Search PubMed⌕ Search

Biomedical subjects

Leigh Delbridge

Publications and source records attributed to Leigh Delbridge.

At least 19 recordsLinked to original sources
PubMed2006

Routine ipsilateral level VI lymphadenectomy reduces postoperative thyroglobulin levels in papillary thyroid cancer.

BACKGROUND: Lymphadenectomy in clinically node-negative papillary thyroid cancer (PTC) is controversial. The aim of this study is to determine whether routine ipsilateral level VI lymphadenectomy (LNDVI) has advantages over total thyroidectomy (TT) alone. METHODS: A retrospective cohort study was performed. Patients undergoing surgery for clinically node-negative PTC >1 cm were included. Group A had TT and LNDVI. Group B had TT alone. The number of radioiodine treatments and postablative stimulated serum thyroglobulin (TG) levels were compared. RESULTS: From 1995 to 2005, 447 patients with clinically node-negative PTC underwent surgery. Group A (n = 56) had TT and LNDVI. Group B (n = 391) had TT alone. Tumor size was equivalent (group A, 20 mm; group B, 23 mm; P = .14) as were MACIS (metastasis, age, completeness of resection, invasion, and size) scores (group A, 4.70; confidence interval, 4.23-5.17; group B, 4.73; confidence interval, 4.4-5.05). Serum postablative TG levels were lower in group A (0.4 microg/L) compared with group B (9.3 microg/L), P = .02. More patients had undetectable TG levels in group A (72%) than in group B (43%) (P < .001). Long-term complications rates were the same. CONCLUSIONS: In PTC the addition of routine LNDVI results in lower postablation levels of TG and higher rates of athyroglobulinemia when compared with TT alone.

Adult↗
PubMed2006

Intraoperative parathyroid hormone measurement during minimally invasive parathyroidectomy: does it "value-add" to decision-making?

BACKGROUND: Routine use of intraoperative parathyroid hormone levels (IOPTH) during minimally invasive parathyroidectomy (MIP) has been challenged simply because the test works best when needed least, ie, once a solitary adenoma has been resected, and is less accurate with multiple gland disease. It has also been shown not to be cost-effective. The aim of this study was to determine if IOPTH "value-added" to decision-making during MIP. STUDY DESIGN: The study group comprised 100 consecutive patients with sporadic hyperparathyroidism and an unequivocally positive sestamibi scan who were undergoing MIP in our unit from June 2004 until October 2005, from whom blood was collected for parathyroid hormone measurement preoperatively, preexcision, and at 10 and 30 minutes postremoval. No action was taken on the results of the test. RESULTS: Ninety-eight patients were cured by MIP alone. Two patients had persistent hyperparathyroidism, one of whom was cured with subsequent open reexploration and removal of a second adenoma, and the other remains hypercalcemic despite additional open neck exploration. IOPTH in both patients failed to fall in retrospect, only the first would have been cured by conversion at the time of operation. The value-added accuracy of IOPTH was really only 1%. In an additional nine patients, IOPTH at 10 minutes had failed to fall by > 50% from the highest level, those patients (9%) would have been subjected to an unnecessary conversion on the basis of a false-negative result. CONCLUSIONS: IOPTH does not substantially value-add to decision-making during MIP. Most patients will be cured with appropriate selection for MIP based on preoperative localization studies.

Adult↗
PubMed2006

Solitary thyroid nodule: current management.

Clinically, solitary thyroid nodules are common, being present in up to 50% of the elderly population. The majority are benign with thyroid cancer representing an uncommon clinical problem. Investigation should include careful history and examination and thyroid function tests. Toxic or autonomous nodules are rarely malignant and require radionuclide scan for assessment. If euthyroid, then fine needle biopsy provides direct specific information about the cytology of the nodule from which the histology can be inferred. Thyroid 'incidentalomas' are a common management problem. Non-palpable nodules greater than 1.0 to 1.5 cm represent an absolute indication to perform an ultrasound-guided fine needle biopsy. An atypical fine needle biopsy mandates formal diagnostic excision. Because it is not possible to distinguish a follicular carcinoma from a follicular adenoma on cytological grounds alone, this category must simply be interpreted as indicating a follicular tumour and up to 20% will be malignant. Hemithyroidectomy via a 'collar' incision, with submission of the specimen to formal pathological examination, remains the standard of care, with completion total thyroidectomy for cancers other than low risk papillary cancer and 'minimally invasive' follicular cancer without vascular invasion. The issue of whether follicular adenomas can potentially develop into follicular carcinomas has yet to be satisfactorily resolved. The major challenge in the management of the solitary thyroid nodule remains the assessment as to which nodules require surgical excision and which can be followed conservatively.

Biopsy, Fine-Needle↗
PubMed2005

Intrathyroid dermoid cyst presenting as a unilateral "Cold" nodule.

A dermoid cyst arising in the left lobe of the thyroid gland in a 5-year-old boy was managed with a left hemi-thyroidectomy. While congenital lesions feature frequently in the differential diagnosis of childhood neck masses, dermoid cysts presenting as a unilateral neck mass are rare. When found within the thyroid, their pathogenesis may be explained by a disruption of normal thyroid development. Excision appears the treatment of choice.

Child, Preschool↗
PubMed2005

Surgery for hyperparathyroidism: does morphology or function matter most?

BACKGROUND: With minimally invasive parathyroidectomy (MIP) not all enlarged parathyroid glands are necessarily removed, and intraoperative measurement of parathyroid hormone levels (IO-PTH) does not necessarily predict multiple enlarged glands. The aim of this study was to compare morphology with function, using Ca(2+)-regulated PTH secretion. METHODS: PTH secretion was determined by perifusion: (1) cells from 12 normal parathyroids were compared with 14 parathyroid adenomas; (2) functional characteristics (PTH secretion, sestamibi uptake, IO-PTH decrease) were correlated with morphologic characteristics; (3) PTH secretion as a predictor of IO-PTH decrease was determined in 7 patients with 2 enlarged parathyroids. RESULTS: (1) There were significant differences between normal and pathological parathyroid cells consistent with reduced sensitivity to Ca(2+). Maximum secretion rates for normal and adenomatous cells were, respectively, 3.9 +/- 0.4 fg min(-1) cell(-1) and 2.0 +/- 0.4 fg min(-1) cell(-1) (P = .002) and minimum secretion rates, 0.7 +/- 0.1 fg min(-1) cell(-1) and 0.4 +/- 0.1 fg min(-1) cell(-1) (P = .008). However, the IC(50) value for Ca(2+) was elevated in adenomatous cells indicating an apparent loss of extracellular Ca(2+) sensitivity being 1.1 +/- 0.02 mmol/L for normal and 1.2 +/- 0.02 mmol/L for adenomatous cells (P = .02). (2) There was no overall correlation between PTH secretion and gland morphology. (3) In 5 of 7 cases, PTH secretion correctly predicted the decrease in IO-PTH. CONCLUSION: Parathyroid adenomas generally exhibit abnormal PTH secretory function; however, enlarged parathyroid glands that do not contribute to the biochemical changes of hyperparathyroidism do exist, and, in these cases, cellular secretory function is a useful predictor of IO-PTH dynamics.

Adenoma↗
PubMed2005

How effective is email communication for patients requiring elective surgery?

BACKGROUND: Patients increasingly use the Internet for communication as well as to obtain information, but there are few published reports on either the utilization or effectiveness of email as a means of communication between patient and surgeon. The aim of the present study is to examine the effectiveness of email communication by patients prior to undergoing elective surgery. METHODS: This is a retrospective cohort study of 306 patients undergoing thyroid or parathyroid surgery at a tertiary referral centre who had been provided with an information sheet promoting email communication compared to 352 patients in a control group who had not been provided with the same information. RESULTS: In the study group 50 of 306 patients (16%) utilized email communication. There was a statistically significant difference (P = 0.0004) in the age distribution between those who did (mean: 46.2, 95% confidence interval (CI): 42.0-50.4) and those who did not (mean: 54.6, 95%CI: 52.7-56.4) utilize emails, with the email users representing a younger population. In the control group, only 10 of 352 (3%) used email, a significantly lower percentage (P = 0.0001) than in the study group. A total of 101 emails were sent by 50 patients in the study group. Of these, the majority did so only once (n = 28-56%), with one patient sending seven separate emails. Most emails sent focused on only one issue, but some patients raised multiple issues with the most being seven issues in a single email. CONCLUSIONS: Despite concerns about potential medicolegal issues and other disadvantages, routine email communication between physician and patient provides an effective means of communication for patients undergoing elective surgery.

Communication↗
PubMed2004

L-amino acids regulate parathyroid hormone secretion.

Parathyroid hormone (PTH) secretion is acutely regulated by the extracellular Ca(2+)-sensing receptor (CaR). Thus, Ca(2+) ions, and to a lesser extent Mg(2+) ions, have been viewed as the principal physiological regulators of PTH secretion. Herein we show that in physiological concentrations, l-amino acids acutely and reversibly activated the extracellular Ca(2+)-sensing receptor in normal human parathyroid cells and inhibited parathyroid hormone secretion. Individual l-amino acids, especially of the aromatic and aliphatic classes, as well as plasma-like amino acid mixtures, stereoselectively mobilized Ca(2+) ions in normal human parathyroid cells in the presence but not the absence of the CaR agonists, extracellular Ca(2+) (Ca(2+)(o)), or spermine. The order of potency was l-Trp = l-Phe > l-His > l-Ala > l-Glu > l-Arg = l-Leu. CaR-active amino acids also acutely and reversibly suppressed PTH secretion at physiological ionized Ca(2+) concentrations. At a Ca(2+)(o) of 1.1 mm and an amino acid concentration of 1 mm, CaR-active amino acids (l-Phe = l-Trp > l-His = l-Ala), but not CaR-inactive amino acids (l-Leu and l-Arg), stereoselectively suppressed PTH secretion by up to 40%, similar to the effect of raising Ca(2+)(o) to 1.2 mm. A physiologically relevant increase in the -fold concentration of the plasma-like amino acid mixture (from 1x to 2x) also reversibly suppressed PTH secretion in the Ca(2+)(o) concentration range 1.05-1.25 mm. In conclusion, l-amino acids acutely and reversibly activate endogenous CaRs and suppress PTH secretion at physiological concentrations. The results indicate that l-amino acids are physiological regulators of PTH secretion and thus whole body calcium metabolism.

Amino Acids↗
PubMed2004

Adrenocortical cancer: recent clinical and molecular advances.

PURPOSE OF REVIEW: Adrenocortical cancer (ACC) is an uncommon disorder that remains a challenge to the surgeon and oncologist. When the disease is localized to the adrenal gland and readily amenable to surgical resection, reasonable 5-year survival rates are possible. Locally invasive disease carries a poorer prognosis, and metastatic disease is uniformly fatal within 1 year. In this review, we summarize the current knowledge regarding the clinical management of ACC and the molecular mechanisms underlying the disease. RECENT FINDINGS: The clinical manifestations, staging, and current treatment for ACC has been well documented. Surgery is still the mainstay of treatment, but identifying molecular targets for chemotherapeutic agents or monoclonal antibodies would be a great advance. At present, our understanding of pathogenic mechanisms is crude; however, the molecular events regulating this aggressive disease are beginning to emerge, especially in the last few years. The advent of laparoscopic adrenalectomy has also created its own dilemmas regarding the appropriate surgical approach to the large, potentially malignant adrenal mass. SUMMARY: The challenge in the management of this disease lies in understanding the molecular mechanisms that underlie the development of ACC with the diagnostic and therapeutic benefits that would ensue.

Adrenal Cortex Neoplasms↗
PubMed2004

A 23-hour care centre model for the management of surgical patients.

BACKGROUND: Much of the emphasis on gaining efficiencies in surgical care have, to date, focused on increasing day only (DO) facilities and increasing the utilization of day of surgery admissions (DOSA) for longer stay cases. However, for the majority of cases requiring surgery, both elective and acute, the episode of care can generally be delivered within an envelope of 23 h during which time patients require only pain relief and monitoring in a supervised setting until fit for discharge. The aim of the present study was to evaluate a pilot of a 23-h care centre at a principal referral hospital. METHODS: A 23-h care centre was established at a principal referral hospital in January 2003 in association with an existing DO and DOSA facility. All patients, both emergency and elective as well as surgical and medical, who fitted the following criteria were admitted as '23-h patients' to the centre: absolute expectation of discharge within 24 h; preadmission screening by a nurse screener (if elective); agreed clinical guidelines in place; agreement to protocol-based, nurse-initiated discharge. Outcomes were evaluated after 3 months. Existing admission criteria for DO and DOSA patients were maintained. RESULTS: Over 3 months, 1601 patients utilized the 23-h care centre as follows: 593 DO patients, 410 DOSA patients and 598 23-h patients. Transfers from the emergency department constituted 47% of all 23-h patients. Utilization varied with the departments of hand surgery, ear, nose and throat/head and neck surgery, and gastrointestinal surgery all managing more than 55% of their operative workload as 23-h patients (excluding DO and DOSA patients). Excluding inappropriate admissions, overall discharge compliance was 83%. Three departments achieved the compliance benchmark of 90% of admitted patients discharged within 23 h. Only 1% of patients discharged required referral back to the emergency department, with a further 2% being reviewed by their general practitioner. CONCLUSION: The 23-h care centre model, incorporating DO, DOSA and 23-h patients, offers a workable system of healthcare delivery for patients who do not require a prolonged stay in hospital including, potentially, the majority of surgical patients.

Day Care, Medical↗
PubMed2003

Novel succinate dehydrogenase subunit B (SDHB) mutations in familial phaeochromocytomas and paragangliomas, but an absence of somatic SDHB mutations in sporadic phaeochromocytomas.

Phaeochromocytomas arising in adrenal or extra-adrenal sites and paragangliomas of the head and neck, in particular of the carotid bodies, occur sporadically and also in a familial setting. In addition to mutations in RET and VHL in familial disease, germline mutations in SDHD and SDHB genes that encode subunits of mitochondrial complex II have also been associated with the development of familial phaeochromocytomas. To further investigate the role of SDHD and SDHB in the development of these tumours we determined the occurrence of germline SDHD and SDHB mutations in four patients with a family history of phaeochromocytoma with associated head and neck paraganglioma, one patient with a family history of phaeochromocytoma only and two patients with apparently sporadic extra-adrenal phaeochromocytoma, one of whom had early onset disease. Secondly, we investigated whether somatic SDHB mutations correlated with loss of heterozygosity at 1p36 in a subgroup of 11 sporadic and three MEN 2-associated RET-mutation-positive phaeochromocytomas. Novel SDHB mutations were identified in the probands from four families and two apparently sporadic cases (six of seven probands studied), including two missense mutations, a single nonsense and frameshift mutation, as well as two splice site mutations, one of which was shown to have partial penetrance resulting in 'leaky' splicing. Further, five intronic polymorphisms in SDHB were found. No SDHD mutations were identified. In addition, no somatic SDHB mutations were found in the remaining allele of the 11 sporadic adrenal phaeochromocytomas with allelic loss at 1p36 or the three MEN 2-associated RET-mutation-positive phaeochromocytomas. Therefore, we conclude that SDHB has a major role in the pathogenesis of familial phaeochromocytomas, but the possible role of SDHB in sporadic tumours showing allelic loss at 1p36 has yet to be ascertained.

Adolescent↗
PubMed2003

Chronic amiodarone-induced inhibition of the Na+-K+ pump in rabbit cardiac myocytes is thyroid-dependent: comparison with dronedarone.

OBJECTIVE: To examine the thyroid-dependence of the effect of amiodarone on the sarcolemmal Na(+)-K(+) pump, and the effect on the pump of dronedarone, a deiodinated amiodarone congener without influence on thyroid status. METHODS: New Zealand white rabbits underwent total thyroidectomy, sham thyroidectomy or thyroidectomy and concomitant oral amiodarone therapy. After 5 weeks, Na(+)-K(+) pump current was measured using the whole-cell patch-clamp technique in isolated ventricular myocytes. Pump current was also measured in myocytes isolated from a separate group of rabbits not subjected to thyroidectomy but treated with dronedarone, or placebo for 3 weeks. RESULTS: Treatment of thyroidectomised rabbits with amiodarone caused a significant prolongation of the corrected QT interval (QT(c)) and sinus cycle length. Na(+)-K(+) pump current measured in myocytes isolated from thyroidectomised rabbits was significantly lower than pump current in myocytes from sham-operated controls. However, treatment of thyroidectomised rabbits with amiodarone did not cause any additional decrease in pump current. Treatment with dronedarone caused prolongation of QT(c). However, it had no effect on Na(+)-K(+) pump current. CONCLUSIONS: The inhibitory effect of amiodarone on Na(+)-K(+) pump current is thyroid-dependent, whereas the effects on heart rate and QT(c) are at least partially mediated by thyroid-independent mechanisms. In contrast to its parent compound, dronedarone has no significant effects on the activity of the Na(+)-K(+) pump.

Amiodarone↗
PubMed2003

Minimally invasive parathyroidectomy: the Australian experience.

Minimally invasive parathyroidectomy (MIP) was introduced into Australia after endocrine surgeons agreed that it should only be undertaken in the context of a feasibility study or controlled trial, and under the auspices of the Australian Safety and Efficacy Register of New Interventional Procedures - Surgical (ASERNIP-S). Feasibility of endoscopic-assisted parathyroidectomy was studied at Royal North Shore Hospital (RNS) and 49 cases were completed. Subsequently, the technique of a focused lateral approach using a 2-cm incision placed directly over the site of the localized adenoma was developed and has now become the standard technique for the unit. To date, 357 MIPs using the focused lateral approach have been performed with a 1.5% rate of negative neck exploration and a permanent recurrent laryngeal nerve palsy rate of 0.8%. The use of intraoperative rapid measurement of parathyroid hormone (PTH, IO-QPTH) as an assessment of completeness of resection of abnormal parathyroid tissue has been replaced by simply measuring PTH levels 30 minutes postoperatively, a technique that is more cost-effective, and which still allows same-day discharge whilst avoiding false-positive results with IO-QPTH. The introduction of MIP appears to be a factor in the increasing number of referrals for parathyroid surgery.

Adenoma↗
PubMed2003

Total thyroidectomy: the evolution of surgical technique.

The present paper outlines the development of thyroid surgery from early times to the twenty-first century. The significant changes that have occurred in the past few decades in relation to the evolution of techniques for safe and effective total thyroidectomy are then summarized. In the last 25 years total thyroidectomy has replaced bilateral subtotal thyroidectomy as the preferred option for the management of all patients with bilateral benign multinodular goitre, Graves' disease, and all but very low-risk thyroid cancer patients. The principal change in operative technique has been the move from 'lateral dissection' to 'capsular dissection'. Associated with that has been a focus on 'encountering' the recurrent laryngeal nerve (RLN), recognizing sympathetic-laryngeal nerve anastomoses, and routinely identifying the external branch of the superior laryngeal nerve (EBSLN). Completeness of resection has been assured by moving from an anatomically based approach to an embryologically based approach. This requires an awareness of the vagaries of thyroid development including attention to pyramidal remnants, to abnormalities associated with the tubercle of Zuckerkandl, and to thyrothymic thyroid rests. Preservation of parathyroid function has moved from the time-consuming technique of dissection of a vascularized pedicle in all cases, to initially selective, and then routine, parathyroid autotransplantation. These changes have ensured that total thyroidectomy can now be offered as a safe and efficacious procedure with a minimal complication rate.

Graves Disease↗
PubMed2003

Detection of the PAX8-PPAR gamma fusion oncogene in both follicular thyroid carcinomas and adenomas.

Chromosomal translocations encoding fusion oncoproteins are common in hematological malignancies, sarcomas, and papillary thyroid carcinomas. A recent study of follicular thyroid carcinomas reported a novel chromosomal translocation, t(2;3)(q13;p25), that fused the thyroid-specific transcription factor PAX8 with a nuclear receptor, peroxisome proliferator-activated receptor gamma (PPAR gamma). Herein we report the detection of this putative oncoprotein in 6 of 17 (35%) follicular thyroid carcinomas as well as in 6 of 11 (55%) follicular thyroid adenomas. Concordant expression of protein was found in 91% of those tumors in which PAX8-PPAR gamma mRNA was detected by RT-PCR, whereas a further 20% of follicular tumors were positive for PPAR gamma immunohistochemistry alone. Our findings suggest that the PAX8-PPAR gamma fusion protein promotes differentiated follicular thyroid neoplasia, although it is not sufficient per se for carcinogenesis.

Adenocarcinoma, Follicular↗
PubMed2003

Genome-wide copy number imbalances identified in familial and sporadic medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is a malignant tumor of the calcitonin-secreting parafollicular C cells of the thyroid occurring sporadically and as a component of the multiple endocrine neoplasia type 2/familial medullary thyroid carcinoma syndrome. The primary genetic cause of multiple endocrine neoplasia type 2 is germline mutation of the RET protooncogene. Somatic point mutations in RET also occur in sporadic MTC. Although RET mutation is likely sufficient to cause C-cell hyperplasia, the precursor lesion to MTC, tumor progression is thought to be due to clonal expansion caused by the accumulation of somatic events. Using the genome-scanning technique comparative genomic hybridization, we identified chromosomal imbalances that occur in MTC including deletions of chromosomes 1p, 3q26.3-q27, 4, 9q13-q22, 13q, and 22q and amplifications of chromosome 19. These regions house known tumor suppressor genes as well as genes encoding subunits of the multicomponent complex of glycosylphosphatidylinositol-linked proteins (glial cell line-derived neurotrophic factor family receptors alpha-2-4) and their ligands glial cell line-derived neurotrophic factor, neurturin, persephin, and artemin that facilitate RET dimerization and downstream signaling. Chromosomal imbalances in the MTC cell line TT were largely identical to those identified in primary MTC tumors, consolidating its use as a model for studying MTC.

Adolescent↗