ORCID Profile
0000-0003-0762-0977
Current Organisations
Garvan Institute of Medical Research
,
Royal North Shore Hospital
,
Sloan Kettering Institute
,
University of Sydney
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Publisher: Springer Science and Business Media LLC
Date: 16-10-2014
DOI: 10.1245/S10434-014-4142-3
Abstract: The external branch of the superior laryngeal nerve (EBSLN) is at risk during thyroid surgery. Despite meticulous dissection and visualization, the EBSLN can be mistaken for other structures. The nerve integrity monitor (NIM) allows EBSLN confirmation with cricothyroid twitch on stimulation. The aim of this study was to assess any difference in identification of EBSLN and its anatomical sub-types by dissection alone compared to NIM-aided dissection. Routine intra-operative nerve monitoring (IONM) was used, when available, for 228 consecutive thyroid operations (129 total thyroidectomies, 99 hemi-thyroidectomies) over a 10-month period. EBSLN identification by dissection alone (with NIM confirmation of cricothyroid twitch) and by NIM-assisted dissection was recorded prospectively. Anatomical sub-types were defined by the Cernea classification. Of 357 nerves at risk, 97.2 % EBSLNs (95 % confidence interval [CI], 95.5-98.9) were identified by visualization and NIM-aided dissection compared to 85.7 % (95 % CI, 82.1-89.3) identified by dissection alone (<0.001). EBSLN frequency was 34 % for type 1, 55 % for type 2a, and 11 % for type 2b. All identified EBSLNs were stimulated to confirm a cricothyroid twitch after superior thyroid vessel ligation. Using the NIM and meticulous dissection of the upper thyroid pole improves EBSLN identification. As the EBSLN is at risk during thyroidectomy and can lead to voice morbidity, the NIM can aid identification of the EBSLN and provide a functional assessment of the EBSLN after thyroid resection.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Wiley
Date: 24-06-0001
DOI: 10.1111/ANS.17783
Abstract: In this article, we aim to describe our modern‐day approach to total thyroidectomy, detailing the subtle refinements of our technique, as it has evolved over three decades and 21 000 cases. Since Delbridge's seminal paper in 2003, the major changes to our approach include a retrograde approach to the recurrent laryngeal nerve that allows dissection of the distal RLN from fascial bands within the ligament of Berry before medialisation of the thyroid lobe. Routine use of intraoperative nerve monitoring systems has increased our awareness of temporary neuropraxia, facilitated a reduction in the risk of bilateral RLN palsy and improved our identification and preservation of the external branch of the superior laryngeal nerve. The increasing use of advanced energy devices has been associated with a reduction in post‐operative haematoma rates. We adopt a low threshold to parathyroid auto‐transplantation, unless all glands are assessed to be clearly not at risk, and routinely supplement patients with Caltrate in the immediate post‐operative period to minimize the risk of symptomatic hypocalcaemia. Ultimately, when we reflect on the subtle refinements that have contributed to improved outcomes, the fundamental principles of exposure and dissection that have evolved over decades remain the basis of our surgical approach and must continue to do so.
Publisher: Wiley
Date: 16-02-2021
DOI: 10.1111/ANS.16652
Publisher: Wiley
Date: 29-04-2022
DOI: 10.1111/ANS.17741
Publisher: Jaypee Brothers Medical Publishing
Date: 2019
Publisher: Wiley
Date: 10-10-2014
DOI: 10.1111/ANS.12406
Abstract: Sutureless thyroid surgery utilizing thermal sealing is now well established. However, incremental advances in technology still require formal clinical evaluation in order to ensure that added technology does not compromise safety. In this study, we compared a new thermal sealing device incorporating a tissue ider (LigaSure Small Jaw) with the device we have previously reported for use in total thyroidectomy (LigaSure Precise). A cohort study was undertaken of 872 total thyroidectomies over a 2-year period. Patients were selected for each group on the basis of device availability within four institutions and outcomes were obtained from a prospectively maintained database. Small Jaw was used in 399 cases and Precise in 473. No significant differences between patient demographics (sex, age), operation indication or pathology were found. Significantly more Small Jaw operations were performed in private versus public hospitals (P < 0.01). Regarding outcomes, there was no significant difference in the incidence of any complication (haematoma, temporary ermanent hypoparathyroidism or temporary ermanent recurrent laryngeal nerve injury). In a subgroup analysis of operations performed in the public hospital system, Small Jaw was found to be significantly faster (mean operative time: 79 versus 103 min) (95% CI 74-84 and 96-110 min) (P < 0.01). The incorporation of a tissue ider into thermal sealing devices is efficacious and safe, with no compromise in clinical outcome, while providing the added benefit of a significant reduction in operative times.
Publisher: Bioscientifica
Date: 11-2020
DOI: 10.1530/ERC-20-0279
Abstract: COVID-19 has modified the way we practice medicine. For thyroid cancer, there have been several significant impacts. First, the diagnosis has been delayed due to social isolation, reduced access to investigations and staff redeployment. Secondly, treatment planning has needed to take into account the risk to patients and/or staff of nosocomial transmission of the virus. Finally, there are some specific concerns with respect to interactions between the virus, its treatments and cancer. This mini-review aims to address each of these impacts and to provide some guidance and confidence to our patients and colleagues during this challenging time.
Publisher: Oxford University Press (OUP)
Date: 27-03-2019
DOI: 10.1634/THEONCOLOGIST.2018-0849
Abstract: Adrenocortical carcinoma (ACC) is a rare endocrine cancer with treatments limited in efficacy for metastatic disease. New molecular targeted therapies have yet to improve patient outcomes. In contrast, established treatment regimens of adrenolytics and chemotherapy have demonstrated treatment benefit, although admittedly in a minority of patients. Identification of microRNAs (miRNAs) in patients responsive to adjuvant therapy may offer a means to sensitize patients with progressive disease to existing adjuvant regimens. S les from primary ACC tumors of 10 Stage IV patients were examined for differentially expressed miRNAs between a “sensitive” and “resistant” cohort. Candidate microRNAs were restored via transfection in two functional ACC cell lines. Gain of function and effects on apoptosis and cell cycle were assessed. microRNA-431 (miR-431) was underexpressed in patients with ACC with progressive disease undergoing adjuvant therapy. Restoration of miR-431 in vitro decreased the half maximal inhibitory concentrations of doxorubicin and mitotane, with markedly increased apoptosis. We found that a reversal of epithelial-mesenchymal transition underlies the action of miR-431 with doxorubicin treatment, with Zinc Finger E-Box Binding Homeobox 1 implicated as the molecular target of miR-431 in ACC. This is the first report of the potential of miRNA therapy to sensitize ACC to current established adjuvant therapy regimens, which may mitigate the resistance underlying treatment failure in patients with advanced ACC. Effective and well-studied methods of targeted miRNA delivery in existence hints at the imminent translatability of these findings.
Publisher: Springer Science and Business Media LLC
Date: 13-02-2015
DOI: 10.1007/S00268-015-3017-5
Abstract: A recent study of focused minimally invasive parathyroidectomy (FPTX) in sporadic primary hyperparathyroidism (pHPT) using intraoperative parathyroid hormone (ioPTH) measurements shows that inadequate ioPTH drop and multiglandular disease are more commonly found when a first gland<200 mg is resected. Our aim was to study if a resected gland that weighed <200 mg was associated with an increased persistence rate after FPTX. This is a cohort study of FPTX for pHPT performed in the period 1998-2013. FPTX was performed in patients with pHPT where Sestamibi and Ultrasound imaging localized single-gland disease, only one gland was excised and the weight recorded. IoPTH was not used routinely. Two groups were composed according to the weight of the resected gland: Group A<200 mg and Group B≥200 mg. Persistent or recurrent disease was defined if it occurred within, or after 6 months. The primary outcome measure was the rate of persisting pHPT. A total of 3,511 parathyroidectomies were performed, and a total 1,745 FPTX (1,347 female) met inclusion criteria. There were 245 and 1,500 patients in groups A and B, respectively. The rate of persistent pHPT was higher in Group A, 6.1 versus 2.0% (p<0.001). Findings at re-operative surgery showed that the ipsilateral gland was diseased in 47% (7/15) of persistent cases in group A. The risk of persistent disease after MIP was higher if the resected gland weighed ≤200 mg, and this corroborates the findings of a recent study. A heightened awareness of the possibility of multigland disease should be raised, and ioPTH monitoring, identification of the ipsilateral gland or bilateral exploration may be advisable in such cases.
Publisher: Mary Ann Liebert Inc
Date: 09-2022
Publisher: Springer Science and Business Media LLC
Date: 28-08-2022
DOI: 10.1007/S00268-022-06696-6
Abstract: Encapsulated angioinvasive follicular thyroid carcinoma (EAFTC) is associated with an increased risk of distant metastasis and reduced survival compared to minimally invasive follicular thyroid carcinoma (MIFTC). There is controversy regarding the extent of surgery and adjuvant radioactive iodine therapy for angioinvasive follicular thyroid carcinoma when stratified by number of foci of angioinvasion. All follicular thyroid carcinoma cases from 1990-2018 were identified from a thyroid cancer database. Primary outcomes were distant metastasis-free survival (DMFS) and disease-specific survival (DSS) with factors of interest being age, gender, tumour size, treatment, foci of angioinvasion and histological subtype. A total of 292 cases were identified 139 MIFTC, 141 EAFTC and 12 widely invasive follicular thyroid carcinoma (WIFTC). Over a follow-up period of 6.25 years, DMFS was significantly reduced (p < 0.001) with 14.2% (EAFTC) and 50% of WIFTC developing metastasis. The risk of metastasis in EAFTC with ≥ 4 foci of angioinvasion was 31.7% (HR = 5.89, p = 0.004), 6.3% for EAFTC with < 4 foci of angioinvasion (HR = 1.74, p = 0.47), compared to 3.6% MIFTC. Age ≥ 50 years (HR = 4.24, p = 0.005) and tumour size (HR = 1.27, p = 0.014) were significantly associated with increased risk of distant metastasis. DSS was reduced significantly (p < 0.001), with 7.8% EAFTC patients dying of disease. For EAFTC patients, DSS was 96.8% for < 4 foci and 82.6% for ≥ 4 foci of angioinvasion (p = 0.003). EAFTC is at increased risk of distant metastasis related to the extent of angioinvasion. Tumours with < 4 foci of angioinvasion should be considered for a total thyroidectomy, particularly in older patients.
Publisher: American Medical Association (AMA)
Date: 2020
Publisher: Elsevier BV
Date: 04-2010
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.JSS.2021.07.009
Abstract: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) surgical risk calculator provides an estimation of 30-d post-operative complications including mortality. This tool has the potential to both aid in decision-making for patients and their families and also in optimizing the clinical management of high-risk patients. However, it's utility in patients requiring emergency abdominal surgery has shown to be inconsistent outside of NSQIP participating institutions. This study undertook a meta-analysis to assess the calculator's accuracy in predicting mortality in these patients. A literature search of PubMed, Medline and Cochrane databases was conducted between October 2019 to April 2020. The PubMed, Medline and Cochrane Databases were searched for relevant studies. The search strategy included studies from January 2013 to April 2020. Studies including elective surgery were excluded. A random effects model was used and fitted using restricted maximum likelihood estimation. The O:E ratio was used to validate the calculator's accuracy in predicting mortality. Six studies were included in the meta-analysis, with a total of 1835 patients undergoing emergency intra-abdominal surgery. The summary estimate of the O:E ratio of the ACS-NSQIP surgical risk calculator in predicting 30-d post-operative mortality was 1.06 (95% CI 0.74-1.51). There was significant heterogeneity between studies with a Cochrane Q of 11.96 (P = 0.04) and I The ACS-NSQIP surgical risk calculator is a reliable predictor of mortality in this external cohort and has potential to be utilised in the multi-disciplinary care of patients undergoing emergency abdominal surgery.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.SURG.2021.05.030
Abstract: Concern regarding suboptimal cure rates has led to some endocrine surgery units abandoning focused parathyroidectomy for primary hyperparathyroidism in favor of open bilateral neck exploration or making intraoperative parathyroid hormone estimation mandatory in focused parathyroidectomy. This study explores whether focused parathyroidectomy for radiologically localized primary hyperparathyroidism without intraoperative parathyroid hormone is still a valid approach. Retrospective review of a tertiary referral endocrine surgery unit database. All parathyroidectomies for primary hyperparathyroidism over 6 years (2013-2019) were included. Lithium-induced hyperparathyroidism, reoperations, familial disease, and concurrent thyroid surgery were excluded. Characteristics and outcomes for focused parathyroidectomy and open bilateral neck exploration were compared by intention-to-treat and treatment delivered. Persistence and recurrence, conversions and complications were analyzed as endpoints. A total of 2,828 parathyroidectomies were performed and 2,421 analyzed. By intention to treat there were 1,409 focused parathyroidectomies and 1,012 open bilateral neck explorations. Focused parathyroidectomy patients were younger: 63 vs 66 years (P < .01) however, gender (77%, 79% female), preoperative peak serum calcium (2.72, 2.70 mmol/L [P = .23]), and serum parathyroid hormone (11.5, 11.0 pmol/L [P = .52]) did not differ. In total, 229 (16.3%) focused parathyroidectomies were converted to open bilateral neck exploration. Multiple gland disease was confirmed in 54.5% of converted patients. Median follow-up was 41 months (3-60 months). Persistence or recurrence requiring reoperation totaled 2.2% and did not differ between focused parathyroidectomy and open bilateral neck exploration in either intention to treat or final treatment analyses. Complications occurred in 1.2% of focused parathyroidectomy and 3.2% open bilateral neck exploration (P < .01). In experienced hands and with a ready-selective approach to conversion, focused parathyroidectomy based on concordant imaging and without intraoperative parathyroid hormone may deliver equivalent cure rates to open bilateral neck exploration with significantly fewer complications. Focused parathyroidectomy without intraoperative parathyroid hormone should therefore be maintained in the endocrine surgeon's armamentarium.
Publisher: Wiley
Date: 2019
DOI: 10.1111/ANS.15032
Abstract: Adrenocortical carcinoma is a rare and heterogeneous malignancy with poor outcomes. Recent research has suggested that outcomes may be improved by centralization of care in specialist centres. We review our evolving 21-year experience in managing adrenocortical carcinoma with a view towards outcomes and lessons learnt. A retrospective study of patients treated in our specialist endocrine surgical unit over 21 years was undertaken. Thirty-five patients were treated from diagnosis, 29 forming a primary study cohort. Additionally, seven patients were referred to us for quaternary care, forming a secondary study cohort. The European Network for the Study of Adrenal Tumours (ENSAT) stage and immunohistochemical marker Ki-67 index were strong prognostic indicators for survival. Early stage, complete resection and Ki-67 <10% are the best prognosticators for survival. Aggressive surgical resection at index operation and of recurrent oligometastatic disease along with multimodal adjuvant treatment has led to long-term survivors of patients with Stage 4 disease in our aggregate cohort.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 2022
DOI: 10.1200/JCO.21.01329
Abstract: Medullary thyroid carcinoma (MTC) is an aggressive neuroendocrine tumor (NET) arising from the calcitonin-producing C cells. Unlike other NETs, there is no widely accepted pathologic grading scheme. In 2020, two groups separately developed slightly different schemes (the Memorial Sloan Kettering Cancer Center and Sydney grade) on the basis of proliferative activity (mitotic index and/or Ki67 proliferative index) and tumor necrosis. Building on this work, we sought to unify and validate an internationally accepted grading scheme for MTC. Tumor tissue from 327 patients with MTC from five centers across the United States, Europe, and Australia were reviewed for mitotic activity, Ki67 proliferative index, and necrosis using uniform criteria and blinded to other clinicopathologic features. After reviewing different cutoffs, a two-tiered consensus grading system was developed. High-grade MTCs were defined as tumors with at least one of the following features: mitotic index ≥ 5 per 2 mm 2 , Ki67 proliferative index ≥ 5%, or tumor necrosis. Eighty-one (24.8%) MTCs were high-grade using this scheme. In multivariate analysis, these patients demonstrated decreased overall (hazard ratio [HR] = 11.490 95% CI, 3.118 to 32.333 P .001), disease-specific (HR = 8.491 95% CI, 1.461 to 49.327 P = .017), distant metastasis-free (HR = 2.489 95% CI, 1.178 to 5.261 P = .017), and locoregional recurrence-free (HR = 2.114 95% CI, 1.065 to 4.193 P = .032) survivals. This prognostic power was maintained in subgroup analyses of cohorts from each of the five centers. This simple two-tiered international grading system is a powerful predictor of adverse outcomes in MTC. As it is based solely on morphologic assessment in conjunction with Ki67 immunohistochemistry, it brings the grading of MTCs in line with other NETs and can be readily applied in routine practice. We therefore recommend grading of MTCs on the basis of mitotic count, Ki67 proliferative index, and tumor necrosis.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2021
DOI: 10.1007/S00268-021-06099-Z
Abstract: In the midst of the COVID-19 pandemic, patients have continued to present with endocrine (surgical) pathology in an environment depleted of resources. This study investigated how the pandemic affected endocrine surgery practice. PanSurg-PREDICT is an international, multicentre, prospective, observational cohort study of emergency and elective surgical patients in secondary/tertiary care during the pandemic. PREDICT-Endocrine collected endocrine-specific data alongside demographics, COVID-19 and outcome data from 11–3-2020 to 13–9-2020. A total of 380 endocrine surgery patients (19 centres, 12 countries) were analysed (224 thyroidectomies, 116 parathyroidectomies, 40 adrenalectomies). Ninety-seven percent were elective, and 63% needed surgery within 4 weeks. Eight percent were initially deferred but had surgery during the pandemic less than 1% percent was deferred for more than 6 months. Decision-making was affected by capacity, COVID-19 status or the pandemic in 17%, 5% and 7% of cases. Indication was cancer/worrying lesion in 61% of thyroidectomies and 73% of adrenalectomies and calcium 2.80 mmol/l or greater in 50% of parathyroidectomies. COVID-19 status was unknown at presentation in 92% and remained unknown before surgery in 30%. Two-thirds were asked to self-isolate before surgery. There was one COVID-19-related ICU admission and no mortalities. Consultant-delivered care occurred in a majority (anaesthetist 96%, primary surgeon 76%). Post-operative vocal cord check was reported in only 14% of neck endocrine operations. Both of these observations are likely to reflect modification of practice due to the pandemic. The COVID-19 pandemic has affected endocrine surgical decision-making, case mix and personnel delivering care. Significant variation was seen in COVID-19 risk mitigation measures. COVID-19-related complications were uncommon. This analysis demonstrates the safety of endocrine surgery during this pandemic.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-05-2020
Publisher: Mary Ann Liebert Inc
Date: 07-2022
Publisher: Oxford University Press (OUP)
Date: 06-02-2019
DOI: 10.1002/BJS5.50137
Publisher: The Endocrine Society
Date: 05-2023
Abstract: Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors of the adrenal medulla chromaffin cells, usually associated with features of catecholamine excess. Clinically and biochemically silent pheochromocytoma without adrenergic symptoms or elevated catecholamine concentrations are rare. A 71-year-old female presented with acute right flank pain with abdominal computed tomography (CT) scan revealing a hemorrhagic right adrenal mass. She had no preceding adrenergic symptoms, and normal serum electrolytes, on a background of well-controlled hypertension on amlodipine monotherapy. After conservative management and discharge, an outpatient CT adrenal scan confirmed an 88 × 64 mm right adrenal mass demonstrating intense avidity (maximum standardized uptake value, 20.2) on fluorodeoxyglucose F 18-positron emission tomography (FDG-PET)/CT scan. Biochemical screening supported a nonfunctional adrenal lesion with normal-range plasma normetanephrines and metanephrines. She underwent a right adrenalectomy for presumed nonfunctioning adrenocortical cancer however, histopathology demonstrated a 120-mm pheochromocytoma. Succinate dehydrogenase subunit B (SDHB) and fumarate hydratase (FH) staining were retained however, weakly positive 2SC staining raised concerns for FH-deficient pheochromocytoma. Germline DNA sequencing was negative for pathogenic RET, VHL, SDHB, SDHD, or FH variants. Tumor cells stained positive for tyrosine hydroxylase and negative for dopamine β hydroxylase. Four months postoperatively, progress FDG-PET/CT scan demonstrated no focal avidity. Massive biochemically silent pheochromocytomas are exceedingly rare, and we discuss various mechanisms that may predispose patients to this phenomenon.
Publisher: Informa UK Limited
Date: 28-11-2015
DOI: 10.1586/17434440.2015.985650
Abstract: Since its invention nearly 20 years ago, the Covidien LigaSure device along with its ForceTriad generator has dominated the Electrothermal Bipolar Vessel Sealing market. The LigaSure was used for surgical procedures, both open and laparoscopic. The purpose of this review is to provide evidence of the safety and utility of the LigaSure device compared to more traditional means of hemostasis and its ultrasonic competitor, particularly in laparoscopic applications. We will provide evidence related to electrothermal bipolar vessel sealing in general and look specifically at Covidien's newest product, the LigaSure Maryland Jaw Device.
Publisher: Springer Science and Business Media LLC
Date: 22-12-2023
Publisher: Informa UK Limited
Date: 09-01-2014
DOI: 10.1586/17446651.2014.877342
Abstract: The presentation of differentiated thyroid cancer in children often includes dissemination to lymph nodes. Despite this, the long-term prognosis is excellent with appropriate treatment. A few known hereditary syndromes are associated with paediatric thyroid cancer, although most tumours are sporadic. Ultrasound and cytology is used to evaluate suspect thyroid nodules, and treatment consists of surgery, radioactive iodine and thyroxine suppression therapy. Follow-up includes serum thyroglobulin measurements, serial ultrasounds of the neck, radioiodine whole body scans and occasionally other cross-sectional imaging or positron emission tomography. This review focuses on paediatric well differentiated follicular and papillary thyroid cancer, diagnosis and preoperative evaluation, underlying genetic mechanisms, surgery, other treatment options and follow-up.
Publisher: Wiley
Date: 02-05-2023
DOI: 10.1111/ANS.18443
Abstract: In the context of minimally invasive adrenal surgery, there remains debate about whether the transperitoneal adrenalectomy (TPA) and posterior retroperitoneoscopic adrenalectomy (PRA) approach have equivalent indications. This study aims to examine complication and conversion rates associated with three surgical approaches for adrenal tumours over the last 17 years in a specialized endocrine surgical unit. All adrenalectomy cases performed in the period 2005–2021 were identified within a prospectively maintained surgical database. A retrospective cohort study was undertaken with patients ided into two cohorts (2005–2013 and 2014–2021). Surgical approach (open adrenalectomy (OA), TPA, PRA), tumour size, histopathology, complication and conversion rates were compared. During the study period, 596 patients underwent adrenalectomy with 31 and 40 cases each year per cohort. The dominant surgical approach per cohort significantly changed from TPA (79% versus 17%) to PRA (8% versus 69%, P 0.001), whilst the frequency of OA remained stable (13% versus 15%). TPA removed larger tumours (3.0 ± 2.9 cm) than PRA (2.8 ± 2.2 cm, P = 0.02), with the median size increasing from 3.0 ± 2.5 to 4.5 ± 3.5 cm per cohort ( P 0.001). The maximum tumour sizes treated by TPA and PRA were 15 and 12 cm, respectively. Adrenocortical adenoma was the commonest pathology treated by either laparoscopic technique. Complication rates were greatest for OA (30.1%) with no significant difference between minimally invasive approaches (TPA 7.3%, PRA 8.3%, P = 0.7). Both laparoscopic techniques had equivalent conversion rates (3.6%). PRA was preferably converted to TPA (2.8%) over OA (0.8%). This study demonstrates the transition from TPA to PRA, offering similarly low complication and conversion rates.
Publisher: Wiley
Date: 29-04-2020
DOI: 10.1111/ANS.15892
Publisher: Future Medicine Ltd
Date: 02-2016
DOI: 10.2217/IJE.15.28
Abstract: Adrenocortical carcinoma (ACC) has poor outcomes and there is a need for novel effective treatments for metastatic disease and adjuvant therapy. miRNAs are small endogenous noncoding RNAs that control gene expression. miRNAs are dysregulated in all cancers and manipulation of miRNA levels is under investigation as a novel therapy in other cancers with poor outcomes such as mesothelioma. In this review, the rationale for miRNA therapy will be presented along with the current understanding of the role of miRNA dysregulation and miRNA regulation of ACC. Potential therapeutic approaches of miRNA therapy using established delivery systems such as liposomes and targeted nanocells will be presented, along with the future challenges of establishing miRNA therapy in clinical trials for ACC.
Publisher: Oxford University Press (OUP)
Date: 05-02-2015
DOI: 10.1634/THEONCOLOGIST.2014-0392
Abstract: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. The aim of this study was to identify novel protein signatures that would predict clinical outcomes in a large cohort of patients with ACC based on data from previous gene expression microarray studies. A tissue microarray was generated from the paraffin tissue blocks of 61 patients with clinical outcomes data. Selected protein biomarkers based on previous gene expression microarray profiling studies were selected, and immunohistochemistry staining was performed. Staining patterns were correlated with clinical outcomes, and a multivariate analysis was undertaken to identify potential biomarkers of prognosis. Median overall survival was 45 months, with a 5-year overall survival rate of 44%. Median disease-free survival was 58 months, with a 5-year disease-free survival rate of 44%. The proliferation marker Ki-67 and DNA topoisomerase TOP2A were associated with significantly poorer overall and disease-free survival. The results also showed strong correlation between the transcriptional repressor EZH2 and TOP2A expression, suggesting a novel role for EZH2 as an additional marker of prognosis. In contrast, increased expression of the BARD1 protein, with its ubiquitin ligase function, was associated with significantly improved overall and disease-free survival, which has yet to be documented for ACC. We present novel biomarkers that assist in determining prognosis for patients with ACC. Ki-67, TOP2A, and EZH2 were all significantly associated with poorer outcomes, whereas BARD1 was associated with improved overall survival. It is hoped that these biomarkers may help tailor additional therapy and be potential targets for directed therapy.
Publisher: Springer Science and Business Media LLC
Date: 08-11-2021
Publisher: Wiley
Date: 18-04-2017
DOI: 10.1111/ANS.13606
Abstract: The use of routine intraoperative neuromonitoring (IONM) is controversial in thyroid surgery. Guidelines have been published to standardize IONM. This study examines the impact of routine IONM on a high-volume thyroid surgeon. A prospective study was conducted using IONM between May 2013 and December 2014. Demographics, type of operation, pathology, recurrent laryngeal nerve (RLN) and external branch of the superior laryngeal nerve (EBSLN) visualization and sub-type classification, cricothyroid or cricopharyngeal twitch/electrode depolarization were obtained, and complications were recorded. Outcomes were compared with 500 thyroidectomies performed by the same surgeon without neuromonitoring. Two hundred and ninety-nine total thyroidectomies and 191 hemithyroidectomies were performed with IONM resulting in 789 RLN and 789 EBSLN at risk of injury. Demographics, indication, pathology and complications were similar between the two groups. IONM provided additional information for 58 RLN dissections (7.4%) stratifying surgical decision-making. Loss of signal was detected in 1.8% of nerves at risk. IONM assisted in identification of 109 (13.8%, P < 0.0001) EBSLN, including a 15.8% improvement in identifying type 2b EBSLN. Utility of IONM was not predicted by surgery indication however, multinodular goitre was a significant predictor of IONM assisted identification of type 2b EBSLN (OR = 2.24, P = 0.01). Routine IONM provides intraoperative information to a high-volume thyroid surgeon regarding the recurrent and external nerves over and above direct visualization alone, and its utility could not be predicted by operative indication.
Publisher: MDPI AG
Date: 06-08-2020
Abstract: Adrenocortical Carcinoma (ACC) is a rare but aggressive malignancy with poor prognosis and limited response to available systemic therapies. Although complete surgical resection gives the best chance for long-term survival, ACC has a two-year recurrence rate of 50%, which poses a therapeutic challenge. High throughput analyses focused on characterizing the molecular signature of ACC have revealed specific micro-RNAs (miRNAs) that are associated with aggressive tumor phenotypes. MiRNAs are small non-coding RNA molecules that regulate gene expression by inhibiting mRNA translation or degrading mRNA transcripts and have been generally implicated in carcinogenesis. This review summarizes the current insights into dysregulated miRNAs in ACC tumorigenesis, their known functions, and specific targetomes. In addition, we explore the possibility of particular miRNAs to be exploited as clinical biomarkers in ACC and as potential therapeutics.
Publisher: The Endocrine Society
Date: 25-03-2023
Abstract: Management of sporadic medullary thyroid microcarcinoma smaller than 1 cm (micro-MTC) is controversial because of conflicting reports of prognosis. As these cancers are often diagnosed incidentally, they pose a management challenge when deciding on further treatment and follow-up. We report the outcomes of surgically managed sporadic micro-MTC in a specialist endocrine surgery and endocrinology unit and identify associations for recurrence and disease-specific survival in this population. Micro-MTCs were identified from a prospectively maintained surgery database, and slides were reviewed to determine pathological grade. The primary end points were recurrence, time to recurrence and disease-specific survival. Prognostic factors assessed included size, grade, lymph node metastasis (LNM), and postoperative calcitonin. From 1995 to 2022, 64 patients were diagnosed with micro-MTC with 22 excluded because of hereditary disease. The included patients had a median age of 60 years, tumor size of 4 mm, and 28 (67%) were female. The diagnosis was incidental in 36 (86%) with 4 (10%) being high grade, 5 (12%) having LNM and 9 (21%) having elevated postoperative calcitonin. Over a 6.6-year median follow-up, 5 (12%) developed recurrence and 3 (7%) died of MTC. High grade and LNM were associated with 10-year survival estimates of 75% vs 100% for low grade and no LNM (hazard ratio = 831 P & .01). High grade, LNM, and increased calcitonin were associated with recurrence (P & .01). Tumor size and type of surgery were not statistically significantly associated with recurrence or survival. No patients with low grade micro-MTC and normal postoperative calcitonin developed recurrence. Most sporadic micro-MTCs are detected incidentally and are generally associated with good outcomes. Size is not significantly associated with outcomes. Using grade, LNM, and postoperative calcitonin allows for the identification of patients at risk of recurrence to personalize management.
Publisher: Wiley
Date: 31-10-2015
DOI: 10.1111/ANS.12435
Publisher: Informa UK Limited
Date: 06-2013
DOI: 10.2147/OTT.S34956
Publisher: Wiley
Date: 28-10-2013
DOI: 10.1111/ANS.12433
Publisher: Springer Science and Business Media LLC
Date: 26-11-2020
DOI: 10.1007/S00268-019-05302-6
Abstract: We investigated outcomes in a cohort of patients with a biochemical diagnosis of primary hyperparathyroidism (pHPT) undergoing surgery for asymptomatic disease or target organ damage, where a focussed or four-gland operation was undertaken and the histopathology only reported a "large normal" parathyroid gland (LNP). Patients subjected to a parathyroidectomy for pHPT between 2012 and 2018 with a pathology of LNP were included. Patients with fat depletion or additional histological features of adenoma or hyperplasia in any of the resected glands were excluded. A control group was formed from 50 consecutive patients with the histological finding of adenoma or hyperplasia during the same study period. The primary outcome was biochemical normalisation of pHPT at 1-2 weeks and after 6 months post-operatively. Forty-eight LNP patients (2% of all parathyroidectomies) were included in the study group with 50 matched controls. LNP patients had a lower biochemical cure rate (81% vs. 98% P < 0.05) and a higher risk of recurrence (10% vs. 0%, P = 0.06). LNP patients had a milder form of pHPT (Ca This study highlights a controversial area in pHPT and reports LNP as a cause of pHPT. The biochemical analysis of this LNP group supports a benefit in resection in the setting of pHPT, although the risk of failure (persistence/recurrence) is higher than those with adenoma or hyperplasia. Stricter post-operative follow-up of LNP patients should be considered.
Publisher: American Association for Cancer Research (AACR)
Date: 15-03-2016
DOI: 10.1158/1538-7445.NONRNA15-B04
Abstract: Background & Aims: Adrenocortical carcinoma (ACC) has recurrence rates of ~50% and new methods of predicting recurrence are required to complement existing biomarkers (Ki-67 staining) to tailor adjuvant therapy. We have shown expression of PRINS, a long noncoding RNA (lncRNA) can predict ACC recurrence, which is the first clinical association of this lncRNA with outcome in cancer.(1) In keratinocytes where PRINS was discovered, PRINS interacts with the protein nucleophosphmin (NPM) allowing its translocation from the cytoplasm to the nucleus.(2) In the nucleus NPM binds to TP53 to increase its transcriptional activity.(3) TP53 mutations are a key driver of ACC. The aim of this study was to establish a biological basis for PRINS as a biomarker by investigating a tumour suppressor RNA action in ACC. Method: PRINS expression was quantified in clinical s les using RT-qPCR and Ki-67 staining using immunohistochemistry (IHC). PRINS expression in ACC cells (NCI-H295R) was restored using the mammalian expression vector containing full length of PRINS cDNA transcript (pcDNA3.1[PRINS]). Cell phenotypes were compared to cells transfected with an empty vector (pcDNA3.1[Blank]). Transcriptome analysis was performed on clinical s les of ACC (n=10) and normal adrenal cortex (n=6) using the ArrayStar Human LncRNA V3.0 microarray. Results: Using RT-PCR NCI-H295R cells were found to have low expression of PRINS compared to clinical s les of normal adrenal cortex (Fold change 0.37, P& .05) and ACC (Fold change 0.51, P& .05). Transfection with pcDNA3.1[PRINS] lead to restoration of PRINS expression above that of normal adrenal cortex (P& .05). In the pcDNA3.1[PRINS] NCI-H295R cells, rates of apoptosis were increased by 49.8% as assessed by Annexin V assays (P& .05) and cPARP protein expression compared to pcDNA3.1[Blank] transfected cells. Reduced cell proliferation of 30-40% was also found using MTS assays (P& .05) in PRINS transfected cells. Using RNA FISH, PRINS was localised to the cell cytoplasm. Correlation of ~26,000 mRNA transcripts found PRINS expression to be correlated with 48 mRNAs (Pearson Correlation Coefficients & 80%, corrected P& .05), including p53 related genes – TNFRSF11B, MKI-67 and TTK. MKI67 codes for the protein Ki-67 and in clinical s les, PRINS relative expression had a moderate negative linear relationship to Ki-67 IHC scoring (n=14, R2=0.38, P=0.02). Following PRINS restoration in NCI-H295R cells, MKI-67 was unchanged, however TP53 was increased (Fold change 1.5, P& .001) and TNFRSF11B reduced (Fold change 0.56, P& .05) supporting a mechanism of increased apoptosis. Conclusions: This first report of PRINS acting as a tumour suppressor in cancer supports the association with ACC outcomes. As PRINS is also under-expressed in breast and prostate cancer it offers potential as a biomarker in other cancers to improve quality of life and further opportunities for research into a novel mechanism of TP53 action in cancer. This project was supported by a Sydney Vital Research Scholarship Grant. 1. Glover, A. R. et al. Long noncoding RNA profiles of adrenocortical cancer can be used to predict recurrence. Endocrine-Related Cancer 22, 99–109 (2014). 2. Szegedi, K. et al. Expression and Functional Studies on the Noncoding RNA, PRINS. Int J Mol Sci 14, 205–225 (2011). 3. Colombo, E., Marine, J.-C., Danovi, D., Falini, B. & Pelicci, P. G. Nucleophosmin regulates the stability and transcriptional activity of p53. Nature Cell Biology 4, 529–533 (2002). Citation Format: Anthony R. Glover, Jing T. Zhao, Lauren J S Joo, Anthony J. Gill, Bruce G. Robinson, Stan B. Sidhu. The long noncoding RNA - PRINS as a novel recurrence biomarker and tumor suppressor for adrenocortical carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines 2015 Dec 4-7 Boston, MA. Philadelphia (PA): AACR Cancer Res 2016 (6 Suppl):Abstract nr B04.
Publisher: Mary Ann Liebert Inc
Date: 30-06-2022
Abstract: Background: The goal of radioactive iodine (RAI) in differentiated thyroid cancer (DTC) is to treat metastasis and reduce recurrence risk. International guidelines provide broad risk stratification to aid treatment decisions, but a more nuanced approach to in idualize care is warranted. We developed a predictive risk model for DTC. Methods: We performed a retrospective multivariable analysis of 899 patients who received RAI after thyroidectomy at a quaternary center in Australia between 2008 and 2016. Collected data included age, gender, histology, stimulated thyroglobulin (sTg), and 8th American Joint Committee Cancer (AJCC) staging. The ATA Modified Initial Risk (ATA) was calculated retrospectively. Recurrence was defined as clinically significant progression requiring either surgical intervention or administration of a second activity of RAI. Synchronous metastasis was defined as distant metastasis (i.e., outside of the neck) that was present at the time of diagnosis on structural imaging or initial post-iodine treatment scan. The features significantly associated with synchronous metastasis or recurrence were employed in the generation of a predictive risk model. A separate cohort of 393 patients who received RAI in 2017-2021 was used for validation. Results: On multivariate analysis, sTg ≥10 μg/L, extrathyroidal extension (ETE) and lymph node involvement predicted recurrence. Independent of ATA, patients with sTg ≥10 μg/L had a shorter disease-free survival (DFS) than those with sTg μg/L ( p 0.001). The ETE stratified by four histological categories was significantly associated with worse DFS ( p 0.001). In a subset of patients, the presence of thyroglobulin antibody (TgAb) did not influence recurrence in patients with sTg μg/L. On multivariate analysis, widespread ETE, sTg ≥10 μg/L, multifocal papillary thyroid cancer and follicular thyroid cancer were positively associated with synchronous metastasis. A predictive risk model was developed to estimate synchronous metastasis/recurrence risk and validated successfully in the second cohort. Conclusions: Our novel predictive risk model modifies and extends ATA stratification by including sTg and ETE, which we found to be independent predictors of both recurrence and synchronous metastasis in DTC.
Publisher: Springer Science and Business Media LLC
Date: 05-11-2022
Publisher: Springer Science and Business Media LLC
Date: 25-05-2021
Publisher: Springer Science and Business Media LLC
Date: 17-05-2016
DOI: 10.1245/S10434-016-5254-8
Abstract: Papillary thyroid cancer (PTC) frequently disseminates into cervical lymph nodes. Lateral node involvement is described in up to 50 % patients undergoing prophylactic lateral neck dissection. This study aimed to assess this finding and identify which factors predict for occult lateral node disease. Patients with fine needle aspiration-confirmed PTC (Bethesda V or VI), without evidence of cervical lymph node metastases, underwent a total thyroidectomy with prophylactic ipsilateral central and level 3 dissection. Level 3 nodes were removed by compartmental dissection or by s ling the sentinel nodes overlying the jugular vein, according to surgeon preference. Data were collected prospectively from January 2011 to August 2014. Statistical analysis was performed by SPSS software. A total of 137 patients underwent total thyroidectomy with prophylactic ipsilateral central and level 3 dissection for PTC. The incidence of occult level 3 disease was 30 % (41/137 patients). A total of 48 % of patients (66/137) harbored occult central neck disease. A total of 80.5 % of patients with pN1b disease had macrometastases (≥2 mm), and 15 % exhibited skip metastases with central compartment sparing. In patients with pN1b disease, a median of 6 level 3 nodes were retrieved, with an average involved nodal ratio of 0.29. Multivariate regression demonstrated risk factors for occult lateral neck metastasis include tumor size (odds ratio 1.1), upper pole tumors (odds ratio 6.6), and vascular invasion (odds ratio 3.2) (p < 0.05). PTC is associated with a significant incidence of occult central and lateral nodal metastases. In patients undergoing prophylactic central neck dissection, inclusion of level 3 dissection should be considered in patients with large upper lobe cancers.
Publisher: Wiley
Date: 12-01-2021
DOI: 10.1111/ANS.16553
Publisher: Wiley
Date: 09-08-2021
DOI: 10.1111/ANS.17128
Publisher: Oxford University Press (OUP)
Date: 05-08-2022
DOI: 10.1093/BJS/ZNAC276
Abstract: The mortality rate is low in endocrine surgery, making it a difficult outcome to use for quality improvement in in idual units. Lessons from population data sets are of value in improving outcomes. Data from the Australian and New Zealand Audit of Surgical Mortality (ANZASM) were used here to understand and elucidate potential systems issues that may contribute to preventable deaths. ANZASM data relating to 30-day mortality after thyroidectomy, parathyroidectomy, and adrenalectomy from 2009 to 2020 were reviewed. Mortality rates were calculated using billing data. Thematic analysis of independent assessor reports was conducted to produce a coding framework. A total of 67 deaths were reported, with an estimated mortality rate of 0.03–0.07 per cent (38 for thyroidectomy (0.03–0.06 per cent), 16 for parathyroidectomy (0.03–0.06 per cent), 13 for adrenalectomy (0.15–0.33 per cent)). Twenty-seven deaths (40 per cent) were precipitated by clinically significant adverse events, and 18 (27 per cent) were judged to be preventable by independent ANZASM assessors. Recurrent themes included inadequate preoperative assessment, lack of anticipation of intraoperative pitfalls, and failure to recognize and effectively address postoperative complications. Several novel themes were reiterated, such as occult ischaemic heart disease associated with death after parathyroid surgery, unexpected intraoperative difficulties from adrenal metastasis, and complications due to anticoagulation therapy after thyroid surgery. This study represents a large-scale national report of deaths after endocrine surgery and provides insights into these rare events. Although the overall mortality rate is low, 27 per cent of deaths involved systems issues that were preventable following independent peer review.
Publisher: Wiley
Date: 11-2018
DOI: 10.1111/ANS.14804
Publisher: MDPI AG
Date: 04-08-2020
Abstract: The incidence of thyroid cancer is rapidly increasing, mostly due to the overdiagnosis and overtreatment of differentiated thyroid cancer (TC). The increasing use of potent preclinical models, high throughput molecular technologies, and gene expression microarrays have provided a deeper understanding of molecular characteristics in cancer. Hence, molecular markers have become a potent tool also in TC management to distinguish benign from malignant lesions, predict aggressive biology, prognosis, recurrence, as well as for identification of novel therapeutic targets. In differentiated TC, molecular markers are mainly used as an adjunct to guide management of indeterminate nodules on fine needle aspiration biopsies. In contrast, in advanced thyroid cancer, molecular markers enable targeted treatments of affected signalling pathways. Identification of the driver mutation of targetable kinases in advanced TC can select treatment with mutation targeted tyrosine kinase inhibitors (TKI) to slow growth and reverse adverse effects of the mutations, when traditional treatments fail. This review will outline the molecular landscape and discuss the impact of molecular markers on diagnosis, surveillance and treatment of differentiated, poorly differentiated and anaplastic follicular TC.
Publisher: The Endocrine Society
Date: 28-06-2023
Publisher: Springer Science and Business Media LLC
Date: 18-03-2020
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.SURG.2019.05.078
Abstract: Papillary thyroid microcarcinoma is a subtype of thyroid cancer that may be managed with active surveillance rather than immediate surgery. Active surveillance decreases complication rates and may decrease health care costs. This study aims to analyze complication rates of thyroid surgery, papillary thyroid microcarcinoma recurrence, and survival rates. Additionally, the costs of surgery versus hypothetic active surveillance for papillary thyroid microcarcinoma are compared in an Australian cohort. Papillary thyroid microcarcinoma patients were included from a prospectively collected surgical cohort of patients treated for papillary thyroid cancer between 1985 and 2017. The primary outcomes were the complications of thyroid surgery, recurrence-free survival, overall survival, and cost of surgical treatment and active surveillance. In a total of 349 patients with papillary microcarcinoma with a median age of 48 years (range, 18-90 years), the permanent operative complications rate was 3.7%. Postoperative radioactive iodine did not decrease recurrence-free survival (P = .3). The total cost of surgical treatment was $10,226 Australian dollars, whereas hypothetic active surveillance was at a yearly cost of $756 Australian dollars. Estimated cost of surgical papillary thyroid microcarcinoma treatment was equivalent to the cost of 16.2 years of active surveillance. Surgery may have a long-term economic advantage for younger Australian patients with papillary thyroid microcarcinoma who are likely to require more than 16.2 years of follow-up in an active surveillance scheme.
Publisher: Springer Science and Business Media LLC
Date: 29-10-2021
DOI: 10.1245/S10434-021-10980-5
Abstract: Medullary thyroid carcinoma (MTC) can be targeted with tyrosine kinase inhibitors (TKIs). We aimed to report the outcomes of surgically managed MTC and to evaluate the impact of TKI use on patient survival. Consecutive patients treated surgically for MTC from 1986 to 2020 were identified from a prospectively collected database and were compared on the basis of stage at operation and TKI use. The primary outcome was overall survival (OS). Among 154 patients with a median age of 52 years, 40% presented with stage I/II disease and 60% presented with advanced (stage III or IV) disease. During a median follow-up of 7.5 years, 21% received TKIs for systemic disease. Those presenting with advanced disease were more likely to receive a TKI (31% vs. 7%), present with tumor invasion of the recurrent laryngeal nerve (RLN 12% vs. 0%) and undergo reoperation (42% vs. 23%) compared with stage I-II patients. For the 11 patients found to have invasion of the RLN, five had preoperative functional vocal cords. Five-year OS was 84% for advanced disease, and stage IV patients who received TKIs had a median survival of 21 years, versus 15 years for those who did not (p = 0.3). Surgery achieves long-term survival for patients with advanced disease, however these patients are at greater risk of requiring RLN resection due to invasion. A significant OS benefit was not seen for TKI use. For patients with local invasion, neoadjuvant TKI therapy may have a role in reducing local morbidity if confirmed to be of benefit in clinical trials.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 07-2018
Publisher: Oxford University Press (OUP)
Date: 16-10-2014
DOI: 10.1634/THEONCOLOGIST.2014-0135
Abstract: Papillary thyroid cancer (PTC) is the major contributor to the dramatically increasing incidence of thyroid cancer. Low-risk PTC shows the most rapid rate of increase because of changing trends in neck imaging and the use of fine needle aspiration to investigate thyroid nodules. The need for a paradigm shift in the management of these patients, to provide personalized treatment and surveillance plans, has led to the focus on molecular biomarker research. MicroRNAs (miRNAs) compose a class of molecules with promising applications for every stage of PTC management, including diagnosis, prognosis, treatment, and surveillance. Although most of the miRNA studies are currently preclinical, given the rapid progress of scientific discovery, clinical trials will not be far away. Thyroid clinicians will be expected to have good insights into the current status of PTC-related molecular translational research. This article focuses on the potential roles of miRNA in PTC management in the context of contemporary recommended clinical practice.
Publisher: Bioscientifica
Date: 02-2015
DOI: 10.1530/ERC-14-0457
Abstract: Adrenocortical carcinoma (ACC) is an aggressive malignancy with high rates of recurrence following surgical resection. Long noncoding RNAs (lncRNAs) play an important role in cancer development. Pathogenesis of adrenal tumours have been characterised by mRNA, microRNA and methylation expression signatures, but it is unknown if this extends to lncRNAs. This study describes lncRNA expression signatures in ACC, adrenal cortical adenoma (ACA) and normal adrenal cortex (NAC) and presents lncRNAs associated with ACC recurrence to identify novel prognostic and therapeutic targets. RNA was extracted from freshly frozen tissue with confirmation of diagnosis by histopathology. Focused lncRNA and mRNA transcriptome analysis was performed using the ArrayStar Human LncRNA V3.0 microarray. Differentially expressed lncRNAs were validated using quantitative reverse transcriptase-PCR and correlated with clinical outcomes. Microarray of 21 s les (ten ACCs, five ACAs and six NACs) showed distinct patterns of lncRNA expression between each group. A total of 956 lncRNAs were differentially expressed between ACC and NAC, including known carcinogenesis-related lncRNAs such as H19 , GAS5 , MALAT1 and PRINS ( P ≤0.05) 85 lncRNAs were differentially expressed between ACC and ACA ( P ≤0.05). Hierarchical clustering and heat mapping showed ACC s les correctly grouped compared with NAC and ACA. Sixty-six differentially expressed lncRNAs were found to be associated with ACC recurrence ( P ≤0.05), one of which, PRINS , was validated in a group of 20 ACCs and also found to be associated with metastatic disease on presentation. The pathogenesis of adrenal tumours extends to lncRNA dysregulation and low expression of the lncRNA PRINS is associated with ACC recurrence.
Publisher: Impact Journals, LLC
Date: 10-2015
Publisher: Bioscientifica
Date: 2021
DOI: 10.1159/000516358
Abstract: b i Objective: /i /b Our study aimed to analyse temporal trends in radioactive iodine (RAI) treatment for thyroid cancer over the past decade to analyse key factors associated with clinical decisions in RAI dosing and to confirm lower activities of RAI for low-risk patients were not associated with an increased risk of recurrence. b i Methods: /i /b Retrospective analysis of 1,323 patients who received RAI at a quaternary centre in Australia between 2008 and 2018 was performed. Prospectively collected data included age, gender, histology, and American Joint Committee on Cancer stage (7th ed). American Thyroid Association risk was calculated retrospectively. b i Results: /i /b The median activities of RAI administered to low-risk patients decreased from 3.85 GBq (104 mCi) in 2008–2016 to 2.0 GBq (54 mCi) in 2017–2018. The principal driver of this change was an increased use of 1 GBq (27 mCi) from 1.3% of prescriptions in 2008–2011 to 18.5% in 2017–2018. In patients assigned as low risk per ATA stratification, lower activities of 1 GBq or 2 GBq (27 mCi or 54 mCi) were not associated with an increased risk of recurrence. In patients assigned to intermediate- or high-risk categories who received RAI as adjuvant therapy, there was no difference in risk of recurrence between 4 GBq (108 mCi) and 6 GBq (162 mCi). b i Conclusions: /i /b Our data demonstrate an evolution of RAI activities consistent with translation of ATA guidelines into clinical practice. Use of lower RAI activities was not associated with an increase in recurrence in low-risk thyroid cancer patients. Our data also suggest lower RAI activities may be as efficacious for adjuvant therapy in intermediate- and high-risk patients.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.SURG.2019.06.048
Abstract: Postoperative follow-up of papillary thyroid cancer includes serial serum thyroglobulin levels. This study aimed to determine whether stimulated thyroglobulin levels measured in the early postoperative period can accurately quantify the risk of recurrence in papillary thyroid cancer. We undertook a cohort study of patients who underwent total thyroidectomy for papillary thyroid cancer ≥10 mm in the period 2000 to 2016 with complete biochemical data. All patients had a postoperative stimulated thyroglobulin measured within 3 months after total thyroidectomy. Structural recurrence was defined as disease detected on imaging and confirmed on histology. Biochemical disease was defined as patients with stimulated serum thyroglobulin ≥1 ng/mL with no evidence of structural disease. This study included 502 patients with a mean age of 50 years and median tumor diameter of 20 mm. Median follow-up was 18 months. Stimulated postoperative thyroglobulin was measured before radioiodine-ablation and was categorized into 3 groups: (1) 219 (44%) patients had thyroglobulin <1 ng/mL (2) 55 (11%) had 1ng/mL ≤ thyroglobulin <2 ng/mL and (3) 228 (45%) had thyroglobulin ≥2 ng/mL. The structural recurrence rate for each group was 5%, 2%, and 30%, respectively (P < .0001). In patients undergoing total thyroidectomy for papillary thyroid cancer, early postoperative stimulated thyroglobulin accurately quantifies the risk of structural disease recurrence.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.MCE.2017.03.014
Abstract: Medullary thyroid carcinoma (MTC) is an aggressive and rare cancer with limited treatment options for metastatic disease. Due to this, there is a need for a better understanding of MTC biology in the hope of improved treatments. One area of improved understanding of cancer biology is epigenetics. Epigenetics is defined as cellular processes which alter gene expression independent of changes in the primary DNA sequence. These processes include modifications such as DNA methylation, microRNA deregulation and post-translational histone modifications, all of which have been implicated in tumorigenesis of MTC. Transcription of the main driver of MTC - the REarranged during Transfection (RET) proto-oncogene can also be modulated by epigenetic alterations. This review will present a review of MTC and its epigenetic links with a particular focus on targeting epigenetic mechanisms as novel therapeutic strategies.
Publisher: Springer Science and Business Media LLC
Date: 16-10-2015
DOI: 10.1245/S10434-014-4133-4
Abstract: Adrenocortical carcinoma (ACC) is a rare malignancy that carries a poor prognosis. There has yet to be a large Australian series that documents the characteristics of ACC and there are a paucity of data on management and the long-term outcomes. We sought to provide a unique insight into the management of ACC in Australia as well as to identify factors associated with prognosis and survival. A multivariate analysis of a cohort of patients identified with ACC between 1998 and 2013 was undertaken. Recurrence-free survival (RFS) and overall survival (OS) were assessed as the main outcome measures and correlated with multiple clinical variables in order to identify prognostic markers. Of the 104 patients identified, a total of 98 patients with complete clinical and outcome data were included in the study. Median OS was 56 months, with the 5-year survival being 48 % (95 % confidence interval 36-59). On multivariate analysis, age ≥50 years, metastases at presentation, and evidence of extra-adrenal invasion were found to be statistically associated with reduced OS. RFS was analyzed in patients without metastases. On multivariate analysis, extra-adrenal invasion and no preoperative endocrine investigations were found to be statistically significant poor prognostic factors, with a non-significant trend for higher in idual surgeon volume to be associated with improved resection margins and RFS. We present clinical outcomes and prognostic factors for patients with ACC in a landmark Australian series. We suggest that management in a specialized tertiary endocrine and/or surgical oncology unit is more likely to lead to improved outcomes.
Publisher: Bioscientifica
Date: 07-2019
DOI: 10.1530/ERC-19-0036
Abstract: Adrenocortical carcinoma (ACC) has high recurrence rates and poor prognosis with limited response to conventional cancer therapy. Recent contributions of high-throughput transcriptomic profiling identified microRNA-497 (miR-497) as significantly underexpressed, while lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) as overexpressed in ACC. miR-497 is located in the chromosomal region 17p13.1, in which there is a high frequency of loss of heterozygosity in ACC. We aim to investigate the interaction of miR-497 and MALAT1 in ACC and its functional roles in the process of tumourigenesis. In this study, we demonstrated miR-497 post-transcriptionally repressed MALAT1 while MALAT1 also competes for miR-497 binding to its molecular target, EIF4E (eukaryotic translation initiation factor 4E). We showed that overexpression of miR-497 and silencing of MALAT1 suppressed cellular proliferation and induced cell cycle arrest through downregulation of EIF4E expression. Furthermore, MALAT1 directly binds to SFPQ (splicing factor proline and glutamine rich) protein, indicating its multifaceted roles in ACC pathophysiology. This is the first study to identify the feedback axis of miR-497- MALAT1 / EIF4E in ACC tumourigenesis, providing novel insights into the molecular functions of noncoding RNAs in ACC.
Publisher: Springer Science and Business Media LLC
Date: 19-07-2021
Publisher: Oxford University Press (OUP)
Date: 22-04-2014
DOI: 10.1002/BJS.9502
Abstract: Patients who present with palpable inguinal melanoma nodal metastasis have two surgical options: inguinal or ilioinguinal lymph node dissection. Indications for either operation remain controversial. This study examined survival and recurrence outcomes following ilioinguinal dissection for patients with palpable inguinal nodal metastasis, and assessed the incidence and preoperative predictors of pelvic nodal metastasis. This was a retrospective clinicopathological analysis of consecutive surgical patients with stage III malignant melanoma. All patients underwent a standardized ilioinguinal dissection at a specialist tertiary oncology hospital over a 12-year period (1998–2010). Some 38·9 per cent of 113 patients had metastatic pelvic nodes. Over a median follow-up of 31 months, the 5-year overall survival rate was 28 per cent for patients with metastatic inguinal and pelvic nodes, and 51 per cent for those with inguinal nodal metastasis only (P = 0·002). The nodal basin control rate was 88·5 per cent. Despite no evidence of pelvic node involvement on preoperative computed tomography (CT), six patients (5·3 per cent) with a single metastatic inguinal lymph node had metastatic pelvic lymph nodes. Logistic regression analysis showed that the number of metastatic inguinal nodes (odds ratio 1·56 P = 0·021) and suspicious CT findings (odds ratio 9·89 P = 0·001) were both significantly associated with metastatic pelvic nodes. The specificity of CT was good (89·2 per cent) in detecting metastatic pelvic nodes, but the sensitivity was limited (57·9 per cent). Metastatic pelvic nodes are common when palpable metastatic inguinal nodes are present. Long-term survival can be achieved following their resection by ilioinguinal dissection. As metastatic pelvic nodes cannot be diagnosed reliably by preoperative CT, patients presenting with palpable inguinal nodal metastasis should be considered for ilioinguinal dissection.
Publisher: Future Medicine Ltd
Date: 08-2014
DOI: 10.2217/IJE.14.3
Publisher: Wiley
Date: 28-10-2013
DOI: 10.1002/CNCR.28254
Abstract: Papillary thyroid cancer (PTC) persistence or recurrence and the need for long-term surveillance can cause significant inconvenience and morbidity in patients. Currently, recurrence risk stratification is accomplished by using clinicopathologic factors, and serum thyroglobulin is the only commercially available marker for persistent or recurrent disease. The objective of this study was to determine microRNA (miRNA) expression in PTC and determine whether 1 or more miRNAs could be measured in plasma as a biomarker for recurrence. Patients with recurrent PTC (Rc-PTC) and those without recurrence (NR-PTC) were retrospectively recruited for a comparison of their tumor miRNA profiles. Patients with either newly diagnosed PTC or multinodular goiter who were undergoing total thyroidectomy were prospectively recruited for an analysis of preoperative and postoperative circulating miRNA levels. Healthy volunteers were recruited as the control group. MicroRNA-222 and miR-146b were over-expressed 10.8-fold and 8.9-fold, respectively, in Rc-PTC tumors compared with NR-PTC tumors (P = .014 and P = .038, respectively). In plasma from preoperative PTC patients, levels of miR-222 and miR-146b were higher compared with the levels in plasma from healthy volunteers (P < .01 for both). Reductions of 2.7-fold and 5.1-fold were observed in the plasma levels of miR-222 and miR-146b, respectively, after total thyroidectomy (P = .03 for both). This study demonstrated that tumor levels of miR-222 and miR-146b are associated with PTC recurrence and that miR-222 and miR-146b levels in the circulation correspond to the presence of PTC. The potential of these miRNAs as tumor biomarkers to improve patient stratification according to the risk of recurrence and as circulating biomarkers for PTC surveillance warrants further study.
Publisher: Georg Thieme Verlag KG
Date: 19-07-2023
Abstract: Background Frontline doctors managing the current novel coronavirus 2019 (COVID-19) pandemic work under stressful conditions due to change in workload, working pattern, and worries about the infection to themselves and families with frequently changing treatment protocols. Their psychological well-being is necessary for the effective management of the health crisis. Objectives This study aims to assess the psychological state and worries of frontline doctors while dealing with the COVID-19 pandemic, the various coping skills employed by them for maintaining their mental health, and the knowledge about illness and related myths and misinformation among them. A further objective is to compare the above between two groups of frontline doctors: the consultants and the junior residents (JR) working in the hospital. Materials and Methods A total of 164 participants (76 consultants and 88 JRs) were cross-sectionally evaluated online using a prevalidated questionnaire within a period of 3 months after obtaining institutional ethics approval Statistical Analysis The study s le and results were described using descriptive analysis. The association between the categorical variables was measured using chi-squared test. Results Most participants frequently updated themselves through reliable sources (consultants = 92%, JR = 73.9%) predominantly from the hospital task force and university. Overall, 71% of consultants and 58% of JRs were worried about being infected. JRs were significantly more worried about the spread of infection due to faulty sterilization of the protective equipment as compared to the consultants (p = 0.031). Most participants were worried about their families getting infected (consultants = 79%, JR =89.8%). Both consultants (18.4%) and JRs (35.2%) had sleep disturbances. Although most did not have syndromal depressive features and COVID-19-related anxiety, tiredness (45.1%) and worrying too much (47.5%) were the most common psychological symptoms. Almost all participants (consultants = 76.3%, JR = 80.7%) used multiple coping styles, such as avoiding thinking about COVID-19, listening to music, and physical activities. Conclusion Frontline doctors overall reported higher worries regarding their family being infected and protective equipment-related issues, whereas they had less core depressive and anxiety symptoms. They had adequate COVID-19-related awareness and used multiple coping skills.
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2020
End Date: 2019
Funder: Cancer Institute of New South Wales
View Funded ActivityStart Date: 2016
End Date: 2020
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2016
End Date: 2019
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2014
End Date: 2014
Funder: Royal Australasian College of Surgeons
View Funded ActivityStart Date: 2013
End Date: 2013
Funder: Royal North Shore Hospital
View Funded ActivityStart Date: 2015
End Date: 2015
Funder: Royal Australasian College of Surgeons
View Funded Activity