Clinico-pathologic conference: 12-year-old girl with fatigue, anemia, weight loss, abdominal distention, and occasional nausea and vomiting.

A clinicopathologic case is presented. The patient was a 12-year-old white girl with a history of fatigue and dizziness, occasional nausea and vomiting, and anemia, who showed abdominal distention, especially in the epigastrium. An epigastric mass was palpable. Gastroscopy was done, and surgery followed. Pertinent laboratory findings are presented, and clinical discussion follows. The pathology is then presented and discussed.

Comparison of three high-resolution digitizers for radiochromic film dosimetry.

A recently introduced radiographic film scanner from Howtek is evaluated and compared to two other commercially available densitometry systems for its use in radiochromic (RC) film dosimetry in the clinical dose range 0-100 Gy. It has a high-intensity red LED light-source centered at 662 nm (near the major absorption peak for RC film), and is coupled to a CCD linear array detector. This new densitometry system is directly compared to two high-resolution film scanners commonly employed in RC film dosimetry, namely the Lumiscan 75 digitizer (He-Ne laser light source) and the Vidar VXR-16 digitizer (fluorescent light source). A spot densitometer (Nuclear Associates Radiochromic Densitometer) with a filtered 671 nm laser-diode light source is also included as a reference for comparison. The response of the spot densitometer and three high-resolution digitizers is characterized by the dose required to reach a net optical density of 1 (DNOD1), and is 16.0, 37.3, and 46.4 Gy for the Nuclear Associates Radiochromic Densitometer, Howtek MultiRAD 460 and Lumiscan 75 digitizer, respectively. The Vidar VXR-16 does not reach a net optical density of 1. The minimum usable dose at which a 2% level of uncertainty can be achieved (MUD2%) on the three digitizers are 2.6, 6.0, and 38.5 Gy for the Howtek MultiRAD 460, Lumiscan 75, and Vidar VXR-16, respectively. The Howtek MultiRAD 460 shows the greatest sensitivity, lowest MUD2% and best signal-to-noise ratio in the clinical dose range 0-100 Gy. Furthermore, it has no apparent interference (moiré) artifacts that severely limit the low optical density region of the He-Ne laser digitizer. For high-resolution radiochromic dosimetry in the clinical dose range 0-100 Gy, the high-intensity red LED light-source digitizer proves to be the superior modality.

A new geometric and mechanical verification device for medical LINACs.

The goal of quality assurance (QA) for a radiation oncology medical LINAC is to maintain an acceptable level of equipment performance and reliability. The increasing complexity of Radiation Oncology equipment and treatment techniques have led to increased demands on the work load of the medical physicist. Regular testing needs to be as efficient as possible. Generally, the QA tests, as recommended by the AAPM Task Group 40 for medical LINACs, can be grouped into two categories: dosimetry and mechanical checks. A new QA device has been developed that facilitates many of the daily and monthly mechanical QA checks. Its efficiency and speed is achieved through a set of QA tools that are mounted on a single platform, which is designed to fit into the accessory mount of the medical LINAC. Named Mini-GARD (MG), it verifies the accuracy of the digital readouts for gantry angles, collimator angles, and field sizes. It also tests crosshair position, the optical distance indicator (ODI), and patient setup laser alignment. It uses two calibrated digital levels for the gantry and collimator angle verification, an electronic tape measure for ODI verification, and a calibrated transparent projection scale for the remaining tests. This paper evaluates the stability and accuracy of the device in clinical tests over a period of a year. Results show that the MG is reliable and capable of measuring gantry and collimator angle constancy to +/-0.3 degrees, ODI constancy to +/-0.05 cm, and field size accuracies to +/-0.05 cm.

The use of an inexpensive red acetate filter to improve the sensitivity of GAFChromic dosimetry.

The sensitivity of GAFChromic dosimetry using a conventional broad band light source densitometer has significantly been improved twofold using an inexpensive red acetate filter overlay during the densitometric measurements. This thin sheet of red acetate enhances the dosimetric analysis of radiochromic blue image distributions recorded on GAFChromic films. The combination provides higher sensitivity in the optical density measurements than the more expensive He-Ne laser-scanning densitometers.

The thermal characteristics of different diodes on in vivo patient dosimetry.

Diode sensitivity variations with temperature (SVWT) have been reported to vary from small negative values up to 0.6% per degrees C. Thus it is possible for diode calibration factors established at room temperature (approximately 20 degrees C) to yield errors in the range of -1% to +9% when diodes are placed on a patient's skin (approximately 30 degrees C) for in vivo entrance dose measurements. In this study we simulated several skin temperatures using a temperature-controlled aluminum surface in contact with a section of Bolus. The internal temperatures of several diodes with different buildup thickness were monitored as a function of time when placed in contact with the heated bolus. Our results indicate that for different combinations of room temperature (18 degrees C-23 degrees C) and patient skin temperature (28 degrees C-34 degrees C) diodes reached 90% of their equilibrium temperature within 3-5 min. In addition, the range of typical skin temperatures was determined by measurements performed on a number of actual patients under clinical conditions. Based on the results of our experiments a protocol was developed to minimize the temperature based errors for in vivo dosimetry.

Evaluation of the use of botulinum toxin in children with achalasia.

BACKGROUND: Achalasia is rare in children. Recently, injection of botulinum toxin into the lower esophageal sphincter has been studied as an alternative to esophageal pneumatic dilatation or surgical myotomy as treatment for achalasia. In the current study, the effects of botulinum toxin were investigated in the largest known series of children with achalasia. METHODS: Treatment for achalasia was assessed in 23 pediatric patients who received botulinum toxin from June 1995 through November 1998. Those who continued to receive botulinum toxin and did not subsequently undergo pneumatic dilatation or surgery were considered repeat responders. Results were compared with those of published studies evaluating the use of botulinum toxin in adults with achalasia. RESULTS: Nineteen patients initially responded to botulinum toxin. Mean duration of effect was 4.2 months +/- 4.0 (SD). At the end of the study period, three were repeat responders, three experienced dysphagia but did not receive pneumatic dilatation or surgery, three underwent pneumatic dilatation, eight underwent surgery, three underwent pneumatic dilatation with subsequent surgery, and three awaited surgery. Meta-analysis shows that, in the current study group, the data point expressing time of follow-up evaluation versus percentage of patients needing one injection session without additional procedures (botulinum toxin injection, pneumatic dilatation, or surgery) falls within the curve for those in studies on adult patients receiving botulinum toxin for achalasia. CONCLUSIONS: Botulinum toxin effectively initiates the resolution of symptoms associated with achalasia in children. However, one half of patients are expected to need an additional procedure approximately 7 months after one injection session. The authors recommend that botulinum toxin be used only for children with achalasia who are poor candidates for either pneumatic dilatation or surgery.

Calculation of dose distribution near an innovative concentric balloon catheter for endovascular brachytherapy.

PURPOSE: Using a radioactive solution-filled catheter for intravascular irradiation has the potential problem of chemical and radiological toxicity in the case of a balloon rupture. In order to reduce this risk, an innovative concentric balloon catheter was developed. METHODS AND MATERIALS: The concentric balloon was made by inner and outer balloons filled with saline and radioactive solution, respectively. The optimal inner radius was determined by comparing the dose rate reduction vs. the volume reduction for various inner and outer radii for 188Re, 32P, and 90Y solutions. RESULTS: For a balloon with an outer radius of 1.5 mm, there was no advantage of a concentric balloon. For balloons with outer radii of 3.0 and 5 mm, the optimal inner radius was 1.5 and 3 mm, respectively. CONCLUSIONS: With the newly designed concentric balloon, the risk of toxicity can be reduced while keeping the dose rate high enough so that the treatment times within tolerable limits are still maintained.

Evaluation of an innovative plastic cube phantom designed to improve the efficiency of accelerator QA.

A new cubic phantom was designed to improve the efficiency on the QA measurement of accelerator. It has a variety of applications, such as dose constancy check, depth dose verifications, and symmetry and flatness evaluations. In particular, this new design makes it much easier to perform the check on output constancy vs. gantry angles as a cylindrical ion chamber positioned at the center of the phantom. The reproducibility of the setup using this phantom has been investigated. The charge effect of the phantom is found to be insignificant. It also reduces the monthly dosimetric QA time spent on a typical multimodality accelerator by approximately 40%.

A rapid colour stabilization technique for radiochromic film dosimetry.

Various forms of GAFChromic film have been used for several years as radiographic media for measuring dose distributions of brachytherapy sources and small radiation fields. Upon irradiation the film changes colour and darkens with time post-irradiation. The darkening is most rapid in the first 24 h, and it has been suggested that for accurate dosimetry a waiting period of 24 h should occur before any optical density (OD) measurements are taken. A more rapid colour stabilization (RCS) procedure has been developed and is evaluated. The procedure consists of heating the film post-irradiation for a period of 2 h at 45 degrees C. The RCS procedure is compared with a control group and the dose response is tested for linearity, stability and reproducibility using two densitometers with light sources at different wavelengths (632.8 nm and 671 nm). The rise in net optical density (NOD) for the period 3-168 h is less than 3% for the RCS group as compared with 12% for the controls. In the first 24 h, the increase in NOD for the RCS samples is less than 0.5%, as opposed to 6% for the control group.

The use of improved radiochromic film for in vivo quality assurance of high dose rate brachytherapy.

GAFChromic film has become increasingly popular for radiation dosimetry. In this study we explore the use of GAFChromic film as an in vivo dosimeter for quality assurance (QA) of fractionated high dose rate 192Ir treatments. Accuracy of dose distribution is explored for the simple vaginal cylinder geometry for which the dose can be easily calculated for comparison. Source dwell times for several patients were optimized to deliver 500 cGy at 0.5 cm from the surface of the vaginal cylinder applicator using a commercial treatment planning system. GAFChromic film was taped to the vaginal cylinder applicator and was enclosed in a leak proof rubber sleeve prior to its insertion. Optical densities were measured along the film at 2 mm spacing, using a densitometer with filtered red light. Density corrections for transient film darkening effects were made and optical densities were converted to absorbed dose in cGy. In vivo patient dose distribution measured for different patients and different fractions were compared with the calculated values along the applicator surface. The variation between the calculated and measured dose was +/- 10%. the reproducibility of dose measurement for different fraction was within +/- 5%. This study demonstrates the potential usefulness of the film as an in vivo for brachytherapy QA.

Desensitization to pancreatic enzyme intolerance in a child with cystic fibrosis.

OBJECTIVE: Pancreatic enzyme is essential in the treatment of cystic fibrosis (CF), but intolerance to it occasionally occurs. We encountered a child who was intolerant to multiple commercially available preparations of pancreatic enzymes and, hence, desensitization was attempted, with success. CASE PRESENTATION: A 33-month-old girl was diagnosed with CF at 6 months of age. Initially, she was started on Pancrease MT 16, which was subsequently discontinued because fecal fat studies were normal and she seemed to do well on Nutramigen and vitamin supplements. At 29 months of age, she developed diarrhea with bulky stools and weight loss. A fecal fat 72-hour study revealed a coefficient of absorption of 50%. She was treated with Pancrease MT 16, but had consistent vomiting 1 to 2 hours after administration of enzymes. The vomiting occurred on switching to different pancreatic enzymes preparations, ie, Creon 10, Viokase, and Pancrease MT 16. Vomiting occurred even with small doses of enzymes disguised in food. She had no history suggestive of gastroesophageal reflux, peptic ulcer, or pork allergy, and no vomiting on days when enzymes were not given. This was suggestive of type I hypersensitivity reaction. Pancreatic enzymes were discontinued, and she was given a low-fat, high-carbohydrate diet with satisfactory weight gain. METHODS: Double-blind, placebo-controlled titrated oral challenges with pancreatic enzymes resulted in definite vomiting within 1 to 1.5 hours after challenges with Viokase and Pancrease MT 16, but not with placebo. Rush oral desensitization with Viokase solution was attempted, starting with 5 mg, and the dose was doubled every 20 minutes, aiming to reach a cumulative dose of 700 mg. However, the child vomited when a cumulative dose of 315 mg was reached. Another trial of slower desensitization was done using Pancrease MT 16 (1 capsule: 16 000 U of lipase, 48 000 U of amylase, and 48 000 U of protease), starting with 1/4 capsule per day, with increments of 1/4 capsule every 3 days, until an entire capsule was reached by day 10, then increased by approximately 1/2 capsule every 4 days until reaching the therapeutic dose of 1 capsule with each meal by day 25. RESULTS: The patient tolerated this fairly well and has been on this treatment and regular diet for >1 year, without any adverse reaction. This illustrates a rare case of gastrointestinal adverse reaction to pancreatic enzymes that was treated successfully with desensitization. CONCLUSION: Pancreatic enzyme intolerance, although rare, would be a major problem in the management of patients with CF. Hence, desensitization would be essential and may be accomplished successfully using the protocol described in this report.

Evaluation of a new sealed reentrant well chamber for HDR and LDR brachytherapy calibrations.

A new reentrant ionization chamber SNC 1008 has been introduced for low dose rate (LDR) and high dose rate (HDR) brachytherapy source calibrations. There is no air density correction requirement for the chamber since it is hermetically sealed. In this study we evaluate its use for HDR as well as LDR source calibrations. The magnitude of the ionization current collected was found to be independent of the sign of the polarizing voltage within +/- 0.5%. The axial response curve of the well chamber reveals a "plateau region" (+/- 0.5% dose variation) of 4.2 cm, which is larger than the published values for other commercially available chambers. Long-term stability of the chamber was evaluated. Short-term response and source positioning reproducibility were tested using both LDR and HDR sources. Ion collection efficiency was found to be high, making the chamber suitable for HDR 192Ir sources.

A feasibility study of automated inverse treatment planning for cancer of the prostate.

PURPOSE: The development of automated "inverse planning," utilizing intensity-modulated radiation therapy (IMRT) raises the question of whether this new technique can provide a practical and efficient means of dose escalation in conformal treatment of cancer of the prostate. The purpose of this feasibility study was to determine a single set of inverse-planning parameters that can be used for a variety of different prostate patient geometries to automatically generate escalated dose (> or = 81 Gy) IMRT plans that satisfy normal tissue constraints for rectal and bladder walls. METHODS: We studied a subset of the 46 patients who were previously treated at Memorial Sloan Kettering Cancer Center (MSKCC) to a total dose of 81 Gy using a 3D conformal approach. Six patients were selected for our study and replanned using an analytical inverse-planning algorithm (referred to as OPT3D) applied to 8 intensity modulated, co-axial radiation beams. A set of more than a dozen inverse planning parameters were adjusted by trial and error until the resulting dose distributions satisfied the critical organ dose-volume constraints imposed by our study rules (D30 < or = 75.6 Gy and D10 < or = 80 Gy for the rectal wall; D15 < or = 80 Gy for the bladder wall) for the sample of patients selected. The OPT3D-generated plans were compared to hand-generated BEV plans using cumulative DVH analysis. RESULTS: A single set of inverse-planning parameters was found that was able to automatically generate IMRT plans meeting all critical organ dose-volume constraints for all but one of the patients in our study. [The exception failed to meet bladder dose constraints for both IMRT and BEV methods, due to extensive overlap between the planning target volume (PTV) and bladder contours]. Based upon analysis of the cumulative dose-volume histogram (DVH) for the prostate PTV, the D95 (DX is defined such that x% of the volume receives a dose > or = DX), averaged over all patients, was approximately 81 Gy. The average D90 and mean dose values were 85 Gy and 93 Gy, respectively. Although a similar D95 was achieved using the BEV-generated plans, the D90 and mean dose values were substantially higher for the inverse planning (OPT3D) method. CONCLUSION: This limited "paper study" shows IMRT with inverse planning to be a promising technique for the treatment of prostate cancer to high doses. We determined a small set of inverse-planning parameter values that was able to automatically design intensity-modulated radiotherapy (IMRT) plans for a subset of 6 patients previously treated at MSKCC to 81 Gy using BEV planning techniques. With one minor exception, the resulting plans succeeded in meeting predetermined dose-volume constraints while at the same time allowing an increase in the mean dose and D90 to the prostate PTV. These 8 field plans also resulted in reduced dosage to the femoral heads. This automated technique is efficient in terms of planning effort and, with proper software for computer-controlled MLC, may be appropriate for clinical use. The clinical feasibility of this approach for a larger group of patients is currently under study.

A new genetic algorithm technique in optimization of permanent 125I prostate implants.

Real time optimized treatment planning at the time of the implant is desirable for ultrasound-guided transperineal 125I permanent prostate implants. Currently available optimization algorithms are too slow to be used in the operating room. The goal of this work is to develop a robust optimization algorithm, which is suitable for such application. Three different genetic algorithms (sGA, sureGA and securGA) were developed and compared in terms of the number of function evaluations and the corresponding fitness. The optimized dose distribution was achieved by searching the best seed distribution through the minimization of a cost function. The cost function included constraints on the periphery dose of the planned target volume, the dose uniformity within the target volume, and the dose to the critical structure. Adjustment between the peripheral dose, the dose uniformity and critical structure dose can be achieved by varying the weighting factors in the cost function. All plans were evaluated in terms of the dose nonuniformity ratio, the conformation number and the dose volume histograms. Among these three GA algorithms, the securGA provided the best performance. Within 2500 function evaluations, the near optimum results were obtained. For a large target volume (5 cm x 4 cm x 4.5 cm) including urethra with 20 needles, the computer time needed for the optimization was less than 5 min on a HP735 workstation. The results showed that once the best set of parameters was found, they were applicable for all sizes of prostate volume. For a fixed needle geometry, the optimized plan showed much better dose distribution than that of nonoptimized plan. If the critical structure was considered in the optimization, the dose to the critical structure could be minimized. In the cases of irregular and skewed needle geometry, the optimized treatment plans were almost as good as ideal needle geometry. It is concluded that this new genetic algorithm (securGA) allows for an efficient and rapid optimization of dose distribution, which is suitable for real time treatment planning optimization for ultrasound-guided prostate implant.

The investigation of 32P wire for catheter-based endovascular irradiation.

The dose distribution from a 32P source has been measured and calculated in order to evaluate its application in endovascular irradiation. The source dimension was 27 mm in length and 0.3 mm in diameter and was embedded in the end of a Ni-Ti wire. Dose measurements were performed using radiochromic film in several specially designed tissue equivalent phantoms. Loevinger's point dose kernel was used for the calculation. The approximate dose rate at a radial distance of 1.5 mm from the center of the source was found to be 6.75 cGy/s per GBq (0.25 cGy/s per mCi), which allows the delivery of a therapeutic dose in a short time interval with a satisfactory homogeneity without stepping the source. However, the dose rate falls off almost exponentially along the radial distance. Therefore it may not be suitable for treating large diameter vessel from a centrally located source. The effect of a curved 32P wire source on the radial dose distribution was also investigated. The results showed that for a maximum bend of 180 degrees the dose rate was increased by as much as 20% along the inner radial distance but decreased by as much as 20% along the outer radial distance compared to the dose along a straight wire. However, for curvatures normally encountered in a clinical situation, the dose rate was changed less than 5%.

Comparison of dose response of radiochromic film measured with He-Ne laser, broadband, and filtered light densitometers.

Dose response curves for GAFChromic MD-55-2 film were measured using three different densitometer systems: a He-Ne laser densitometer, a broadband (white light) densitometer, and a filtered red light densitometer. These were found to differ significantly; the dose needed to achieve a net optical density of 1 (DNOD1) was greater than 100 Gy for the white light densitometer, 56 Gy for the He-Ne densitometer, and only 14.8 Gy for the filtered red light densitometer. This represents approximately a fourfold increase in response for the filtered red light versus the He-Ne laser densitometer, which is a significant improvement. For some patient prescriptions this enables us to achieve an accuracy and precision sufficient to verify daily dose to within 5%.

Paradoxical reactions in children associated with midazolam use during endoscopy.

All 2,617 children who received midazolam and meperidine for a variety of endoscopic procedures were monitored for the development of adverse behavioral problems. Thirty-six (1.4%) of the children (ages 1-17 years) experienced a paradoxical behavioral reaction, which consisted of inconsolable crying, combativeness, disorientation, dysphoria, tachycardia, agitation, and restlessness. The reaction occurred at a mean of 17 minutes after the administration of midazolam. Following treatment with flumazenil, the reaction dissipated within a mean of 14 minutes. Three of the 36 patients underwent additional endoscopic procedures utilizing only meperidine. No similar reaction was observed in these patients. Awareness of the reaction and prompt administration of flumazenil decreased the duration of the reaction.

Predicting optical densitometer response as a function of light source characteristics for radiochromic film dosimetry.

Various forms of GAFChromic (GC) film have been used for several years as radiographic media for measuring dose distributions of brachytherapy sources and small radiation fields. In order to optimize the measurement sensitivity and thus improve precision, we describe a method to calculate the dose response curves (net optical density at a give wavelength or spectrum versus absorbed dose) for different densitometer light sources using measured GC film absorption spectra. Comparison with measurements on the latest version of GC film (model MD-55-2) using four types of densitometers [He-Ne laser, broadband (white light) densitometer, and two LED (red-light) filtered densitometers] confirm the accuracy of this predictive model. The linearity and sensitivity of the dose response curves are found to be highly dependent on the light source spectrum. Initial slope is a function of the average weighted absorbance. Early saturation and decreased linearity of the dose response curves are ascribed to the nonuniform transmission of the light source through the GC film. We found that an LED (red-light) source with a narrow bandpass filter centered at 671 nm near the major absorption peak achieves nearly the maximum possible sensitivity (almost four times more sensitive than He-Ne laser, 632.8 nm) and may be suitable for in vivo dosimetry.