Mark S Sywak

Kolling Institute of Medical Research, Sydney, New South Wales, Australia

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Publications (128)408.6 Total impact

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    ABSTRACT: Background The accepted management of lithium-associated hyperparathyroidism (LiHPT) is open four-gland parathyroid exploration (OPTX). This approach has recently been the subject of controversy. A recent study has shown very high long-term recurrence rates after OPTX, whereas some have promoted unilateral focused parathyroidectomy as appropriate management. The aim was to evaluate long-term outcomes after surgery for LiHPT and to assess the accuracy of preoperative imaging.Methods This was a retrospective cohort study that comprised all patients undergoing initial surgery for LiHPT between 1990 and 2013. The cumulative recurrence rate was calculated by the Kaplan–Meier method. The sensitivity and specificity of sestamibi scintigraphy and ultrasound imaging for identification of single-gland versus multigland disease was investigated using intraoperative assessment as reference.ResultsOf 48 patients, 45 had OPTX and three underwent focused parathyroidectomy. Multiglandular disease was documented in 27 patients and 21 had a single adenoma. The median follow-up was 5·9 (range 0·3–22) years and 16 patients died during follow-up. The 10-year cumulative recurrence rate was 16 (95 per cent confidence interval 2 to 29) per cent. No permanent complications occurred after primary surgery for LiHPT. Twenty-four patients had at least one preoperative ultrasound or sestamibi scan. For concordant sestamibi scintigraphy and ultrasound imaging, the sensitivity and specificity for identifying single-gland versus multigland disease was five of nine and five of eight respectively.Conclusion Surgery provided a safe and effective management option for patients with LiHPT in this series, with a long-term cure rate of well over 80 per cent.
    British Journal of Surgery 07/2014; · 4.84 Impact Factor
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    ABSTRACT: Assessment for thyroid nodules includes ultrasound (US) and cytology according to the Bethesda classification. There is no firm consensus regarding clinical management for nodules classified as Bethesda III. Our aim was investigate the value of US to predict malignancy in these nodules. Patients with Bethesda III nodules who underwent thyroid surgery from July 2011 to July 2013 were included. Inclusion criteria mandated that US were available for review by two observers blinded to each other's results and histological outcome. The nodules were scrutinized with six US criteria: hypoechoic attenuation (HA), irregular margins (IM), taller than wide, microcalcifications (MC), loss of halo, and increased central vascularity. Disagreements between observers were solved by consensus. There were 141 patients (121 women) with a mean age of 55 years. Mean nodule size was 25 mm. The malignancy rate was 13 %. Interobserver ratios were moderate to very strong for all six predictors (kappa = 0.60-0.94). However, only HA, IM, and MC were predictors of malignancy by univariate analysis (all p < 0.002). Logistic regression revealed an odds ratio of malignancy versus no malignancy for HA 4.8, IM 3.3, and MC 4.0 (all p < 0.05). The positive and negative predictive value for malignancy when having one or more of these three criteria was 22 % and 98 %, respectively. HA, IM, and MC were predictors of malignancy in Bethesda III nodules. In addition, the negative predictive value for any of these three criteria was high; a nodule that lacks all of these three criteria is thus unlikely to be malignant.
    Annals of Surgical Oncology 05/2014; · 4.12 Impact Factor
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    ABSTRACT: IntroductionFour-dimensional computed tomography (4DCT) is a new parathyroid localization technique not previously reported in Australia. It provides both functional and anatomical imaging in a single test, with superior sensitivity compared with sestamibi scintigraphy (SeS). This study examines the utility of 4DCT in defined clinical situations.Methods This is a retrospective cohort study in a tertiary referral hospital setting. One hundred consecutive operative cases of primary hyperparathyroidism (99 patients) undergoing both preoperative 4DCT and SeS. Localization studies were correlated with operative findings, histopathology and clinical outcomes. The utility of 4DCT was analysed in three common clinical settings: primary cases with positive SeS (Group A, n = 68), primary cases with negative SeS (Group B, n = 21) and re-operative cases (Group C, n = 11).ResultsThe overall sensitivity of 4DCT was 92% compared with 70% for SeS. The sensitivity of 4DCT was superior to SeS in Groups B and C (76% versus 0% and 91% versus 46%, respectively). The overall cure rate was 98%, with 94% of cases completed as minimally invasive procedures. Up to 62% of Group B cases potentially avoided a bilateral neck exploration owing to a positive 4DCT.Conclusions4DCT is an accurate technique providing both functional and anatomical localization of abnormal parathyroid glands. However, the advantage of speed and simplicity in image acquisition needs to be balanced against the small risk of increased radiation exposure in the younger patient group.
    ANZ Journal of Surgery 04/2014; · 1.50 Impact Factor
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    ABSTRACT: IntroductionAcute suppurative thyroiditis and recurrent abscess formation due to third and fourth branchial anomalies typically present in children. However, thyroid abscesses in branchial anomalies may occur in adulthood as well. Failure to recognize and delayed drainage of a neck abscess may lead to a fulminant life-threatening outcome.Methods This is a retrospective case series. The study group comprised all patients presenting over a 12-month period from January to December 2012 with thyroid abscesses and a branchial cleft anomaly in two centres, one adult and the other paediatric. Patient demographics, clinical presentation, imaging, surgical management, definitive histology and outcomes were documented.ResultsFive patients were identified with a history of thyroid abscesses. Only one was a child (aged 9 years) with the other four being adults (aged 20, 34, 37 and 41 years). All patients had third or fourth left branchial cleft anomalies, presenting as suppurative thyroiditis with a left-sided thyroid abscess. Management options ranged from abscess drainage on initial presentation, primary thyroid lobectomy or delayed thyroid lobectomy following abscess drainage.Conclusion Acute suppurative thyroidits and thyroid abscesses is not just a paediatric diagnosis but may present at any age. In both children and adults, a thyroid abscess almost always arises from branchial cleft anomalies.
    ANZ Journal of Surgery 04/2014; · 1.50 Impact Factor
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    ABSTRACT: MiR-210 is a key regulator of response to hypoxia. Pheochromocytomas (PCs) and paragangliomas (PGLs) with germline SDHx or VHL mutations have pseudohypoxic gene expression signatures. We hypothesized that PC/PGLs containing SDHx or VHL mutations, and SDH-deficient gastrointestinal stromal tumours (GISTs), would overexpress miR-210 relative to non-SDH or -VHL-mutated counterparts. MiR-210 was analysed by quantitative PCR in: (a) 39 PC/PGLs, according to genotype (1 SDHA, 5 SDHB, 7 VHL, 3 NF1, 7 RET, 15 sporadic, 1 unknown) and pathology (18 benign, 8 atypical, 11 malignant, 2 unknown); (b) 18 gastrointestinal stromal tumours, according to SDHB immunoreactivity (9 SDH-deficient and 9 SDH-proficient); and (c) two novel SDHB-mutant neurosphere cell lines. MiR-210 was higher in SDHx- or VHL-mutated PC/PGLs (7.6 fold) compared to tumours without SDHx or VHL mutations (p=0.0016). MiR-210 was higher in malignant than in unequivocally benign PC/PGLs (p=0.05) but significance was lost when benign and atypical tumours were combined (p=0.08). In multivariate analysis, elevated miR-210 was significantly associated with SDHx or VHL mutation, but not with malignancy. In GISTs, miR-210 was higher in SDH-deficient (median 2.58) compared to SDH-proficient tumours (median 0.60; p=0.0078). MiR-210 was higher in patient-derived neurosphere cell lines containing SDHB mutations (6.5-fold increase) compared to normal controls, in normoxic conditions (p<.01). Furthermore, siRNA-knockdown of SDHB in HEK293 cells increased miR-210 by 2.7-fold (p = 0.001) under normoxia. Overall, our results suggest that SDH deficiency in PC, PGL and GISTs induces miR-210 expression and substantiates the role of aberrant hypoxic-type cellular responses in the development of these tumours.
    Endocrine Related Cancer 03/2014; · 5.26 Impact Factor
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    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. Cancer 2013;119:4358-4365. © 2013 American Cancer Society.
    Cancer 12/2013; 119(24):4358-65. · 5.20 Impact Factor
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    ABSTRACT: Primary hyperaldosteronism (PA) is a common cause of secondary hypertension. Two recurrent mutations (G151R and L168R) in the potassium channel gene KCNJ5 have been identified that affect the Kir3.4 potassium channel found in the cells of the zona glomerulosa of the adrenal gland. The aim of this study was to determine the prevalence of KCNJ5 mutations in an Australian cohort of patients and to correlate these findings with clinical outcome data, in order to describe the clinical impact on patients who harbour this mutation. Direct Sanger sequencing for KCNJ5 on DNA from adrenal tumour tissue of 83 patients with PA in a cohort study was undertaken and mutation status correlated with clinical outcome data. Seventy-one of 83 patients (86%) had adrenocortical adenomas and 12 patients (14%) had bilateral adrenal hyperplasia. A total of 34 (41%) patients were found to have heterozygous somatic mutations in KCNJ5, G151R and L168R. No germ line mutations were identified. Patients with mutations were predominately female (68% versus 49%) and significantly younger at presentation (48 versus 55 years). When correlated with clinical data, our results demonstrated that patients with KCNJ5 mutations were more likely to be cured following surgery without the requirement for ongoing medications. Our findings in a large Australian cohort show that patients with mutations in KCNJ5 present earlier with the signs and symptoms of PA benefit from surgical intervention. Moreover, our results highlight the importance of a thorough workup and management plan for younger patients who present with hypertension.
    ANZ Journal of Surgery 11/2013; · 1.50 Impact Factor
  • ANZ Journal of Surgery 10/2013; · 1.50 Impact Factor
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    ABSTRACT: BACKGROUND: Papillary thyroid cancer (PTC) persistence or recurrence and the need for long-term surveillance can cause sig-nificant inconvenience and morbidity in patients. Currently, recurrence risk stratification is accomplished by using clinicopatho-logic 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. METHODS: Patients with recurrent PTC (Rc-PTC) and those without recur-rence (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. RESULTS: 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 5.014 and P 5.038, respectively). In plasma from preoperative PTC patients, levels of miR-222 and miR-146b were higher compared with the lev-els 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 5.03 for both). CONCLUSIONS: This study demonstrated that tumor lev-els 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. Cancer 2013;000:000-000. V C 2013 American Cancer Society.
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    ABSTRACT: Papillary thyroid carcinoma (PTC) is uncommonly associated with tumor-related mortality, although local recurrence can be a frequent and difficult problem. This study was conducted to clarify the pattern of structural locoregional recurrence in PTC. A retrospective cohort study of patients undergoing surgical intervention for PTC was undertaken. Data were collected from a comprehensive thyroid cancer database maintained within a single tertiary referral center. The primary outcome measure was cancer recurrence requiring surgical intervention. Secondary outcome measures were site of recurrence, time to recurrence, and risk factors for recurrence. In the period 1980-2013, 1,183 patients with PTC were included in the study. The overall rate of structural recurrence requiring reoperative surgery was 7.9 %. The median time to reoperation was 31 months. Younger age, male gender, large primary tumor diameter, and number of positive lymph nodes at initial presentation were all significantly associated with disease recurrence. The lateral compartments (levels I, II, III, IV, V) were involved almost twice as frequently as the central compartment (level VI) (67 vs 32 %, P < 0.01). The distribution of recurrences was level I (1 %), level II (12 %), level III (18 %), level IV (18 %), level V (17 %), level VI (32 %), level VII (2 %). In a center with a liberal approach to central compartment lymph node dissection for PTC, the lateral neck compartment is the most common site of structural recurrence requiring reoperative surgery.
    World Journal of Surgery 10/2013; · 2.23 Impact Factor
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    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 divider (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/permanent hypoparathyroidism or temporary/permanent 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 divider 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.
    ANZ Journal of Surgery 10/2013; · 1.50 Impact Factor
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    ABSTRACT: The histopathological criteria for carcinoma proposed by the World Health Organization (WHO) are imperfect predictors of the malignant potential of parathyroid tumors. Negative parafibromin (PF) and positive protein gene product 9.5 (PGP9.5) staining are markers of CDC73 mutation and occur commonly in carcinoma but rarely in adenomas. We investigated whether PF and PGP9.5 staining could be used to predict the behavior of atypical parathyroid adenomas-tumors with atypical features that do not fulfill WHO criteria for malignancy. Long-term outcomes were compared across four groups: group A, WHO-positive criteria/PF-negative staining; group B, WHO(+)/PF(+), group C; WHO(-)/PF(-); and group D, WHO(-)/PF(+). Eighty-one patients were included in the period 1999-2012: group A (n = 13), group B (n = 14), group C (n = 21), and group D (n = 33). Mortality and recurrence rates, respectively, for group A were 15 and 38 %, for group B 7 and 36 %, for group C 0 and 10 %, and for group D 0 and 0 %. The PGP9.5(+) ratios for groups A to D were 85, 78, 71, and 12 %, further informing prognosis. Five-year disease-free survival for groups A to D were 55, 80, 78, and 100 %, respectively. Tumor recurrence was significantly associated with PF (p = 0.048) and PGP9.5 (p = 0.003) staining. Although WHO criteria are essential to differentiate parathyroid carcinoma from benign tumors, the presence of negative PF staining in an atypical adenoma predicts outcome better, whereas PF-positive atypical adenomas do not recur and can be considered benign. PF-negative atypical adenomas have a low but real recurrence risk and should be considered tumors of low malignant potential.
    Annals of Surgical Oncology 10/2013; · 4.12 Impact Factor
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    ABSTRACT: Background Central compartment lymph node metastases in papillary thyroid carcinoma (PTC) are difficult to detect pre-operatively and the role of routine or prophylactic central compartment lymph node dissection (CLND) in managing PTC remains controversial. The aim of this project was to create a nomogram able to predict the occurrence of central compartment lymph node metastasis using readily available pre-operative clinical characteristics. Methods Records from patients undergoing total thyroidectomy and lymph node dissection for PTC in the period 1968-2012 were analysed. Nodal status was based on results of serial H&E examination. Age, sex, tumor size, tumor site and multifocality were included in a multivariable logistic regression model to predict lymph node metastasis. A coefficient-based nomogram was developed and validated using an external patient cohort. Results The study population included 914 patients (80% females) with an average central compartment nodal yield of 8 per patient. Central compartment lymph node metastases were present in 390 patients (42.7%). The variables with the strongest predictive value were age (p<0.001), male sex (p<0.001), increasing tumor size (p<0.001) and tumor multifocality (p<0.05). The nomogram had good discrimination with a concordance index of 76.4% (95%CI 73.3% to 79.4%), supported by an external validation point estimate of 61.5% (95%CI 49.5% to 73.6%). An online calculator and smartphone application were developed for point of care use. Conclusions A validated nomogram utilizing readily available preoperative variables has been developed to give a predicted probability of central lymph node metastases in patients presenting with PTC. This nomogram may help guide surgical decision making in PTC.
    Thyroid: official journal of the American Thyroid Association 10/2013; · 2.60 Impact Factor
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    ABSTRACT: Many authors advocate routine subtotal parathyroidectomy or total parathyroidectomy and autotransplantation for patients with multiple endocrine neoplasia type 1 (MEN1). Many of these patients are young and recurrence may take decades. Four-gland parathyroid exploration carries a higher risk of complication than minimally invasive parathyroidectomy (MIP). The aim of this study was to assess the role of selective removal of only abnormal glands for MEN1 in the era of MIP. For this retrospective, cohort study we collected data on patients undergoing parathyroidectomy for MEN1 from an endocrine surgery database. We reviewed preoperative localization studies, operative findings, histopathology, and clinical outcomes. Twenty-six patients underwent parathyroidectomy for MEN1-associated hyperparathyroidism over the 23-year study period. Six of 10 (60%) patients in the total parathyroidectomy group and 4 of 10 (40%) patients in the subtotal parathyroidectomy group developed hypocalcemia. The subtotal and total parathyroidectomy groups both had a recurrence rate of 30% with a mean follow-up rate of 106 and 133 months, respectively. The MIP group had no hypocalcemia or recurrence with a mean follow-up of 19 months. MIP with excision of only documented abnormal parathyroid glands provides an acceptable outcome for patients with MEN1, avoiding the potential for permanent hypoparathyroidism in young patients. It is accepted that recurrent disease is inevitable in these patients; however, such recurrence may take decades to occur and may be able to be dealt with by a further focused procedure.
    Surgery 07/2013; 154(1):101-5. · 3.37 Impact Factor
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    ABSTRACT: BRAF V600E is a prominent oncogene in papillary thyroid cancer (PTC), but its role in PTC-related patient mortality has not been established. To investigate the relationship between BRAF V600E mutation and PTC-related mortality. Retrospective study of 1849 patients (1411 women and 438 men) with a median age of 46 years (interquartile range, 34-58 years) and an overall median follow-up time of 33 months (interquartile range, 13-67 months) after initial treatment at 13 centers in 7 countries between 1978 and 2011. MAIN OUTCOMES AND MEASURES: Patient deaths specifically caused by PTC. Overall, mortality was 5.3% (45/845; 95% CI, 3.9%-7.1%) vs 1.1% (11/1004; 95% CI, 0.5%-2.0%) (P < .001) in BRAF V600E-positive vs mutation-negative patients. Deaths per 1000 person-years in the analysis of all PTC were 12.87 (95% CI, 9.61-17.24) vs 2.52 (95% CI, 1.40-4.55) in BRAF V600E-positive vs mutation-negative patients; the hazard ratio (HR) was 2.66 (95% CI, 1.30-5.43) after adjustment for age at diagnosis, sex, and medical center. Deaths per 1000 person-years in the analysis of the conventional variant of PTC were 11.80 (95% CI, 8.39-16.60) vs 2.25 (95% CI, 1.01-5.00) in BRAF V600E-positive vs mutation-negative patients; the adjusted HR was 3.53 (95% CI, 1.25-9.98). When lymph node metastasis, extrathyroidal invasion, and distant metastasis were also included in the model, the association of BRAF V600E with mortality for all PTC was no longer significant (HR, 1.21; 95% CI, 0.53-2.76). A higher BRAF V600E-associated patient mortality was also observed in several clinicopathological subcategories, but statistical significance was lost with adjustment for patient age, sex, and medical center. For example, in patients with lymph node metastasis, the deaths per 1000 person-years were 26.26 (95% CI, 19.18-35.94) vs 5.93 (95% CI, 2.96-11.86) in BRAF V600E-positive vs mutation-negative patients (unadjusted HR, 4.43 [95% CI, 2.06-9.51]; adjusted HR, 1.46 [95% CI, 0.62-3.47]). In patients with distant tumor metastasis, deaths per 1000 person-years were 87.72 (95% CI, 62.68-122.77) vs 32.28 (95% CI, 16.14-64.55) in BRAF V600E-positive vs mutation-negative patients (unadjusted HR, 2.63 [95% CI, 1.21-5.72]; adjusted HR, 0.84 [95% CI, 0.27-2.62]). In this retrospective multicenter study, the presence of the BRAF V600E mutation was significantly associated with increased cancer-related mortality among patients with PTC. Because overall mortality in PTC is low and the association was not independent of tumor features, how to use BRAF V600E to manage mortality risk in patients with PTC is unclear. These findings support further investigation of the prognostic and therapeutic implications of BRAF V600E status in PTC.
    JAMA The Journal of the American Medical Association 04/2013; 309(14):1493-501. · 29.98 Impact Factor
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    ABSTRACT: BACKGROUND: Therapeutic central neck dissection (CND) is an accepted part of the management of papillary thyroid carcinoma (PTC), while prophylactic CND remains controversial. Regardless of the indication for CND, the lower anatomic border of the central compartment, specifically the inclusion or otherwise of level VII, is not always clearly defined in the literature. This study aimed to determine if the routine inclusion of level VII lymph node dissection as part of CND confers increased utility in the detection of macrometastatic lymph nodes compared with level VI dissection alone. METHOD: This was a prospective cohort study of patients undergoing CND for PTC at a tertiary referral center. All patients received either a prophylactic or therapeutic CND. The CND specimens were divided by the surgeon into level VI and level VII at the level of the suprasternal notch and submitted separately for histopathology. Criteria for macroscopic lymph node disease were taken from the American Joint Committee on Cancer (AJCC) recommendations for breast cancer. RESULTS: A total of 45 patients with PTC underwent total thyroidectomy and routine CND, at a tertiary referral center; 77 % of the therapeutic CND group had positive level VI lymph nodes, and 38 % had positive level VII lymph nodes. Of the prophylactic CND group, 50 % of patients had positive level VI nodes and 16 % has positive level VII nodes detected. All patients with positive level VII lymph nodes in the prophylactic CND group had macrometastatic disease. Temporary hypocalcemia rate was 31 % in the therapeutic group and 6 % in the prophylactic CND group. One patient experienced permanent hypoparathyroidism. There was no vascular injury or recurrent laryngeal nerve palsy in either group. CONCLUSIONS: CND incorporating both level VI and level VII can be undertaken safely through a cervical incision with no increased risk of permanent complications of hypoparathyroidism or recurrent laryngeal nerve injury. Failure to include level VII as part of CND will leave significant macrometastatic nodal disease behind in both therapeutic and prophylactic dissections. As level VII is in direct anatomic continuity with the pretracheal level VI nodes, it should be routinely included as part of every CND.
    Annals of Surgical Oncology 01/2013; · 4.12 Impact Factor
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    ABSTRACT: BACKGROUND: The prognostic influence of lateral neck nodal metastases present at the time of diagnosis of papillary thyroid cancer (PTC) remains controversial. This study aims to document disease outcomes and nodal recurrence rates in such patients. METHODS: Patients with PTC and lateral neck nodal metastases who underwent concurrent total thyroidectomy, central and lateral compartment neck dissection between 2000 and 2010 were identified from the prospectively maintained surgical databases of The University of Sydney and University of Wisconsin Endocrine Surgical Units. Disease outcomes and nodal recurrence rates were compared at 12 months post-operatively and in longer-term follow-up. RESULTS: During this 11-year period, 121 patients were identified. Mean age was 45 years; 58% were female and 98% underwent post-operative radioactive iodine ablation. At a median follow-up of 31 months (range 12-140), there were no disease-specific deaths and disease-free survival (defined by stimulated serum thyroglobulin (Tg) < 2.0 μg/L, negative clinical and radiological examination) was 66%. Of the 50 patients with persistently elevated Tg measured 12 months post-operatively, 15 developed clinical lateral neck nodal recurrence. All have undergone re-operative surgery. Elevated stimulated Tg at 12 months post-operatively and a nodal ratio of >30% were significantly associated with an increased risk of lateral neck nodal recurrence. CONCLUSION: With total thyroidectomy, formal compartmental neck dissection and radioactive iodine treatment, disease-free survival can be achieved in the majority of patients with PTC and synchronous lateral neck nodal metastases. A persistently elevated Tg post-operatively and a high ratio of metastatic nodes identify patients at increased risk of locoregional recurrence.
    ANZ Journal of Surgery 01/2013; · 1.50 Impact Factor
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    ABSTRACT: Background Our aim was to compare the rate of structural recurrence between patients who had lesser doses of radioactive iodine (RAI) and those who had traditional greater doses for remnant ablation after total thyroidectomy for papillary thyroid carcinoma (PTC). Methods A retrospective cohort study of patients who had undergone thyroidectomy and RAI for PTC was undertaken. We divided the cohort into those who had ≤3 GBq (75 mCi) RAI (group A) and those who had >3 GBq (75 mCi) RAI (group B). The primary outcome measure was the rate of structural recurrence. Results Of 1,171 patients with PTC from 1990 to 2012 who were followed for a mean of 60 months, 970 with T1–T3 tumors underwent RAI in addition to thyroidectomy. The mean first dose of RAI was 2.5 GBq (68 mCi) for group A (n = 153) and 4.7 GBq (127 mCi) for group B (n = 817; P < .001). The overall rate of recurrence was 8%. When corrected for T stage, the recurrence rates were not different for T1 tumors (2% group A versus 4% group B; P = .54) nor for T2 and T3 tumors (P = .36 and .55, respectively). On multivariate analysis, the dose of RAI was not an independent predictor for structural recurrence. Conclusion Decreasing the dose of RAI at initial ablation for patients with pT1–pT3 PTC does not seem to be associated with an increased risk of structural cancer recurrence.
    Surgery 01/2013; 154(6):1337–1345. · 3.37 Impact Factor
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    ABSTRACT: Identification of BRAFV600E in thyroid neoplasia may be useful because it is specific for malignancy, connotes a worse prognosis and is the target of novel therapies currently under investigation. Sanger sequencing is the 'gold-standard' for mutation detection but is subject to sampling error and requires resources beyond many diagnostic pathology laboratories. In this study, we compared immunohistochemistry using a BRAFV600E mutation-specific monoclonal antibody to Sanger sequencing on DNA from formalin fixed paraffin embedded tissue, in a well characterised cohort of 101 PTC patients. For all cases an IHC result was available, however five cases failed Sanger sequencing. Of the 96 cases with molecular data, 68 (71%) were BRAFV600E positive by IHC and 59 (61%) were BRAFV600E positive by sequencing. Eleven cases were discordant. One case was negative by IHC and initially positive by sequencing. Repeat sequencing of that sample and sequencing of a macrodissected sample were negative for BRAFV600E. Of 10 cases positive by IHC but negative by sequencing on whole sections, repeat sequencing on macrodissected tissue confirmed the IHC result in 7 cases (suggesting these were false negatives of sequencing on whole sections). In 3 cases repeat sequencing on recut tissue remained negative (including using massive parallel sequencing), but these cases demonstrated relatively low neoplastic cellularity. We conclude that immunohistochemistry for BRAFV600E is more sensitive and specific than Sanger sequencing in the routine diagnostic setting and may represent the new gold standard for detection of BRAFV600E mutation in PTC.
    Endocrine Related Cancer 09/2012; · 5.26 Impact Factor
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    ABSTRACT: BACKGROUND: Intraoperative sentinel lymph node (SLN) examination during breast cancer surgery guides the need for immediate axillary clearance. This may be difficult to implement when surgery is performed distant to the centres where pathological examination is undertaken. We aimed to implement and validate a telepathology service for the remote examination of breast SLN by frozen section (FS). METHODS: We tested an Internet-based remote microscopy system to report intraoperative FS in real time from two district hospitals without on-site anatomical pathology services. RESULTS: FS was performed remotely on 52 patients. Seventeen out of 52 patients had metastases, of which there were six false-negative diagnoses comprising four of micrometastatic disease and two of isolated tumour cells (ITCs). There were no false-negative diagnoses for macrometastatic disease and no false-positive diagnoses. As a control, we audited our experience with 239 consecutive SLN FS examined by on-site pathologists. Sixty out of 239 patients had metastases, of which there were 24 false-negative diagnoses comprising 12 cases of ITC, 5 of micrometastases and 7 of macrometastases. The accuracy of remote FS was equivalent to that of in-house FS (88.2% versus 89.9%). CONCLUSION: Remote FS for breast SLN is an accurate procedure ,which is not inferior to FS performed on site.
    ANZ Journal of Surgery 08/2012; · 1.50 Impact Factor

Publication Stats

1k Citations
408.60 Total Impact Points

Institutions

  • 2009–2013
    • Kolling Institute of Medical Research
      Sydney, New South Wales, Australia
  • 2006–2013
    • University of Sydney
      Sydney, New South Wales, Australia
    • Royal Brisbane Hospital
      Brisbane, Queensland, Australia
  • 2004–2013
    • Royal North Shore Hospital
      Sydney, New South Wales, Australia
  • 2011
    • Baylor College of Medicine
      • Department of Surgery
      Houston, TX, United States
  • 2010
    • University of Wisconsin, Madison
      • Department of Surgery
      Madison, MS, United States
  • 2007
    • Alfred Hospital
      Melbourne, Victoria, Australia
  • 2005
    • Children's Hospital at Westmead
      Sydney, New South Wales, Australia
  • 2002–2004
    • The University of Calgary
      Calgary, Alberta, Canada
  • 2003
    • Tom Baker Cancer Centre
      Calgary, Alberta, Canada