Effect of acid suppressant medications on the laxative action of magnesium preparations in patients with opioid-induced constipation: A pharmacovigilance analysis of the FDA Adverse Event Reporting System.

Objective: Magnesium oxide is widely used for treating opioid-induced constipation, a serious analgesic-associated problem. Opioid analgesic users are often prescribed non-steroidal anti-inflammatory drugs, which are sometimes combined with acid suppressants to prevent gastrointestinal adverse events. Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect. This study was aimed at evaluating the effect of magnesium preparations combined with acid suppressants on the incidence of opioid-induced constipation by using the Food and Drug Administration Adverse Event Reporting System. Methods: Adverse events were defined per the Medical Dictionary for Regulatory Activities; the term 'constipation (preferred term code: 10010774)' was used for analysis. After adjusting for patient background factors using propensity score matching, acid suppressants' effect on constipation incidence was evaluated in opioid users prescribed magnesium preparations alone as laxatives by using a test for independence. Key Findings: The Food and Drug Administration Adverse Event Reporting System contains 14,475,614 reports for January 2004 to December 2021. Significantly increased constipation incidence was related to magnesium preparations combined with acid suppressants, especially proton pump inhibitors (P < 0.0001, McNemar's test). Conclusion: Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect; healthcare professionals should pay attention to this issue.

Pancreastatin-like immunoreactivity in urine.

The concentration and molecular form of pancreastatin-like immunoreactivity (PST-LI) in urine of normal subjects and patients with noninsulin-dependent diabetes mellitus or chronic renal failure were examined. PST-LI output (mean +/- SEM) in urine of normal subjects was 74.6 +/- 8.5 pmol/day and 87.1 +/- 11.7 pmol/g creatinine. That in patients with noninsulin-dependent diabetes mellitus was 78.1 +/- 9.0 (SEM) pmol/day and 85.6 +/- 9.0 pmol/g creatinine and was not significantly different from that in normal subjects. Gel filtration analysis showed that PST-LI molecules excreted in urine of these two groups were smaller than human pancreastatin (43-52) (hPST-10) of C-terminal fragment. The PST-LI molecular forms were deduced to be nonbioactive from the result that hPST-10 did not inhibit pancreatic exocrine secretion. PST-LI excretion in patients with chronic renal failure was 258.5 +/- 62.9 pmol/day and 713.2 +/- 219.6 pmol/g creatinine. A molecular form corresponding to hPST-52 and a larger form eluted in the high mol wt region (approximately mol wt 15 K) were detected by gel filtration of urine from these patients, indicating that PST-LI is excreted in urine without degradation in patients with chronic renal failure. These results support the suggestion that the kidney may play an important role in PST degradation or metabolism.

Voluntary control of saccadic eye movement in patients with frontal cortical lesions and parkinsonian patients in comparison with that in schizophrenics.

To investigate whether the abnormalities of antisaccades in schizophrenics could be explained by a dysfunction of the frontal cortex, we examined 10 patients with frontal cortical lesions and 22 patients with idiopathic Parkinson's disease with mild symptoms (Yahr I-II) using the same tasks, and compared the results with those obtained in schizophrenics. The frontal patients with lesions covering the frontal eye field and prefrontal cortex showed more errors, longer latencies, and lower peak velocities in the antisaccade task, despite giving normal results in the visually guided saccade task. This was similar to the results observed in schizophrenics. Parkinsonian patients did not consistently show a significant difference in the antisaccade task. These results indicate specific abnormalities of antisaccades in schizophrenics and patients with frontal cortical lesions but not consistently in Parkinsonian patients. This suggests that the abnormalities of antisaccades in schizophrenics might be explained by a frontal cortical dysfunction.

Mouse cholecystokinin type-A receptor gene and its structural analysis.

The mouse cholecystokinin type-A receptor (CCK(A)R) gene was cloned and sequenced, and the exon/intron boundaries were determined by cDNA cloning. The gene, approximately 10 kb in length, contains the entire coding region, and consists of five exons. The deduced amino acid sequence was homologous with that of other species, with the exception of an additional DNA sequence encoding 7 amino acids in exon 5. A region of the 5' end of exon 2 appeared to be alternatively spliced, and generated an isoform shorter by 52 bases. The shorter isoform may encode an 48 amino acid open reading frame due to frameshift of translation. These two mRNA isoforms were expressed equally in the mouse gallbladders.

Disrupted cholecystokinin type-A receptor (CCKAR) gene in OLETF rats.

OLETF rats develop hyperglycemia, hyperinsulinemia and mild obesity, which is characteristic of human non-insulin-dependent diabetes mellitus (NIDDM). We cloned and sequenced the cholecystokinin type-A receptor (CCKAR) gene in the rats. Comparing the DNA sequences of the OLETF CCKAR gene and LETO CCKAR gene, normal gene, we found a deletion in the OLETF gene, 6847 bases in length, which was flanked by two 3-base-pair direct repeats (5'-TGT-3') at positions -2407/-2405 and 4441/4443, numbered according to the LETO gene sequence, one of which was lost. The promoter region, the first and second exons were missing in the mutant. The region upstream and downstream of the deletion, including exons 3, 4 and 5, was conserved between the two strains, and did not contain any base changes. We found that the gene mapped to chromosome 14 in rats. OLETF rats are the naturally occurring knockout animals with the homozygously disrupted CCKAR gene.

The importance of the C-terminal amide structure of rat pancreastatin to inhibit pancreatic exocrine secretion.

A C-terminal fragment of rat pancreatatin, a 26 residue peptide amide and a fragment without a C-terminal amide were synthesized by Fmoc-based solid phase methods and their biological activities were compared. The rat C-terminal fragment inhibited pancreatic exocrine secretions produced by the intravenous injection of 2-deoxy-D-glucose (a central vagal nerve stimulation), whereas the fragment without a C-terminal amide showed no effect on pancreas. These results indicate that the C-terminal amide of this peptide is necessary to reveal its biological activity.

Gene structure of human cholecystokinin (CCK) type-A receptor: body fat content is related to CCK type-A receptor gene promoter polymorphism.

The transcriptional start site of the human cholecystokinin (CCK)-A receptor gene was determined by the Capsite Hunting method. Two sequence changes were detected, a G to T change in nucleotide -128, and an A to G change in nucleotide -81. The homozygote (T/T, G/G) was detected in 25 of 1296 individuals (1.9%) in the cohort study. This polymorphism showed a significantly higher percent body fat and higher levels of serum insulin and leptin, compared with wild type and heterozygotes. Our study provided the possibility that polymorphism in the promoter region of the CCK-A receptor gene may be one of genetic factors affecting fat deposition.

Lymphatic lipid transport is not impaired in ageing rat intestine.

Lymphatic lipid transport in the intestine of adult and ageing rats was compared. Adult (8-10 months old) and old (24-26 months old) male Wistar rats were cannulated into the mesenteric lymph under ethrane anesthesia. On the following day, lipid emulsion containing 35.4 mg/h of olive oil was infused intraduodenally for 7 h and lymph collected hourly was assayed for triglyceride and apolipoprotein A-IV (apo A-IV). The results showed there was no difference in lymphatic lipid and apo A-IV transport between adult and old rats. Since apo A-IV synthesis in the enterocytes is linked to the intracellular assembly of lipoprotein, it is likely that in addition to lymphatic transport, production of chylomicrons is not impaired in ageing rats.

The role of radiotherapy in the management of spinal cord glioma.

PURPOSE: To determine the role of radiotherapy in the management of spinal cord gliomas. METHODS AND MATERIALS: Thirty-six patients with spinal cord glioma treated between 1979 and 1993 were examined. The patients had 13 astrocytic tumors (7 astrocytomas, 4 anaplastic astrocytomas, 2 glioblastomas), 22 ependymal tumors (18 ependymomas, 4 myxopapillary ependymomas), and 1 unclassified glioma. Fifteen of the patients were treated by surgery alone, but the remaining 21 patients also received postoperative radiotherapy. Total resection was performed on 1 astrocytoma and 13 ependymomas. In general, 40-50 Gy/16-20 fractions/4-5 weeks were given after parital resection, but no radiotherapy was given after total resection. RESULTS: Actuarial survival was significantly better for patients with ependymal tumors than for those with astrocytic tumors (p = 0007), 5-year actuarial survival rates being 96% and 50% for patients with ependymal tumors and astrocytic tumors, respectively. For patients with ependymal tumors, there was no difference in motor function and survival between those with total resection and those with partial resection followed by radiotherapy. Actuarial 3-year survival was 80% for patients with astrocytomas and 40% for those with anaplastic astrocytomas plus glioblastomas. The difference in the degree of motor function between the patients treated with radiotherapy and those without radiotherapy was not statistically significant. One anaplastic astrocytoma and one glioblastoma patient have lived longer than 4 years after radical treatment including radiocordectomy, or irradiation using doses larger than the tolerance threshold of the spinal cord. CONCLUSION: Postoperative conventional radiotherapy is indicated after less than total resection of low-grade ependymal tumors and astrocytomas but not after total resection of ependymomas. Radiocordectomy may be an option for certain cases with high-grade astrocytic tumors.

Preirradiation evaluation and technical assessment of involved-field radiotherapy using computed tomographic (CT) simulation and neoadjuvant chemotherapy for intracranial germinoma.

PURPOSE: To investigate the importance of preirradiation mental and endocrinological evaluation, and the effectiveness of involved-field radiotherapy following neoadjuvant chemotherapy. METHODS AND MATERIALS: Following etoposide and cisplatin with or without ifosfamide, 13 patients with nondisseminated disease received involved-field irradiation of 24 Gy in 12 fractions within 3 weeks and 2 patients with disseminated germinoma received 24 Gy craniospinal irradiation (CSI). CT simulation was used to cover the tumor bed. RESULTS: Full-scale intelligence quotient (IQ) tests given at the time of the initial radiotherapy showed less than 90 in 7 of 11 patients who had tumors involving the neurohypophyseal region, but the 4 patients who had solitary pineal tumors showed higher scores. Panhypopituitarism was observed in 9 patients with tumors involving the neurohypophyseal region. All patients are alive without disease, with a median follow-up period of 40 months. No in-field relapse was noted after the involved-field radiotherapy. One patient experienced a recurrence outside of the planning target volume. CONCLUSION: Decline of neurocognitive and endocrine functions were often seen in patients with tumors involving the hypophyseal region, but not in patients with solitary pineal germinoma before radiotherapy. Involved-field radiotherapy using 24 Gy is effective with the help of CT simulation and neoadjuvant chemotherapy.

High-speed magnetic resonance imaging for four-dimensional treatment planning of conformal radiotherapy of moving body tumors.

PURPOSE: High-speed magnetic resonance imaging (MRI) was applied to the determination of the planning target volume (PTV) of moving hepatobiliary tumors. METHODS AND MATERIALS: Three moving tumors, including two metastatic hepatic tumors and one bile duct tumor, were examined using high-speed MRI and reference fiducial markers before external radiotherapy. Patients were examined for 30 seconds under conditions of normal breathing during the examination. The coordinates of the center of the tumor contours were shown on sagittal and coronal images displayed on the monitor. RESULTS: The maximum length of movement was 10.6 +/- 7.0 mm in a craniocaudal direction; 5.2 +/- 1.8 mm in a lateral direction; and 4.6 +/- 1.6 mm in a ventrodorsal direction. When the PTV was determined using MRI at exhalation phase with a 10-mm safety margin, clinical target volume (CTV) was not covered in 19% of all images in the 3 patients. With MRI at inhalation phase with a 10-mm safety margin, CTV was not covered in 36% of all images. CONCLUSION: Four-dimensional treatment planning using high speed MRI, and integrating time and spatial information, has the potential to determine the planning target volume of moving body tumors more precisely than does conventional CT planning.

Use of an implanted marker and real-time tracking of the marker for the positioning of prostate and bladder cancers.

PURPOSE: A real-time tracking radiotherapy was investigated to assess its usefulness in precise localization and verification of prostate and bladder cancers. METHODS AND MATERIALS: The real-time tracking radiation therapy (RTRT) system consists of implantation of a 2.0-mm gold marker into a clinical target volume (CTV), three-dimensional radiation treatment planning (3DRTP) system, and the use of two sets of diagnostic x-ray television systems in the linear accelerator room, image processing units, and an image display unit. The position of the patient can be corrected by adjusting the actual marker position to the planned marker position, which has been transferred from the 3DRTP and superimposed on the fluoroscopic image on the display unit of the RTRT system. The position of the markers can be visualized during irradiation and after treatment delivery to verify the accuracy of the localization. Ten patients with prostate cancer and 5 patients with bladder cancer were examined using this system for the treatment setup on 91 occasions. RESULTS: After manual setup using skin markers, the median of absolute value of discrepancies between the actual position of the marker and the planned position of the marker for prostate cancer was 3.4 (0.1-8.9) mm, 4.1 (0.2-18.1) mm, and 2.3 (0.0-10.6) mm for the lateral, anteroposterior, and craniocaudal directions, respectively. The 3D median distance between the actual and planned positions of the marker was 6.9 (1.1-18.2) mm for prostate cancer and 6.9 (1.7-18.6) mm for bladder cancer. After relocation using RTRT, the 3D distance between the actual and planned position of the marker was 0.9 +/- 0.9 mm. Median 3D distances between actual positions after treatment delivery and planned positions were 1.6 (0.0-6.3) mm and 2.0 (0.5-8.0) mm during daily radiotherapy for the marker in patients with prostate cancer and bladder cancer, respectively. CONCLUSION: We believe the new positioning system can reduce uncertainty due to setup error and internal organ motion, although further improvement is needed for the system to account for the rotational and elastic changes of the affected tissues.

Skull-base invasion of nasopharyngeal carcinoma: magnetic resonance imaging findings and therapeutic implications.

PURPOSE: To evaluate the value of skull-base abnormality on MRI for predicting local recurrence in nasopharyngeal carcinoma. MATERIALS AND METHODS: Between November 1988 and February 1997, 48 patients with NPC were examined with both MRI (1.5 T) and CT prior to radiation therapy. T classification (1987 UICC) based on physical examination and CT findings were T1 in 3 cases, T2 in 22, T3 in 9, and T4 in 14. On MRI, low-intensity tissue with Gd enhancement in the marrow of the skull was considered to be a suspicious finding of skull-base invasion. CT simulation was performed in all patients. The total dose to the primary tumor was 60-75 Gy (mean, 67 Gy). The mean follow-up period was 42 months. RESULTS: All 14 T4 patients had abnormal tissue in the marrow of the skull base on MRI. Thirty-eight percent (13 of 34) of T1-3 patients were suspected to have skull-base invasion based on MRI (0% for T1, 27% [6 of 22] for T2, and 78% [7 of 9] for T3). The 5-year local control rate was significantly different between T1-3 and T4 tumors (97% vs. 69%, p < 0.025) but was not different by the presence of the MRI abnormality in the skull base. CONCLUSION: Skull-base invasion suspected solely by MRI does not relate to local recurrence provided that careful treatment planning is performed with the aid of MRI and CT simulator.

Detection of lung tumor movement in real-time tumor-tracking radiotherapy.

PURPOSE: External radiotherapy for lung tumors requires reducing the uncertainty due to setup error and organ motion. We investigated the three-dimensional movement of lung tumors through an inserted internal marker using a real-time tumor-tracking system and evaluated the efficacy of this system at reducing the internal margin. METHODS AND MATERIALS: Four patients with lung cancer were analyzed. A 2.0-mm gold marker was inserted into the tumor. The real-time tumor-tracking system calculates and stores three-dimensional coordinates of the marker 30 times/s. The system can trigger the linear accelerator to irradiate the tumor only when the marker is located within the predetermined "permitted dislocation." The value was set at +/-1 to +/-3 mm according to the patient's characteristics. We analyzed 10,413-14,893 data sets for each of the 4 patients. The range of marker movement during normal breathing (beam-off period) was compared with that during gated irradiation (beam-on period) by Student's t test. RESULTS: The range of marker movement during the beam-off period was 5.5-10.0 mm in the lateral direction (x), 6.8-15.9 mm in the craniocaudal direction (y) and 8.1-14.6 mm in the ventrodorsal direction (z). The range during the beam-on period was reduced to within 5.3 mm in all directions in all 4 patients. A significant difference was found between the mean of the range during the beam-off period and the mean of the range during the beam-on period in the x (p = 0.007), y (p = 0.025), and z (p = 0.002) coordinates, respectively. CONCLUSION: The real-time tumor-tracking radiotherapy system was useful to analyze the movement of an internal marker. Treatment with megavoltage X-rays was properly given when the tumor marker moved into the "permitted dislocation" zone from the planned position.

Remote verification in radiotherapy using digitally reconstructed radiography (DRR) and portal images: a pilot study.

PURPOSE: To use digitally reconstructed radiography (DRR) and digitally compressed portal images in distant consultation using a telecommunications network, the verification performance of DRR and digitally compressed portal images on the image console was investigated. METHODS AND MATERIALS: A human thoracic phantom was scanned with computed tomography (CT). Radiotherapy was planned at 5 different anatomic locations. A digitally reconstructed radiograph was made; verification films of the phantom were then taken with 6-MV X-rays. The treatment center was intentionally dislocated. Fifty sets of DRR and portal images were seen by 7 doctors on a conventional view-box (view-box method) to judge whether the treatment center was dislocated. These image sets were digitalized by a film scanner, compressed to 1/10 Joint Photographic Experts Group (JPEG) format, and compared on an image console by the same physicians (image-console method). The verification performance of the image console method was compared with that of the view-box method by means of receiver operating characteristic (ROC) analysis. Clinically, 159 portal-image-sets were verified with the image-console method and the appropriateness of the decision was later assessed by the view-box method. RESULTS: The accuracy of the treatment verification was estimated to be 88.8% by the conventional view-box method and 88.3% by the image-console method. There was no statistically significant difference in the verification performances of the conventional method (Az = 0.86+/-0.02) and the image console method (Az = 0.84+/-0.07). Frequent digital image-processing modification was positively related to the accuracy of verification. Clinically, there were 3 (1.8%) major corrections, 31 (19.5%) minor corrections, and 123 cases with no correction. No further correction was called for by the re-evaluation using the view-box method. CONCLUSION: The verification performance of DRR and digitally compressed portal images on the image console was as accurate as the conventional method. Distant consultation using DRR and portal images through telecommunication is usable in clinical practice.

Magnetic resonance imaging system for three-dimensional conformal radiotherapy and its impact on gross tumor volume delineation of central nervous system tumors.

PURPOSE: We developed an MRI system for three-dimensional planning in radiotherapy. Its contribution on gross tumor volume (GTV) delineation of central nervous system (CNS) diseases was evaluated. METHODS AND MATERIALS: The MRI system, with corrected distortion, was registered on computed tomography (CT) by means of fiducial/anatomic landmarks. In 41 consecutive patients with various CNS diseases, GTVs determined by MRI/CT registration (MR/CT-GTV) and CT alone (CT-GTV) were compared. Hard copies of diagnostic MRI were shown to doctors when CT-GTV was determined to simulate a conventional planning situation. Multi-observer volumetric analysis was conducted, assessing interobserver deviations among four radiation oncologists and intermethodological deviations between MR/CT-GTV and CT-GTV. RESULTS: Overall, the mean of geometric distortion was significantly reduced from 1.08 mm to 0.3 mm by distortion correction (p < 0.0001). The contribution of the correction was apparent at >12.0 cm radius from the center of the magnetic field. Interobserver deviation was significantly reduced by MR/CT registration (p = 0.005). The improvement was significant for acoustic neurinoma (p = 0.038), astrocytomas (p = 0.043), and lesions at the cerebellum/brainstem (p = 0.008). The regression coefficient between MR/CT-GTV and CT-GTV was <0.9 for cerebellum/brainstem lesions, suggesting that MRI/CT-GTV was smaller than CT-GTV. CONCLUSIONS: This system is feasible for three-dimensional planning and was shown to reduce interobserver deviations in GTV delineation for CNS diseases.

Analysis of long-term treatment of intracranial germinoma.

PURPOSE: To determine an appropriate treatment policy for intracranial germinoma. METHODS AND MATERIALS: From 1976 to 1992, 51 patients with germinoma (18 with pathologically verified germinoma and 33 diagnosed as having germinoma by neuroimagings) were treated by radiation therapy. Various radiation doses and treatment fields were used. RESULTS: The 10-year cause-specific survival rate for pathologically verified and unverified germinoma was 100% and 96%, respectively. Relapses were noted in four patients, three of whom died from the disease. Two of the four patients with a tumor larger than 4 cm in gross diameter experienced relapse. Two relapses occurred in a nonirradiated spinal canal and two occurred in the irradiation area treated by 25 Gy in 10 fractions and 30 Gy in 20 fractions. No relapse was noted in patients in whom the whole ventricle field was determined precisely using three-dimensional treatment planning. Five patients who were followed at an outpatient clinic experienced significant late neurocognitive dysfunction, which set in after radiotherapy. CONCLUSION: After pathological confirmation, 40 Gy whole-ventricle irradiation using precise three-dimensional treatment planning is appropriate as a standard treatment for most intracranial germinoma.

Stereotactic irradiation without whole-brain irradiation for single brain metastasis.

PURPOSE: The effectiveness of stereotactic irradiation (STI) alone without whole-brain irradiation (WBI) for a single metastatic brain tumor was analyzed retrospectively. METHODS AND MATERIALS: Forty-four patients with this condition were treated using radiosurgery (RS) alone or fractionated stereotactic radiotherapy (FSR) without WBI. RESULTS: The initial response rate was 92% and the overall local control rate was 84% (37 of 44 patients). A total of 39% (18 of 44) of patients experienced intracranial relapse outside the initial target area. Forty-eight percent (21 of 44) of patients required salvage treatment for intracranial relapse. All 7 patients who received WBI as salvage treatment required no further salvage treatment, but 5 of the 14 patients who received salvage STI without WBI required three to four treatments for brain metastasis. Late radiation damage was not seen with initial treatment but was observed with retreatment. The overall median survival time was 261 days, with a standard error of 64 days. Actuarial survival at 12 and 24 months was 34% and 9%, respectively. The actuarial survival rate was significantly affected by the existence of active extracranial disease (p = 0.041). CONCLUSION: The high response rate and short treatment period of STI alone are advantageous in the treatment of single brain metastasis in patients with active extracranial disease with WBI reserved for relapse. Because of the low complication rate, STI alone may be also useful in patients with good prognosis, without extracranial disease.

Comparison between observation policy and fractionated stereotactic radiotherapy (SRT) as an initial management for vestibular schwannoma.

PURPOSE: To compare the use of an observation policy with that of stereotactic radiotherapy (SRT) for treatment of vestibular schwannoma. METHODS AND MATERIALS: The study group consisted of 27 patients who underwent observation as an initial treatment (observation group) and 50 who received SRT (SRT group). The mean follow-up period was 35 months and 31 months, respectively. Stereotactic radiotherapy consisted of small-field fractionated radiotherapy (36-44 Gy in 20-22 fractions over 6 weeks) with or without a subsequent 4-Gy single irradiation boost. RESULTS: Actuarial tumor control rate of the SRT group was significantly better than that of the observation group (p < 0.0001). The mean growth was 3.87 mm/year in the observation group and -0.75 mm/year in the SRT group (p < 0.0001). Eleven patients (41 %) in the observation group and 1 (2 %) in the SRT group received salvage therapy (p < 0.001). There was no difference in the actuarial Gardner and Robertson's class preservation curves for 5 years after the initial presentation. CONCLUSION: Stereotactic radiotherapy using a fractionated schedule provides a better tumor control rate and a similar rate of deterioration for hearing levels compared to an observation policy. Initial SRT may be a reasonable alternative to a wait-and-see policy.

Reduction of radiation-induced xerostomia in nasopharyngeal carcinoma using CT simulation with laser patient marking and three-field irradiation technique.

PURPOSE: Tumor control and reduction of postirradiation xerostomia in patients with nasopharyngeal carcinoma (NPC) using the three-field irradiation technique based on the CT-based simulation with laser patient marking was investigated. METHODS AND MATERIALS: Seventy-eight patients with NPC were consecutively treated between 1983 and 1993. In 33 patients treated before 1987, target volume was determined using a conventional x-ray simulator with a reference of CT images, and the primary site was treated by the conventional parallel-opposed two-field technique (Group I). In 45 patients treated from 1987, target volume was determined using a CT simulator slice by slice, the treatment field was projected onto the patient's skin by a laser beam projector mounted on a C-arm, and the primary site was irradiated by a three-fields (anterior and bilateral) technique (Group II). In Group II, the shape of each field was determined using a beam's eye view to reduce the dose to the bilateral parotid glands. The three-field technique reduced the dose to the superficial lobe of parotid gland to about two-thirds of the dose given by the two-field technique. Radiation-induced xerostomia was evaluated by clinical symptoms and radioisotope sialography. RESULTS: The 5-year survival rate and disease-free survival rate were 46.6 and 31.2% in Group I, and 46.8 and 46.5% in Group II. A large variation in the volume of parotid glands were demonstrated, ranging from 9 cm3 to 61 cm3 among patients treated with CT simulation. Forty percent of the patients in Group II showed no or mild xerostomia, whereas all of the patients in Group I showed moderate to severe xerostomia (p < 0.01). The radioisotope sialography study showed that the mean secretion ratio by acid stimulation was improved from 3.8% in the Group I to 15.2% in the Group II (p < 0.01). CONCLUSIONS: CT simulation was useful to determine the size and shape of each field to reduce the dose to the parotid gland, of which size varies largely among individual patients. The three-field technique based on CT simulation with laser patient markings is suggested to result in superior complication-free survival in terms of salivary dysfunction than did the conventional two-field technique with x-ray simulatior for NPC.