Geographic disparities in thyroid cancer staging at presentation: Insights from an Australian context.

BACKGROUND: Thyroid cancer diagnoses have increased over recent decades at a rate much higher than that of any other cancer in Australia. Rural patients are known to have reduced access to healthcare and may have different thyroid cancer presentation rates. This study examined the relationship between thyroid cancer diagnosis and patient rurality. METHODS: Data from the Australia and New Zealand Thyroid Cancer Registry from 2017 to 2022 were analyzed, stratifying patient postcodes into rurality groups using the Australian Statistical Geography Standard. The American Thyroid Association (ATA) guidelines were used to stratify risk categories and management to compare treatment adequacy between the groups. Statistical analysis assessed demographic, clinical, and management differences. RESULTS: Among 1766 patients, 70.6% were metropolitan (metro) and 29.4% were non-metropolitan (non-metro). Non-metro patients were older at diagnosis (median 56 vs. 50 years, p < 0.001), presented more frequently with T stage greater than 1 (stage 2-4, 41.9% vs. 34.8%, and p = 0.005), AJCC stage greater than 1 (stage 2-4, 18.5% vs. 14.6%, and p = 0.019), and cancers larger than 4 cm (14.3% vs. 9.9%, p = 0.005). No significant differences in treatment adequacy were observed between the groups for ATA low-risk cancers. CONCLUSIONS: Non-metropolitan patients in the registry present with more advanced thyroid cancer, possibly due to differences in healthcare access. Further research should assess long-term survival outcomes and influencing factors. Understanding the impact on patient outcomes and addressing healthcare access barriers can optimize thyroid cancer care across geographic regions in Australia.

Artificial Intelligence for Pre-operative Diagnosis of Malignant Thyroid Nodules Based on Sonographic Features and Cytology Category.

BACKGROUND: Current diagnosis and classification of thyroid nodules are susceptible to subjective factors. Despite widespread use of ultrasonography (USG) and fine needle aspiration cytology (FNAC) to assess thyroid nodules, the interpretation of results is nuanced and requires specialist endocrine surgery input. Using readily available pre-operative data, the aims of this study were to develop artificial intelligence (AI) models to classify nodules into likely benign or malignant and to compare the diagnostic performance of the models. METHODS: Patients undergoing surgery for thyroid nodules between 2010 and 2020 were recruited from our institution's database into training and testing groups. Demographics, serum TSH level, cytology, ultrasonography features and histopathology data were extracted. The training group USG images were re-reviewed by a study radiologist experienced in thyroid USG, who reported the relevant features and supplemented with data extracted from existing reports to reduce sampling bias. Testing group USG features were extracted solely from existing reports to reflect real-life practice of a non-thyroid specialist. We developed four AI models based on classification algorithms (k-Nearest Neighbour, Support Vector Machine, Decision Tree, Naïve Bayes) and evaluated their diagnostic performance of thyroid malignancy. RESULTS: In the training group (n = 857), 75% were female and 27% of cases were malignant. The testing group (n = 198) consisted of 77% females and 17% malignant cases. Mean age was 54.7 ± 16.2 years for the training group and 50.1 ± 17.4 years for the testing group. Following validation with the testing group, support vector machine classifier was found to perform best in predicting final histopathology with an accuracy of 89%, sensitivity 89%, specificity 83%, F-score 94% and AUROC 0.86. CONCLUSION: We have developed a first of its kind, pilot AI model that can accurately predict malignancy in thyroid nodules using USG features, FNAC, demographics and serum TSH. There is potential for a model like this to be used as a decision support tool in under-resourced areas as well as by non-thyroid specialists.

Hypotension in Posterior Retroperitoneoscopic Versus Transperitoneal Laparoscopic Adrenalectomy.

INTRODUCTION: Despite preoperative optimization, hemodynamic instability can be a major challenge during adrenalectomy. Even brief episodes of intraoperative hypotension can be associated with ischemia-reperfusion injury. This study aimed to compare intraoperative hemodynamic parameters between posterior retroperitoneoscopic adrenalectomy (PRA) and transperitoneal laparoscopic adrenalectomy (TPA). METHODS: This is a retrospective study of patients undergoing PRA and TPA without conversion or concomitant intraabdominal pathology from 2008 to 2019. The primary outcome was intraoperative hypotension defined by mean arterial pressure <60 mm Hg or the need for ≥1 intravenous vasopressors at least 30 min after anesthetic induction. RESULTS: Overall, 108 patients met the inclusion criteria; 33 (30.6%) had pheochromocytoma, 26 (24.1%) had aldosterone excess, 8 (7.4%) had corticosteroid excess, and 41 (38.0%) had nonfunctioning adrenal tumors. Of these, 68 (63.0%) underwent PRA and 40 (37.0%) underwent TPA. Age, sex, body mass index, preinduction blood pressure, number of preoperative antihypertensives, and histopathological diagnosis were similar in the two groups. Tumor size was greater in the TPA group. The presence of pheochromocytoma was an independent risk factor for hypotension. Multivariate analysis revealed that PRA was associated with a higher risk of experiencing a mean arterial pressure <60 mm Hg (odds ratio 4.44, 95% confidence interval 1.27-15.54, P = 0.02) and the need for ≥1 intravenous vasopressors (odds ratio 9.97, 95% confidence interval 3.34-29.78, P < 0.001) compared with TPA. CONCLUSIONS: Although PRA offers several advantages over TPA, it carries a greater risk of intraoperative hypotension. A prospective trial is required to validate these findings. Nevertheless, institution of risk reduction strategies is encouraged to be considered for individuals undergoing PRA.

Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery.

BACKGROUND: Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, and there is concern about impaired organ perfusion. METHODS: In a pragmatic, international trial, we randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death. RESULTS: During and up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters (interquartile range, 2.9 to 4.9), as compared with 6.1 liters (interquartile range, 5.0 to 7.4) in 1493 patients in the liberal fluid group (P<0.001). The rate of disability-free survival at 1 year was 81.9% in the restrictive fluid group and 82.3% in the liberal fluid group (hazard ratio for death or disability, 1.05; 95% confidence interval, 0.88 to 1.24; P=0.61). The rate of acute kidney injury was 8.6% in the restrictive fluid group and 5.0% in the liberal fluid group (P<0.001). The rate of septic complications or death was 21.8% in the restrictive fluid group and 19.8% in the liberal fluid group (P=0.19); rates of surgical-site infection (16.5% vs. 13.6%, P=0.02) and renal-replacement therapy (0.9% vs. 0.3%, P=0.048) were higher in the restrictive fluid group, but the between-group difference was not significant after adjustment for multiple testing. CONCLUSIONS: Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and was associated with a higher rate of acute kidney injury. (Funded by the Australian National Health and Medical Research Council and others; RELIEF ClinicalTrials.gov number, NCT01424150 .).

Primary hyperparathyroidism in adults-(Part II) surgical management and postoperative follow-up: Position statement of the Endocrine Society of Australia, The Australian & New Zealand Endocrine Surgeons, and The Australian & New Zealand Bone and Mineral Society.

OBJECTIVE: To develop evidence-based recommendations to guide the surgical management and postoperative follow-up of adults with primary hyperparathyroidism. METHODS: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing eight key questions. RESULTS: Diagnostic imaging does not determine suitability for surgery but can guide the planning of surgery in suitable candidates. First-line imaging includes ultrasound and either parathyroid 4DCT or scintigraphy, depending on local availability and expertise. Minimally invasive parathyroidectomy is appropriate in most patients with concordant imaging. Bilateral neck exploration should be considered in those with discordant/negative imaging findings, multi-gland disease and genetic/familial risk factors. Parathyroid surgery, especially re-operative surgery, has better outcomes in the hands of higher volume surgeons. Neuromonitoring is generally not required for initial surgery but should be considered for re-operative surgery. Following parathyroidectomy, calcium and parathyroid hormone levels should be re-checked in the first 24 h and repeated early if there are risk factors for hypocalcaemia. Eucalcaemia at 6 months is consistent with surgical cure; parathyroid hormone levels do not need to be re-checked in the absence of other clinical indications. Longer-term surveillance of skeletal health is recommended. CONCLUSIONS: This position statement provides up-to-date guidance on evidence-based best practice surgical and postoperative management of adults with primary hyperparathyroidism.

Primary hyperparathyroidism in adults-(Part I) assessment and medical management: Position statement of the endocrine society of Australia, the Australian & New Zealand endocrine surgeons, and the Australian & New Zealand bone and mineral society.

OBJECTIVE: To formulate clinical consensus recommendations on the presentation, assessment, and management of primary hyperparathyroidism (PHPT) in adults. METHODS: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing nine key questions. RESULTS: PHPT is a biochemical diagnosis. Serum calcium should be measured in patients with suggestive symptoms, reduced bone mineral density or minimal trauma fractures, and in those with renal stones. Other indications are detailed in the manuscript. In patients with hypercalcaemia, intact parathyroid hormone, 25-hydroxy vitamin D, phosphate, and renal function should be measured. In established PHPT, assessment of bone mineral density, vertebral fractures, urinary tract calculi/nephrocalcinosis and quantification of urinary calcium excretion is warranted. Parathyroidectomy is the only definitive treatment and is warranted for all symptomatic patients and should be considered for asymptomatic patients without contraindications to surgery and with >10 years life expectancy. In patients who do not undergo surgery, we recommend annual evaluation for disease progression. Where the diagnosis is not clear or the risk-benefit ratio is not obvious, multidisciplinary discussion and formulation of a consensus management plan is appropriate. Genetic testing for familial hyperparathyroidism is recommended in selected patients. CONCLUSIONS: These clinical consensus recommendations were developed to provide clinicians with contemporary guidance on the assessment and management of PHPT in adults. It is anticipated that improved health outcomes for individuals and the population will be achieved at a decreased cost to the community.

Patient Reported Experience on Consenting for Surgery - Elective Versus Emergency Patients.

INTRODUCTION: Informed consent for surgery is a medical and legal requirement, but completing these does not necessarily translate to high patient satisfaction. This patient-reported experience study aimed to examine the surgical consent process, comparing the patients' experience in elective and emergency settings. METHODS: Over a 6-mo period, postoperative patients at The Alfred Hospital Breast and Endocrine Surgical Unit were invited to participate in a survey on the surgical consent process - including perceived priorities, information provided and overall experience. Standard statistical techniques were used, with a significant P-value of < 0.05. RESULTS: A total of 412 patients were invited, with 130 (32%) responses. More patients underwent elective surgery (N= 90, 69%) than emergency surgery (N = 40, 31%). Emergency patients were more likely to sign the consent form regardless of its contents (93% versus 39%, P < 0.001) and more likely to be influenced by external pressures (63% versus 1%, P < 0.001). Elective patients were more likely to want to discuss their surgery with a senior surgeon (74% versus 23%, P < 0.001) and more likely to seek advice from external sources (83% versus 10%, P < 0.001). Both groups highly valued the opportunity to ask questions (67% versus 63%, P = 0.65). CONCLUSION: This study shows patients have a range of different priorities in preparation for surgery. Therefore, each consent process should be patient-specific, and focus on providing the patient with quality resources that inform decision-making.

Hereditary Endocrine Tumors and Associated Syndromes: A Narrative Review for Endocrinologists and Endocrine Surgeons.

OBJECTIVE: Hereditary endocrine tumors (HET) were among the first group of tumors where predisposition syndromes were recognized. The utility of genetic awareness is having the capacity to treat at an earlier stage, screen for other manifestations and initiate family cascade testing. The aim of this narrative review is to describe the most common hereditary syndromes associated with frequently encountered endocrine tumors, with an emphasis on screening and surveillance. METHODS: A MEDLINE search of articles for relevance to endocrine tumors and hereditary syndromes was performed. RESULTS: The most common hereditary syndromes associated with frequently encountered endocrine tumors are described in terms of prevalence, genotype, phenotype, penetrance of malignancy, surgical management, screening, and surveillance. CONCLUSION: Medical practitioners involved in the care of patients with endocrine tumors should have an index of suspicion for an underlying hereditary syndrome. Interdisciplinary care is integral to successful, long-term management of such patients and affected family members.

Oncologic Outcomes After Isolated Limb Infusion for Advanced Melanoma: An International Comparison of the Procedure and Outcomes Between the United States and Australia.

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose chemotherapy to extremities affected by locally advanced or in-transit melanoma. This study compared the outcomes of melanoma patients treated with ILI in the United States of America (USA) and Australia (AUS). METHODS: Patients with locally recurrent in-transit melanoma treated with ILI at USA or AUS centers between 1992 and 2018 were identified. Demographic and clinicopathologic characteristics were collected. Primary outcomes of treatment response, in-field progression-free survival (IPFS), distant progression-free survival (DPFS), and overall survival (OS) were evaluated by the Kaplan-Meier method. Multivariable analysis evaluated whether availability of new systemic therapies affected outcomes. RESULTS: More ILIs were performed in AUS (n = 411, 60 %) than in the USA (n = 276, 40 %). In AUS, more ILIs were performed for stage 3B disease than in the USA (62 % vs 46 %; p < 0.001). The reported complete response rates were similar (AUS 30 % vs USA 29 %). Among the stage 3B patients, AUS patients had better IPFS (p = 0.001), whereas DPFS and OS were similar between the two countries. Among the stage 3C patients, the USA patients had better OS (p < 0.001), whereas IPFS and DPFS were similar. Availability of new systemic therapies did not affect IPFS or DPFS in either country. However, the USA patients who received ILI after ipilimumab approval in 2011 had significantly improved OS (hazard ratio, 0.62; p = 0.013). CONCLUSIONS: AUS patients were treated at an earlier disease stage than the USA patients with better IPFS for stage 3B disease. The USA patients treated after the availability of new systemic therapies had a better OS.

International Multicenter Experience of Isolated Limb Infusion for In-Transit Melanoma Metastases in Octogenarian and Nonagenarian Patients.

BACKGROUND: Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON). PATIENTS AND METHODS: ON patients (≥ 80 years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (< 80 years). A cytotoxic drug combination of melphalan and actinomycin-D was used. RESULTS: Of the 687 patients undergoing a first ILI, 160 were ON patients (median age 84 years; range 80-100 years). Compared with the younger cohort (n = 527; median age 67 years; range 29-79 years), ON patients were more frequently female (70.0% vs. 56.9%; p = 0.003), had more stage IIIB disease (63.8 vs. 53.3%; p = 0.02), and underwent more upper limb ILIs (16.9% vs. 9.5%; p = 0.009). ON patients experienced similar Wieberdink limb toxicity grades III/IV (25.0% vs. 29.2%; p = 0.45). No toxicity-related limb amputations were performed. Overall response for ON patients was 67.3%, versus 64.6% for younger patients (p = 0.53). Median in-field progression-free survival was 9 months for both groups (p = 0.88). Median distant progression-free survival was 36 versus 23 months (p = 0.16), overall survival was 29 versus 40 months (p < 0.0001), and melanoma-specific survival was 46 versus 78 months (p = 0.0007) for ON patients compared with younger patients, respectively. CONCLUSIONS: ILI in ON patients is safe and effective with similar response and regional control rates compared with younger patients. However, overall and melanoma-specific survival are shorter.

Changes in Tracheal Tube Cuff Pressure and Recurrent Laryngeal Nerve Conductivity During Thyroid Surgery.

BACKGROUND: The aetiology of recurrent laryngeal nerve (RLN) neurapraxia is unclear in most RLN palsies post-thyroidectomy. We hypothesised that high intralaryngeal pressures impede RLN conductivity, in turn contributing to RLN palsy. Therefore, we measured tracheal tube (TT) cuff pressure (as a surrogate for intralaryngeal pressure) and RLN conduction during ten standard manoeuvres in thyroidectomy, to assess for correlation between cuff pressure and RLN conductivity. METHODS: A prospective cohort study of thyroidectomy during 2018. For each thyroid lobe, TT cuff pressure was continuously measured via an air pressure transducer. RLN conduction (amplitude and latency) was measured using continuous neuromonitoring. Changes in mean TT cuff pressure and median nerve conduction from baseline measurements were analysed using Student's t test and Wilcoxon signed-rank test. RESULTS: In a total of 50 RLNs, the mean baseline TT cuff pressure of 19.5 ± 8.9 mmHg increased significantly to 22.0 mmHg during anteromedial rotation of the thyroid (p < 0.05). RLN conduction changed during manipulation of the superior thyroid pole with shortening of latency (-0.49% from baseline, p = 0.05) and reduction in amplitude (-12.0% from baseline, p = 0.02). The timing of these deviations did not correlate with the increased TT cuff pressure. In three cases of temporary RLN palsy, the mean cumulative case TT cuff pressure was significantly higher (24.8 mmHg, p = 0.02). CONCLUSIONS: This study demonstrates that TT cuff pressure and RLN conductivity can change significantly with manipulation of the thyroid and that high TT cuff pressures may be associated with RLN injuries.

Anti-Thyroid Antibodies and TSH as Potential Markers of Thyroid Carcinoma and Aggressive Behavior in Patients with Indeterminate Fine-Needle Aspiration Cytology.

BACKGROUND: Indeterminate fine-needle aspiration cytology (FNAC) imposes challenges in the management of thyroid nodules. This study aimed to examine whether preoperative anti-thyroid antibodies (Abs) and TSH are indicators of thyroid malignancy and aggressive behavior in patients with indeterminate FNAC. METHODS: This was a retrospective study of thyroidectomy patients from 2008 to 2016. We analyzed Abs and TSH levels, FNAC, and histopathology. Serum antibody levels were categorized as 'Undetectable', 'In-range' if detectable but within normal range, and 'Elevated' if above upper limit of normal. 'Detectable' levels referred to 'In-range' and 'Elevated' combined. RESULTS: There were 531 patients included. Of 402 patients with preoperative FNAC, 104 (25.9%) had indeterminate cytology (Bethesda III-V). Of these, 39 (37.5%) were malignant and 65 (62.5%) benign on histopathology. In the setting of indeterminate FNAC, an increased risk of malignancy was associated with 'Elevated' thyroglobulin antibodies (TgAb) (OR 7.25, 95% CI 1.13-77.15, P = 0.01) and 'Elevated' thyroid peroxidase antibodies (TPOAb) (OR 6.79, 95% CI 1.23-45.88, P = 0.008). Similarly, while still 'In-range', TSH ≥ 1 mIU/L was associated with an increased risk of malignancy (OR 3.23, 95% CI 1.14-9.33, P = 0.01). In all patients with malignancy, the mean tumor size was 8 mm larger in those with TSH ≥ 1 mIU/L (P = 0.03); furthermore, in PTC patients, 'Detectable' TgAb conferred a 4 × risk of lymph node metastasis (95% CI 1.03-13.77, P = 0.02). CONCLUSION: In this cohort, in indeterminate FNAC patients, Abs and TSH were associated with an increased risk of malignancy. Additionally, TgAb and TSH were potential markers of aggressive biology. As such, they may be diagnostic and prognostic adjuncts.

Long-Term Oncologic Outcomes After Isolated Limb Infusion for Locoregionally Metastatic Melanoma: An International Multicenter Analysis.

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose regional chemotherapy to patients with locally advanced or in-transit melanoma located on a limb. The current international multicenter study evaluated the perioperative and long-term oncologic outcomes for patients who underwent ILI for stage 3B or 3C melanoma. METHODS: Patients undergoing a first-time ILI for stage 3B or 3C melanoma (American Joint Committee on Cancer [AJCC] 7th ed) between 1992 and 2018 at five Australian and four United States of America (USA) tertiary referral centers were identified. The primary outcome measures included treatment response, in-field (IPFS) and distant progression-free survival (DPFS), and overall survival (OS). RESULTS: A total of 687 first-time ILIs were performed (stage 3B: n = 383, 56%; stage 3C; n = 304, 44%). Significant limb toxicity (Wieberdink grade 4) developed in 27 patients (3.9%). No amputations (grade 5) were performed. The overall response rate was 64.1% (complete response [CR], 28.9%; partial response [PR], 35.2%). Stable disease (SD) occurred in 14.5% and progressive disease (PD) in 19.8% of the patients. The median follow-up period was 47 months, with a median OS of 38.2 months. When stratified by response, the patients with a CR or PR had a significantly longer median IPFS (21.9 vs 3.0 months; p < 0.0001), DPFS (53.6 vs 12.7 months; p < 0.0001), and OS (46.5 vs 24.4 months; p < 0.0001) than the nonresponders (SD + PD). CONCLUSION: This study is the largest to date reporting long-term outcomes of ILI for locoregionally metastatic melanoma. The findings demonstrate that ILI is effective and safe for patients with stage 3B or 3C melanoma confined to a limb. A favorable response to ILI is associated with significantly longer IFPS, DPFS, and OS.

Thyroidectomy Then and Now: A 50-Year Australian Perspective.

BACKGROUND: Since the mid-1800s, thyroidectomy has transformed from a procedure associated with high to near-zero mortality. Nonetheless, surgeons must continue to strive to improve patient care. Using historical records and contemporary data, this study compares the practice and outcomes of thyroid surgery at a tertiary institution during two periods, 50 years apart. METHODS: 'The Alfred Hospital Clinical Reports' recorded all cases of surgically managed thyroid disease from 1946 to 1959. These historical cases were compared to contemporary thyroidectomy cases at the Alfred Hospital from 2007 to 2016. Cases were compared for surgical indication and post-operative outcomes. RESULTS: There were 746 patients in the historical group (mean age 53 years; 87% female) and 787 patients in the contemporary group (mean age 52 years; 80% female). The most common indication for thyroidectomy in both groups was non-toxic nodular goitre. A greater proportion of the contemporary group were diagnosed with thyroid malignancy (27% vs. 8%; p < 0.001). The contemporary group recorded significantly fewer cases of thyrotoxic crisis (2.1% vs. 0%; p = 0.001), permanent nerve palsy (4.6% vs. 0.4%; p < 0.001) and bilateral nerve palsy (1.2% vs. 0%; p = 0.01). There were no mortalities in the contemporary group, while the historical data recorded three deaths (0.44%). CONCLUSIONS: This study compared thyroid surgery in two cohorts separated by a 50-year period. While it is not surprising that outcomes of thyroidectomy have improved, this study uniquely demonstrates trends of thyroid surgery over time and areas in which further improvements may be made.

Safety and Efficacy of Isolated Limb Infusion Chemotherapy for Advanced Locoregional Melanoma in Elderly Patients: An Australian Multicenter Study.

BACKGROUND: Isolated limb infusion (ILI) offers a minimally invasive treatment option for locally advanced extremity melanoma. OBJECTIVE: The aim of the current study was to evaluate the safety and efficacy of ILI in elderly patients in an Australian multicenter setting. METHODS: The results of 316 first ILI procedures, performed between 1992 and 2008 in five Australian institutions, were identified and analyzed, with the main focus on elderly patients (≥75 years of age). All institutions used the same protocol: melphalan was circulated in the isolated limb for 20-30 min (±actinomycin D), and toxicity, responses, and survival were recorded. RESULTS: Characteristics of patients aged ≥75 years (n = 148) were similar to those aged <75 years (n = 168), except that older patients had more melanoma deposits (median 4 vs. 5; p = 0.035) and lower limb volumes (5.4 vs. 6.5 L; p = 0.001). Median drug circulation times were lower in the older group (21 vs. 24 min; p = 0.04), and older patients experienced less limb toxicity (grade III/IV in 22 and 37% of patients, respectively; p = 0.003). A complete response (CR) was seen in 27% of patients aged ≥75 years and in 38% of patients aged <75 years (p = 0.06), while overall response rates were 72 and 77%, respectively (p = 0.30). No difference in survival was seen (p = 0.69). CONCLUSIONS: The ILI technique proved safe and effective in elderly patients. When present, toxicity was localized, and lower compared with younger patients, possibly due to shorter drug circulation times. CR rates were higher in younger patients, although not significantly, while overall response and survival were equal. Optimization of perioperative factors in elderly patients may allow response rates to be raised further, while maintaining low toxicity.

Australian Multicenter Study of Isolated Limb Infusion for Melanoma.

PURPOSE: Isolated limb infusion (ILI) offers a less invasive alternative to isolated limb perfusion (ILP) for the treatment of locally advanced extremity melanoma. In Australia, ILI has essentially completely replaced ILP. The aim of this study was to collect and evaluate the results of ILI in an Australian multicenter setting. PATIENTS AND METHODS: The results of 316 first ILI procedures, performed between 1992 and 2008 in five Australian institutions, were collectively analyzed, with all five institutions using the same protocol. Melphalan was circulated in the isolated limb for 20-30 min (±actinomycin D). Response was determined using the World Health Organization criteria, and limb toxicity was assessed using the Wieberdink scale. RESULTS: The median patient age was 74 years (range 28-100) and 59 % of patients were female. Overall response rate was 75 % (complete response [CR] 33 %; partial response 42 %). Stable disease was seen in 18 % of patients and progressive disease in 7 %. Wieberdink grade III or higher was seen in 30 % of the cases. No toxicity-related amputations occurred, and median survival was 44 months. In patients with a CR, median survival was 80 months (p = 0.014). On multivariate analysis, Breslow thickness, lower-limb ILI, and a procedure performed at the Melanoma Institute Australia remained significant predictors for response, although not for survival. CONCLUSIONS: This Australian multicenter study of ILI is the largest reported to date. ILI is a useful technique that can be safely and effectively performed across tertiary referral centers for the successful management of advanced extremity melanoma. Increased optimization of perioperative factors might allow response rates to be raised further, while maintaining acceptable toxicity.

Frequency of residual melanoma in wide local excision (WLE) specimens after complete excisional biopsy.

OBJECTIVE: We sought to better understand the role of wide local excision (WLE) in the treatment of cutaneous melanoma by analyzing residual or locally metastatic disease in WLE specimens of melanomas initially diagnosed with a complete excisional biopsy. METHODS: This was a retrospective review of 807 consecutive WLEs of melanomas diagnosed after complete excisional biopsy. All specimens were reviewed by a single dermatopathologist. Risk of residual or locally metastatic disease was analyzed using univariate and multivariate logistic regression models. RESULTS: In the 807 WLE specimens, further melanoma was found in 34 cases (4.2%; 95% confidence interval [CI] 2.9-5.8). Residual primary melanoma was found in 33 of these. On univariate analysis, features associated with residual or locally metastatic disease were histologic subtype (odds ratio 3.0; 95% CI 1.3-7.1, P = .01) and tumor location (odds ratio 7.3; 95% CI 2.0-26.6, P < .01). On multivariate analysis, lentigo maligna was independently associated with melanoma remaining in WLE specimens (odds ratio 2.7; 95% CI 1.0-7.3, P = .04). CONCLUSION: Residual melanoma in WLE specimens after histologically assessed complete excisional biopsy is not uncommon. Patients with lentigo maligna subtype melanomas are most at risk. Our findings indicate that the procedure of WLE is most important therapeutically for its role in controlling the primary tumor, rather than in preventing local metastatic recurrence.

No need to abandon focused parathyroidectomy: a multicenter study of long-term outcome after surgery for primary hyperparathyroidism.

OBJECTIVE: The aim of this study was to investigate long-term outcomes after focused parathyroidectomy (FPTX) and open 4-gland parathyroid exploration (OPTX) for primary hyperparathyroidism (pHPT). BACKGROUND: Concerns about increased long-term recurrence rates after FPTX in conjunction with decreased operative times for OPTX have led some groups to abandon FPTX in favor of routine 4-gland exploration. METHODS: This is a multicenter retrospective cohort study of patients undergoing parathyroidectomy for pHPT from 1990 to 2013. The patient cohort was divided into 2 groups, FPTX and OPTX, based on intention-to-treat analysis. The primary outcome measure was the persistence of pHPT. Secondary outcome measures were differences in the long-term recurrence rate of persisting pHPT and surgical complications. RESULTS: A total of 4569 patients (3585 females) were included. The overall persistence and recurrence rates were 2.2% and 0.9%, respectively, after a median follow-up of 6.5 years. There were 2531 FPTX cases and 2038 OPTX cases. The initial persistence rate was higher for FPTX than for OPTX (2.7% vs 1.7%, P = 0.036); however, the long-term recurrence rate was not different (5-year 0.6% vs 0.4%, log-rank P = 0.08). Complications were more common in OPTX than in FPTX (7.6% vs 3.6%, P < 0.001). CONCLUSIONS: FPTX was associated with fewer operative complications and an equivalent rate of long-term recurrence than with OPTX. Although initial persistence rates were higher after FPTX than after OPTX, most were readily resolved with subsequent early reoperation. FPTX should not be abandoned in patients with positive preoperative localization.

Papillary thyroid cancer-derived exosomes contain miRNA-146b and miRNA-222.

BACKGROUND: With the increasing diagnosis of indolent papillary thyroid cancer (PTC), the task of identifying those likely to suffer from recurrence is becoming ever more challenging. MicroRNA (miRNA/miR) in the circulation has been demonstrated as potential biomarkers of recurrence in PTC. This study aimed to investigate in vitro if extracellular miRNAs are contained in exosomes, and their potential effect on other cells. METHODS: TPC-1 (PTC) and NTHY (normal thyroid follicular) cell lines were treated with exosome isolates and conditioned medium (CM), both containing miR-146b and miR-222. The changes in proliferation over a 72-h period of TPC-1 and NTHY were compared. Student t-test and analysis of variance were used for significance testing, and P < 0.05 was considered significant. RESULTS: Exosomes derived from TPC-1 cells were demonstrated to contain miR-146b and miR-222 in relative abundance. These exosomes caused a negative proliferative effect on both TPC-1 and NTHY cells. Exosomes derived from NTHY cells did not exert a significant proliferative effect on either cell line. CM from both cell types caused an initial increase in TPC-1 proliferation at 24 h. No significant change in proliferation was seen with NTHY cells when treated with either of the CM. CONCLUSIONS: The results showed that PTC cells overexpress miR-146b and miR-222 in exosomes; and that factors released by both normal thyroid and PTC cells alter proliferation of other cells in a complex manner. The intercellular interactions were likely conferred in part by exosomal miRNA, which can potentially be developed as biomarkers of PTC recurrence.

MicroRNA expression profiles in the management of papillary thyroid cancer.

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.