Anesthetic considerations for pediatric abdominal solid organ transplantation.

While many pediatric patients undergo abdominal solid organ transplants every year worldwide, each is unique due to varying age, size, and comorbidities; thus, they require a careful anesthesia plan to undergo surgery safely. This article reviews the anesthetic considerations and management of patients undergoing liver and kidney transplantation. Preoperative, intraoperative, and post-operative management are discussed, including induction, access, monitoring, and maintenance. Blood transfusion is also addressed.

Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer.

BACKGROUND: Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation. METHODS: This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery. RESULTS: Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases. CONCLUSIONS: The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00137852 , registered August 29, 2005.

Monitoring of an esterification reaction by on-line direct liquid sampling mass spectrometry and in-line mid infrared spectrometry with an attenuated total reflectance probe.

A specially designed thermal vaporiser was used with a process mass spectrometer designed for gas analysis to monitor the esterification of butan-1-ol and acetic anhydride. The reaction was conducted at two scales: in a 150 mL flask and a 1L jacketed batch reactor, with liquid delivery flow rates to the vaporiser of 0.1 and 1.0 mLmin(-1), respectively. Mass spectrometry measurements were made at selected ion masses, and classical least squares multivariate linear regression was used to produce concentration profiles for the reactants, products and catalyst. The extent of reaction was obtained from the butyl acetate profile and found to be 83% and 76% at 40°C and 20°C, respectively, at the 1L scale. Reactions in the 1L reactor were also monitored by in-line mid-infrared (MIR) spectrometry; off-line gas chromatography (GC) was used as a reference technique when building partial least squares (PLS) multivariate calibration models for prediction of butyl acetate concentrations from the MIR spectra. In validation experiments, good agreement was achieved between the concentration of butyl acetate obtained from in-line MIR spectra and off-line GC. In the initial few minutes of the reaction the profiles for butyl acetate derived from on-line direct liquid sampling mass spectrometry (DLSMS) differed from those of in-line MIR spectrometry owing to the 2 min transfer time between the reactor and mass spectrometer. As the reaction proceeded, however, the difference between the concentration profiles became less noticeable. DLSMS had advantages over in-line MIR spectrometry as it was easier to generate concentration profiles for all the components in the reaction. Also, it was possible to detect the presence of a simulated impurity of ethanol (at levels of 2.6 and 9.1% mol/mol) in butan-1-ol, and the resulting production of ethyl acetate, by DLSMS, but not by in-line MIR spectrometry.

O-GlcNAcylation regulates cancer metabolism and survival stress signaling via regulation of the HIF-1 pathway.

The hexosamine biosynthetic pathway elevates posttranslational addition of O-linked ß-N-acetylglucosamine (O-GlcNAc) on intracellular proteins. Cancer cells elevate total O-GlcNAcylation by increasing O-GlcNAc transferase (OGT) and/or decreasing O-GlcNAcase (OGA) levels. Reducing O-GlcNAcylation inhibits oncogenesis. Here, we demonstrate that O-GlcNAcylation regulates glycolysis in cancer cells via hypoxia-inducible factor 1 (HIF-1α) and its transcriptional target GLUT1. Reducing O-GlcNAcylation increases α-ketoglutarate, HIF-1 hydroxylation, and interaction with von Hippel-Lindau protein (pVHL), resulting in HIF-1α degradation. Reducing O-GlcNAcylation in cancer cells results in activation of endoplasmic reticulum (ER) stress and cancer cell apoptosis mediated through C/EBP homologous protein (CHOP). HIF-1α and GLUT1 are critical for OGT-mediated regulation of metabolic stress, as overexpression of stable HIF-1 or GLUT1 rescues metabolic defects. Human breast cancers with high levels of HIF-1α contain elevated OGT, and lower OGA levels correlate independently with poor patient outcome. Thus, O-GlcNAcylation regulates cancer cell metabolic reprograming and survival stress signaling via regulation of HIF-1α.

Critical role of O-Linked ß-N-acetylglucosamine transferase in prostate cancer invasion, angiogenesis, and metastasis.

Cancer cells universally increase glucose and glutamine consumption, leading to the altered metabolic state known as the Warburg effect; one metabolic pathway, highly dependent on glucose and glutamine, is the hexosamine biosynthetic pathway. Increased flux through the hexosamine biosynthetic pathway leads to increases in the post-translational addition of O-linked ß-N-acetylglucosamine (O-GlcNAc) to various nuclear and cytosolic proteins. A number of these target proteins are implicated in cancer, and recently, O-GlcNAcylation was shown to play a role in breast cancer; however, O-GlcNAcylation in other cancers remains poorly defined. Here, we show that O-GlcNAc transferase (OGT) is overexpressed in prostate cancer compared with normal prostate epithelium and that OGT protein and O-GlcNAc levels are elevated in prostate carcinoma cell lines. Reducing O-GlcNAcylation in PC3-ML cells was associated with reduced expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF, resulting in inhibition of invasion and angiogenesis. OGT-mediated regulation of invasion and angiogenesis was dependent upon regulation of the oncogenic transcription factor FoxM1, a key regulator of invasion and angiogenesis, as reducing OGT expression led to increased FoxM1 protein degradation. Conversely, overexpression of a degradation-resistant FoxM1 mutant abrogated OGT RNAi-mediated effects on invasion, MMP levels, angiogenesis, and VEGF expression. Using a mouse model of metastasis, we found that reduction of OGT expression blocked bone metastasis. Altogether, these data suggest that as prostate cancer cells alter glucose and glutamine levels, O-GlcNAc modifications and OGT levels become elevated and are required for regulation of malignant properties, implicating OGT as a novel therapeutic target in the treatment of cancer.

Quantitation of trace components in liquid process streams by direct liquid sampling mass spectrometry.

This paper describes the development of a liquid sampling approach for trace analysis by electron impact ionization magnetic sector mass spectrometry, with no chromatographic separation. Development of a liquid sample introduction interface based on the principle of Programmable Temperature Vaporizing (PTV) GC injection is shown. A univariate procedure for the analysis of trace (mg kg(-1)) propanoic acid in acetic acid was developed. Results from the laboratory-based analysis of acetic acid are presented and compared with conventional GC analysis. The detection limit was 16 mg l(-1) and the speed of analysis was employed to acquire 30 scans per minute thus reducing the confidence intervals of the results and potentially allowing production plants to run much closer to sales specifications. For the analysis of more complex samples where the analytes contained no unique ions, multivariate analysis was employed and up to three scans per minute were acquired. Results from the analysis of an ester for six trace impurities are shown. Calibration was by partial least squares regression. The detection limits for these components were 20-30 mg kg(-1), well within the required product specifications. The system proved to be robust and easy to operate, with analyses being carried out over a period of several months requiring no maintenance of the spectrometer and only cleaning of the injection liner of the PTV injector on a monthly basis.