A Critical Assessment of Diagnostic Criteria for the Tall Cell Subtype of Papillary Thyroid Carcinoma-How Much? How Tall? And When Is It Relevant?

Tall cell papillary thyroid carcinoma (TC-PTC) is considered adverse histology. However, previous studies are confounded by inconsistent criteria and strong associations with other adverse features. It is therefore still unclear if TC-PTC represents an independent prognostic factor in multivariate analysis and, if it does, what criteria should be employed for the diagnosis. We retrospectively reviewed 487 PTCs from our institution (where we have historically avoided the prospective diagnosis of TC-PTC) for both the height of tall cells (that is if the cells were two, or three, times as tall as wide) and the percentage of tall cells. On univariate analysis, there was significantly better disease free survival (DFS) in PTCs with no significant tall cell component (< 30%) compared to PTCs with cells two times tall as wide (p = 0.005). The proportion of tall cells (30-50% and > 50%) was significantly associated with DFS (p = 0.012). In a multivariate model including age, size, vascular space invasion, and lymph node metastasis, the current WHO tall cell criteria, met by 7.8% of PTCs, lacked statistical significance for DFS (p = 0.519). However, in the subset of tumours otherwise similar to the American Thyroid Association (ATA) guidelines low-risk category, WHO TC-PTC demonstrated a highly significant reduction in DFS (p = 0.004). In contrast, in intermediate to high-risk tumours, TC-PTC by WHO criteria lacked statistical significance (p = 0.384). We conclude that it may be simplistic to think of tall cell features as being present or absent, as both the height of the cells (two times versus three times) and the percentage of cells that are tall have different clinical significances in different contexts. Most importantly, the primary clinical significance of TC-PTC is restricted to PTCs that are otherwise low risk by ATA guidelines.

A Detailed Histologic and Molecular Assessment of the Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma.

Diffuse sclerosing variant papillary thyroid carcinoma (DS-PTC) is characterized clinically by a predilection for children and young adults, bulky neck nodes, and pulmonary metastases. Previous studies have suggested infrequent BRAFV600E mutation but common RET gene rearrangements. Using strict criteria, we studied 43 DS-PTCs (1.9% of unselected PTCs in our unit). Seventy-nine percent harbored pathogenic gene rearrangements involving RET, NTRK3, NTRK1, ALK, or BRAF; with the remainder driven by BRAFV600E mutations. All 10 pediatric cases were all gene rearranged (P = .02). Compared with BRAFV600E-mutated tumors, gene rearrangement was characterized by psammoma bodies involving the entire lobe (P = .038), follicular predominant or mixed follicular architecture (P = .003), pulmonary metastases (24% vs none, P = .04), and absent classical, so-called "BRAF-like" atypia (P = .014). There was no correlation between the presence of gene rearrangement and recurrence-free survival. Features associated with persistent/recurrent disease included pediatric population (P = .030), gene-rearranged tumors (P = .020), microscopic extrathyroidal extension (P = .009), metastases at presentation (P = .007), and stage II disease (P = .015). We conclude that DS-PTC represents 1.9% of papillary thyroid carcinomas and that actionable gene rearrangements are extremely common in DS-PTC. DS-PTC can be divided into 2 distinct molecular subtypes and all BRAFV600E-negative tumors (1.5% of papillary thyroid carcinomas) are driven by potentially actionable oncogenic fusions.

Surgery alone for papillary thyroid microcarcinoma is less costly and more effective than long term active surveillance.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Treatment strategy of end stage renal disease-related hyperparathyroidism before, during, and after the era of calcimimetics.

BACKGROUND: Since 2004, end-stage renal disease related hyperparathyroidism patients are treated mainly with cinacalcet, which ceased to be subsidized through the Australian Pharmaceutical Benefits Scheme in 2015. We aimed to investigate the impact of these changes on the treatment strategy in the Australian end-stage renal disease population. METHODS: The following groups were formed according to the date of parathyroidectomy: A, before calcimimetics; B, during the era of calcimimetics; and C, after cinacalcet removal by the Australian Pharmaceutical Benefits Scheme. The primary outcome was time from start of dialysis to parathyroidectomy. Regression analysis was used to examine trends in parathyroidectomy rates. RESULTS: Between 1998 and 2016, 195 parathyroidectomies were performed. Median time to referral was 69 (33-123), 67 (31-110) and 44 (23-102) months for groups A, B, and C, respectively (P = .55). Parathyroidectomy rates increased throughout the years (CI 0.09-1.13, R2=0.27, P = .02). A trend toward a dip in parathyroidectomy rates was seen during the era of cinacalcet (P = .08). Median preoperative parathyroid hormone levels increased significantly (842 [418-1,553] versus 1,040 [564-1,810] versus 1,350 [1,037-1,923] pg/mL, for groups A, B, and C, respectively [P < .01]). CONCLUSION: Parathyroidectomy rates seem to vary according to the availability of cinacalcet. This change in treatment strategy is accompanied with increased preoperative parathyroid hormone levels, reflecting delayed surgery and increased disease severity.

Sonographic Volumetric Assessment Is a More Accurate Measure Than Maximum Diameter Alone in Papillary Thyroid Cancer.

BACKGROUND: Tumor size is an important prognostic factor in papillary thyroid cancer (PTC). Management guidelines, staging systems, and pathological definitions use maximum diameter (Dmax) as a surrogate marker of tumor size. However, PTC nodules are three-dimensional (3D) structures, with behavior reflective of tumor cell count, which is directly proportional to volume. We explored the relationship between sonographically determined Dmax, volume, and lymph node status (LNS) in a cohort of patients with PTC. METHODS: All patients treated for PTC between 2003 and 2015 in our institution who had sonographic 3D nodule measurements available were evaluated. We examined the relationship between diameter, volume, and LNS. RESULTS: A total of 159 nodules in 153 patients met the inclusion criteria. Mean nodule dimensions were 2.4 × 1.9 × 1.5 cm, giving "ideal" nodule dimensions of y × 0.78y × 0.62y, where y is the Dmax. Observed volumes differed from predicted nodule volumes by an average of 26.2%. For PTC ≤2 cm, the coefficient of variation was 26.7%. Dmax did not correlate with the presence of lymph node metastases (Pearson coefficient 0.08), whereas volume very weakly correlated with LNS (Pearson coefficient 0.22). However, both Dmax and volume correlated very strongly with the number of nodal metastases (Pearson coefficients 0.93 and 0.89, respectively). CONCLUSIONS: PTC nodules demonstrated significant volume heterogeneity, rendering Dmax an inaccurate marker of true tumor size. Although there was little difference between Dmax and volume in predicting nodal status or nodal disease burden, we propose that a prospective, randomized trial might demonstrate a clear clinical advantage of 3D sonographic nodule measurement over Dmax alone.

Role of DOTATATE-PET/CT in preoperative assessment of phaeochromocytoma and paragangliomas.

CONTEXT: Diagnosis of paragangliomas (PGL) and phaeochromocytomas (PC) can be challenging particularly if the tumour is small. Detection of metastatic disease is important for comprehensive management of malignant PC/PGL. Somatostatin receptor imaging (SRI) agents have high sensitivity for these tumours, particularly the DOTA family of radiopharmaceuticals labelled with 68 Gallium. OBJECTIVE: To describe the utility of SRI in primary assessment (ie before surgery) for PC/PGL and whether measures of maximum standardized uptake (SUVmax) could be used to distinguish between adrenal adenomas and PCs. DESIGN: Retrospective analysis of patients with PC and PGL between 2012 and 2017. PATIENTS: Somatostatin receptor imaging (SRI) was performed for suspected PC (n = 46) or PGL (n = 27) of which 36 were during primary assessment and 37 during secondary assessment (follow-up after surgery). For comparison of adrenal SUVmax, scans from 30 patients without suspected PC/PGL (20 with normal adrenals; 10 with incidental adenomas) were evaluated. MEASUREMENTS: Baseline description, sensitivity, specificity, Youden's index. RESULTS: Sensitivity of DOTATATE-PET was 88% for PC and 100% for PGL. False-negative scans were seen in 2/10 PCs < 28 mm and in 1/14 PCs > 28 mm which had features of cystic degeneration. SUVmax of PCs and PGLs was more than double compared to adrenal adenomas (P > .001). CONCLUSION: Somatostatin receptor imaging (SRI) has high sensitivity in primary assessment for PC and PGL. We recommend that SRI should be performed as part of primary assessment in all suspected PGLs (due to higher risk of multifocal lesions) and in PCs suspected to be associated with hereditary syndromes or metastases.

A prospective study of heart rate variability in endocrine surgery: surgical training increases consultant's mental strain.

BACKGROUND: The aim of this study was to determine whether instructing surgical trainees in technically demanding procedures causes alterations in heart rate variability (HRV) and mental strain in supervising surgeons. METHODS: A prospective study of HRV in two consultant surgeons and three endocrine surgical fellows undertaking 50 total thyroidectomy procedures was performed. Fellows and consultant surgeons performed 50 lobectomies as primary operator and 50 as assistants in a cross-over design. HRV was measured during dissection around the recurrent laryngeal nerve. The overall heart rate, time, and frequency domain parameters of HRV, specifically the low frequency/high frequency (LF/HF) ratio, which was used as a measure of cardiac and mental stress, were correlated with the surgical role, particularly teaching surgical fellows at critical points. RESULTS: HRV data were collected between October 2009 and March 2010. There was no statistically significant difference in the mean heart rate for either group of participants regardless of role. Energy expenditure was greater for fellows when operating (p = 0.03). Fellows demonstrated a higher LF/HF ratio when acting as the primary operator (p = 0.02). All time domain parameters of HRV increased when attending surgeons were operating, denoting more cardiac relaxation. Similarly, the LF/HF ratio was significantly greater for attending surgeons when teaching (p = 0.05), suggesting an increase in mental strain. CONCLUSIONS: The teaching of complex but common endocrine surgical procedures is associated with a measurable increase in mental strain of consultant surgeons, as determined by HRV. Fellows demonstrated increased levels of stress when acting as primary operators.

Sutureless total thyroidectomy: a safe and cost-effective alternative.

BACKGROUND: Advanced vessel sealing devices provide an alternative to conventional ligation techniques for thyroidectomy. To date, most studies have been inadequately powered to explore differences in the infrequent post-operative complications following thyroidectomy. This study is designed to compare the outcomes of sutureless thyroidectomy and conventional thyroidectomy for recurrent laryngeal nerve (RLN) injury, permanent hypoparathyroidism, and haematoma formation. METHODS: A cohort study of consecutive patients undergoing total thyroidectomy using conventional versus sutureless techniques was performed. Sutureless thyroidectomy was performed using either Ligasure Precise (Covidien) or Harmonic Focus (Johnson and Johnson) devices. The primary outcome measures were post-operative haemorrhage, permanent RLN injury and hypoparathyroidism. Secondary outcome measures were operative time, temporary hypoparathyroidism and vocal cord dysfunction. A cost minimization analysis comparing the two techniques was performed. RESULT: From January 2006 to July 2009, 1935 consecutive patients underwent total thyroidectomy. Of these, 772 underwent conventional thyroidectomy and 1163 were performed using a sutureless technique. The mean operative time was significantly lower in the sutureless group (71 versus 86 min, P = 0.02). There was no difference in the post-operative complications of haematoma (0.78% conventional versus 1.12% sutureless, P = 0.46), permanent hypoparathyroidism (1.30% conventional versus 0.52% sutureless, P = 0.06) or permanent RLN injury (0.26% conventional versus 0.52% sutureless, P = 0.39). There was an overall cost saving of AUD$14,300 per 100 total thyroidectomy cases performed using the sutureless technique. CONCLUSIONS: Sutureless thyroidectomy is a safe and efficient way of performing total thyroidectomy and has the potential to reduce operating room costs.

Does the surgical approach affect quality of life outcomes?--a comparison of minimally invasive parathyroidectomy with open parathyroidectomy.

BACKGROUND: Quality of life has been shown to improve significantly after successful parathyroid surgery and normalisation of serum calcium levels. What is not known is how much of that effect is related to the patient's perception of their procedure, and whether or not patients may perceive that a minimally invasive operation provides a better outcome than that of an open procedure. METHODS: Two hundred and two consecutive patients who had undergone parathyroid surgery were selected for telephone interview. Of that group, 152 had had an open parathyroidectomy and 50 a minimally invasive approach, either an endoscopic assisted or a direct minimal access approach. Post-operative quality of life was assessed with both the Short Form-36 Health Survey (SF-36) and a disease-specific questionnaire. The SF-36 results were compared with a matched Australian population. RESULTS: Patients who underwent a direct minimal access parathyroidectomy had significantly better vitality and emotional role limitation scores than those having an open procedure. The health status scores of all patients having surgery for primary hyperparathyroidism were significantly lower in five out of the eight domains than those of a matched Australian population. There was a significantly lower incidence of post-operative symptoms in the minimally invasive group as a whole. CONCLUSIONS: Minimally invasive parathyroidectomy is associated with a greater improvement in post-operative quality of life than the open technique despite the fact that both result in equivalent normalisation of serum calcium levels. It is not clear if this is due to differences in the technique itself or is related to the patients' perceptions of having had a "less invasive" surgical procedure.

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

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