with a minimum of 1-year followup. Favorable surgical outcome was identified in 49% of patients at 1 year, and 35% at 4-year. On scalp EEG, an ictal onset pattern consisting of focal beta-frequency discharge (>13–125 Hz) was associated with favorable surgical outcome (P=0.02). Similarly, a focal fast-frequency oscillation (>13–125 Hz) on iEEG at ictal onset was associated with favorable outcome (P=0.03). Discussion. A focal fast-frequency discharge at ictal onset identifies nonlesional MRI, extratemporal epilepsy patients likely to have a favorable outcome after resective epilepsy surgery.