The effect of ionizing irradiation on vasomotor reactivity in the rat thoracic aorta in vitro.

PURPOSE: Ionizing irradiation inhibits restenosis in animal models and human. Vasomotor tone preservation during and after radiation therapy is of clinical importance. We therefore investigated vascular reactivity following radiation therapy. METHODS AND MATERIALS: Wistar Sabra rats were treated with a single dose of 1000 cGy external X-ray irradiation. Vascular reactivity of 192 segments of rat thoracic aorta was studied in vitro in four groups (12 rats in each group, four segments from each aorta). Immediately after in vivo irradiation, immediately after ex vivo irradiation, 1 month after irradiation, and no irradiation (control). RESULTS: Vasoconstriction to phenylephrine (PE) 10(-9)-10(-5) M or KCl 118.0 mM in all the irradiated groups was similar to controls. Endothelium-dependent vasorelaxation to acetylcholine (ACh) 10(-9)-10(-5) M in segments studied immediately after in vivo irradiation was increased compared to controls at all concentrations (109.7+/-35. and 90.0+/-40.0%, respectively, at 10(-5) M, P=.006). Endothelium-independent relaxation to nitroglycerin 10(-9)-10(-5) M in all irradiated groups was similar to controls. CONCLUSIONS: External-ionizing irradiation with 1000 cGy in the rat aortic model induces acute and transient increase in endothelium-dependent relaxation to ACh, and does not alter vasoconstriction and endothelium-independent relaxation.

[Brief preoperative radiotherapy reduces local recurrences and improves survival in rectal cancer].

Locoregional recurrence of rectal cancer ranges between 20%-50% following apparently radical surgery. Radiation has the potential of reducing this high rate of recurrence and residual disease. A retrospective analysis of 78 patients with locally advanced, biopsy proven, adenocarcinoma of the rectum treated between 1980-1987 was conducted. 28 (36%) were treated by surgery alone (surgery); 29 (37%) by surgery and postoperative radiotherapy (post-op); and 21 (27%) by surgery and preoperative radiotherapy (pre-op). 41 were females and 37 males. The median age was 62 years (range 25-90). All tumors were resectable. 42 patients (54%) underwent abdomino-perineal resection and 36 (46%) anterior resection [8 patients Dukes B1 (10%); 37 B2 (47%); 2 C1 (3%); 31 C2 (40%)]. Local recurrences were verified by transanal or ultrasound guided needle biopsy. The 5-year actuarial survival rates by the Kaplan-Meier method for 75 evaluated patients was 55%. Overall 5-year actuarial survival was significantly higher (p = 0.001) in pre-op radiotherapy (95%) compared to surgery alone (45%), or surgery with postoperative radiotherapy (32%). The data were significant (p = 0.006) for patients with stage B tumors, but not stage C. This trend of improved survival held also at 8-year follow-up (80% pre-op; 32% post-op; 27% surgery). The 5-year actuarial local control was significantly better (p = 0.03) for the pre-op irradiated patients (22%), compared with surgery only (56%) and post-op radiotherapy (38%). Local control was better (p = 0.02) for Dukes B tumors in the preoperative group, but not Dukes C tumors. Actuarial 5-year survival of those without distant metastases was 87% for pre-op patients, 62% for surgery alone and 48% for post-op radiotherapy. As all patients were clinically classified as advanced rectal tumors, tumor downstaging by preoperative radiotherapy seems to be paramount for local control. Improved local control translates into a significant advantage in overall actuarial survival.

Effect of natural beta-carotene supplementation in children exposed to radiation from the Chernobyl accident.

Attempts were made to evaluate 709 children (324 boys and 385 girls) who had been exposed long-term to different doses of radiation during and after the Chernobyl accident and had moved to Israel between 1990 and 1994. Upon arrival, all of them underwent a check-up for most common clinical disorders and were then divided into three groups according to their residences (distance from the reactor) and the level of irradiation exposure: no radiation, <5 Ci/m2, and >5 Ci/m2, respectively. Blood serum analyses for total carotenoids, retinol, alpha-tocopherol and oxidized conjugated dienes in 262 of the children showed increased HPLC levels of conjugated dienes, indicating increased levels of oxidation of in vivo blood lipids in children from the contaminated areas. The levels were higher in girls than in boys. Some 57 boys and 42 girls were given a basal diet with a diurnal supplementation of 40 mg natural 9-cis and all-trans equal isomer mixture beta-carotene in a capsulated powder form of the alga Dunaliella bardawil, for a period of 3 months. Blood serum analyses were regularly conducted before supplementation to determine the baseline effect of radiation exposure to the children, after 1 and 3 months of natural beta-carotene supplementation. After supplementation, the levels of the oxidized conjugated dienes decreased in the children's sera without any significant changes in the level of total carotenoids, retinol or alpha-tocopherol. Other common blood biochemicals were within the normal range for all tests and no statistical differences before or after supplementation of beta-carotene were noted. High pressure liquid chromatography (HPLC) analyses for carotenoids in the blood detected mainly oxycarotenoids, and to a lesser extent, all-trans beta-carotene, alpha-carotene, but not 9-cis beta-carotene. The results suggest that irradiation increases the susceptibility of lipids to oxidation in the Chernobyl children and that natural beta-carotene may act as an in vivo lipophilic antioxidant or radioprotector.

Natural beta-carotene and whole body irradiation in rats.

beta-carotene and other carotenoids are reported to be potent free radical quenchers, singlet oxygen scavengers, and lipid antioxidants. Whole-body irradiation is known to cause an immunosuppression effect in mammals through the possible initiation and production of reactive oxygen species. We decided to test the possible antioxidative effect against whole-body irradiation of a natural beta-carotene, composed of equal amounts of the all-trans and 9-cis isomers, obtained from the unicellular alga Dunaliella bardawil. Rats were fed on ground commercial food enriched with natural beta-carotene (50 mg/kg diet). On completion of 1 week with beta-carotene, the rats were exposed to a single dose of 4 Gy whole-body irradiation, after which their livers and blood were removed for beta-carotene and retinol analysis in comparison with control livers of animals irradiated or not, or supplemented with beta-carotene after irradiation. A normal increase in body weight with no ill effects was noted in the groups of rats whose diet was supplemented by beta-carotene before and after irradiation, compared with the reduction in the specific growth rate in the group of rats irradiated without beta-carotene. Liver beta-carotene and retinol decreased significantly after irradiation compared with the rats which were not irradiated. This decrease was not shown in rats fed beta-carotene prior to irradiation, and the effect of irradiation was partially cured by supplementation with beta-carotene after irradiation. High-pressure liquid chromatography (HPLC) analysis of the irradiated animals showed a selective decline in 9-cis beta-carotene and in retinol over all-trans beta-carotene and retinyl-esters. These results suggest that 9-cis beta-carotene and retinol protect in vivo against the cellular damage by free radicals induced after whole-body irradiation.

Irradiation induced blood flow changes in the breast during radiotherapy--a pilot study.

Skin blood flow and underskin temperature were measured in breasts during the complementary radiotherapy following lumpectomy, using the noninvasive transient thermal clearance method. On average, blood flow and tissue temperature increased at the start of the irradiation then slightly decreased. The response varied significantly among the patients. The increase in blood flow is associated with the vasodilatation which accompanies irradiation-induced inflammation and the method enables the assessment of this vasodilatation during the irradiation treatment. The decrease of blood flow after the initial increase is attributed to vascular damage. The method provides a noninvasive means for the evaluation of radiation effects on individual patients during radiotherapy.

The role of brachytherapy in the treatment of stage III vaginal cancer. A report of 3 cases.

Advanced vaginal cancer has a grim prognosis: management is complicated. It may include surgery which needs to be exenterative if cure is intended, and/or radiation therapy (RT), the dose of which is limited by the radiosensitivity of adjacent structures. We report on 3 cases, in each of which the tumor was located in different anatomic sites, and we demonstrate how therapy was tailored to each situation. All 3 patients had Stage III, squamous cell carcinoma of the vagina. They received external beam irradiation (EBI) 4000-5000 cGy to the pelvis. This is the maximal tolerable dose by most pelvic organs, but is not curative. Therefore brachytherapy was combined with EBI. In one patient brachytherapy was given intraoperatively, following extensive removal of residual tumor in the pelvis. Two patients are alive and free of disease three and six and a half years later, and one patient died of disease five years following therapy. For eradication of advanced vaginal cancer, treatment includes the combination of EBI and brachytherapy with or without debulking surgery, the role of which was not previously described in this setting. Treatment strategy should be adapted to the anatomic location of the tumor, its intravaginal extension and the age of the patient.

[Brachytherapy: endobronchial irradiation for primary and secondary bronchial tumors].

Intrabronchial obstruction is one of the serious complications of primary and secondary lung tumors. Brachytherapy (intraluminal irradiation) aims at palliation and opening airway obstruction. Of our first 10 patients, 4 had primary and 6 metastatic pulmonary lesions. Brachytherapy was administered through the fiberoptic bronchoscope under topical anesthesia from a 192iridium source delivered with an afterload system. In 3 patients laser therapy was used initially. In 6 complete opening of the airway was achieved, and in 3 others partial opening. In all patients there was symptomatic relief without significant side-effects. We conclude that endobronchial brachytherapy is a safe, useful procedure for palliation of malignant endobronchial obstruction.

Giant melanoma of the inner thigh: a homeopathic life-threatening negligence.

The strange case of a 37-year-old modern, Western woman who presented with a giant black mass on her inner right thigh is presented. She was treated 10 months before this present admission by an excision of a nodular melanoma, and she was treated, thereafter, by a homeopathic practitioner until she came late to follow-up. The woman is discussed with special attention to the fact that alternative medicine does not always constitute good advice, and the relevant literature is reviewed.

Modulatory effect of fluoride and irradiation on rat molar rate of wear.

The hypothesis was tested that fluoride (F-) modulates molar wear rate in the irradiated rat and that enamel solubility and dentin hardness are involved in this process. Seventy five 21 day-old rats were divided into 5 groups. Groups received either F-(25 ppm) in the drinking water or irradiation to the head (15 Gy in a single dose), or a combination of the two. The rate of occlusal wear was assessed by computerized planimetry. The amount of wear was significantly higher in the F- and irradiation monotreated rats, while under combined treatment it did nor differ significantly from the control values. Fluoridation or irradiation suppressed enamel solubility, as measured by calcium release in the etchant. Dentin microhardness, expressed in Vickers hardness number, was enhanced after either treatment, but remained unaffected when F- administration preceded irradiation. Enamel solubility and dentin microhardness did not correlate significantly with the rate of occlusal wear.

[Interstitial radiotherapy for brain tumors].

Interstitial radiotherapy (brachytherapy) for brain tumors has radiobiological advantages over conventional teletherapy. With this method the tumor area can be exposed to effective, high dose irradiation with minimal damage to surrounding tissues.

Radiation therapy for locally advanced breast cancer: prognostic factors and complication rate.

A retrospective analysis was carried out in 100 patients with locally advanced breast cancer without distant metastases treated by radiotherapy between 1960 and 1979. The primary tumor was irradiated to a total dose of 60 Gy in 76 patients and to doses ranging between 60 and 80 Gy in 24 patients. The regional lymphatics were treated with doses between 50 and 60 Gy. Following radiotherapy, chemotherapy was administered to 58 patients and hormonal therapy to 29, while 13 patients received no further therapy. Locoregional recurrences were documented in 29% and distant metastases in 49% of patients. The actuarial survival was 56% at 5 years, 21% at 10 years and 14% at 15 years. At 10 years 90% of the surviving patients had some degree of radiation damage.

Interstitial pneumonitis after total body irradiation: effect of partial lung shielding.

The potential beneficial effects of partial lung shielding were investigated in 44 patients conditioned by whole body radiotherapy as part of the conditioning for bone marrow transplantation (BMT). The first 23 patients were irradiated with fractionated total body irradiation (TBI) to a total dose of 12 Gy. In the second series of 21 patients a 50% transmission lung shield was utilized following 6 Gy TBI. This treatment was combined in the second group with four fractions of 1.5 Gy total lymphoid irradiation (TLI), given in 2 d. The rate of idiopathic interstitial pneumonitis (IP) was 26% in the first group, compared to none in the second.

Hodgkin's Lymphoma: Results of ABVD Chemotherapy in 40 Patients with Advanced or Bulky Disease.

During 1980-1986, 40 patients with advanced Hodgkin's disease or bulky disease were treated with six cycles of ABVD chemotherapy, and adjuvant radiotherapy was added to sites of bulky disease when required. Twenty-seven of the 40 patients (67.5%) were treated with ABVD as primary therapy and 13 (32.5%) received it as salvage therapy after initial failure. Twenty-seven patients (67.5%) had advanced stages 3 or 4 disease, while 13 (32.5%) had stage 2 with bulky mediastinal disease (more than 30% chest diameter). Only 7.5 % of the patients had no response to ABVD while 75% achieved CR and 17.5% PR. Seventy-four per cent of the patients with advanced stages 3 and 4 achieved CR and 15% reached PR, with only two failures to ABVD. The median survival for the entire group is currently more than 41 months, with a median disease-free interval (DFI) of 27.5 months for all treated patients. The results compare favorably with those reported from other major centers dealing with larger series of patients. New approaches for future treatment employing alternating shorter courses of MOPP/ABV are discussed, and the importance of radiotherapy for bulky disease is emphasized.

Metastatic maxillary sinus melanoma treated by local excision and brachytherapy.

Malignant melanoma has traditionally been considered a radioresistant tumor. A rare case of metastatic malignant melanoma into the nose and maxillary sinus is presented. Local control was achieved by a combination of local excision and teleradio and brachytherapy. The response of melanomas to radiation treatment is discussed in light of the recent literature.

Development and decay of systemic thermotolerance in rats.

The development and decay of thermotolerance to the lethal effect of systemic hyperthermia was investigated in Sprague-Dawley rats. Systemic hyperthermia was induced by partial submersion of gas-anesthetized rats into a temperature-controlled water bath. Survival was determined in rats challenged for periods of 10 to 90 min at 42.5 C, 24 to 144 h after a sublethal conditioning exposure of 41.8 C for 1 h. Survival curves of various exposure times at 42.5 C lethal to 50% of the animals (LD50) were determined for the conditioned animals and compared with those obtained for simultaneously treated control (unconditioned) rats. The thermotolerance ratios (TTR-LD50 for conditioned animals at various times after sublethal conditioning exposure divided by the LD50 for the control animals) were calculated and compared with the ratios reported in the literature for cells heated in vitro and for tissues heated locally in vivo. Pretreatment of rats at 41.8 C for 1 h resulted in an increase in the LD50 when rats were challenged 24 to 96 h later, with a maximum increased noted at 48 h (56.5 vs. 25.0 min for control; TTR = 2.3). The animals remained relatively resistant to the second heat treatment at 96 h and returned to control levels of heat sensitivity by 120 h. The development and kinetics of thermotolerance to lethality induced by whole-body hyperthermia need to be considered when multiple-fraction hyperthermia treatment plans are designed.

Interstitial pneumonitis in T cell-depleted bone marrow transplantation.

The incidence of interstitial pneumonitis (IP) was reviewed in 80 consecutive patients who received allogeneic T lymphocyte-depleted bone marrow transplantation (BMT) for malignant and non-malignant diseases. Pretransplant conditioning used in malignant disorders included total lymphoid irradiation (TLI) 150 cGy x 4, total body irradiation (TBI) 200 cGy x 6, and cyclophosphamide (CY) 120 mg/kg. In non-malignant diseases conditioning included no TBI, but adjusted doses of TLI in addition to CY (severe aplastic anemia) or CY and busulfan (severe beta-thalassemia major). In the malignant group only one patient developed graft-versus-host disease (GVHD) grade I; IP developed in 12 out of 61 patients (19.7%) and IP-associated fatality occurred in five patients (8.2%). Cytomegalovirus (CMV) was associated with only two of the five fatal IP. In the non-malignant group there was no GVHD; one patient out of 19 (5.2%) had IP, which was fatal and not associated with CMV. These data indicate that fatal IP may appear in the absence of GVHD. The relatively low incidence of IP-related mortality in recipients of allogeneic T lymphocyte-depleted BMT suggests that although prevention of GVHD and elimination of drugs used for GVHD prevention may reduce the incidence of fatal pulmonary complications, other approaches have to be investigated for complete prevention of IP which still represents a major complication in patients with malignant hematologic disorders treated by allogeneic BMT.

Testicular seminoma: the Hadassah University Hospital experience.

A retrospective study of all cases of pure testicular seminoma treated at the Hadassah University Hospital in Jerusalem from 1978 through 1986 was conducted. Of the 22 patients, 15 (70%) presented in Stage I, 4 (18%) in Stage II, 2 (9%) in Stage III and 1 (4%) in Stage IV. The results of treatment were evaluable for 20 of these patients. After a median follow-up of 4 years, only the patient with Stage IV disease died of disseminated seminoma. The remaining 19 patients are all alive and disease free, including 3 after radiotherapy for recurrent disease. Elevated beta-human chorionic gonadotropin levels before treatment did not predict an unfavorable outcome. Our excellent results are similar to those obtained at larger treatment centers.