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Biomedical subjects

M J O'Doherty

Publications and source records attributed to M J O'Doherty.

At least 19 recordsLinked to original sources

The role of sentinel lymph node biopsy in patients with differentiated thyroid carcinoma.

AIM: To evaluate the "state of art" of clinical role of sentinel lymph node (SLN) biopsy procedure in patients affected by differentiated thyroid carcinoma. METHODS: All papers cited on PubMed/MEDLINE until June 2005, published in English, and referred to the key words "sentinel lymph node biopsy" AND "thyroid carcinoma" OR "thyroid cancer" were reviewed for the purpose of the present study. RESULTS: The first method used for SLN biopsy in thyroid carcinoma patients was the vital blue dye technique. This technique had some disadvantages as: (a) risk of disruption of the lymphatic channels deriving from the thyroid cancer; (b) difficulty in disclosing SLN lying outside the central compartment; (c) parathyroid glands can take up blue dye and, thus, can be misinterpreted as lymph nodes. Some of the above cited disadvantages were overcome by using the lymphoscintigraphy and intraoperative gamma probe technique. A combination of the blue dye and gamma probe technique has also been proposed with synergic results. CONCLUSION: The reported advantages of the SLN biopsy in small differentiated thyroid carcinoma patients can be resumed as follows: (a) better selection of patients who would benefit from compartment oriented nodal dissection; (b) more accurate lymph node staging; (c) better selection of patients who can require (131)I treatment after surgery (SLN positive for metastasis); (d) better identification of SLN located out of the central compartment.

Coloring Agents↗

FDG-PET after two to three cycles of chemotherapy predicts progression-free and overall survival in high-grade non-Hodgkin lymphoma.

BACKGROUND: Less than 50% of all high-grade non-Hodgkin lymphoma (NHL) patients experience lasting disease-free survival. Risk-adapted treatment strategies require better tools for prediction of outcome. This investigation aimed to assess the value of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) after two to three cycles of chemotherapy for prediction of progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: One hundred and twenty-one patients with high-grade NHL underwent FDG-PET. The therapy response on FDG-PET was correlated to PFS and OS using Kaplan-Meier survival analysis. Cox regression analyses were employed to test for independence of known pretreatment prognostic factors. RESULTS: Fifty FDG-PET scans were negative, 19 scans showed minimal residual uptake (MRU), and 52 scans were positive. The estimated 5 year PFS was 88.8% for the PET-negative group, 59.3% for the MRU group, and 16.2% for the PET-positive group. Kaplan-Meier analyses showed strong associations between FDG-PET results and PFS (P <0.0001) and OS (P <0.01). Early interim FDG-PET was independent of the other prognostic factors. CONCLUSIONS: Early interim FDG-PET is an accurate and independent predictor of PFS and OS. An early assessment of chemotherapy response with FDG-PET could provide the basis for selection of patients for alternative therapeutic strategies.

Adult↗

Use of imaging in the management of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an increasingly prevalent tumour. The death rate associated with MPM is predicted to peak in the next 10 years, although radiologists and clinicians will be encountering cases for the next few decades. Contrast-enhanced CT is an established technique for evaluating suspected malignant pleural disease, but MPM can be reliably diagnosed only by histological sampling. However, even with adequate sampling and the use of immunocytochemistry, histological diagnosis is known to be difficult; definitive diagnosis may involve a combination of clinical presentation, radiological and histological appearances. Percutaneous biopsy is a promising technique for sampling the pleura. In view of its pattern of growth, MPM is a challenging disease to image by any method, and it behaves quite differently from lung cancer. This review aims to highlight the practical aspects of assessing malignant pleural mesothelioma.

Biopsy, Needle↗

The impact of PET scanning on management of paediatric oncology patients.

PURPOSE: Limited information is available on the use of positron emission tomography (PET) in paediatric oncology. The aim of this study was to review the impact of PET on the management of paediatric patients scanned over a 10-year period. METHODS: One hundred and sixty-five consecutive oncology patients aged 11 months to 17 years were included. Two hundred and thirty-seven scans were performed. Diagnoses included lymphoma (60 patients), central nervous system (CNS) tumour (59), sarcoma (19), plexiform neurofibroma with suspected malignant change (13) and other tumours (14). A questionnaire was sent to the referring clinician to determine whether the PET scan had altered management and whether overall the PET scan was thought to be helpful. RESULTS: One hundred and eighty-nine (80%) questionnaires for 126 patients were returned (63 relating to lymphoma, 62 to CNS tumours, 30 to sarcoma, 16 to plexiform neurofibroma and 18 to other tumours). PET changed disease management in 46 (24%) cases and was helpful in 141 (75%) cases. PET findings were verified by histology, clinical follow-up or other investigations in 141 cases (75%). The returned questionnaires indicated that PET had led to a management change in 20 (32%) lymphoma cases, nine (15%) CNS tumours, four (13%) sarcomas, nine (56%) plexiform neurofibromas and four (22%) cases of other tumours. PET was thought to be helpful in 47 (75%) lymphoma cases, 48 (77%) CNS tumours, 24 (80%) sarcomas, 11 (69%) neurofibromas and 11 (61%) cases of other tumours. PET findings were verified in 44 (70%) lymphoma cases, 53 (85%) CNS tumours, 21 (70%) sarcomas, 12 (75%) neurofibromas and 11 (61%) other tumour cases. CONCLUSION: PET imaging of children with cancer is accurate and practical. PET alters management and is deemed helpful (with or without management change) in a significant number of patients, and the results are comparable with the figures published for the adult oncology population.

Adolescent↗

Comparison of sestamibi, thallium, echocardiography and PET for the detection of hibernating myocardium.

The detection of hibernating myocardium is important because revascularisation results in improved function and prognosis in patients with hibernation but not in those with non-viable myocardium. The primary aim of this study was to compare the diagnostic accuracy of four techniques with respect to hibernation in the same study population with 6-12 months of follow-up. Twenty-five males underwent rest-stress sestamibi and delayed (>18 h) thallium scintigraphy, high-dose dobutamine stress echocardiography and nitrogen-13 ammonia/fluorine-18 fluorodeoxyglucose (NH(3)/FDG) positron emission tomography (PET). The pre-operative ejection fraction was 36.2% (+/-7.3%). Follow-up was 8.1 (+/-2.8) months. Using postoperative improvement in wall motion on echocardiography as the gold standard, 6/34 dysfunctional vascular territories were hibernating. The mean uptake of all tracers was significantly higher in hibernating than in non-viable territories ( P<0.05). Normal perfusion or mismatch on PET (FDG>NH(3) uptake) and the pattern of response to dobutamine on echocardiography were also predictive of recovery ( P<0.001 and P=0.02 respectively). Univariate logistic regression identified sestamibi, ammonia and FDG as independent predictors of hibernation. FDG-PET was, however, the only independent predictor using multivariate analysis. The nuclear techniques had high negative predictive values (NPV) of >or=95% but lower positive predictive values (PPV) of 45%-75% as compared with echocardiography, which had an NPV of 87% and a PPV of 100%. PET was the most powerful predictor of hibernation although the combination of a technique with a high PPV (echocardiography) and a high NPV (PET or sestamibi) may represent the optimal clinical choice.

Adult↗

Parathyroid imaging: preoperative localization.

The role of parathyroid localization is as a preoperative localization procedure. This is becoming increasingly important with the trend towards limited surgical approaches. Although there are a variety of methods used to identify the site of parathyroid adenomas, 99mTc sestamibi is at present the agent of choice. Debate continues as to whether imaging is best performed using a subtraction technique or delayed imaging/dual phase technique. There is also discussion as to which collimator to use and whether surgery should be directed by the combined use of ultrasound and radionuclide imaging. These areas are discussed within this review. The technique of choice is a subtraction 99mTc sestamibi scan of the neck using a pinhole collimator. This should be combined with a mediastinal view using a parallel hole collimator. There is sufficient evidence to suggest that combining subtraction imaging with high resolution ultrasound will improve the sensitivity and give greater information to the surgeon.

Humans↗

99mTc-SnF2 colloid "LLK": particle size, morphology and leucocyte labelling behaviour.

99mTc-SnF2 colloid (Radpharm LLK) leucocyte labelling agent is used in whole blood, exploiting phagocytosis. The objectives of this work were to optimize leucocyte labelling in leucocyte-enriched plasma, and to investigate: (i) the effect of temperature and other factors on labelling efficiency; (ii) the selectivity for different leucocyte types; (iii) the viability of the labelled cells and efflux of the radiolabel; and (iv) the physical characteristics of the colloid. Density gradient centrifugation was used to investigate the labelling efficiency, cell selectivity and efflux, Trypan blue to study the viability, and laser scattering, electron microscopy and membrane filtration to investigate particle size and morphology. Particles appeared as loose, coiled, chain-like aggregates of much smaller particles (<0.05 microm). The aggregate diameter ranged from <0.1 to >5 microm and increased with time. The distribution of radioactivity amongst the particle sizes varied widely. The labelling efficiency in leucocyte-rich plasma was enhanced at 37 degrees C compared to room temperature, and by centrifuging during labelling. The selectivity for different leucocyte types varied markedly between batches and blood samples, in some cases showing preference for mononuclear cells and in others for granulocytes. Viability was excellent and comparable with 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO)-labelled cells. A significant fraction of radiolabel, comparable to that observed with 99mTc-HMPAO, was lost from leucocytes during incubation in vitro over 4 h. Thus, 99mTc-SnF2 is a convenient, efficient labelling agent for leucocytes, but shows variable cell selectivity which may be linked to particle size variability, and there is significant efflux of radioactivity from labelled cells.

Cell Survival↗

Can FDG PET be used to successfully direct preoperative biopsy of soft tissue tumours?

Magnetic resonance imaging (MRI) has been the most useful tool in the anatomical definition of soft tissue sarcoma, although there remains the problem of defining the lesions as benign or malignant. The management of such lesions requires biopsy prior to surgical resection. If the most malignant area could be defined more accurately, then this area could be targeted for biopsy. Fluorodeoxyglucose positron emission tomography (FDG PET) has been found to be useful in identifying malignancy and variations in grade in soft tissue masses. The aim of this study was to assess the use of FDG PET scanning with or without co-registered MRI to indicate the most appropriate biopsy site. Twenty consecutive patients presented with soft tissue masses with clinical signs of malignancy. All patients underwent MRI and FDG PET scanning and the two images were co-registered. A biopsy site that was the most likely to be malignant was defined on the PET scan. All patients underwent an initial biopsy and then complete surgical resection of the mass. The histological results from the mass were compared with those from the biopsy specimen obtained from the site suggested by the PET scan. In malignant masses the biopsy site suggested by the FDG PET scan was found to be representative of the most malignant site on the whole mass histology. Benign lesions had low or no FDG uptake. In no case did the co-registered image add significantly to the appropriate biopsy site. FDG PET can be used to appropriately direct biopsy in soft tissue sarcoma and potentially may lead to computed tomography/MRI directed outpatient biopsy prior to definitive treatment.

Adult↗

FDG-PET as a "metabolic biopsy" tool in non-lung lesions with indeterminate biopsy.

The differentiation of benign versus malignant disease in a lesion identified on conventional imaging is a commonly encountered problem. Attempted biopsy is often unsuccessful or falsely reassuring and may lead to the patient being sent for more invasive and potentially morbid investigations. Having previously identified the value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in this circumstance in patients with lung lesions, our current aim was to investigate the role of FDG-PET in helping to identify more accurately those patients with malignant lesions outside the lung. FDG-PET scanning was performed in 50 patients; most had undergone unsuccessful biopsy of a lesion outside the lung, while in a smaller number no attempt at biopsy had been made as it had been considered too dangerous. Follow-up was by histology or, if this was unavailable, by clinical progress to death or a minimum of 12 months post scan. Visual and quantitative analysis was performed. On visual analysis, the positive and negative predictive values were 89% and 100%, respectively. On quantitative (SUV>2.5) analysis, positive and negative predictive values were 93% and 86%, respectively. A negative FDG-PET study in these circumstances virtually excludes malignancy and allows the patient to be reassured. A positive scan encourages the clinician to pursue further biopsy to confirm a histological diagnosis. FDG-PET therefore assists in deciding which patients need to undergo further investigation.

Adult↗

Positron emission tomography in the management of lymphomas.

Positron emission tomography is a functional imaging modality that capitalizes on biochemical changes within tumour cells to localize these changes within the body. As a functional imaging tool, unlike an anatomical imaging tool such as CT, it does not require enlargement of lymph nodes affected by disease but does require sufficient numbers of tumour cells to be present with altered biochemical function to visualize these disease sites. These changes are most commonly monitored using a glucose mimic fluorodeoxyglucose which is not only taken up into tumour cells but is trapped within these cells owing to alterations of the hexokinase and dephosphorylase enzymes. This review examines the current role of FDG PET imaging in patients with Hodgkins and Non-Hodgkins lymphoma and also speculates on future roles for this imaging modality.

Fluorodeoxyglucose F18↗

Imaging of abdominal infection using 99m Tc stannous fluoride colloid labelled leukocytes.

Radiolabelling of leukocytes using labelled phagocytosed technetium-99m (99mTc) colloidal radiopharmaceuticals has been reported as a method for imaging infection. This in vivo study compares the use of leukocytes labelled using 99mTc stannous fluoride colloid with leukocytes labelled using indium-111 (111In) oxinate. A total of 26 patients (10 male, 16 female; mean age 52 years, range 23-88 years) referred for the investigation of possible infection were studied using both leukocyte labelling methods simultaneously. Images were acquired 4h and 24h after re-injection of the labelled cells. The images were evaluated qualitatively by two nuclear medicine physicians. The results show a high degree of concordance between the techniques: 11 of the 28 images showed a focus of leukocyte accumulation with both techniques at 24h, and 13 out of 28 showed a normal appearance at 24h with both methods. In four cases the results were discordant; the 99mTc stannous fluoride colloid labelled leukocytes gave a false positive appearance at 24h in three patients and a false negative in one. In conclusion, colloid labelling of leukocytes offers a sensitive method for the detection of infective foci coupled with the high resolution imaging offered by 99mTc. It has the advantage over other in vitro labelling methods of being a simpler, non-labour-intensive procedure employing whole blood, and its use should be considered by departments that have limited facilities for in vitro leukocyte labelling.

Abdominal Abscess↗

Effect of corrections for blood glucose and body size on [18F]FDG PET standardised uptake values in lung cancer.

Standardised uptake values (SUVs) are commonly used as a semi-quantitative index of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) tracer uptake in positron emission tomography (PET). Studies have shown that SUVs may depend on body size and blood glucose concentration and corrections for these effects have been proposed in the literature. This retrospective study investigated the effect of the proposed corrections on SUVs from a group of 154 patients with lung cancer who had scans on a dedicated PET scanner. A total of 252 SUVs were requested as an aid to staging during consideration for surgical resection. SUVs were calculated normalised to body weight (SUVw), lean body mass (SUV(LBM)) and body surface area (SUV(BSA)). The following correlations were examined: SUV with height, weight and body surface area for the different body size normalisations; SUVw and SUVw x blood glucose (SUV(BG)) with blood glucose; SUVw with scan time post injection; and SUVw with apparent lesion diameter. Significant correlations were only observed between: SUV(LBM) and height (P=0.007); SUVw and scan time (P=0.007); SUVw and lesion diameter (P=0.0005); and SUV(BG) and blood glucose (P<0.00001). The correlation between SUV(LBM) and height suggests that lean body mass as a function of height alone should not be used to normalise SUVs; however, the lean body mass calculated from a height and weight nomogram did not show this effect. The strong correlation between SUV(BG) and blood glucose concentration suggests that for non-diabetic fasted patients, lung tumour SUVs should not be adjusted for blood glucose.

Adult↗

FDG-PET as a "metabolic biopsy" tool in thoracic lesions with indeterminate biopsy.

A common problem encountered in clinical medicine is the classification of a lung lesion (nodule/opacity) on conventional imaging. Often attempts at biopsy are unsuccessful or are falsely reassuring, and the decision to send the patient for more invasive and potentially morbid procedures can be difficult. Our aim was to investigate the role of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in helping to identify more accurately those patients with malignant lesions. Sixty-three patients underwent FDG-PET scans following unsuccessful biopsy of a lung lesion or, in a lesser number of cases, when an attempt at biopsy was considered too dangerous. Follow-up was by histology or, if this was unavailable, by clinical progress to death or a minimum of 18 months post scan. Visual and quantitative analysis was performed. On visual analysis, positive and negative predictive values were 90% and 100%, respectively. On quantitative (SUV>2.5) analysis, positive and negative predictive values were 90% and 85%, respectively. We interpret these results as showing that the use of FDG-PET scans in patients in this circumstance is non-invasive and highly sensitive in diagnosing malignancy. The high positive predictive value suggests that those with a positive scan must undergo further investigation, while the 100% negative predictive value means those with no FDG uptake can safely be spared further invasive investigations

Adolescent↗

In vivo evaluation of 111In-DTPA-N-TIMP-2 in Kaposi sarcoma associated with HIV infection.

Matrix metalloproteinases are the major agents responsible for the degradation of extracellular matrix and are produced at high levels by transformed and tumour cells, where they participate in the metastatic process by allowing local invasion. They are also more active at sites of new normal growth and angiogenesis. In the early stages of Kaposi sarcoma (KS), in vitro studies have demonstrated that vascular invasion can be inhibited by inhibitors of matrix metalloproteinases. Imaging of visceral and cutaneous KS presents a problem and therefore the potential use of a labelled inhibitor of metalloproteinases, N-TIMP-2, with indium-111 was thought to present a possible imaging tool. The biokinetics, dosimetry and potential for imaging with 111In-DTPA-N-TIMP-2 were assessed in five patients with HIV infection and KS. Between 103.1 and 108.0 MBq of this agent was injected into each patient, and the dynamic uptake over the kidneys was assessed, whole body scans were performed and blood samples were obtained. The clearance from the blood was rapid, with a first component half-time of 16.6+/-3.4 min and a second component half-time of 9.68+/-2.68 h. Two out of five patients experienced minor shivering but one of these patients was generally unwell before the study. The last three patients had no such problems. The tracer distributed predominantly to the kidneys and did not localise in other tissues. No KS lesions were clearly identified. 111In-DTPA-N-TIMP-2 can be successfully prepared and administered to patients safely, with a biodistribution and dosimetry which would allow its use as an imaging tracer. It is unlikely to be of use for imaging KS, but may have a role in other tumours that produce matrix metalloproteinases.

Adult↗