Citations

The use of the transseptal transsphenoidal approach to the pituitary gland has gained acceptance as a safe, relatively atraumatic means of removing pituitary tumors. The outcome in adult patients has been successful; however, the outcome in pediatric patients whose noses may still be developing is not well described. We reviewed the outcomes in 41 patients younger than age 18 years who underwent transseptal transsphenoidal pituitary surgery at our institution between 1986 and 1997 (20 boys and 21 girls; age, 3 to 17 years; mean age, 13.4 years). The most common diagnosis was prolactin-secreting adenoma (14 patients), followed by craniopharyngioma (7 patients). Presenting symptoms included headache (20 patients), galactorrhea (13 patients), and menstrual irregularities (11 patients). The most common early complication was transient diabetes insipidus (20 patients). No patient experienced serious bleeding at pack removal and no patient developed a cerebrospinal fluid leak postoperatively. Follow-up ranged from 3 months to 12.7 years, with 7 patients experiencing recurrent or residual disease between 6 days and 2 years after their original transseptal procedure. The most common long-term surgical complication was nasal obstruction in 5 patients, 3 of whom also complained of seasonal allergies. Four patients complained of recurrent sinus infections, and 4 patients noted an external nasal deformity as a result of the surgery.

AbstractBackground: Zn-α2 glycoprotein (ZAG) is a relatively abundant glycoprotein that has potential as a biomarker for prostate cancer. We present a high-flow liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for measuring serum ZAG concentrations by proteolytic cleavage of the protein and quantification of a unique peptide.Methods: We selected the ZAG tryptic peptide 147EIPAWVPEDPAAQITK162 as the intact protein for quantification and used a stable isotope-labeled synthetic peptide with this sequence as an internal standard. Standards using recombinant ZAG in bovine serum albumin, 50 g/L, and a pilot series of patient sera were denatured, reduced, alkylated, and digested with trypsin. The concentration of ZAG was calculated from a dose–response curve of the ratio of the relative abundance of the ZAG tryptic peptide to internal standard.Results: The limit of detection for ZAG in serum was 0.08 mg/L, and the limit of quantification was 0.32 mg/L with a linear dynamic range of 0.32 to 10.2 mg/L. Replicate digests from pooled sera run during a period of 3 consecutive days showed intraassay imprecision (CV) of 5.0% to 6.3% and interassay imprecision of 4.4% to 5.9%. Mean (SD) ZAG was higher in 25 men with prostate cancer [7.59 (2.45) mg/L] than in 20 men with nonmalignant prostate disease [6.21 (1.65) mg/L, P = 0.037] and 6 healthy men [3.65 (0.71) mg/L, P = 0.0007].Conclusions: This LC-MS/MS assay is reproducible and can be used to evaluate the clinical utility of ZAG as a cancer biomarker.

Abstract Purpose: To evaluate the effects of combining the multiple receptor tyrosine kinase inhibitor AEE788 and histone deacetylase (HDAC) inhibitors on cytotoxicity in a broad spectrum of cancer cell lines, including cisplatin-resistant ovarian adenocarcinoma cells. Experimental Design: Multiple cancer cell lines were treated in vitro using AEE788 and HDAC inhibitors (LBH589, LAQ824, and trichostatin A), either alone or in combination. Effects on cytotoxicity were determined by growth and morphologic assays. Effects of the combination on cell signaling pathways were determined by Western blotting, and the results were confirmed using pathway-specific inhibitors and transfection of constitutively active proteins. Results: Cell treatment with AEE788 and HDAC inhibitors (LBH589, LAQ824, and trichostatin A) in combination resulted in synergistic induction of apoptosis in non–small cell lung cancer (MV522, A549), ovarian cancer (SKOV-3), and leukemia (K562, Jurkat, and ML-1) cells and in OV202hp cisplatin-resistant human ovarian cancer cells. AEE788 alone or in combination with LBH589 inactivated mitogen-activated protein kinase (MAPK) and Akt cascades. Inhibition of either MAPK and/or Akt enhanced LBH589-induced apoptosis. In contrast, constitutively active MAPK or Akt attenuated LBH589 or LBH589 + AEE788–induced apoptosis. Increased apoptosis was correlated with enhanced reactive oxygen species (ROS) generation. The free radical scavenger N-acetyl-l-cysteine not only substantially suppressed the ROS accumulation but also blocked the induction of apoptosis mediated by cotreatment with AEE788 and LBH589. Conclusion: Collectively, these results show that MAPK and Akt inactivation along with ROS generation contribute to the synergistic cytotoxicity of the combination of AEE788 and HDAC inhibitors in a variety of human cancer cell types. This combination regimen warrants further preclinical and possible clinical study for a broad spectrum of cancers.

In this study, we propose a quality control program for MR‐guided focused ultrasound (FUS) ablation treatment to assess FUS beam positioning accuracy, FUS power delivery accuracy, MR imaging quality, and FUS ablation system safety. A total of 353 sonication points in Lucite cards were measured, the average placement errors were in the SI direction and in the LR direction. Temperature elevation was calculated from MR phase difference images and the measured water proton chemical shift (WPCS) temperature coefficient. WPCS temperature calibration for phantoms yielded a temperature coefficient of 0.011 ppm/°C. Sixteen experiments were conducted using six different phantoms to test the reliability of FUS power delivery. SNR and RF power calculated from phantom images were analyzed and stored at the MR console. A computer program was developed to integrate the system power delivery and the MR image quality control into one automated process. In the clinical trial at our institution, we expect this quality control program to be carried out before each patient treatment. If measured quality control values exceeds or below the preset values, a system service and retest should be conducted before the treatment.PACS number(s): 87.61.–c, 87.54.–n

The Modern Technology of Radiation Oncology, Vol. 2, edited by Jacob Van Dyk, Medical Physics Publishing, 2005, ISBN‐10:1‐930524‐25‐0 (hard cover), list price $120 hard cover, $100 soft cover

The purpose of this study was to evaluate electronic portal imaging (EPI) as a means of identifying and correcting field displacement in patients with problematic external beam radiotherapy setups. Fourteen patients with problematic setups were identified for pretreatment daily EPI beam monitoring as part of a physician‐directed therapist intervention protocol. Pretreatment EPIs were used to realign fields as necessary to bring the setup within the physician‐prescribed tolerance level. For comparison, daily EPIs were available for 12 control patients who had no particular setup difficulties and for whom online beam realignment was not made. Anatomy‐matching software was used to measure setup variation along medial‐lateral, superior‐inferior, and anterior‐posterior axes. Online field realignment yielded a significant improvement when comparing initial and final setup variations. The mean standard deviation of setup displacement averaged over three axes was reduced from 6.4 mm to 3.1 mm after realignment. The final variation of protocol patients was comparable to that of control patients. In conclusion, EPI provided effective means to perform online beam realignment in a group of difficult‐to‐position patients. This procedure resulted in a reduction in setup displacement that was statistically significant, clinically relevant, and approached that of a more typical patient group.PACS number: 87.53.Oq

This manuscript presents a case of early stage squamous cell carcinoma of the left buccal mucosa treated with intensity‐modulated radiation therapy (IMRT) followed by a high‐dose rate (HDR) brachytherapy boost. With limited literature available on HDR mold (stent) radiotherapy for oral cancer, a discussion on the issues encountered during treatment planning and delivery may prove to be insightful for facilities faced with a similar challenge.PACS numbers: 87.53.Jw, 87.53.Tf, 87.59.Ci, 87.59.Fm

We have recently commissioned a temporary radiation therapy facility that is novel in two aspects: it was constructed using modular components, and the LINAC was installed in one of the modular sections before it was lifted into position. Additional steel and granular fill was added to the modular sections on‐site during construction. The building will be disassembled and removed when no longer needed. This paper describes the radiation shielding specifications and survey of the facility, as well as the ramifications for acceptance testing occasioned by the novel installation procedure. The LINAC is a Varian 21EX operating at 6 MV and 18 MV. The radiation levels outside the vault satisfied the design criteria, and no anomalous leakage was detected along the joints of the modular structure. At 18 MV and 600 monitor units (MU) per minute, the radiation level outside the primary barrier walls was of photons; there were no detectable neutrons. Outside the direct‐shielded door, the levels were of photons and of neutrons. The isocentricity of the accelerator met the acceptance criteria and was not affected by its preinstallation into an integrated baseframe and subsequent transport to the building site.PACS numbers: 87.52.Df, 87.52.Ga

A method to investigate light and radiation field congruence utilizing a commercially available amorphous silicon electronic portal imaging device (EPID) was developed. This method employed an EPID, the associated EPI software, and a diamond‐shaped template. The template was constructed from a block tray in which Sn/Pb wires, 1 mm in diameter, were embedded into a diamond shaped groove milled into the tray. The collimator jaws of the linac were aligned such that the light field fell directly on the corners of the diamond. A radiation detection algorithm within the EPI software determined the extent of the radiation field. The light and radiation field congruence was evaluated by comparing the vertexes of the diamond reference structure to the detected radiation field. In addition, the digital jaw settings were recorded and later compared to the light field detected on the films and EPIs. Three linear accelerators were tracked for a period ranging from 2–8 months. Light radiation field congruence tests with films and EPIs were comparable, yielding a difference of less than 0.6 mm, well within the allowed 2‐mm tolerance. A disparity was observed in the magnitude of the detected light field. The X and Y dimensions of the light field measured with film differed by less than or equal to 1.4 mm from the digital collimator settings, whereas the values extracted from the EPIs differed by up to 2.5 mm. Based on these findings, EPIs were found to be a quick and reliable alternative to film for qualitative and relative analyses.PACS number(s): 87.53.Xd, 87.56.Fc, 87.53.Oq, 87.52.–g, 87.53.–j

Our goal in this work was to compare the results of common phantom tests made using matched and mixed ultrasound (US) scanner‐transducer combinations. Sets of common US quality assurance (QA) measurements were made using matched US scanner‐transducer combinations (i.e., transducers purchased for use with a particular scanner), as well as unmatched (mixed) combinations. Measurements of vertical and horizontal distance accuracy, and depth of penetration were performed using three common transducer types. Means, standard deviations, and differences between the mean mix and match measurements divided by the standard deviation (match‐mix difference, or MMD), and two‐sided, paired t‐tests were computed for the groups of mixed and matched measurements. MMDs for vertical and horizontal distance accuracy test results were less than 0.87 in all cases, well below our threshold value of 2.0, which indicates that a significant difference exists. MMDs for the depth of penetration measurements were less than 1.50, again below the threshold value. These results suggest that all of the mixed and matched data sets were very similar. The more sensitive t‐tests indicate statistically significant differences in only 2 of the 18 pairs of data sets. In conclusion, this study suggests that QA measurements generated by mixed or matched scanner‐transducer combinations are very comparable. The ability to obtain QA phantom test data from mixed scanner‐transducer combinations reduces the time required for US QA testing.PACS number(s): 87.57.–s, 87.62.+n