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Biomedical subjects

R Sealy

Publications and source records attributed to R Sealy.

At least 37 records · Page 2Linked to original sources

Improved cosmesis in retinoblastoma patients treated with iodine-125 orbital irradiation.

Patients who are at risk for developing an orbital recurrence after enucleation of the eye for retinoblastoma are those with full thickness choroidal invasion or further extension into the sclera or extension into the optic nerve beyond the lamina cribrosa. The authors have treated these patients routinely with external irradiation to the orbit but this usually resulted in a dry contracted socket that often would not accept a prosthesis. An orbital implant was designed with 125I seeds in an attempt to improve the cosmetic result. It consisted of seven rows of 125I seeds, six of which were partially screened and implanted around the periphery of the orbit so that the contents were irradiated whilst reducing the dose to the bony orbit. The seventh central row was unscreened. A metal disc, with 125I seeds sealed to the posterior surface, was sutured beneath the eyelids thus protecting them and the accessory lacrimal glands. A TDF of 90-100 over two to three days was given. Thirteen patients have been treated, nine prophylactically and four therapeutically. Three of the latter patients have died of metastases but no local recurrences have been seen. All 13 patients were left with a moist socket that accepted a prosthesis.

Brachytherapy↗

Palliative topical and systemic misonidazole with low-dose irradiation for recurrent carcinoma of the cervix uteri.

This report concerns a determinate series of 11 patients with progressive recurrent cancer of the cervix uteri, who were treated with misonidazole (1 g) applied locally for 24 hours and an oral dose of 2.9 g/m2 four hours before a single mid-plane dose of 5.00 Gy. Four of 11 (36%) remained free of disease at one year. It is suggested that this is largely a hypoxic cell cytotoxic effect and is a useful method of palliation.

Carcinoma, Squamous Cell↗

Irradiation with misonidazole and hyperbaric oxygen: final report on a randomized trial in advanced head and neck cancer.

One hundred and thirty patients with locally advanced squamous carcinoma of the head and neck were treated in a prospective randomized trial to compare conventional irradiation (63.00 Gy in 30 fractions) with a combination sensitizer regimen of misonidazole and hyperbaric oxygen. The drug (2.0 gm/m2) was given with each of six fractions of 6.0 Gy in hyperbaric oxygen at 3 ATA. The results support a previous study and favor the combination at 1 year at better than the 10% level. This regimen could be useful for bulky primary or nodal disease.

Carcinoma, Squamous Cell↗

A feasibility study of a new approach to clinical radiosensitisation: hypothermia and hyperbaric oxygen in combination with pharmacological vasodilatation.

It is proposed that hyperbaric oxygen fails in the clinical situation due to a high proportion (greater than 33%) of hypoxic cells in human tumours. The means of overcoming this problem are reviewed. Additional to hyperbaric oxygenation, moderate hypothermia (30 degrees C) to allow redistribution of oxygen in the tumour is proposed. A system of externally controlled intravenous anaesthesia has been developed for the single-subject hyperbaric cylinder. Pharmacological vasodilatation is induced in the anaesthetised patient who is then fluid loaded and cooled. Initial single-sensitising treatments are advocated. Twenty-nine patients with advanced mouth cancer have completed a course of this treatment, of whom five of nine were free of disease after 2 years and 10 of 21 at 1 year, with three intercurrent deaths. Fifteen have experienced local failure. This approach would appear to be practical, safe and promising.

Anesthesia, Intravenous↗

Single-dose relative biological effectiveness and toxicity studies under conditions of hypothermia and hyperbaric oxygen.

An approach to using hyperbaric oxygen with radiation in a clinical situation has been described in the preceding paper in this issue. To ascertain whether there might be a change in the relative biological effectiveness of radiation on normal mammalian tissue treated under conditions of hypothermia and hyperbaric oxygen, the acute reaction to radiation of pig skin was studied. A single dose enhancement ratio at the erythema reaction level of 1.4 +/- 0.08 was obtained when compared with irradiation at normal body temperature in air. We studied also a series of antioxidant enzymes in rat liver and lung after exposure to hypothermia and hyperbaric oxygen. Enzyme changes were such as to combat oxygen toxicity which might develop as a result of the pre-treatment.

Animals↗

Computerized staging of cancer of the maxillary sinus.

There are numerous, different recommended systems for staging cancer of the maxillary sinus. No single system is known to be better than another. We have developed a method of simultaneously staging a tumour of the maxillary sinus into each of six different TNM staging classifications. This enables a comparison of the various classifications and provides a number of advantages: staging can be done quickly and easily, and is automatically standardised; it assists careful documentation of tumour extent and it ensures comparisons of like with like, which should enable a more critical and useful appraisal of the results of treatment.

Computers↗

Pineal malignant neoplasm in association with hereditary retinoblastoma.

A patient with unilateral hereditary retinoblastoma who was successfully treated at the age of 7 weeks developed a tumour in the pineal region two and a half years later. The initial response to radiation treatment of the latter lesion was not maintained. Subsequent necropsy findings are described. Clinically and pathologically this case represents an example of the recently described trilateral retinoblastoma. The response to treatment after early recognition was disappointing.

Brain↗

Interstitial misonidazole. A preliminary report on a new perspective in clinical radiation sensitization and hypoxic cell chemotherapy.

The actions of misonidazole as a radiation sensitizer, hypoxic cytotoxic, and metabolic inhibitor are all concentration-dependent, and the commonly prescribed oral dose (12 g/m2) appears to be inadequate. The drug has, therefore, been given interstitially in solid form, when local tissue doses of the order of tens of millimolar are attained, to four patients, all with advanced disease. In the three cases (two squamous carcinomas and a malignant melanoma) in whom the drug concentration was considered to be adequate, a beneficial effect was obtained, which, in two instances, was associated with doses of radiation of 6 and 8 Gy, respectively. This approach has a wide potential application in cancer therapy.

Aged↗

The treatment of locally advanced head and neck cancer with misonidazole, hyperbaric oxygen and irradiation: an interim report.

Thirty-one patients with advanced inoperable squamous carcinoma of the mouth were treated in a pilot study with misonidazole (2.0 gm/m2) with each of six fractions of 6.0 Gy in hyperbaric oxygen at 3 ATA. The one and two year disease free survival was 48 and 26%, respectively. A prospective randomized trial is now being conducted comparing this regimen with 63.0 Gy in 30 fractions in 38 days in air. One hundred-fourteen patients have been entered; 91 are available for analysis at six months or more. The preliminary results at 6 and 12 months favor the combination of sensitizers. There is no added toxicity.

Adult↗

Comparison of chemotherapy alone versus chemotherapy and radiation therapy of extensive small cell carcinoma of the lung.

In a randomized study 145 patients with extensive small cell carcinoma of the lung were treated with chemotherapy alone (Cytoxan, CCNU, methotrexate) or with the same drug regimen and with radiation therapy to the brain, chest, and abdomen. One hundred eighteen of these patients were evaluable. Those patients receiving radiation had a better response rate (55% vs 31%, P = .016) but significantly greater toxicity. There was no significant difference in rates of complete response (7% vs 8%) or in survival (median 18.4 vs 15.3 weeks) between the two groups overall. The median survival of those patients with a partial response to therapy was 18 weeks; for those achieving a complete response it was 46 weeks. However, a clear difference in survival comparing responders with non-responders was evident only for patients who were assigned to chemotherapy alone. Partial regressions have little, if any, correlation with improvement in survival. Therapy in this disease must be oriented toward inducing complete response.

Aged↗

Radical irradiation and misonidazole in the treatment of T2 grade III and T3 bladder cancer.

The results of 2 pilot studies using a new radiation fractionation schedule plus misonidazole (MISO) in the radical radiotherapy of T2 Grade III and T3 carcinoma of the bladder are presented. Forty Gy in 20 daily fractions of 2 Gy was administered to the whole pelvis over 4 weeks followed by 12 Gy in 2 weekly fractions of 6 Gy. These last 2 doses were given after MISO administration. In an initial pilot study (Pilot Study I) MISO was administered orally only. The first two patients received MISO at a dose of 4.5g/m2 orally with each radiation fraction, after which the dose was reduced to 3.0g/m2 because of drug toxicity. In the second pilot study (Pilot Study II) MISO was administered orally at a dose of 3.0g/m2 and intravesically at a dose of 1.0g to 22 patients. The complete response rate at cystoscopy at 6 months in the latter group of patients is 73%, which is significantly better than that of 43% obtained in a retrospective study of historical controls. There have been no late radiation complications in any of the patients nor any MISO toxicity apart from nausea in the patients receiving 3.0g/m2 orally with or without the intravesical MISO.

Administration, Oral↗

Carcinoma of the cervix--anaemia, radiotherapy and hyperbaric oxygen.

Further analyses of the material contained in trials of the hyperbaric oxygen chamber in the radiotherapy of carcinoma of the cervix have shown that patients who were severely anaemic prior to radiotherapy, and who required blood transfusion, showed very poor local tumour control when conventionally treated after transfusion, but very good local tumour control when treated in hyperbaric oxygen. The finding of a special sub-group where hypoxia would seem to be an important cause of radiation failure, and where hyperbaric oxygen was successful in overcoming it, may have importance in the evaluation of other methods for overcoming the hypoxia, including the use of chemical sensitising agents.

Anemia↗

Syndrome of inappropriate antidiuretic hormone secretion following dis-dichlorodiammineplatinum II in a patient with malignant thymoma.

A patient with malignant thymoma is reported, in whom the syndrome of inappropriate antidiuretic hormone secretion (SIADH) occurred 36-48 hours after being given cis-Dichlorodiammineplatinum II (CPPD) with a mannitol diuresis. The SIADH was treated by fluid restriction and demeclocycline and subsided after approximately 72 hours. Subsequent courses of CPPD with mannitol diuresis were given with demeclocycline prophylactically and no untoward effects noted. The precise mechanism for the SIADH following the use of CPPD is unknown, but may be life-threatening, especially since preloading with fluid followed by forced diuresis is used when CPPD is given to avoid nephrotoxicity. The patient has survived 37 months, with 24 months of relapse-free survival following treatment with CPPD, irradiation and surgery.

Cisplatin↗

Radiotherapy of regional epidermoid carcinoma of the lung: a study in fractionation.

This paper reports a prospective randomized multicenter trial of two fractionation schemes in the supervoltage radiotherapy of locally inoperable epidermoid lung cancer. This study was stimulated by the need to provide improved and more acceptable treatment methods for patients with this condition, the most common cell type of lung cancer. The majority of such patients are not suitable for resection because of metastasis or because of extensive local disease, even though exploratory thoracotomy may be performed. It was therefore considered important to identify preferred methods of irradiation in this situation which is found in a large proportion of patients with lung cancer.

Adult↗