Colorectal Cancer Related to Chronic Strongyloides stercoralis Infection.

The majority of individuals with Strongyloides stercoralis (S. stercoralis) colitis are clinically asymptomatic. Symptomatic individuals may complain of nonspecific gastrointestinal symptoms, such as abdominal pain, intermittent or persistent diarrhea, nausea, or loss of appetite. In addition, skin manifestations such as recurrent urticaria can occur. If infection is not diagnosed and left untreated, it can lead to chronic inflammation of the gastrointestinal tract. It is well documented that chronic colitis such as inflammatory bowel disease can predispose individuals to colorectal cancer. Additionally, there is evidence of chronic parasitic infections inducing the development of cancers in other organs within the gastrointestinal tract. In this case vignette, we describe a case of chronic Strongyloides stercoralis infection in a Peruvian woman presenting with colorectal cancer.

Sevelamer Carbonate Crystal-Induced Colitis.

Hyperphosphatemia is a common and well-described complication of end-stage renal disease. Despite strict dietary constraints and compliance, phosphate binders such as calcium acetate and/or sevelamer carbonate are also needed to treat secondary hyperparathyroidism. This case vignette describes an underrecognized adverse effect of a phosphate binder, sevelamer carbonate, inducing colitis in a 47-year-old male with insulin-dependent diabetes complicated by end-stage renal disease. He presented for recurrent abdominal pain with associated nausea and was found to have multiple circumferential lesions on computed tomography including distal ascending, transverse, and proximal descending colon. Colonoscopy demonstrated nearly obstructing lesions worrisome for colonic ischemia or inflammatory bowel disease. Pathological review of histology demonstrated ragged colonic mucosa with ulcerative debris and nonpolarizing crystalline material at the sites of ulceration, morphologically consistent with the phosphate binder, sevelamer carbonate. Sevelamer carbonate was discontinued, and the patient was transitioned to calcium carbonate with strict dietary restrictions. His symptoms improved with the cessation of sevelamer, and he was subsequently discharged home. He eventually underwent renal transplant without redevelopment of symptoms. Recognition of this underreported complication of sevelamer carbonate, phosphate binder, is of utmost importance in directing appropriate therapy with cessation of this medication in the setting of gastrointestinal complaints or more specifically enteritis and colitis. Clinicians providing care to end-stage renal patients taking either sevelamer and/or sodium polystyrene sulfonate should have increased awareness of the possible gastrointestinal side effects.

Adipose lipid turnover and long-term changes in body weight.

The worldwide obesity epidemic1 makes it important to understand how lipid turnover (the capacity to store and remove lipids) regulates adipose tissue mass. Cross-sectional studies have shown that excess body fat is associated with decreased adipose lipid removal rates2,3. Whether lipid turnover is constant over the life span or changes during long-term weight increase or loss is unknown. We determined the turnover of fat cell lipids in adults followed for up to 16 years, by measuring the incorporation of nuclear bomb test-derived 14C in adipose tissue triglycerides. Lipid removal rate decreases during aging, with a failure to reciprocally adjust the rate of lipid uptake resulting in weight gain. Substantial weight loss is not driven by changes in lipid removal but by the rate of lipid uptake in adipose tissue. Furthermore, individuals with a low baseline lipid removal rate are more likely to remain weight-stable after weight loss. Therefore, lipid turnover adaptation might be important for maintaining pronounced weight loss. Together these findings identify adipose lipid turnover as an important factor for the long-term development of overweight/obesity and weight loss maintenance in humans.

Accelerated partial-breast irradiation using intensity-modulated proton radiotherapy: do uncertainties outweigh potential benefits?

OBJECTIVE: Passive scattering proton beam (PSPB) radiotherapy for accelerated partial-breast irradiation (APBI) provides superior dosimetry for APBI three-dimensional conformal photon radiotherapy (3DCRT). Here we examine the potential incremental benefit of intensity-modulated proton radiotherapy (IMPT) for APBI and compare its dosimetry with PSPB and 3DCRT. METHODS: Two theoretical IMPT plans, TANGENT_PAIR and TANGENT_ENFACE, were created for 11 patients previously treated with 3DCRT APBI and were compared with PSPB and 3DCRT plans for the same CT data sets. The impact of range, motion and set-up uncertainties as well as scanned spot mismatching between fields of IMPT plans was evaluated. RESULTS: IMPT plans for APBI were significantly better regarding breast skin sparing (p<0.005) and other normal tissue sparing than 3DCRT plans (p<0.01) with comparable target coverage (p=ns). IMPT plans were statistically better than PSPB plans regarding breast skin (p<0.002) and non-target breast (p<0.007) in higher dose regions but worse or comparable in lower dose regions. IMPT plans using TANGENT_ENFACE were superior to that using TANGENT_PAIR in terms of target coverage (p<0.003) and normal tissue sparing (p<0.05) in low-dose regions. IMPT uncertainties were demonstrated for multiple causes. Qualitative comparison of dose-volume histogram confidence intervals for IMPT suggests that numeric gains may be offset by IMPT uncertainties. CONCLUSION: Using current clinical dosimetry, PSPB provides excellent dosimetry compared with 3DCRT with fewer uncertainties compared with IMPT. ADVANCES IN KNOWLEDGE: As currently delivered in the clinic, PSPB planning for APBI provides as good or better dosimetry than IMPT with less uncertainty.

SU-E-T-519: Experimental Evaluation of Deterministic Acuros XB Radiation Transport Algorithm for Heterogeneity Dose Calculation Using the Radiological Physics Center's Lung Phantom.

PURPOSE: To evaluate the heterogeneity corrected dose calculations from the Acuros XB (AXB), a novel deterministic dose calculation algorithm based on grid-based Boltzmann transport equation solver (GBBS), for IMRT and VMAT plans. METHODS: The Radiological Physics Center's lung phantom was used to create clinically equivalent IMRT and VMAT plans (RapidArc) with the Eclipse planning system 10.0 that were delivered using a Varian 23 iX. Absolute doses and relative dose distributions were measured with thermoluminescent dosimeters (TLDs) and radiochromic film. The measured dose distributions were compared with calculated doses from both AXB (11.0.3) and AAA (10.0.24) dose calculation algorithms. The AXB calculated dose-to-water and dose-to-medium were both compared to measurements. Gamma analysis (±7%/4mm, ±5%/3mm, and ±3%/3mm) was used to quantify correspondence between AXB dose distributions and the film measurements. The computation time between AAA and AXB were also evaluated. RESULTS: For TLD point doses, both AAA and AXB heterogeneity corrected dose calculations are within 5% inside the PTV for both IMRT and VMAT plans. The agreements observed between the measured and calculated doses for both AXB dose reporting methods are better than those observed with the AAA algorithm. The gamma analysis showed that the differences between AAA, AXB and film measurement met the RPC ±7%/4 mm criteria. The percent of pixels passing rate for both the AXB dose to medium and AXB dose to water are higher than AAA. The computation time between AAA and AXB are comparable for IMRT plans but AXB is significantly faster (4 times) than AAA for VMAT plans. CONCLUSIONS: The AXB implemented in the Eclipse planning system calculates a more accurate heterogeneity corrected dose than the AAA algorithm as compared to measurement in lung and improve the calculation speed for VMAT radiotherapy. Work supported by grants CA10953, CA81647, 2R44CA105806-02, CA016672 (NCI, DHHS).

TU-C-218-02: Effective Oncology Physics Education.

The education of medical physicists has historically been quite varied and medical physicists have entered the field through several pathways including specialized educational programs, postdoctoral fellowships, and on-the-job training. It is argued that the contributions of viewpoints from different branches of physics has contributed to the development of novel solutions and advances in radiation oncology. However, there also has been an effort recently to make graduate education of medical physicists more consistent and uniform, particularly for the preparation of clinically oriented therapy physicists. The trend towards a more systematic approach has been guided in part by the requirements for graduate program accreditation developed by CAMPEP and by the requirements for medical physicist certification by the ABR. At the same time, there has been criticism of this approach as being too confining and guiding graduates toward a career as technicians rather than independent thinkers. Educational programs have had to balance the requirements of accreditation and certification against the goal of preparing students for careers as independent researchers. Three speakers will describe the approaches taken by their graduate educational programs to meet the requirements of CAMPEP and adequately prepare graduates for certification by the ABR, while maintaining a commitment to providing a comprehensive education in medical physics. LEARNING OBJECTIVES: 1. Understand the requirements for graduate program accreditation 2. Understand the education and experience requirements for certification 3. Learn the approaches taken by several graduate programs to meet the requirements for accreditation and certification while providing a comprehensive education in medical physics.

SU-E-T-528: Appraisal of Acorus XB and Convolution Dose Algorithms in Field Junction of Breast Tangential/superclavicular Fields.

PURPOSE: Dose accuracy injunction regions of breast-tangential therapy is a challenge, and inaccurate dose predictions may lead to unreal hot/cold spots. Availability of the novel deterministic radiation transport method Acuros XB (AXB) provides a potential for more accurate dose predictions. This study assesses relative dose accuracies of this and the widely used other algorithms: collapsed cone convolution (CCC) and anisotropic analytical algorithm (AAA) against film measurements. METHODS: A typical tangential and superclav fileld combination was planned for an anthropomorphic body phantom using Pinnacle-9.0 treatment-planning system (TPS). The created plan employing 6MV beam was delivered to the phantom on a Varian linac. In region of the field junction of tangentials & superclav, films (EBT2) were placed in coronal planes at two depths (∼ 2 and 4 cm). Optical density was measured along and ± 5mm away from the field-match line, and converted to dose using film-calibration curve specific to the batch of film. The same plan was also imported to Eclipse TPS using an import filter written in MATLAB. Algorithms Pinnacle CCC 9.0, Eclipse AAA 10.0.24 and AXB 11.0.3 were used for calculations. Comparison of the measured doses (assumed as gold standard) against doses calculated from planning-systems were preformed in a MATLAB platform. RESULTS: In general, dose distributions from all three TPS algorithms are found to agree closely with film data. Agreements between AXB and CCC dose calculations were found to be reasonable. AXB appears to be better in modeling the backscatter effects in the heterogeneous regions. AAA calculations gives acceptable results, but with less accuracy compared to CCC and AXB. CONCLUSIONS: The novel deterministic algorithm AXB in Eclipse is found to provide better agreement with measured data in breast-tangential therapy. Benefits of using Acuors XB algorithm in tangential fields planning requires further investigation. This work was funded by National Institutes of Health through grant 2R44CA105806-02 and MD Anderson’s Cancer Center Support Grant CA0 16672.

Preliminary evaluation of implantable MOSFET radiation dosimeters.

In this paper, we report on measurements performed on a new prototype implantable radiation detector that uses metal-oxide semiconductor field effect transistors (MOSFETs) designed for in vivo dosimetry. The dosimeters, which are encapsulated in hermetically sealed glass cylinders, are used in an unbiased mode during irradiation, unlike other MOSFET detectors previously used in radiotherapy applications. They are powered by radio frequency telemetry for dose measurements, obviating the need for a power supply within each capsule. We have studied the dosimetric characteristics of these MOSFET detectors in vitro under irradiation from a 60Co source. The detectors show a dose reproducibility generally within 5% or better, with the main sources of error being temperature fluctuations occurring between the pre- and post-irradiation measurements as well as detector orientation. A better temperature-controlled environment leads to a reproducibility within 2%. Our preliminary in vitro results show clearly that true non-invasive in vivo dosimetry measurements are feasible and can be performed remotely using telemetric technology.

Prognosis for papillary serous carcinoma of the endometrium after surgical staging.

BACKGROUND: To investigate the pattern of failure and the prognosis following pathological staging for uterine papillary serous carcinoma (UPSC). PATIENTS AND METHODS: A retrospective review was conducted of 22 patients with UPSC, treated between 1989 and 1998 at a single institution. All patients were surgically staged. Two patients with advanced disease received chemotherapy only. Two patients with early-stage disease were followed without further treatment. Eighteen patients received postoperative irradiation; eight patients received whole abdominal irradiation (WART), and the remaining 10 patients, pelvic irradiation (PRT). In addition, seven of these patients received vaginal cuff irradiation with low-dose-rate or high-dose-rate brachytherapy. Toxicity, pattern of failure, and survival were evaluated and compared to the literature. RESULTS: Seven patients (32%) developed distant metastases, three out of seven (42%) after WART. Four out of seven patients who had distant metastases died from disease progression during subsequent chemotherapy. All patients with distant metastases had locally advanced-stage disease at presentation (six stage III, one stage IV). Four patients with pelvic recurrences developed concurrent (2) and subsequent (2) distant metastases. Three patients had isolated distant metastases. No patient with early stage-disease (stage I and II) died from disease progression. CONCLUSION: Pathological staging should be performed for all patients with UPSC to determine the prognosis as well as to tailor the treatment. The role of abdominal irradiation in the treatment of UPSC is yet to be determined; however, such an approach may not be necessary for the control of disease for patients with early-stage (I and II) disease. Patients with locally advanced-stage (stage III) disease are at risk of local regional failures and distant metastases despite WART. Therefore, the benefit of WART for advanced-stage disease is also questionable. Paclitaxel-based chemotherapy is currently being investigated in this setting.

Interferon-alpha combined with radiotherapy in the treatment of unresectable melanoma.

A case of recurrent and twice resected sinonasal melanoma is presented. The large recurrent tumor was found to regress by a concurrent combination of 6660 cGy photon radiation and subcutaneous interferon-alpha injections given for a period of 8 weeks. Possible mechanisms of potentiation between interferon and radiation are discussed. The unexpected result in this case report raises interesting questions about this treatment combination.

Combined preoperative chemotherapy and radiation for locally advanced rectal carcinoma.

To determine the efficacy of combined preoperative chemotherapy and radiation therapy for locally advanced rectal carcinoma and the rate of sphincter conservation, a retrospective survey of 39 patients with locally advanced rectal carcinoma treated with various 5-fluorouracil- and leukovorin-based chemotherapy regimens and radiation prior to surgery in a single institution was reviewed. Toxicity, local control and survival were evaluated and compared to previous studies with similarly staged patients. Long-term follow-up was available on 35 patients. The actuarial local failure was 5.7% while the actuarial 5-year survival was 87%. The mortality rate was low (2.5%) and the rate of long-term serious complications acceptable (11.4%). Combined preoperative chemotherapy and radiation provided excellent local regional control despite the poor prognostic factors associated with size, fixation, and the initial advanced tumor stage with acceptable morbidity. In addition, patients with tumors located in the lower third of the rectum may be able to undergo sphincter-sparing surgery. Although the median follow-up is relatively short (32.4 months), the results are in accordance with previous studies of neoadjuvant combined chemotherapy and radiation for locally advanced rectal carcinoma in terms of local and distant control.

Micronuclei in lymphocytes of prostate cancer patients undergoing radiation therapy.

To further verify the applicability of the micronucleus (MN) assay in biodosimetry, we measured the MN yield in cytokinesis-blocked (CB) peripheral blood lymphocytes (PBL) of eight prostate cancer (PC) patients. These patients had no previous chemotherapy or radiotherapy (xRT). They were treated with standardized schemes of fractionated pelvic xRT. Before xRT, and at one random time-point during the course of xRT, blood samples were collected from each patient for the following purposes: (1) to verify the relationship between the MN yield in PBL and the estimated equivalent (EQ) total-body absorbed dose; and (2) to evaluate the individual differences of ex vivo radiation dose-response (1-4 Gy) relationship of MN yield in PBL before xRT. The number of xRT fractions, cumulative tumor dose, and EQ total-body absorbed doses of these patients represented a wide range. We found in PBL of these patients that (1) MN yield (Y) increased linearly with the estimated EQ total-body absorbed dose as Y=14.6+9.2D (R(2)=0.7, p=0.007); the distributions of MN yield were overdispersed; the ratio of relative increment of MN yield per 1000 binucleated (BN) PBL ranged from 0.9 to 8.2 (median: 4.1) folds above that of the respective baseline levels; and (2) before xRT, the MN yields also increased linearly with the ex vivo radiation dose; at each radiation dose level, the distributions of MN yield were overdispersed in most patients. In two of the three patients with xRT-induced early side effects (cystitis, diarrhea), the MN yield in PBL induced by ex vivo irradiation before xRT was significantly higher than in the other patients without xRT-induced side effects. These findings suggest that MN yields in CB PBL can be used as an in vivo biodosimeter. Since the differences in individual ex vivo radiation dose-response relationship of MN yield in PBL before xRT appeared to be significant, our preliminary results also suggest that it may be possible to identify individual intrinsic radiosensitivity before the start of xRT.

Neuroblastoma producing spinal cord compression: rapid relief with low dose of radiation.

Symptomatic spinal cord compression requires emergency treatment to alleviate symptoms and to avoid irreversible damage. We describe a successful decompression by low dose radiation to a progressing neuroblastoma in a child. Magnetic resonance imaging post radiation should be performed to assess the response of the tumor to radiation.

Comparison of CT-based treatment planning and retrograde urethrography in determining the prostatic apex at simulation.

In 20 consecutive patients who underwent treatment planning, localization of the prostatic apex with CT-based techniques at simulation was compared to location of the apex as defined by retrograde urethrography. In addition, the location of the urethrogram-defined prostatic apex was compared with the bottom of the ischial tuberosities, which is often recommended as the inferior margin of the field. In 15% of the patients there was agreement between the CT-defined apex and the urethrogram-defined apex; in 85% there was discordance. In a majority of patients with discordance, the urethrogram apex was located caudad to the CT-defined apex (71%) with a median difference of .65 cm. In 29% of the patients the urethrogram apex was located superior to the CT-defined apex. Overall, 75% of the patients had discordance between the urethrogram apex and the CT apex of 0.5 cm or greater; 30% had an absolute difference of 1.0 cm or greater. Comparing the location of the prostatic apex with the bottom of the ischial tuberosities revealed that in 15% of the patients the apex was 1.0 cm or less from the bottom of the tuberosities and in 45% it was less than 1.5 cm. This would place the apex of the prostate in the penumbra region of the field and risk undertreatment of the prostate if the bottom of the ischial tuberosities was the inferior margin of the field. Measuring the location of the prostatic apex from the top of the symphysis pubis revealed that a distance of 4.9 cm encompassed the apex in all 20 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Laser-induced desorption of proteins.

Laser-induced desorption mass spectrometry has been applied to a number of proteins in the mass range 5000-150,000 u. The beam from an excimer-laser-pumped dye-laser at 266 nm has been focused to a spot of about 50 microns in diameter with irradiances in the 10(7) W/cm2 region. A linear time-of-flight mass spectrometer has been used for mass spectrometric measurements, where positive and negative secondary ions of large proteins have been studied. The effect of different experimental parameters on the protein ion-signal intensities are discussed.

Molecular weight determinations of proteins by californium plasma desorption mass spectrometry.

The plasma desorption mass spectrometry method is used to determine the molecular weights of larger molecules than before, to determine the molecular weights of proteins and peptides in mixtures, and to monitor protein modification reactions. Proteins up to molecular weight 25,000 can now be studied with a mass spectrometric technique. Protein-peptide mixtures that could not be resolved with conventional techniques were successfully analyzed by this technique. The precision of the method is good enough to permit one to follow the different steps in the conversion of porcine insulin to human insulin.

Californium-252 plasma desorption time of flight mass spectroscopy of proteins.

Fast heavy ions, i.e. fission fragments from a 252Cf-source, have been used to desorb and ionize peptides and proteins from a sample surface. Masses of the desorbed ions have been determined by the time-of-flight technique. The mass interval of the molecules studied is 1000-14 000 u. Quasi-molecular ions of higher masses than earlier reported have been observed. The results include the detection of quasi-molecular ions of proinsulins, cytochrome-C, ribonuclease and two phospholipases. The general features of mass spectra of proteins using this ionization method are described. Emphasis is put on the discussion of metastable ion decay, neutral components, multiply charged ions, isotopic broadening, and cluster ion formation. Also the precision which can be obtained with a straight time-of-flight mass spectrometer will be discussed. Future applications of the technique are outlined.