Dynamic hybrid-phase computed tomography simulation in lung stereotactic body radiotherapy: A feasibility study.

To assess the feasibility of dynamic hybrid-phase computed tomography (CTDHP) simulation when patients undergo lung stereotactic body radiation therapy (SBRT). Eighteen non-small-cell lung-cancer patients were immobilised in a stereotactic body frame with abdominal compression. All underwent dynamic hybrid-phase CT scans that were compared with cone-beam CT (CBCT). We also determined the internal target volume (ITV) and evaluated the following four metrics: the "AND" function in the Boolean module of Eclipse, volume overlap (VO), Dice similarity coefficient (DSC), and dose-volume histogram. The average ITV values of 4DCTDHP and 3D-CBCT were respectively 12.82±10.42 and 14.6±12.18 cm3 (n=72, p<0.001), and the average ITV value of AND was 11.7±10.1 cm3. The average planning target volume (PTV) of 4DCTDHP and 3D-CBCT was 25.63±18.04 and 28.00±19.82 cm3 (n=72, p<0.001). The median AND difference between ITV and PTV was significant (p<0.01) and had a significantly linear distribution (R2=0.991 for ITV, R2=0.972 for PTV). The average VO of PTV was greater than that of ITV (0.81±0.096; 0.78±0.11). We also observed that the average DSC in PTV (0.83±0.066) was greater than that in ITV (0.81±0.084). The average results indicated that 97.9%±3.44 of ITVCBCT was covered by 95% of the prescribed dose. The average minimum, maximum and mean percentage doses of ITVCBCT were 87.9%±9.46, 107.3%±1.57, and 101.3%±1.12, respectively. This paper has demonstrated that dynamic hybrid-phase CT simulation for patients undergoing lung SBRT and also published evaluation metrics in scientific analysis. Our approach also has the advantage of adequate margin and fewer phases in CT simulation.

Evaluating the benefit of adjuvant radiotherapy after extensive lymph node dissection for gastric cancer: a single-institute retrospective study.

OBJECTIVE: This study aimed to evaluate whether adjuvant radiotherapy (RT) can improve the treatment outcome of patients with locally advanced gastric cancer who underwent extensive lymph node dissection (ELND). MATERIALS AND METHODS: This retrospective study included patients with gastric cancer pathological stages IIA-IIIC at Taipei Tzu Chi Hospital between 2008 and 2015. Patients (a) aged >80 years, (b) with distant metastasis at diagnosis, (c) with coexisting malignancies, (d) who did not complete the prescribed RT course, and (e) who died 1 month after surgery were excluded. Among 420 patients diagnosed with gastric cancer, 98 were included. RESULTS: The median follow-up was 24.5 months. Of 39 patients who underwent adjuvant RT, 38 also received adjuvant chemotherapy (CT). Of 59 patients who did not receive adjuvant RT, only 34 received adjuvant CT. ELND was performed in 67.3% of the patients. The 5-year overall survival (OS) rate was 40%. In the univariate analyses, adjuvant CT regimen, 5-fluorouracil + leucovorin, was associated with worst outcome, while TS-1 was associated with better survival outcome (P = 0.018). The number of involved lymph nodes was strongly related to the OS and disease-free survival (DFS) (P < 0.001). We tried using different numbers of involved lymph nodes as a cutoff point and found that adjuvant RT significantly improved both OS and DFS in patients whose involved lymph nodes were ≥4 (OS, P = 0.017; DFS, P = 0.015). In multivariate analyses, better DFS was associated with negative surgical margin (P = 0.04), earlier disease stage (P = 0.001), adjuvant radiotherapy (P = 0.045), and adjuvant CT regimen TS-1 (P = 0.001). CONCLUSION: Adjuvant RT could improve DFS of patients with locally advanced gastric cancer with or without ELND. When the number of involved lymph nodes is ≥4, adjuvant RT is strongly suggested.

Use of electronic portal images to evaluate setup error and intra-fraction motion during free-breathing breast IMRT treatment.

Before delivering of intensity-modulated radiotherapy, kilo-voltage image-guidance radiotherapy is widely used in setup error correction and monitoring intra-fraction motion effectively. Accordingly, this study proposes and tests an image integration technique for observing intra-fraction motion during beam delivery, with the wider objective of reducing both image-guidance time and the dose delivered to normal breast tissue. The study sample comprised 33 female patients with breast cancer, and 241 sets of portal images acquired using a VARIAN aSi-1000 electronic portal imaging device. Motion amplitudes and vectors were collected and calculated separately by two senior therapists. The setup error in 3 axes was computed for every fraction, with average shifting for lateral, longitudinal and vertical direction was -0.3-mm ± 0.5, -0.1-mm ± 0.5 and -0.6-mm ± 1.6, with the average vector of setup error being 2.9-mm ± 1.4. The average intra-fraction motion for vertical direction was (A: -0.1-mm ± 1.0; B: -0.0 ± 1.1), for longitudinal was (A: -0.4-mm ± 1.7; B: 2.0 ± 1.1), and for lateral direction was (A: 0.3-mm ± 1.3; B: 0.2 ± 1.8). The average intra-fraction vector was 2.9-mm ± 1.3 for therapist A, and 3.4-mm ± 1.8 for therapist B. Offline Review commercial software was utilized for setup error and motion analysis, and data analysis and reliability testing were conducted with statistical package of the social sciences. Pearson correlations between the two therapists was moderate (0.59, p << 0.01), and the Cohen's kappa value for inter rater agreement between different evaluators was fair in the anterior-posterior direction (0.25, p << 0.01), with slight agreement in other two directions and vectors. The study presented efficient and dose reduction method to evaluate setup error and intra-fraction motion during breast intensity-modulated radiotherapy treatment.

Optimal technique of linear accelerator-based stereotactic radiosurgery for tumors adjacent to brainstem.

Stereotactic radiosurgery (SRS) is a well-established technique that is replacing whole-brain irradiation in the treatment of intracranial lesions, which leads to better preservation of brain functions, and therefore a better quality of life for the patient. There are several available forms of linear accelerator (LINAC)-based SRS, and the goal of the present study is to identify which of these techniques is best (as evaluated by dosimetric outcomes statistically) when the target is located adjacent to brainstem. We collected the records of 17 patients with lesions close to the brainstem who had previously been treated with single-fraction radiosurgery. In all, 5 different lesion catalogs were collected, and the patients were divided into 2 distance groups-1 consisting of 7 patients with a target-to-brainstem distance of less than 0.5cm, and the other of 10 patients with a target-to-brainstem distance of ≥ 0.5 and < 1cm. Comparison was then made among the following 3 types of LINAC-based radiosurgery: dynamic conformal arcs (DCA), intensity-modulated radiosurgery (IMRS), and volumetric modulated arc radiotherapy (VMAT). All techniques included multiple noncoplanar beams or arcs with or without intensity-modulated delivery. The volume of gross tumor volume (GTV) ranged from 0.2cm(3) to 21.9cm(3). Regarding the dose homogeneity index (HIICRU) and conformity index (CIICRU) were without significant difference between techniques statistically. However, the average CIICRU = 1.09 ± 0.56 achieved by VMAT was the best of the 3 techniques. Moreover, notable improvement in gradient index (GI) was observed when VMAT was used (0.74 ± 0.13), and this result was significantly better than those achieved by the 2 other techniques (p < 0.05). For V4Gy of brainstem, both VMAT (2.5%) and IMRS (2.7%) were significantly lower than DCA (4.9%), both at the p < 0.05 level. Regarding V2Gy of normal brain, VMAT plans had attained 6.4 ± 5%; this was significantly better (p < 0.05) than either DCA or IMRS plans, at 9.2 ± 7% and 8.2 ± 6%, respectively. Owing to the multiple arc or beam planning designs of IMRS and VMAT, both of these techniques required higher MU delivery than DCA, with the averages being twice as high (p < 0.05). If linear accelerator is only 1 modality can to establish for SRS treatment. Based on statistical evidence retrospectively, we recommend VMAT as the optimal technique for delivering treatment to tumors adjacent to brainstem.

Parotid gland-sparing 3-dimensional conformal radiotherapy results in less severe dry mouth in nasopharyngeal cancer patients: a dosimetric and clinical comparison with conventional radiotherapy.

BACKGROUND AND PURPOSE: This study examined the efficacy of parotid gland sparing of three-dimensional conformal radiotherapy (3DCRT) compared with conventional radiotherapy for NPC patients. Both the dose given to the parotids and clinical assessment of dry mouth were conducted. MATERIALS AND METHODS: Dry mouth was assessed for 108 patients treated with conventional technique and 72 treated with 3DCRT. Dose analysis was performed in 48 patients of the 3DCRT group. A dose of 70 Gy was given to the midplane in conventional radiotherapy and to 90% isodose volume in 3DCRT. Prognostic factors affecting the severity of dry mouth were analyzed using Generalized Estimating Equation (GEE). RESULTS: In the 3DCRT group about 50% of the patients' parotid glands received less than 25 Gy. Parallel analysis of dry mouth shows a significant decrease in the incidence of severe xerostomia after 3DCRT. The proportion of patients without dry mouth was also significantly higher in the 3DCRT group than the conventional group at 1-3 years after completion of radiotherapy. Although 3DCRT delivered a higher dose to the tumor, it spared the parotid gland significantly better than the conventional treatment. Late toxicities were mostly similar between the 2 groups while local control in T4 patients and survival were improved for 3DCRT. CONCLUSION: Dosimetrically and clinically 3DCRT is better than conventional technique regarding parotid gland protection.

Long-term treatment results of invasive cervical cancer patients undergoing inadvertent hysterectomy followed by salvage radiotherapy.

PURPOSE: To evaluate the long-term results of salvage radiotherapy for patients of invasive cervical cancer after inadequate surgery. METHODS AND MATERIALS: Between October 1975 and January 1994, 90 patients were treated with radiotherapy for invasive cervical carcinoma after simple hysterectomy. The inadequate surgery was performed for a variety of reasons. All patients had postoperative external beam irradiation or intravaginal brachytherapy, or both. The end points of this study were local control, survival, and treatment-related toxicity. RESULTS: The patients' age varied between 33 and 76 with a median of 53 years. The most common histopathology was squamous cell carcinoma, which accounted for 91% of the patients. The most frequent reason for inadvertent hysterectomy was understaged disease with preoperative diagnosis as carcinoma in situ for 51 patients (57%). Malignancy was not suspected before surgery in 28 patients (31%). After surgery, 72 patients (80%) were restaged as Ib, 12 patients (13.3%) as IIa, and 6 patients (6.7%) as IIb. Median follow-up time was 83 months. Seventy-three patients had follow-up times of 5 years or more. The overall 5-year and 10-year survival rates of 90 patients were 85.5% and 74.1%, respectively. Disease-specific 5-year and 10-year survival rates were 85.5% and 80.5%, respectively. All 16 patients with either locoregional or distant failure eventually died of disease. Fourteen patients (15.5%) had late morbidities. Radiation proctitis developed in 6 patients, intestinal obstruction in 4 patients, and hemorrhagic cystitis in 3. There was only 1 patient (1%) with terminal ileum stenosis and severe intestinal obstruction requiring surgical intervention. CONCLUSIONS: Most cases of inadequately treated invasive cervical cancer were the result of suboptimal preoperative workups. Patients who had early tumors and no gross residual tumor after inadequate hysterectomy can have excellent prognoses when given postoperative radiotherapy. The severe long-term complication related to salvage radiotherapy is rare.

Dose escalation using twice-daily radiotherapy for nasopharyngeal carcinoma: does heavier dosing result in a happier ending?

PURPOSE: To present our experience using a twice-daily radiotherapy (RT) technique, including hyperfractionated and accelerated-hyperfractionated RT, on nasopharyngeal carcinoma (NPC) patients. The dose to the primary tumor was increased in the hope that local control could be increased without the cost of increased late complications. We analyzed acute and late complications and local control and compared the results with the results of NPC patients treated during the same period using conventional once-daily RT. METHODS AND MATERIALS: Between October 1991 and July 1998, 222 histologically confirmed, Stage M0, previously unirradiated NPC patients completed RT at our hospital. Most patients had American Joint Committee on Cancer (AJCC) 1992 Stage III and IV disease. Among them, 88 received altered fractionated, twice-daily RT; 76 patients received hyperfractionated RT and 12 accelerated-hyperfractionated RT. The remaining 134 patients received a conventional once-daily regimen. Hyperfractionated RT was delivered using 120 cGy b.i.d. separated by 6-h intervals throughout the course. For the accelerated-hyperfractionated patients, 160 cGy b.i.d. was given, also at 6-h intervals. The median dose in the twice-daily group was 7810 cGy (range 6840-8200). In the once-daily regimen, RT was delivered using 180-200 cGy q.d. The median tumor dose to the primary tumor was 7000 cGy (range 6560-8100) given during about 8 weeks. The median follow-up time was 70.5 and 72 months for the twice-daily and once-daily groups, respectively. RESULTS: The incidence of acute toxicities was higher in the twice-daily group with more severe mucositis and moist desquamation than in the once-daily group. Both groups had a similar incidence of late complications, except for 3 cases of temporal lobe necrosis in the twice-daily group, all in patients treated with 160 cGy. No difference was noted in recurrence-free local control between the two groups when the individual T stage was compared using AJCC 1992 or 1997 criteria (p = 0.51 and 0.59, respectively). The 5-year local control rate for T1-3 (AJCC 1997) was 93.2% for the twice-daily group and 86.4% for the once-daily group (p = 0.45). In Stage T4 (AJCC 1997) patients, the local control rate dropped drastically to 43.5% and 36.9% for the twice-daily and once-daily groups, respectively. The overall neck control rate at 5 years was 87.3% and 80.3% for the twice-daily and once-daily patients, respectively (p = 0.16). The overall locoregional control rate was 82.7% for the twice-daily group and 66.6% for the once-daily group. The difference was again not statistically significant, but showed a tendency in favor of the twice-daily regimen (p = 0.055). Locoregional failure occurred mainly in Stage T4 patients with central nervous invasion for whom local control was particularly poor, with a failure rate of about 60%. CONCLUSION: The present data suggest that NPC patients can be safely treated using a 120-cGy twice-daily program with a 6-h interval up to 8000 cGy. The accelerated-hyperfractionated technique is not recommended. A large discrepancy in local control between patients with T1-3 and T4 disease was noted. For T1-3 disease, an excellent local control rate >90% was achieved using the twice-daily regimen. In contrast, failure in the T4 patients was as high as 55% in the twice-daily group and reached 65% in the once-daily group. More rigorous treatment is needed using either additional dose escalation or other strategies for T4 NPC patients. With a dose escalation of 1000 cGy using 120-cGy twice-daily RT, a trend toward better locoregional control and disease-specific survival was noted in the twice-daily group. Whether this difference was truly the result of an increased dose needs additional confirmation in studies with larger patient numbers.

Development of an immunosensor for human ferritin, a nonspecific tumor marker, based on surface plasmon resonance.

A direct human ferritin immunosensor was developed using anti-human ferritin monoclonal antibodies (MAbs) immobilized on the gold surface of a self-assembled surface plasmon resonance (SPR) apparatus. A kind of self-assembled monolayer (SAM) prepared by cystamine-glutaraldehyde method was applied to immobilize the MAbs. The reusability of the sensor chip adopting the SAM was found to be better than the other immobilization methods including adsorption, protein A, concanavalin A method. Ten cycles of measurements could be performed on the same chip regenerated with a 0.1M HCl solution. A linear relationship existed between the angle shifts (millidegrees) and the log values of ferritin concentrations in the range from 0.2 to 200 ng/ml in buffer and human serum. When used for 15 days, the angle shifts were all >95% of those on the response at the first day. A 10 M NaOH solution was used for clearing nonspecific binding in human serum. Correlation coefficient was 0.991 between this SPR method and chemiluminescent immunoassay for determination of ferritin in clinical human serum samples. The SPR sensor offers advantages of simplicity of immobilization, high sensitivity, high specificity, low sample requirement, high reusability, no label and no pretreatment etc.

Treatment of portal vein tumor thrombosis of hepatoma patients with either stereotactic radiotherapy or three-dimensional conformal radiotherapy.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) often have unresectable tumors. Transcatheter arterial chemoembolization (TACE) is one of the limited alternative treatments that can prolong these patients' survival. However, the presence of portal vein tumor thrombosis (PVTT) is a contraindication for TACE and, therefore, HCC patients with PVTT would be depleted of the advantage of TACE. The purpose of this study was to analyze the recanalization rate of thrombosed portal vein and treatment toxicities after stereotactic radiotherapy (SRT) or three-dimensional conformal radiotherapy (3DCRT). METHODS: From March 2002 to November 2004, 43 patients were enrolled in this prospective study. Twenty-two patients were in the SRT group and 21 in the 3DCRT group. For SRT, 3 Gy per fraction, 3 fractions per week, was given to a total dose of 45 Gy. For 3DCRT, a daily dose of 1.8 Gy, 5 fractions per week, was given to a total dose of 45 Gy. RESULTS: Of the 43 patients, 16 completed the planned radiotherapy. Eventually, 14 patients received evaluation for portal vein recanalization, 8 in the SRT and 6 in the 3DCRT group, respectively. For all patients, the crude response rate was 26%. For 14 evaluable patients, the crude response rate was 79%. It was 75% in the SRT group and 83% in the 3DCRT group (P = 0.71). The median survival time was 6.0 and 6.7 months for the SRT and 3DCRT group, respectively (P = 0.911). CONCLUSIONS: Image-based radiotherapy, either SRT or 3DCRT, can recanalize the PVTT in unresectable HCC patients. Responders also had better 1 year and 2 year survivals. A more strict patient selection criterion may maximize the potential benefits of radiotherapy for hepatoma patients with PVTT.

Squamous cell carcinoma of the buccal mucosa: an aggressive cancer requiring multimodality treatment.

BACKGROUND: In our clinical practice, we have observed a high incidence of locoregional failure in squamous cell carcinoma (SCC) of the buccal mucosa. We analyze our treatment results of this cancer and compare these results with those in the literature. We intend to define the pattern and incidence of failure of buccal cancer and provide information for the design of a better multimodality treatment. METHODS: During the period from 1983 through 2003, 121 previously untreated patients with M0 stage SCC of the buccal mucosa were treated with a curative intent at our hospital. Twenty-seven patients received surgery alone, 36 had radiotherapy alone, and 58 underwent surgery plus postoperative radiotherapy. RESULTS: The 5-year locoregional control, overall survival, and cause-specific survival rates for all patients were 36.3%, 34.3%, and 36.9%, respectively. The locoregional recurrence rate was 57% for all patients, with 80% occurring in the primary site alone. Patients with T1-2N0 disease who received surgery alone still had a high local recurrence incidence of 41%. For patients with locally advanced disease, surgery plus postoperative radiotherapy achieved better overall survival and locoregional control rates than surgery alone or radiotherapy alone. T classification was the only prognostic factor affecting locoregional control and survival in the surgery alone group, whereas N classification and skin invasion predicted a poorer survival for the surgery plus postoperative radiotherapy group. CONCLUSIONS: SCC of the buccal mucosa is an aggressive cancer with a high locoregional failure rate even in patients with T1-2N0 disease. Possible reasons include inadequate treatment and an intrinsically aggressive nature. Postoperative radiotherapy has resulted in a better locoregional control rate for patients with T3-4 or N+ disease and should also be considered for patients with T1-2N0 disease for whom adjuvant therapy after radical surgery currently is not recommended by most guidelines.

Determination of alpha-fetoprotein in human serum by a quartz crystal microbalance-based immunosensor.

BACKGROUND: Increased alpha-fetoprotein (AFP) in adult plasma is considered an early indication of hepatocellular carcinoma and teratoblastoma. The aim of this study was to develop a rapid method to measure AFP in human serum by use of a direct immunosensor based on a quartz crystal microbalance (QCM). METHODS: A self-assembled monolayer prepared by the cystamine method was applied to immobilize anti-AFP monoclonal antibodies on the gold surface of a quartz crystal. The frequency shifts of the QCM were measured and related to AFP concentrations. The piazoimmunosensor used no labeled reagent and no pretreatment of samples. RESULTS: Ten cycles of measurements could be performed on the gold surface of the same crystal regenerated with a solution of glycine-HCl. A linear relationship existed between the frequency shifts (Hz) and the log values of AFP concentrations from 0.1 to 100 microg/L in buffer and human serum. When used for 15 days, the frequency shifts were all >95% of those on the response at the first day. The regression equation was y = 1.03x - 0.06 (S(y/x) = 3.92; r = 0.9987) for this QCM method and RIA in 29 clinical human serum samples. CONCLUSIONS: The QCM sensor can measure AFP in buffer and human serum and offers advantages of high specificity, reusability, low detection limit, no label or sample pretreatment, and low sample requirement. The assay format of the immunosensor was more rapid and simpler than conventional methods.

Production of monoclonal and polyclonal antibodies against human alphafetoprotein, a hepatocellular tumor marker.

The objective of this study is to produce and purify monoclonal antibodies and polyclonal antibodies (PAbs) against human alphafetoprotein (AFP). Hyperimmune ICR mice produced PAbs after injection with 0.5 mL pristane, and were injected with NS-1 myeloma cells 2 weeks later. Hyperimmune Balb/c mice were used for the production of MAbs. Mice were immunized four times, given a final boost, and their spleen cells were collected and fused with NS-1 myeloma cells under the presence of PEG 1500. The fused cells were then selected in the hypoxanthine, aminopterine, and thymidine (HAT)-RPMIX medium. Anti-AFP antibody-secreting hybridoma cell lines with high titer were cloned by enzyme-linked immunosorbent assay (ELISA) and then subcloned by limiting dilution in 15% fetal bovine serum (FBS), hypoxanthine, thymidine (HT)-RPMIX medium. Twelve murine hybridoma producing anti-AFP MAbs were obtained and designated as A73F3, A73E8, B73C5, A73G3, A73F8, 67B3, B73C2, B73E1, A73G2, B73G7, B73D7, and B73F4. Isotypes of these MAbs were identified as IgG(1) heavy chain and kappa light chain. The MAbs with high purity were obtained by affinity chromatography. The purity analysis of AFP and the MAbs was performed by capillary electrophoresis.

Synthesis and biological activity of sulfur-containing aryl-aldehyde Schiff bases.

A series of chemically modified aryl-aldehyde Schiff bases has been synthesized and tested for their antioxidant activity and radiation protection. We observed that disulfide-containing aryl-aldehyde Schiff base 6c exhibited potent free radical scavenging, antioxidation, and radioprotection activities.

Synthesis and biological evaluation of ebselen and its acyclic derivatives.

Five ebselen and three acyclic ebselen derivatives were synthesized. These compounds were screened for their glutathione peroxidase (GSH Px)-like activity and scavenging activity against 1,1-diphenyl-2-pycryl-hydrazyl (DPPH) and peroxynitrite radical. All tested compounds displayed similar significant GSH Px-like activity, which are slightly higher than that of ebselen. The peroxynitrite scavenging activity showed that the acyclic allylseleno 4c was five times more potent than ebselen.

Synthesis of symmetrical 1,5-bis-thio-substituted anthraquinones for cytotoxicity in cultured tumor cells and lipid peroxidation.

The synthesis of a series of anthraquinone moieties bearing symmetrical sulfur-linked substituents in the 1 and 5 positions is described. These compounds were evaluated for their ability to inhibit the growth of suspended rat glioma C6 cells and human hepatoma G2 cells, respectively. In addition, the redox property of the compounds was determined based on the inhibition of lipid peroxidation in model membranes. Compounds 2a and 2h in this series compared favorably and exhibited the most potent cytotoxicity (0.02, 0.05 microM) against C6 cells in the XTT colorimetric assay. As far as redox properties are concerned, all bis-thio-anthraquinones show potential lipid peroxidation in model membranes very close to that of mitoxantrone (MX), and 2a, 2d, 2e, 2i, 2j, and 2k have more potential than that of MX. The lack of cytotoxicity of compound 2i cannot be related to lipid peroxidation, but the steric and electronic properties of the side-chain substituent maybe impair effective recognition of the cleavable complex. In contrast to MX, 2a and 2h are cytotoxic in rat glioma C6 cells and do not enhance lipid peroxidation in model membranes.

Effects of oral arginine and glutamine on radiation-induced injury in the rat.

BACKGROUND: Exposure of the abdominal region to ionizing radiation is associated with serious untoward symptoms of intestinal dysfunction and some reports indicate that nutrient supplements may reduce these adverse effects. This study was designed to investigate the possible beneficial effects of oral arginine or glutamine supplementation on the radiation-induced tissue injury. MATERIALS AND METHODS: Rats were given one of three feeding regimens: standard diet and water (control group), diet and water containing 2% arginine (arginine group), diet and water containing 2% glutamine (glutamine group) for 3 days prior to radiation. All rats were then subjected to a single does of 1100 cGy to the abdomen. Several serum biochemical parameters and the histologic alterations in different segments of gastrointestinal tract and liver were measured 4 days after irradiation. RESULTS: All the arginine-fed rats developed diarrhea on Day 4 postirradiation, compared to 71% incidence in control rats and 86% in glutamine-fed rats. Serum levels of aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the arginine group were markedly higher than those in other groups. On histological examination, radiation caused more serious damage to various segments of intestine in the arginine-fed rats compared to rats on other feeding regimens. CONCLUSION: These observations seriously question the beneficial effects of arginine and glutamine supplementations on radiation-induced tissue injury.