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Biomedical subjects

B N Gray

Publications and source records attributed to B N Gray.

At least 19 recordsLinked to original sources
PubMed2001

Status of hyperthermia in the treatment of advanced liver cancer.

The vast majority of patients with malignant liver tumors have inoperable disease. These patients must rely on chemotherapy, radiotherapy, and various locoregional treatments. Although these treatments have demonstrated encouraging response rates, symptom palliation and occasional down staging of tumors, their impact on survival is minor. As a result there has been renewed interest in hyperthermia as a treatment option. This study reviews the current modalities of hyperthermia in terms of clinical results, side effects, limitations, and therapeutic standing.

Carcinoma, Hepatocellular↗
PubMed2001

Targeting liver tumors with hyperthermia: ferromagnetic embolization in a rabbit liver tumor model.

BACKGROUND AND OBJECTIVES: Ferromagnetic embolization hyperthermia (FEH) consists of arterially embolizing liver tumors with ferromagnetic particles, and then applying an external alternating magnetic field to generate hysteretic heating within the embolized particles. The objective of this study was to assess the ability of FEH to selectively target liver tumors with hyperthermia. METHODS: Twenty rabbits containing hepatic VX2 carcinomas were arterially infused with ferromagnetic particles suspended in lipiodol, and then exposed to an external alternating magnetic field. Temperatures in the tumor, normal hepatic parenchyma (NHP), and rectum were recorded. Tumour and NHP were chemically analyzed for iron content, which was then correlated with the observed heating rates. RESULTS: The mean tumor-to-NHP iron concentration ratio was 5.3:1 (P < 0.001, N = 20). The mean tumor heating rates were 3.0-11.5 times greater than those in the NHP (P < 0.001, N = 20). After 5 min of heating, the greatest increase in mean tumor temperature was 11.0 degrees C and the greatest increase in mean NHP temperature was 1.3 degrees C. There was a positive relationship between tumor iron concentration and heating rate (correlation coefficient = 0.82, P < 0.001, N = 20). A tumor iron concentration of 2-3 mg/g resulted in tumor heating rates of 0.5-1.0 degrees C/min. CONCLUSIONS: Hepatic arterial infusion of lipiodol containing ferromagnetic particles can result in excellent targeting of liver tumors with hyperthermia on the subsequent application of an external alternating magnetic field. The promising results of this study warrant further investigation of FEH as a potential treatment for advanced liver cancer.

Animals↗
PubMed2001

Effect of selective internal radiation therapy and hepatic arterial chemotherapy on normal liver volume and spleen volume.

OBJECTIVE: To determine the effect of selective internal radiation therapy (SIRT) and hepatic arterial chemotherapy (HAC) on normal liver volume and spleen volume in patients receiving these treatments for advanced liver cancer. METHODS: In a phase III clinical trial to assess the benefit of SIRT over HAC one group of patients received SIRT + HAC while a second group received HAC only. All patients in this trial who had abdominal CT scans available before treatment, and at 3, 6, and 12 months after treatment were evaluated. Changes in normal hepatic parenchyma (NHP) volume, portal vein diameter and spleen volume were calculated for each patient and analysed for significant trends. RESULTS: The mean NHP volume decreased by 17% (P = 0.001) 12 months after treatment among patients receiving SIRT + HAC (N = 22), while the mean NHP volume among patients treated with HAC only (N = 15) was unchanged at 12 months. The mean portal vein diameter increased by 9% in both treatment groups, P = 0.048 and P < 0.001, respectively. The mean spleen volume increased by 48% (P < 0.001) and 26% (P = 0.001), respectively, in the two groups 12 months after treatment started. There was no clinical evidence of hepatic failure, portal hypertension or splenic dysfunction in any of the patients. CONCLUSIONS: Treatment of patients with SIRT + HAC causes contraction of the normal hepatic parenchyma, while treatment with HAC alone has no significant effect. Treatment with either SIRT + HAC or HAC alone causes a significant increase in portal vein diameter and spleen volume by 12 months after treatment. The increase in spleen volume and portal vein size is likely to be due to portal hypertension resulting from scarring within the liver as a result of chemical and radiation hepatitis.

Aged↗
PubMed1999

Can current models explain the lack of liver complications in Y-90 microsphere therapy?

Normal liver complications have not been observed in Y-90 microsphere therapy of hepatic tumors [selective internal radiation (SIR)], despite clinical studies reporting estimated absorbed doses to normal liver between 100 and 150 Gy. The purpose of the study was to see whether predictions of normal tissue complication probability (NTCP) models for liver based on clinical data from external beam therapy are consistent with clinical results of SIR. Liver NTCP was calculated using a parallel architecture model and normal liver dose-volume histograms that have been proposed for SIR. A parallel model including internal functional subunit structure is also proposed. Dose rate effects are incorporated. A criterion for comparing model calculations with clinical data is presented. For the parallel architecture model, the predicted NTCP is sensitive to the dose distribution in normal liver and to the model parameters, particularly the repair time. With reasonable assumptions about the microsphere distribution, the parallel model with parameters deduced from external beam therapy outcome analysis is consistent with the observed lack of liver complications. Inclusion of FSU structure widens the range of assumptions under which consistency is found. The parallel model can be consistent with the clinically observed lack of liver complications in SIR. More information about the activity distribution and the radiobiology of normal liver under conditions typical of microsphere therapy should be sought.

Humans↗
PubMed1998

Nurses screening for skin cancer: an observation study.

Skin cancer rates in Australia are the highest in the world and it is an important cause of mortality and morbidity. Screening is a method of control for skin cancer/melanoma through early diagnosis and prompt referral and treatment. To date, there have been no controlled trials evaluating the impact of screening on morbidity and mortality, and hence insufficient evidence to recommend for or against routine screening for skin cancer/melanoma by primary care providers. Australian health authorities have called for studies that investigate the viability of using trained observers apart from medical practitioners--such as nurses, pharmacists and physiotherapists--in opportunistic screening for skin cancer in populations that have a high prevalence of these skin cancers, largely on the basis of cost arguments. We conducted a double blind observation screening study comparing the performance of nurses to those plastic surgeons participating in a skin cancer screening program. The role of the nurse in this program was not to diagnose skin cancer, but to not miss lesions that required further specialist examination. Measurements were recorded for 256 screenees. Plastic surgeons issued 77 (30%) individual referrals for lesions suspicious of being skin cancer. Nurse observations noted 73 (95%) of these 77 cases. The case for the pre-screening of large populations for skin/cancer by trained nurses warrants further attention.

Clinical Competence↗
PubMed1996

Research note: the Lions Cancer Institute and the Western Australian Society of Plastic Surgeons skin cancer screening programme.

BACKGROUND: The Lions Cancer Institute, Perth, and the Western Australian Society of Plastic Surgeons have been investigating the feasibility of community based skin cancer screening. Members of the community responded to newspaper advertisements to attend free skin cancer screening events. This report presents preliminary results obtained from the methods development programme. METHODS: Seventeen screening clinics were conducted in Perth (4) and country towns (14) in Western Australia between January 1991 and October 1993. The participants were interviewed and given promotional literature and their personal profiles were determined. A total body skin examination was performed by a specialist plastic surgeon and any suspicious lesions were recorded and, if necessary, recommendations for further treatment was documented. RESULTS: The number of individuals screened was 3397. Of these, 572 patients were referred to general practitioners for further medical attention of suspicious lesions, 79 patients were clinically diagnosed as having suspicious pigmented skin lesions (13.8% of total lesions and 2.3% of total sample screened). Of these, 53 individual patient pathology reports were obtained. Four invasive malignant melanomas and two in situ melanomas arising in Hutchinson's melanotic freckles were detected. CONCLUSIONS: Debates concerning the efficacy of screening for skin cancer have recently received great attention from many medical disciplines. However, as yet the effectiveness of population based skin cancer screening programmes have not been adequately evaluated with randomized controlled studies. The study reported here provides some findings that may be used to enhance future screening studies.

Academies and Institutes↗
PubMed1996

The use of targeted and non-targeted advertising to enrich skin cancer screening samples.

The purpose of this study was to determine whether the risk factor profile of persons attending skin cancer screening clinics could be enriched by appropriate advertising prior to the screening events. Eleven screening clinics were held in eight rural and three suburban communities. Matched communities were randomly assigned to either a target or non-target condition. Targeted communities received an advertisement designed to attract high-risk individuals. The advertisement listed a number of risk factors and encouraged readers with one or more of the listed risk factors to attend the screening. Non-targeted communities received a general advertisement requesting individuals who felt they were at risk of skin cancer to attend the clinic. Risk factor profiles of all participants were measured on the factors listed in the targeted advertisement. The risk factor profiles of screenees and the referral rates for skin lesions requiring attention were significantly higher in the targeted communities than in the non-targeted communities. Lesions suspicious of malignant melanoma or Hutchinson's melanotic freckle also were higher, but not statistically significant, in the targeted communities. Population samples attending community-based skin cancer screening clinics can be enriched by appropriate targeted advertising prior to the screening events. This has important implications for determining the potential cost-effectiveness of population screening programmes.

Adolescent↗
PubMed1995

Adjuvant internal radiation therapy in a model of colorectal cancer-derived hepatic metastases.

Selective internal radiation therapy (SIR therapy) is a technique whereby metastatic liver cancer is irradiated by embolising microspheres containing the radionuclide yttrium-90 into the hepatic arterial circulation. To date this technique has not been used as an adjuvant therapy, but rather to treat established metastases in the liver. This study evaluated the use of two intrahepatic radiation doses delivered on radioactive microspheres for the treatment of small, growing micrometastases. Three groups of five rats were each inoculated with tumour spheroids into the portal vein. The resultant liver micrometastases were treated with either 10 or 20 MBq of yttrium-90 microspheres or a sham dose of non-radioactive microspheres injected into the portal vein 2 days following tumour inoculation. The livers of each animal were examined for the presence of metastases after a further 21 days and liver function tests were performed. At the time of sacrifice there was no obvious normal liver damage in any of the rats treated with microspheres. The livers of the sham-treated animals contained extensive signs of tumour deposition. A mean of 34 tumours were taken from the livers of each of the sham-treated animals, whereas only a single tumour was found in one animal treated with 10 MBq of yttrium and eight small tumours from two animals treated with 20 MBq. Liver function tests demonstrated a significant short-term increase in alkaline phosphatase levels in the radiation-treated animals compared with shams, but there were no other indications of any effects on liver function. These results indicate a potential role for SIR therapy in an adjuvant setting with colorectal cancer.

Animals↗
PubMed1995

Retroperitoneal schwannoma: a case series and review.

Schwannomas account for only a small percentage of retroperitoneal tumours. Presentation is typically varied and non-specific and pre-operative diagnosis is difficult. Herein are described five cases of retroperitoneal schwannoma. Presentation was varied, ranging from abdominal pain, abdominal mass, obstructed labour or an incidental finding. All patients had either an abdominal computed tomography scan and/or ultrasound performed. Pre-operative biopsy either by fine needle aspiration (in one patient) or core biopsy in two patients was unhelpful. In four patients with smaller tumours, complete excision was possible with no apparent long-term morbidity and no clinical evidence of recurrent tumour with follow up from 3.5 months to 11 years. For the largest tumour, complete surgical excision was not attempted as it would have entailed significant morbidity.

Adult↗
PubMed1994

The solution conformation of a trisdecanucleotide containing the consensus binding site of the dnaA initiation protein.

The solution structure of a trisdecanucleotide, d(CCTGTGGATAACA).d(TGTTATCCACAGG) containing the consensus binding site of the dnaA initiation protein has been determined by two-dimensional NMR techniques and restrained molecular dynamics calculations. Interproton distances were obtained by an iterative complete relaxation matrix algorithm, MARDIGRAS. During molecular dynamics runs, the backbone was restricted with the assistance of experimentally derived distance constraints. A family of refined structures with small pairwise root-mean-square deviation values (approximately 0.08 nm) was obtained. All but one of the pyrimidines were found to adopt the C1'-exo conformation while the purines were found to adopt the C2'-endo or C1'-exo conformation. The six-membered rings of the purines were found to stack over the six-membered rings of the pyrimidines while there is virtually no overlap of the pyrimidines over the purines. 5'-purine-purine-3' and 5'-pyrimidine-pyrimidine-3' stacking resembles the observed stacking of these bases in other NMR and X-ray structures of oligonucleotides. The final refined structure exhibited a small curvature and was slightly longer than canonical B-DNA. The variation of twist angle, proposed as a recognition element for proteins, exhibited symmetry about the centre of the consensus binding site.

Bacterial Proteins↗
PubMed1992

Influence of schedule on the therapeutic efficacy of chemoimmunotherapy with doxorubicin and interleukin-2.

Combinations of chemotherapeutic agents with recombinant interleukin-2 are currently under investigation in Phase I/II clinical trials as a possible means of improving response rates for metastatic melanoma, breast cancer, non small cell lung and head/neck carcinomas. As chemotherapy often induces marked immune suppression in vivo, the way in which these agents are combined may be of critical consideration to the therapeutic outcome. Using a rat tumour model, this study aimed to define an optimal schedule for the combined administration of doxorubicin (DOX) with interleukin-2 (IL-2). DOX (4.5 mg/kg bolus i.v.) was administered 24 hours before, during, or 24 hours after, IL-2 immunotherapy (1 x 10(5) Cetus U/rat/day for 5 days continuous i.v. infusion) to WAG rats bearing hind limb solid colonic adenocarcinoma implants. Tumour measurements taken over the 4 weeks study period revealed that there was no significant difference in tumour growth inhibition between the three schedules. Furthermore, DOX invariably caused a marked suppression in the rebound lymphoproliferation after cessation of IL-2 therapy (P less than 0.001). These results demonstrate that the therapeutic efficacy of the DOX/IL-2 combination is not influenced by the schedule for the administration of these agents within the times of administration investigated in this study.

Adenocarcinoma↗
PubMed1992

Dose response and toxicity of doxorubicin microspheres in a rat tumor model.

The therapeutic response and toxic effects of chemotherapy using several doses of doxorubicin in conventional solution form or bound to an ion-exchange resin were compared in a rat tumor model, to assess the relationship of drug dose to therapeutic efficacy and associated toxicity. Single bolus injections of 3.0, 4.5, 6.0, 7.5 and 9.0 mg/kg were administered via the abdominal aorta to rats bearing hindlimb tumors. Tumor size was measured serially and the growth rates of treated groups were compared with a control growth curve. In addition, the effect of empty microspheres on tumor growth rate was assessed. The levels of circulating white blood cells were measured and compared to control levels to provide an indication of the severity of bone marrow toxicity experienced by each form of treatment. Finally, any difference in the distribution of doxorubicin to tumor, hindlimb and cardiac tissue following administration of doxorubicin as free drug or on microspheres was ascertained. Empty ion-exchange resin exerted a small although significant detrimental effect on tumor growth which may be explained by the embolization of microspheres in the precapillary blood vessels of the tumor resulting in a transient delay in tumor growth rate. The lowest dose of doxorubicin produced a significantly better therapeutic response when administered in the free drug form, but higher doses elicited an equivalent delay in tumor growth for both drug microsphere and free drug groups in a dose-dependent manner, with the maximum anti-tumor response occurring at the highest dose. Treatment with free doxorubicin at high doses resulted in significant reductions of circulating white blood cells suggesting the occurrence of bone marrow toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1992

Regression of liver metastases following treatment with yttrium-90 microspheres.

Selective internal radiation (SIR) therapy is a technique developed by our group for concentration of Yttrium-90 microspheres into liver metastases. The technique involves laparotomy, insertion of the catheter into the hepatic artery, redistribution of liver blood flow with vaso-active agents and incremental embolization of Yttrium-90 containing microspheres (SIR spheres) into the liver. Twenty-nine patients with non-resectable liver metastases from primary adenocarcinoma of the large bowel were treated by this technique and followed for a minimum of three months to assess evidence of tumour regression. Response to treatment was measured by serial estimations of carcino-embryonic antigen (CEA) and tumour volumes measured from serial computerized tomography (CT) scanning of the liver. There was a fall in the serum CEA level in all 26 patients in whom the serial estimations of CEA were performed following SIR therapy. The overall mean fall in CEA was 70% of pre-treatment levels with 88% of patients (23 of 26) experiencing more than a 50% fall in pre-treatment CEA levels. In 18 of 22 evaluable patients CT measured tumour volumes decreased following SIR therapy. In 48% of patients (10 of 22 patients) the decrease in tumour volume was more than 50%. SIR therapy results in a high rate of tumour regression in patients with liver metastases secondary to large bowel cancer.

Adenocarcinoma↗
PubMed1992

Evaluation of ion-exchange microspheres as carriers for the anticancer drug doxorubicin: in-vitro studies.

A comparison study of doxorubicin loading, release characteristics and stability within sodium and hydrogen forms of ion-exchange resin microspheres has been performed. It was demonstrated that resins in the Na+ form, although having lower drug loading capacity, showed similar release profiles to resins in the H+ form but still maintain all the drug activity. Resins in the H+ form, despite having high drug loading capacity, caused drug degradation within microspheres due to their strong acidic nature. Therefore, in comparison with the H+ form, resins in the Na+ form can be considered as better carriers for doxorubicin in terms of sustaining the release of drug and maintaining drug activity. Other factors such as the degree of resin cross-linkage and drug/resin mixing time have also been examined in relation to drug loading and release characteristics. Overall, this study demonstrated the significance of the characteristics of matrix materials and their influence on the drug activity and microsphere performance in-vitro.

Chromatography, High Pressure Liquid↗
PubMed1991

Dose distribution following selective internal radiation therapy.

Selective Internal Radiation Therapy is the intrahepatic arterial injection of microspheres labelled with 90Y. The microspheres lodge in the precapillary circulation of tumor resulting in internal radiation therapy. The activity of the 90Y injected is managed by successive administrations of labelled microspheres and after each injection probing the liver with a calibrated beta probe to assess the dose to the superficial layers of normal tissue. Predicted doses of 75 Gy have been delivered without subsequent evidence of radiation damage to normal cells. This contrasts with the complications resulting from doses in excess of 30 Gy delivered from external beam radiotherapy. Detailed analysis of microsphere distribution in a cubic centimeter of normal liver and the calculation of dose to a 3-dimensional fine grid has shown that the radiation distribution created by the finite size and distribution of the microspheres results in an highly heterogeneous dose pattern. It has been shown that a third of normal liver will receive less than 33.7% of the dose predicted by assuming an homogeneous distribution of 90Y.

Humans↗
PubMed1991

Adjuvant post-operative radiotherapy in rectal cancer: results from the ANZ Bowel Cancer Trial (Protocol 8202).

In July 1982 the Gastrointestinal Section of The Clinical Oncological Society of Australia began a multicentre randomized trial to assess the value of post-operative pelvic radiotherapy in the local control of stage B and C carcinoma of the rectum. Patients who had undergone a potentially curative resection were randomized either to no further treatment (NO RT) or to pelvic radiotherapy (RT), 45 Gy in 25 fractions (plus a perineal boost of 5 Gy in 2 fractions after abdomino-perineal resection). The trial was prematurely terminated in December 1985 owing to slow accrual after 70 patients had been randomized: 36 patients to RT and 34 patients to NO RT. Two patients in each group were found to be ineligible after randomization and, for a variety of reasons, thirteen patients who were randomized to RT did not receive that treatment. The incidence of post-operative complications were comparable in both groups, indicating that radiotherapy produced no additional problems. Radiotherapy-related morbidity comprised mainly diarrhoea (grade 1 = 2/21; grade 2 = 5/21; grade 3 = 0/21; grade 4 = 1/21). There were no deaths due to radiotherapy and only one patient, with grade 4 diarrhoea, failed to complete the prescribed course of radiotherapy. After an average follow-up period of 52 months there were 15 local recurrences, 8 in the RT group and 7 in the NO RT group, giving an actuarial 2 year local recurrence rate of 16%. There was no difference in the time to local recurrence, either by randomization group (p = 0.50) or by actual treatment received (p = 0.91).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗