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Biomedical subjects

J E Kingston

Publications and source records attributed to J E Kingston.

At least 19 recordsLinked to original sources
PubMed2001

Imaging-guided core biopsy for the diagnosis of malignant tumors in pediatric patients.

OBJECTIVE: We evaluated the ability of imaging-guided core biopsy to obtain sufficient tissue from pediatric tumors for a definitive diagnosis of malignancy on which treatment could be based. MATERIALS AND METHODS: Thirty-four biopsies (biopsies of the abdomen, 32; of the chest, 2) were performed on 34 children at presentation under CT or sonographic guidance using 14-, 18-, or both 14- and 18-gauge needles. A minimum of two tissue cores was obtained. Most biopsies were performed under general anesthesia, permitting other procedures to be performed. The biopsy results were confirmed by subsequent surgical pathology, bone marrow biopsy, biochemical or clinical features, and follow-up examination. RESULTS: The needle biopsy diagnoses were nephroblastoma (n = 11), neuroblastoma (n = 7), renal cell carcinoma (n = 2), synovial sarcoma (n = 1), non-Hodgkin's lymphoma (n = 2), clear cell sarcoma (n = 1), rhabdoid tumor (n = 1), pulmonary blastoma (n = 2), embryonal rhabdomyosarcoma (n 1), germ cell tumor (n = 1), adrenal carcinoma (n = 1), inflammatory tissue (n = 2), desmoplastic tumor of the mesentery (n = 1), and primitive neuroectodermal tumor (n = 1). In 28 patients, the results were confirmed as correct (22 with surgery and 6 with follow-up examination). Four patients required additional biopsy. In two of these patients, the core biopsy showed inflammatory tissue only, and an open biopsy of a different site was performed; the other two patients did not respond to therapy on the basis of needle biopsy results, and an open biopsy altered the diagnosis. Two patients with widespread disease were excluded because they did not respond to treatment and were too ill to undergo an open biopsy. Only one significant complication was recorded. CONCLUSION: Imaging-guided core biopsy is a safe and reliable means of obtaining sufficient tissue to make a confident histologic diagnosis of malignant pediatric tumors in a high percentage of patients.

Abdominal Neoplasms↗
PubMed1999

Thyroid nodular disease after radiotherapy to the neck for childhood Hodgkin's disease.

Patients who receive radiotherapy to the neck are at risk of developing thyroid dysfunction. This prospective study of patients whose treatment for Hodgkin's disease in childhood included radiotherapy to the neck aimed to investigate the incidence and natural history of thyroid dysfunction and the morphological changes of the gland demonstrated on ultrasound. Forty-seven patients were investigated by clinical examination, thyroid function tests and thyroid ultrasound. Only six patients had a clinically detectable abnormality, but 64% had abnormal thyroid function tests. All patients had an abnormal thyroid ultrasound scan and 42% had at least one focal abnormality. A significant association was found between the presence of a focal lesion on ultrasound and young age at radiotherapy, longer follow-up and the length of time that the thyroid-stimulating hormone (TSH) level had been elevated. During follow-up, 65% of patients not on thyroxine developed new focal abnormalities. The longest time interval between radiotherapy and an increase in TSH level was 94 months, and from radiotherapy to the appearance of a focal abnormality on thyroid ultrasound was over 18 years. Three patients were found to have a thyroid carcinoma. These findings indicate the importance of long-term follow-up for patients treated by neck irradiation for Hodgkin's disease in childhood.

Adolescent↗
PubMed1999

Delay in diagnosis of retinoblastoma: risk factors and treatment outcome.

BACKGROUND: Delay in diagnosis of retinoblastoma causes considerable parental distress; however, the primary healthcare professional (PHP) may have difficulty detecting the most common presenting symptom-leucocoria. Alternatively, the PHP may not appreciate that retinoblastoma is the pathology underlying more common ocular symptoms in infants and young children. METHOD: The parents of 100 recently diagnosed patients with retinoblastoma were interviewed to establish the extent of diagnostic delay, ascertain any associated risk factors, and to determine whether or not delay influenced treatment outcome. RESULTS: Although nearly 50% of patients were referred to an ophthalmologist within 1 week of first consulting a PHP, one quarter waited more than 8 weeks. There was a significantly increased risk of diagnostic delay in younger patients, those presenting with squint rather than leucocoria, and those first presenting to a health visitor rather than to a general practitioner. The risk of local tumour invasion was significantly increased by diagnostic delay. Treatment with primary enucleation was not increased by diagnostic delay. There were no deaths during the study period. CONCLUSION: Primary healthcare professionals require education about the importance of ocular symptoms, especially squint, in paediatric patients.

Age Factors↗
PubMed1999

Asymptomatic carotid arterial disease in young patients following neck radiation therapy for Hodgkin lymphoma.

PURPOSE: To determine the prevalence and severity of asymptomatic carotid arterial disease in young patients following neck radiation therapy for Hodgkin lymphoma and to compare the prevalence of carotid arterial disease following radiation therapy alone with that following radiation therapy and chemotherapy. MATERIALS AND METHODS: Forty-two survivors of childhood or early adult Hodgkin lymphoma aged 18-37 years who had undergone radiation therapy more than 5 years earlier underwent carotid arterial ultrasonography. Common carotid intima-media thickness was measured; carotid vessels were assessed for intima-media abnormalities. Results were compared with those from 33 control subjects. RESULTS: Patients had a significantly greater number of abnormal scans than did control subjects (11 [26%] vs one [3%]; P < .01). Ten patients (24%) had intima-media abnormalities that did not cause significant stenosis; one patient had diffuse bilateral intima-media thickening (mean, 1.99 mm) with greater than 70% stenosis of both common carotid arteries. Intima-media thickness was significantly greater in patients (0.51 mm) than in control subjects (0.43 mm; P < .005). The number of abnormalities in patients with radiation therapy plus chemotherapy (six [19%] of 31 patients) did not differ significantly from the number in patients with only radiation therapy (five [45%] of 11 patients; P = .12); there was no significant difference between median intima-media thicknesses (0.50 mm vs 0.51 mm, P > .2). CONCLUSION: Asymptomatic carotid arterial disease occurs frequently in young patients following neck radiation therapy for Hodgkin lymphoma. No difference in prevalence was shown between only radiation therapy and radiation therapy plus chemotherapy.

Adolescent↗
PubMed1998

Treatment of retinoblastoma vitreous base seeding.

OBJECTIVE: The purpose of the study is to describe results of a new treatment for retinoblastoma vitreous base seeding. DESIGN: The study design was a retrospective review of patients treated at an ocular oncology referral center. PARTICIPANTS: Five eyes of five patients with vitreous base seeding that occurred after previous external beam radiation therapy were treated between October 1987 and December 1994. INTERVENTION: A customized plaque made from iridium-192/platinum wire was placed to deliver 4000 cGy to the tumor apex along its entire length and systemic chemotherapy (consisting of carboplatin, vincristine, and etoposide) was given. MAIN OUTCOME MEASURES: Eye preservation and tumor control were measured. RESULTS: Vitreous base seeding was controlled completely and the eye preserved in four of the five treated eyes with an average follow-up of 26.2 months. CONCLUSIONS: The combination of a customized iridium-192 plaque and systemic chemotherapy is an effective means of treating vitreous base seeding of retinoblastoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

A limited role for VEEP (vincristine, etoposide, epirubicin, prednisolone) chemotherapy in childhood Hodgkin's disease.

The VEEP regimen (vincristine, etoposide, epirubicin, prednisolone), with or without involved field radiotherapy, has been shown to be an effective treatment in adult Hodgkin's disease. In an attempt to avoid the late sequelae of both alkylating agents and radiotherapy this regimen has been studied in a series of 54 children and young adults. Early analysis suggested that the relapse rate was higher with VEEP than with standard alkylating agent-based regimens. Sufficient follow-up has now been achieved to evaluate the likelihood of sustained remission following second-line treatment and therefore the overall long term survival with this treatment approach. The 5-year Overall Survival (OS) and 5-year Progression Free Survival (PFS) for patients with stage I-III disease was 93% and 82% respectively. However, the 5-year OS and PFS for stage IV patients was only 44% and 50%, respectively. Of 13 patients who were initial treatment failures on VEEP, 7 of whom had advanced disease, only 6 were salvaged with second-line therapy. 8 of 33 who attained a complete response (CR) relapsed and there were 2 relapses in those achieving a partial response (PR) (n = 8). All those relapsing from CR/PR were salvaged by second-line alkylating agent chemotherapy +/- radiotherapy, +/- high dose chemotherapy. In conclusion, patients with stage I-IIIA, non-bulky disease, the moderately high relapse rate did not adversely affect the overall high cure rate, although VEEP failures were subjected to a high total treatment burden. VEEP alone is inadequate in patients with stage IV disease, bulky mediastinal disease in/or those with B symptoms in whom there is a high primary failure rate and relatively poor results with second line therapy.

Adolescent↗
PubMed1997

Clinical efficacy of perceived 'CNS friendly' chemoradiotherapy for primary intracranial germ cell tumours.

The optimal treatment of intracranial germ cell tumours (IGCT) is controversial. The late sequelae of craniospinal radiotherapy and the high response rate to chemotherapy have led to new treatment strategies. The morbidity of combined modality therapy has tempered enthusiasm for aggressive chemoradiotherapy. In 1992, we described new lower morbidity chemotherapy and radiotherapy methods to be used in conjunction for IGCT treatment, employing three drugs (vincristine, carboplatin, etoposide) and a differential daily dose neuraxis radiotherapy technique (to replace a shrinking field technique). The chemoradiotherapy had the potential for a graded intensity reduction when high cure rates were maintained. Of 13 IGCT patients treated on this protocol, 8/8 germinomatous GCT and 3/5 non-germinomatous GCTs are in continuing remission. These observations have implications for other CNS tumour treatments in (young) patients, in whom late CNS toxicity (particularly neuropsychological) is a problem.

Adolescent↗
PubMed1997

The RB1 gene mutation in a child with ectopic intracranial retinoblastoma.

The RB1 gene mutation was investigated in a child with ectopic intracranial retinoblastoma using DNA obtained from both the pineal and retinal tumours of the patient. A nonsense mutation in exon 17 (codon 556) of the RB1 gene was found to be present homozygously in both the retinal and the pineal tumours. The same mutation was present heterozygously in the DNA from the constitutional cells of the patient, proving it to be of germline origin. The initial mutation was shown to have occurred in the paternally derived RB1 allele. The mutation is in an area of the gene that encodes the protein-binding region known as the 'pocket' region and has been detected in other cases of retinoblastoma.

Brain Neoplasms↗
PubMed1996

Results of combined chemotherapy and radiotherapy for advanced intraocular retinoblastoma.

OBJECTIVE: To determine the visual anatomical results and survival after combined chemotherapy and whole eye radiotherapy for patients with bilateral Reese-Ellsworth group V retinoblastoma. SETTING: A national referral center for retinoblastoma. PATIENTS: Fourteen patients with bilateral Reese-Ellsworth group V retinoblastoma seen between March 1, 1989, and April 30, 1995, were treated. INTERVENTIONS: Patients were treated with chemotherapy (using carboplatin, etoposide, and vincristine) and whole eye radiotherapy (40-44 Gy in 20-22 equivalent fractions). A medical record review was performed to determine outcomes. MAIN OUTCOME MEASURES: Survival, eye preservation rate, and visual acuity. RESULTS: Two patients died, 1 from a primitive neuroectodermal tumor and the other from the meningeal spread of retinoblastoma. Four eyes were enucleated primarily because of severe disease at presentation. Of the remaining 20 eyes, 6 required enucleation. The disease recurred in 4 of those patients, and neovascular glaucoma developed in 2 patients. Of the 12 surviving children, 5 have a visual acuity better than l/60 in at least 1 eye. CONCLUSION: Although most of the treated group V eyes could be salvaged with chemotherapy plus radiotherapy, the resultant visual acuity was often poor.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Sonographic abnormalities of the thyroid gland following radiotherapy in survivors of childhood Hodgkin's disease.

The aims of this study were as follows. (1) To demonstrate the spectrum, frequency and changes on follow-up of sonographic abnormalities in the thyroid gland of survivors of Hodgkin's disease who had received radiotherapy to the neck in childhood. (2) To compare the sonographic findings with clinical examination and radionuclide imaging. (3) To investigate the association between the presence or absence of focal sonographic abnormalities with age at radiotherapy, the interval from radiotherapy, the presence of a raised thyroid stimulating hormone (TSH) and the length of time the TSH had been raised. 46 patients were scanned prospectively and rescanned at 6-18 months. The mean age at first sonography was 22.7 years, the median age at radiotherapy was 12.5 years, and the median interval post-radiation was 10.3 years. Sonographic abnormalities were seen in all 46 patients. 45 had diffuse atrophy and 30 had focal sonographic abnormalities. 18 patients developed new focal sonographic abnormalities on follow-up. Focal sonographic abnormalities were more commonly associated with longer duration of a raised TSH. Two patients had thyroid carcinoma. Sonographic abnormalities of the thyroid are common in patients following neck radiotherapy in childhood. Focal abnormalities are usually associated with a longer duration of raised TSH.

Adolescent↗
PubMed1996

Combining cyclosporin with chemotherapy controls intraocular retinoblastoma without requiring radiation.

Chemotherapy without radiation has not controlled most intraocular retinoblastoma, perhaps because of the common high expression of multidrug resistance P-glycoprotein that we found in retinoblastoma. Cyclosporin blocks P-glycoprotein-induced efflux of vincristine and teniposide in vitro, and possibly modulates responses to carboplatin. To avoid eye irradiation in bilateral retinoblastoma patients with RB1 germline mutations, which incurs a high second malignancy rate, we added cyclosporin A to a vincristine-teniposide-carboplatin protocol and consolidated chemotherapy responses with focal therapy. We scored patients requiring irradiation, enucleation, or focal ablation of central vision as failures. In 21 study patients, the overall relapse-free rate at a median follow-up of 3.3 years was 76%, with a rate of 92% for newly diagnosed and 50% for previously treated, relapsed retinoblastoma. Our results for the most unfavorable tumors with vitreous seeds (86% at 3.5 years) are better than published success rates of irradiation for similar tumors, or irradiation with the same chemotherapy without cyclosporin (45% at 2. 6 years). These results also exceeded our historic success rate with similar chemotherapy without cyclosporin, focal therapy, and/or radiation in 19 equivalently poor-risk patients (relapse-free rate 37% at a median follow-up of 5.6 years, P = 0.032), 16 of whom were previously untreated (relapse-free rate also 37%, P = 0.012). A better outcome occurred with higher cyclosporin blood levels and projected tissue exposure. Cyclosporin did not enhance the usual chemotoxicity. This clinical study suggests that cyclosporin improves the long-term response of retinoblastoma to chemotherapy, possibly by more than one mechanism.

Antineoplastic Agents↗
PubMed1995

Retinoblastoma in association with the chromosome breakage syndromes Fanconi's anaemia and Bloom's syndrome: clinical and cytogenetic findings.

Two children presenting with sporadic unilateral retinoblastoma and exhibiting a high degree of chromosome breakage were noted to have unusual facies, microcephaly and abnormal skin pigmentation. In the first child the pattern of both spontaneous and mitomycin-C-induced chromosome breakage was characteristic of Fanconi's anaemia although the degree of breakage was extreme. She also exhibited a striking increase in X-ray-induced chromosomal damage in G0 lymphocytes as measured by dicentric formation and increase in chromatid-type aberrations. She had a number of typical clinical features, including cafe-au-lait patches and abnormalities involving the kidney; however, she demonstrated neither the hypoplasia of radius and thumb nor the typical aplastic phase of this disorder. At age 22 months the child became anaemic with trilineage myelodysplasia, which was rapidly followed by the development of acute myeloblastic leukaemia. The early onset (at age 4 months) of retinoblastoma may have been associated with the underlying genomic instability. The second child exhibited a pattern of chromosome breakage characteristic of Bloom's syndrome, in addition to a moderate increase in damage induced by mytomycin-C. She had the typical stunted growth and malar hypoplasia of Bloom's syndrome although she did not demonstrate the frequently described erythematous 'butterfly rash' Although patients with Fanconi's anaemia and Bloom's syndrome are recognised to be at an increased risk of cancer, retinoblastoma has not previously been described in patients with either condition. We suggest that underlying recessive chromosome breakage syndromes may be underdiagnosed in paediatric cancer patients, with important implications for prognosis and genetic counselling.

Bloom Syndrome↗
PubMed1995

External beam radiotherapy for retinoblastoma: I. Whole eye technique.

A retrospective analysis has been performed of the results of external beam radiotherapy for retinoblastoma using a whole eye technique. Local tumour control has been assessed in a consecutive series of 175 eyes in 142 children all of whom received external beam radiotherapy as the primary treatment for retinoblastoma. Follow up ranged from 2 to 17 years (median 9 years). Tumour control rates have been analysed with respect to the Reese Ellsworth classification and the series includes eyes in groups I to V. Focal salvage therapy was given for persistent, recurrent, or new tumours after radiotherapy. Following whole eye radiotherapy alone, the overall ocular cure rate was 57%, though with salvage therapy 80% of eyes could be preserved.

Cataract↗
PubMed1995

External beam radiotherapy for retinoblastoma: II. Lens sparing technique.

A retrospective analysis is presented of the results of external beam radiotherapy for retinoblastoma utilising an accurate lens sparing technique. Local tumour control has been assessed in a consecutive series of 67 eyes in 53 children all of whom received external beam radiotherapy as the primary treatment of retinoblastoma. Follow up ranged from 12 to 82 months (median 35 months) with 76% of the children followed for more than 2 years. Tumour control rates have been analysed with respect to the Reese-Ellsworth classification. The role of adjuvant and salvage focal therapy is emphasised. Following lens sparing radiotherapy with prior adjuvant treatment of anterior tumours, where appropriate, the overall ocular cure rate was 72%. With salvage therapy of persistent, recurrent, or new tumours, 93% of eyes could be preserved in this series which includes mainly eyes classified in Reese-Ellsworth groups I-III. These results compare favourably with those of whole eye external beam radiotherapy for comparable tumours, and with those of lens and anterior segment sparing using other techniques. They were achieved without the ocular morbidity associated with whole eye external beam radiotherapy.

Child↗
PubMed1994

Late deaths and survival after childhood cancer: implications for cure.

OBJECTIVES: To investigate causes of death and survival in subjects who had survived at least five years after diagnosis of childhood cancer; to compare observed mortality with that expected in the general population; and to compare results with a corresponding cohort diagnosed earlier. DESIGN: Retrospective cohort study. SETTING: Population based National Register of Childhood Tumours. SUBJECTS: 9080 five year survivors of childhood cancer diagnosed in Britain during 1971-85, of whom 793 had died. Comparison with corresponding cohort diagnosed during 1940-70. MAIN OUTCOME MEASURES: Cause of death established from all available sources of information (including hospital and general practitioner records and postmortem reports) and underlying cause of death coded on death certificate. RESULTS: Of the 781 deaths for which sufficient information was available, death was attributed to recurrent tumour in 578 (74%) cases, treatment related effect in 121 (15%), second primary tumour in 52 (7%), and other causes in 30 (4%). Comparison of observed mortality with that expected in the general population indicated a fourfold excess of deaths from non-neoplastic causes. The risk of dying of recurrent tumour in the next 10 years after surviving five years from diagnosis during 1940-70 and 1971-85 fell from 12% to 8%. The risk of dying from a treatment related effect increased slightly from 1% to 2%. CONCLUSION: Improvements in five year survival after childhood cancer have been accompanied by a reduction in risk of dying from recurrent tumour during the subsequent 10 years and by a slight increase in risk of dying from treatment related effects. The results provide information relevant to decisions concerning balance between effective treatments and their potentially harmful effects.

Adolescent↗