Risk of needing completion thyroidectomy for low-risk papillary thyroid cancers treated by lobectomy.

Background: Low-risk differentiated thyroid cancers may, according to the American Thyroid Association (ATA) 2015 guidelines, be managed initially with lobectomy. However, definitive risk categorization requires pathological assessment of the specimen, resulting in completion thyroidectomy being recommended when discordance between preoperative and postoperative staging occurs. This study sought to establish the expected rate of completion thyroidectomy in patients with papillary thyroid cancer (PTC) treated by lobectomy. Methods: Patients with PTC treated over 5 years (2013-2017 inclusive) and meeting the ATA criteria for lobectomy were identified from the prospectively developed database of a high-volume, university department of endocrine surgery. Concordance between the ATA initial and final recommendation, and the putative rate of completion thyroidectomy were calculated. Multivariable analysis was used to assess preoperative factors as predictors of the need for total thyroidectomy. Results: Of 275 patients with PTC who met ATA preoperative criteria for lobectomy there was concordance between this and the final recommendation in 158 (57·5 per cent) and discordance in 117 (43·5 per cent). Most common reasons for discordance were: angioinvasion (30·8 per cent), local invasion (23·9 per cent) or both (20·5 per cent). Four patients (1·5 per cent) had permanent hypoparathyroidism. On multivariable analysis, age, sex, tumour size and family history did not independently predict the final treatment required. Conclusion: Although many patients may be treated adequately with lobectomy, just under half would require completion thyroidectomy. Further work is needed on preoperative risk stratification but, before this, total thyroidectomy remains the treatment of choice for low-risk 1-4-cm PTC in the hands of high-volume thyroid surgeons who can demonstrate low complication rates.

The Australian experience with the Bethesda classification system for thyroid fine needle aspiration biopsies.

Fine needle aspiration biopsy (FNAB) is the initial investigation of choice for thyroid nodules. The Bethesda system, which classifies thyroid FNABs into different categories each linked to a risk of malignancy, has been widely adopted. However, the risk of malignancy implied by each Bethesda category is likely to vary due to population characteristics and inconsistency in the application of diagnostic criteria.We present our experience of the Bethesda system in 2076 thyroid nodules from 1410 patients. Categories were as follows: 266 (12.8%) were category 1 (B1) non-diagnostic, 1551 (74.7%) category 2 (B2) benign, 97 (4.7%) category 3 (B3) atypia of uncertain significance, 98 (4.7%) category 4 (B4) suspicious for follicular neoplasm, 16 (0.8%) category 5 (B5) suspicious for malignancy and 48 (2.3%) category 6 (B6) malignant.Surgery was performed on 425 nodules from 315 patients. Malignancy rates in the target nodules were B1 4.2%, B2 0.26%, B3 9.3%, B4 15.3%, B5 79% and B6 100%. Twelve patients with B3 nodules underwent repeat FNAB, with eight reclassified as B2, one as B3, one as B1 and two as B4. An incidental microcarcinoma separate to the target nodule was identified in 11.1%.As applied in our institution, and despite very sparing use of B3 and B5 categories, our audit has demonstrated risks of malignancy broadly in keeping with that predicted. Of note, the risk of malignancy in the clinically indeterminate categories of B1, B3 and B4 were all at the lower ranges of those predicted in the Bethesda atlas and mostly lower than those reported by other studies.

Utilization of a MAB for BRAF(V600E) detection in papillary thyroid carcinoma.

Identification of BRAF(V600E) 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 (IHC) using a BRAF(V600E) mutation-specific MAB to Sanger sequencing on DNA from formalin-fixed paraffin-embedded tissue, in a well-characterized cohort of 101 papillary thyroid carcinoma (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 BRAF(V600E) positive by IHC and 59 (61%) were BRAF(V600E) 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 BRAF(V600E). Of ten cases positive by IHC but negative by sequencing on whole sections, repeat sequencing on macrodissected tissue confirmed the IHC result in seven cases (suggesting that these were false negatives of sequencing on whole sections). In three cases, repeat sequencing on recut tissue remained negative (including using massive parallel sequencing), but these cases demonstrated relatively low neoplastic cellularity. We conclude that IHC for BRAF(V600E) is more sensitive and specific than Sanger sequencing in the routine diagnostic setting and may represent the new gold standard for detection of BRAF(V600E) mutation in PTC.

Reoperative surgery for bilateral multinodular goitre in the era of total thyroidectomy.

BACKGROUND: Total thyroidectomy, rather than bilateral subtotal thyroidectomy, is now accepted as the preferred management for bilateral benign multinodular goitre (BMNG) in order to reduce the need for reoperative surgery. The aim of this study was to examine whether this approach has had an impact on presentation for bilateral reoperative thyroid surgery. METHODS: This was a retrospective cohort study. The study group comprised patients presenting with recurrent BMNG who underwent bilateral reoperative thyroid surgery following previous bilateral subtotal or partial thyroidectomy. They were compared with patients undergoing unilateral reoperative thyroid surgery following previous lobectomy, and those undergoing primary total thyroidectomy for BMNG. RESULTS: Between 1 January 1987 and 31 December 2009, 12 354 consecutive thyroid procedures were undertaken. Among those with BMNG, primary total thyroidectomy was undertaken in 3298 patients, unilateral reoperative thyroidectomy in 337 and bilateral reoperative thyroidectomy in 191. Presentations of patients with recurrent BMNG declined gradually over the study period following the change in policy from subtotal to total thyroidectomy; only five patients (representing less than 0.5 per cent of all thyroid surgery) underwent bilateral reoperative surgery for BMNG in the last year of the study. Four of these patients had their initial operation before 1987 and in another unit, whereas the remaining patient initially had surgery overseas. CONCLUSION: The introduction of a policy of initial total thyroidectomy for bilateral BMNG has essentially eliminated the need for bilateral reoperative surgery for recurrent goitre.

Management of follicular thyroid carcinoma should be individualised based on degree of capsular and vascular invasion.

INTRODUCTION: Follicular thyroid carcinoma (FTC) includes a spectrum of neoplasms with varying propensity for metastasis. The aim of this study is to describe outcomes for FTC following multimodality treatment, with particular reference to the degree of capsular and vascular invasion and to recommend a rational management approach based on these characteristics. METHODS: Patients with histologically confirmed FTC were identified from a prospectively maintained database. Details of intervention and long-term outcomes were obtained. Outcomes were compared between patients with minimally invasive follicular carcinoma (MI FTC) without vascular invasion (Group 1); angioinvasive MI FTC (Group 2); and those with widely invasive FTC (Group 3). RESULTS: Between May 1983 and December 2008, 124 patients with FTC were identified. The overall disease-free survival rate was 85% at a median of 40 months follow-up. Disease-free survival was 97%, 81% and 46%, respectively, in Groups 1, 2 and 3, and significantly different between groups (p<0.001). Thirteen patients in this series developed distant metastases including 2 in Group 1 and 6 in Group 2. Only patients <45 years of age with MI FTC and no vascular invasion had 100% disease-free survival. After multivariate linear regression, age (p=0.03) and the presence of vascular invasion (p=0.03) were the most powerful predictors of distant metastasis. CONCLUSIONS: Survival is improved in those with minimally invasive compared with widely invasive FTC. In patients <45 years with MI FTC without vascular invasion, hemithyroidectomy may be adequate treatment. All other patients with FTC should undergo total thyroidectomy and radioactive iodine ablation.

Laparoscopic surgery is safe for large adrenal lesions.

INTRODUCTION: Laparoscopic adrenalectomy has surpassed open adrenalectomy as the gold standard for excision of benign adrenal lesions. The size threshold for offering laparoscopic adrenalectomy is controversial as the prevalence of adrenocortical carcinoma increases with increasing tumour size. The aim of this paper was to assess the safety of laparoscopic adrenalectomy for large adrenal tumours (tumours > or = 60 mm). METHODS: A retrospective cohort study of patients who underwent adrenalectomy in a single unit during the period 1995-2005 was undertaken. RESULTS: One hundred and seventy patients with 173 tumours were included in this study. Of these, 29 were > or = 60 mm in size, and 16 of these patients underwent laparoscopic adrenalectomy. There were 8 adrenocortical carcinomas in the group with tumours > or = 60 mm in size. Five of these patients underwent an open adrenalectomy, while 2 and 1 patients had laparoscopic and laparoscopic converted to open adrenalectomy respectively. Four of the patients undergoing open adrenalectomy died of their disease while 1 is alive with recurrence 3 years later. The 3 patients who underwent either laparoscopic or laparoscopic converted to open adrenalectomy are alive without evidence of disease after 18 months follow up. CONCLUSION: Our data show that patients with tumours > or = 60 mm with no preoperative or intraoperative evidence of malignancy can undergo laparoscopic adrenalectomy without evidence of recurrence on short term follow up. These findings are concordant with the growing body of literature supporting laparoscopic adrenalectomy for potentially malignant tumours > or = 60 mm in size without preoperative or intraoperative features of malignancy.

Surgical trends in the management of thyroid lymphoma.

AIMS: To determine the changing trends and current role of surgery for the management of thyroid lymphoma. METHODS: A retrospective review of 50 surgical patients with a final diagnosis of thyroid lymphoma over a 35-year period. RESULTS: All patients presented with an enlarging mass, with half having compressive symptoms on presentation. Two-thirds of patients had co-existent histological features of Hashimoto's thyroiditis. Surgery for patients with thyroid lymphoma peaked in the late 1970s (0.79% of all thyroid operations performed) followed by a significant decline in the 1980s with a current frequency of only 0.16% (p=0.009). A larger number of thyroid resections intended as a curative procedure was performed during the first half of this series compared to the latter half (p=0.05). There was no difference in disease-free survival between patients treated by thyroid resection when compared with an open biopsy (p=0.4875). CONCLUSION: The surgical management of thyroid lymphoma has changed with time. Currently a larger proportion of patients are undergoing surgery in order to achieve a histological diagnosis rather than with therapeutic intent, however, an important role for surgery still exists in the management of a patient with severe airways obstruction.

Lymphadenectomy for papillary thyroid cancer: changes in practice over four decades.

AIMS: Lymphadenectomy in the management of papillary thyroid cancer (PTC) has evolved. The aim of this study was to examine the changing role of neck dissection as reflected in the practice of a large thyroid unit over four decades. METHODS: A retrospective cohort study of patients that underwent primary thyroid surgery for papillary cancer in a single unit in the period 1958-2002. Nine 5-year periods were considered and the data relevant to the treatment of the regional lymph nodes reviewed. RESULTS: Nine hundred patients with PTC underwent surgery between 1958 and 2002 of whom 32.7% underwent lymph node dissection (LND). The use of lymphadenectomy increased from 21.4% in 1958-1962 to 48.1% in 1998-2002 of which 84% underwent a selective lymph node dissection (SLND)-a dissection where the LND is determined by the extent of the disease encountered. The mean number of nodes removed during SLND was 12.6 (range 1-56) of which a mean of 3.1 (24.8%) (0-19) were involved by the disease. Cervical levels 6 and level 4 were those most frequently dissected. There was no statistically significant difference in the complication rates in patients undergoing neck dissection and those not. CONCLUSION: The four decade experience reflects a move away from modified radical neck dissection and cherry picking towards SLND. Growing evidence suggests that lymphadenopathy in adult PTC is an adverse prognostic factor. SLND, a lymphadenectomy tailored to the extent of the disease process, is the coherent treatment for PTC since it serves the dual purpose of staging as well as control of local disease. This can be achieved with little morbidity when performed in a specialist centre.

HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours.

BACKGROUND: Hyperparathyroidism is a common endocrinopathy characterised by the formation of parathyroid tumours. In this study, we determine the role of the recently identified gene, HRPT2, in parathyroid tumorigenesis. METHODS: Mutation analysis of HRPT2 was undertaken in 60 parathyroid tumours: five HPT-JT, three FIHP, three MEN 1, one MEN 2A, 25 sporadic adenomas, 17 hyperplastic glands, two lithium associated tumours, and four sporadic carcinomas. Loss of heterozygosity at 1q24-32 was performed on a subset of these tumours. RESULTS: HRPT2 somatic mutations were detected in four of four sporadic parathyroid carcinoma samples, and germline mutations were found in five of five HPT-JT parathyroid tumours (two families) and two parathyroid tumours from one FIHP family. One HPT-JT tumour with germline mutation also harboured a somatic mutation. In total, seven novel and one previously reported mutation were identified. "Two-hits" (double mutations or one mutation and loss of heterozygosity at 1q24-32) affecting HRPT2 were found in two sporadic carcinomas, two HPT-JT-related and two FIHP related tumours. CONCLUSIONS: The results in this study support the role of HRPT2 as a tumour suppressor gene in sporadic parathyroid carcinoma, and provide further evidence for HRPT2 as the causative gene in HPT-JT, and a subset of FIHP. In light of the strong association between mutations of HRPT2 and sporadic parathyroid carcinoma demonstrated in this study, it is hypothesised that HRPT2 mutation is an early event that may lead to parathyroid malignancy and suggest intragenic mutation of HRPT2 as a marker of malignant potential in both familial and sporadic parathyroid tumours.

Impact of timing on completion thyroidectomy for thyroid cancer.

BACKGROUND: It has been stated that completion thyroidectomy for thyroid malignancy should be performed either within 10 days of the primary operation or after 3 months, to reduce the incidence of complications. The aim of this study was to review the impact of timing on the rate of complications following completion thyroidectomy. METHODS: Data were obtained retrospectively from the Endocrine Surgery Thyroid Data Base, to which the records of all patients have been entered since 1957. The patients who had the last 100 consecutive completion thyroidectomies for thyroid cancer comprised the study group. RESULTS: Sixty-three patients had the second operation performed within 10 days or more than 90 days after the initial operation (group 1). Thirty-seven patients had reoperation between 10 and 90 days after the first procedure (group 2). One patient (2 per cent) in group 1 and one patient (3 per cent) in group 2 suffered a permanent complication (P not significant). CONCLUSION: There was no definite impact of the timing of surgery on the rate of complications after completion thyroidectomy.