Molecular testing guides the management of cytologically indeterminate thyroid nodules. We evaluated the real-world clinical benefit of a commercially available thyroid mutation panel plus microRNA ...risk classifier in classifying RAS-mutated nodules.
We performed a subgroup analysis of the results of molecular testing of Bethesda III/IV nodules using the ThyGenX/ThyGeNEXT-ThyraMIR platform at 3 tertiary-care centers between 2017 and 2021, defining a positive result as 10% or greater risk of malignancy.
We identified 387 nodules from 375 patients (70.7% female, median age 59.3 years) who underwent testing. Positive nodules (32.3%) were associated with increased surgical intervention (74.4% vs 14.9%, P < .0001) and carcinoma on surgical pathology (46.4% vs 3.4%, P < .0001) compared to negative modules. RAS mutations were the most common mutations, identified in 71 of 380 (18.7%) nodules, and were classified as ThyraMIR- (28 of 71; 39.4%) or ThyraMIR+ (43 of 71; 60.6%). Among RAS-mutated nodules, there was no significant difference in operative rate (P = .2212) or carcinoma diagnosis (P = .6277) between the ThyraMIR+ and ThyraMIR- groups, and the sensitivity, specificity, negative predictive value, and positive predictive value of ThyraMIR were 64.7%, 34.8%, 40.0%, and 59.5%, respectively.
Although testing positive is associated with malignancy in surgical pathology, the ThyraMIR classifier failed to differentiate between benign and malignant RAS-mutated nodules. Diagnostic lobectomy should be considered for RAS-mutated nodules, regardless of microRNA expression status.
We aimed to evaluate the impact of radioactive iodine on disease-specific survival in intrathyroidal (N0M0) papillary thyroid carcinoma >4 cm, given conflicting data in the American Thyroid ...Association guidelines regarding their management.
The Surveillance, Epidemiology, and End Results database was queried for N0M0 classic papillary thyroid carcinoma >4 cm. Kaplan-Meier estimates were performed to compare disease-specific survival between radioactive iodine-treated and untreated groups. A multivariable Cox regression was performed to identify predictors of disease-specific survival.
There were more patients aged ≥55 (41.7% vs 32.3%, P = .001) and fewer multifocal tumors (25.3% vs 30.6%, P = .006) in the no radioactive iodine group. Ten-year disease-specific survival was similar between the radioactive iodine treated and untreated groups (97.2% vs 95.6%, P = .34). Radioactive iodine was not associated with a significant disease-specific survival benefit (adjusted hazard ratio = 0.78, confidence interval 0.39-1.58, P = .49). Age ≥55 (adjusted hazard ratio = 3.50, confidence interval 1.69-7.26, P = .001) and larger tumor size (adjusted hazard ratio = 1.04, confidence interval 1.02-1.06, P < .001) were associated with an increased risk of disease-specific death. Subgroup analyses did not demonstrate improved disease-specific survival with radioactive iodine in patients ≥55 and in tumors >5 cm.
Adjuvant radioactive iodine administration in classic papillary thyroid carcinoma >4 cm confined to the thyroid did not significantly impact disease-specific survival. Thus, these patients may not require routine treatment with adjuvant radioactive iodine.
Recent advances in research on thyroid carcinogenesis have yielded applications of diagnostic molecular biomarkers and profiling panels in the management of thyroid nodules. The specific utility of ...these novel, clinically available molecular tests is becoming widely appreciated, especially in perioperative decision making by the surgeon regarding the need for surgery and the extent of initial resection.
A task force was convened by the Surgical Affairs Committee of the American Thyroid Association and was charged with writing this article.
This review covers the clinical scenarios by cytologic category for which the thyroid surgeon may find molecular profiling results useful, particularly for cases with indeterminate fine-needle aspiration cytology. Distinct strengths of each ancillary test are highlighted to convey the current status of this evolving field, which has already demonstrated the potential to streamline decision making and reduce unnecessary surgery, with the accompanying benefits. However, the performance of any diagnostic test, that is, its positive predictive value and negative predictive value, are exquisitely influenced by the prevalence of cancer in that cytologic category, which is known to vary widely at different medical centers. Thus, it is crucial for the clinician to know the prevalence of malignancy within each indeterminate cytologic category, at one's own institution. Without this information, the performance of the diagnostic tests discussed below may vary substantially.
Introduction
Endoluminal functional lumen imaging probe (EndoFLIP) provides a real-time assessment of gastroesophageal junction (GEJ) compliance during fundoplication. Given the limited data on ...EndoFLIP measurements during the Hill procedure, we investigated the impact of the Hill procedure on GEJ compliance compared to Toupet fundoplication.
Methods
Patients who underwent robotic Hill or Toupet fundoplication with intraoperative EndoFLIP between 2017 and 2022 were included. EndoFLIP measurements of the GEJ included cross sectional surface area (CSA), intra-balloon pressure, high pressure zone length (HPZ), distensibility index (DI), and compliance. Subjective reflux symptoms, gastroesophageal reflux disease-health related quality of life (GERD-HRQL) score, and dysphagia score were assessed pre-operatively as well as at short- and longer-term follow-up.
Results
One-hundred and fifty-four patients (71.9%) had a Toupet fundoplication while sixty (28%) patients underwent the Hill procedure. The CSA 27.7 ± 10.9 mm
2
vs 42.2 ± 17.8 mm
2
,
p
< 0.0001, pressure 29.5 ± 6.2 mmHg vs 33.9 ± 8.5 mmHg,
p
= 0.0009, DI 0.9 ± 0.4 mm
2
/mmHg vs 1.3 ± 0.6 mm
2
/mmHg,
p
= 0.001, and compliance 25.9 ± 12.8 mm
3
/mmHg vs 35.4 ± 13.4 mm
3
/mmHg,
p
= 0.01 were lower after the Hill procedure compared to Toupet. However, there was no difference in post-fundoplication HPZ between procedures Hill: 2.9 ± 0.4 cm, Toupet: 3.1 ± 0.6 cm,
p
= 0.15. Follow-up showed no significant differences in GERD-HRQL scores, overall dysphagia scores or atypical symptoms between groups (
p
> 0.05).
Conclusion
The Hill procedure is as effective to the Toupet fundoplication in surgically treating gastroesophageal reflux disease (GERD) despite the lower CSA, DI, and compliance after the Hill procedure. Both procedures led to DI < 2 mm
2
/mmHg with no significant differences in dysphagia reporting (12–24) months after the procedure. Further studies to elucidate a cutoff value for DI for postoperative dysphagia development are still warranted.
Background:
Existing evidence is controversial regarding the association between BRAF mutation status and aggressive features of papillary thyroid cancer (PTC). Specifically, no study has ...incorporated multiple surgical practices performing routine central lymph node dissection (CLND) and thus has patients who are truly evaluable for the presence or absence of central lymph node metastases (CLNMs).
Methods:
Consecutive patients who underwent total thyroidectomy and routine CLND at 4 tertiary endocrine surgery centers were retrospectively reviewed. Descriptive and bivariable analyses examined demographic, patient, and tumor-related factors. Multivariable analyses examined the odds of CLNM associated with positive BRAF status.
Results:
In patients with classical variant PTC, bivariate analysis found no significant associations between BRAF mutation and aggressive clinicopathologic features; multivariate analysis demonstrated that BRAF status was not an independent predictor of CLNM. When all patients with PTC were analyzed, including those with aggressive or follicular subtypes, bivariate analysis showed BRAF mutation to be associated with LNM, advanced American Joint Committee on Cancer (AJCC) stage, and histologic subtype. Multivariable analyses showed BRAF, age, size, and extrathyroidal extension to be associated with CLNM.
Conclusion:
Although BRAF mutation was found to be an independent predictor of central LNM in the overall cohort of patients with PTC, this relationship lost significance when only classical variant PTC was included in the analysis. The usefulness of BRAF in predicting the presence of LNM remains questionable. Prospective studies are needed before BRAF mutation can be considered a reliable factor to guide the treatment of patients with PTC, specifically whether to perform prophylactic CLND.
Background
The effectiveness of prophylactic central neck dissection (pCND) in the treatment of patients with papillary thyroid carcinoma (PTC) to prevent local recurrence is controversial. We ...performed a meta-analysis to assess the effect of pCND on local recurrence in PTC.
Methods
Exhaustive search of online search engines identified five retrospective studies that compared the local recurrence rates of PTC in patients without clinically detectable nodal disease in patients undergoing thyroidectomy + pCND (group A) to those undergoing thyroidectomy alone (group B). A meta-analysis was performed by the fixed effects method. Recurrence was documented by imaging, thyroglobulin detection, or reoperation. Location of recurrence was identified in either the central or lateral neck compartment.
Results
A total of 1264 patients were included, 396 in group A and 868 in group B. Follow-up ranged from 6 months to 27 years. The overall recurrence rate was 2.02% in group A versus 3.92% in group B (odds ratio OR = 1.05, 95% confidence interval 95% CI 0.48–2.31). The recurrence rate in the central neck compartment in group A was 1.86% compared to 1.68% in group B (OR = 1.31, 95% CI 0.44–3.91). The recurrence rate in the lateral neck compartment in group A was 3.73% compared to 3.79% in group B (OR = 1.21, 95% CI 0.52–2.75). There was no statistically significant difference in the OR in the local recurrence between the two groups.
Conclusions
This meta-analysis indicates that pCND does not greatly reduce local recurrence in thyroid cancer. However, the available studies have substantial limitations and a prospective multicenter study to determine the indications for pCND is warranted.
The tall cell, columnar, and diffuse sclerosing subtypes are aggressive histologic subtypes of papillary thyroid cancer (PTC) with increasing incidence, yet there is a wide variation in reporting. We ...aimed to identify and compare factors associated with the reporting of these aggressive subtypes (aPTC) to classic PTC (cPTC) and secondarily identify differences in outcomes.
The National Cancer Database was utilized to identify cPTC and aPTC from 2004 to 2017. Patient and facility demographics and clinicopathologic variables were analyzed. Independent predictors of aPTC reporting were identified and a survival analysis was performed.
The majority of aPTC (67%) were reported by academic facilities. Compared to academic facilities, all other facility types were 1.4-2.0 times less likely to report aPTC (P < 0.05). Regional variation in reporting was noted, with more cases reported in the Middle Atlantic, despite there being more total facilities in the South Atlantic and East North Central regions. Compared to the Middle Atlantic, all other regions were 1.4-5 times less likely to report aPTC (P < 0.001). Patient characteristics including race and income were not associated with aPTC reporting. Compared to cPTC, aPTC had higher rates of aggressive features and worse 5-y overall survival (90.5% versus 94.5%, log rank P < 0.001).
Aggressive subtypes of PTC are associated with worse outcomes. Academic and other facilities in the Middle Atlantic were more likely to report aPTC. This suggests the need for further evaluation of environmental or geographic factors versus a need for increased awareness and more accurate diagnosis of these subtypes.
Background
Benign thyroid tumors account for most nodular thyroid disease. Determination of whether a thyroid nodule is benign or malignant is a major clinical dilemma and underlies the decision to ...proceed to surgery in many patients. Although the accuracy of thyroid nodule fine-needle aspiration (FNA) has reduced the need for surgery over the years, questions regarding how to follow FNA-designated benign nodules remain unresolved. This is true at least in part because of uncertainty over whether some benign nodules harbor malignant potential.
Methods
An evidence-based review of recent clinical, pathologic, and molecular data is presented. A summary of data and observations from our own experience is also provided.
Results
Review of our recent 10-year experience indicates that 2% of thyroid malignancies arise within a preexisting benign thyroid nodule. In addition, both cytologic and molecular tumor markers, including Gal-3, CITED1, HBME-1, Ras, RET/PTC, and PAX8/PPARγ, have been identified in some histopathologically classified benign nodules. Gene expression profiling suggests that follicular adenomas and Hürthle cell adenomas have similarities to both benign and malignant tumors, suggesting that some of these tumors are premalignant. In addition, 10% of surgically excised follicular tumors are encapsulated follicular lesions with nuclear atypia, which have been termed “well-differentiated tumors of uncertain malignant potential.” The data available suggest that these tumors could be precursors to carcinoma.
Conclusion
Some benign thyroid nodules have malignant potential. Further molecular testing of these tumors can shed light on the pathogenesis of early malignant transformation.
Although unilateral primary aldosteronism is the most common surgically correctable cause of hypertension, no standard criteria exist to classify surgical outcomes. We aimed to create consensus ...criteria for clinical and biochemical outcomes and follow-up of adrenalectomy for unilateral primary aldosteronism and apply these criteria to an international cohort to analyse the frequency of remission and identify preoperative determinants of successful outcome.
The Primary Aldosteronism Surgical Outcome (PASO) study was an international project to develop consensus criteria for outcomes and follow-up of adrenalectomy for unilateral primary aldosteronism. An international panel of 31 experts from 28 centres, including six endocrine surgeons, used the Delphi method to reach consensus. We then retrospectively analysed follow-up data from prospective cohorts for outcome assessment of patients diagnosed with unilateral primary aldosteronism by adrenal venous sampling who had undergone a total adrenalectomy, consecutively included from 12 referral centres in nine countries. On the basis of standardised criteria, we determined the proportions of patients achieving complete, partial, or absent clinical and biochemical success in accordance with the consensus. We then used logistic regression analyses to identify preoperative factors associated with clinical and biochemical outcomes.
Consensus was reached for criteria for six outcomes (complete, partial, and absent success of clinical and biochemical outcomes) based on blood pressure, use of antihypertensive drugs, plasma potassium and aldosterone concentrations, and plasma renin concentrations or activities. Consensus was also reached for two recommendations for the timing of follow-up assessment. For the international cohort analysis, we analysed clinical data from 705 patients recruited between 1994 and 2015, of whom 699 also had biochemical data. Complete clinical success was achieved in 259 (37%) of 705 patients, with a wide variance (range 17-62), and partial clinical success in an additional 334 (47%, range 35-66); complete biochemical success was seen in 656 (94%, 83-100) of 699 patients. Female patients had a higher likelihood of complete clinical success (odds ratio OR 2·25, 95% CI 1·40-3·62; p=0·001) and clinical benefit (complete plus partial clinical success; OR 2·89, 1·49-5·59; p=0·002) than male patients. Younger patients had a higher likelihood of complete clinical success (OR 0·95 per extra year, 0·93-0·98; p<0·001) and clinical benefit (OR 0·95 per extra year, 0·92-0·98; p=0·004). Higher levels of preoperative medication were associated with lower levels of complete clinical success (OR 0·80 per unit increase, 0·70-0·90; p<0·001).
These standardised outcome criteria are relevant for the assessment of the success of surgical treatment in individual patients and will allow the comparison of outcome data in future studies. The variable baseline clinical characteristics of our international cohort contributed to wide variation in clinical outcomes. Most patients derive clinical benefit from adrenalectomy, with younger patients and female patients more likely to have a favourable surgical outcome. Screening for primary aldosteronism should nonetheless be done in every individual fulfilling US Endocrine Society guideline criteria because biochemical success without clinical success is by itself clinically important and older women and men can also derive post-operative clinical benefit.
European Research Council; European Union's Horizon 2020; Else Kröner-Fresenius Stiftung; Netherlands Organisation for Health Research and Development-Medical Sciences; Japanese Ministry of Health, Labour and Welfare; Ministry of Health, Slovenia; US National Institutes of Health; and CONICYT-FONDECYT (Chile).
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