Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused ...by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery.
This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)-both label free and in combination with indocyanine green-based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery.
Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.
There is epidemiologic evidence that the increasing incidence of thyroid cancer is associated with subclinical disease detection. Evidence for a true increase in thyroid cancer incidence has also ...been identified. However, a true increase in disease would likely be heralded by an increased incidence of thyroid-referable symptoms in patients presenting with disease.
To evaluate whether modes of detection (MODs) used to identify thyroid nodules for surgical removal have changed compared with historic data and to determine if MODs vary by geographic location.
This was a retrospective analysis of pathology and medical records of 1328 patients who underwent thyroid-directed surgery in 16 centers in 4 countries: 4 centers in Canada, 1 in Denmark, 1 in South Africa, and 12 in the US. The participants were the first 100 patients (or the largest number available) at each center who had thyroid surgery in 2019. The MOD of the thyroid finding that required surgery was classified using an updated version of a previously validated tool as endocrine condition, symptomatic thyroid, surveillance, or without thyroid-referable symptoms (asymptomatic). If asymptomatic, the MOD was further classified as clinician screening examination, patient-requested screening, radiologic serendipity, or diagnostic cascade.
The MOD of thyroid nodules that were surgically removed, by geographic variation; and the proportion and size of thyroid cancers discovered in patients without thyroid-referable symptoms compared with symptomatic detection. Data analyses were performed from April 2021 to February 2022.
Of the 1328 patients (mean SD age, 52 15 years; 993 75% women; race/ethnicity data were not collected) who underwent thyroid surgery that met inclusion criteria, 34% (448) of the surgeries were for patients with thyroid-related symptoms, 41% (542) for thyroid findings discovered without thyroid-referable symptoms, 14% (184) for endocrine conditions, and 12% (154) for nodules with original MOD unknown (under surveillance). Cancer was detected in 613 (46%) patients; of these, 30% (183 patients) were symptomatic and 51% (310 patients) had no thyroid-referable symptoms. The mean (SD) size of the cancers identified in the symptomatic group was 3.2 (2.1) cm (median range cm, 2.6 0.2-10.5; 95% CI, 2.91-3.52) and in the asymptomatic group, 2.1 (1.4) cm (median range cm, 1.7 0.05-8.8; 95% CI, 1.92-2.23). The MOD patterns were significantly different among all participating countries.
This retrospective analysis found that most thyroid cancers were discovered in patients who had no thyroid-referable symptoms; on average, these cancers were smaller than symptomatic thyroid cancers. Still, some asymptomatic cancers were large, consistent with historic data. The substantial difference in MOD patterns among the 4 countries suggests extensive variations in practice.
Background
Understanding the patterns of IONM use and training among resident otolaryngologists is essential to ensure that the IONM skills and knowledge gained in residency are optimized for ...successful future practice of IONM.
Method
An electronic survey was distributed to US‐based OHNS residents. Questions evaluated resident experience, implementation, knowledge and understanding of IONM for endocrine surgeries.
Results
One hundred and seven OHNS residents participated, spanning all training levels and US geographic locations. The majority of residents received no didactic teaching on IONM (74.5%) nor had a clear troubleshooting algorithm in the event of a loss of signal (69.8%). The majority of residents were uncertain regarding the advantages/disadvantages of continuous versus intermittent IONM.
Conclusion
The knowledge gap found in our survey study suggests that greater teaching of IONM principles for endocrine head and neck surgeries in OHNS residency programs would help to ensure successful utilization in future practice.
Background
The development of systemic treatment options leveraging the molecular landscape of advanced thyroid cancer is a burgeoning field. This is a multidisciplinary evidence‐based statement on ...the definition of advanced thyroid cancer and its targeted systemic treatment.
Methods
An expert panel was assembled, a literature review was conducted, and best practice statements were developed. The modified Delphi method was applied to assess the degree of consensus for the statements developed by the author panel.
Results
A review of the current understanding of thyroid oncogenesis at a molecular level is presented and characteristics of advanced thyroid cancer are defined. Twenty statements in topics including the multidisciplinary management, molecular evaluation, and targeted systemic treatment of advanced thyroid cancer are provided.
Conclusions
With the growth in targeted treatment options for thyroid cancer, a consensus definition of advanced disease and statements regarding the utility of molecular testing and available targeted systemic therapy is warranted.
Gastrointestinal stromal tumor (GIST) arises from interstitial cells of Cajal (ICC) or their precursors, which are present throughout the gastrointestinal tract. Although gastric GIST is commonly ...indolent and small intestine GIST more aggressive, a molecular understanding of disease behavior would inform therapy decisions in GIST. Although a core transcription factor (TF) network is conserved across GIST, accessory TFs HAND1 and BARX1 are expressed in a disease state-specific pattern. Here, we characterize two divergent transcriptional programs maintained by HAND1 and BARX1, and evaluate their association with clinical outcomes.
We evaluated RNA sequencing and TF chromatin immunoprecipitation with sequencing in GIST samples and cultured cells for transcriptional programs associated with HAND1 and BARX1. Multiplexed tissue-based cyclic immunofluorescence and IHC evaluated tissue- and cell-level expression of TFs and their association with clinical factors.
We show that HAND1 is expressed in aggressive GIST, modulating
and core TF expression and supporting proliferative cellular programs. In contrast, BARX1 is expressed in indolent and micro-GISTs. HAND1 and BARX1 expression were superior predictors of relapse-free survival, as compared with standard risk stratification, and they predict progression-free survival on imatinib. Reflecting the developmental origins of accessory TF programs, HAND1 was expressed solely in small intestine ICCs, whereas BARX1 expression was restricted to gastric ICCs.
Our results define anatomic and transcriptional determinants of GIST and molecular origins of clinical phenotypes. Assessment of HAND1 and BARX1 expression in GIST may provide prognostic information and improve clinical decisions on the administration of adjuvant therapy.
Objective
Endotracheal tube (ETT) surface electrodes are used to monitor the vagus nerve (VN), recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve (EBSLN) during ...thyroid and parathyroid surgery. Alternative nerve monitoring methods are desirable when intubation under general anesthesia is not desirable or possible. In this pilot study, we compared the performance of standard ETT electrodes to four different noninvasive cutaneous recording electrode types (two adhesive electrodes and two needle electrodes) in three different orientations.
Methods
The VN was stimulated directly during thyroid and parathyroid surgery using a Prass stimulator probe. Electromyographic (EMG) responses for each patient were recorded using an ETT plus one of the following four cutaneous electrode types: large‐foot adhesive, small‐foot adhesive, long‐needle and short‐needle. Each of the four electrode types was placed in three orientations: (1) bilateral, (2) ipsilateral mediolateral, and (3) ipsilateral craniocaudal.
Results
Four surgical cases were utilized for data collection with the repetitive measures obtained in each subject. Bilateral electrode orientation was superior to ipsilateral craniocaudal and ipsilateral mediolateral orientations. Regardless of electrodes type, all amplitudes in the bilateral orientation were >100 μV. When placed bilaterally, the small‐foot adhesive and the long‐needle electrodes obtained the highest EMG amplitudes as a percentage of ETT amplitudes.
Conclusion
Cutaneous electrodes could potentially be used to monitor the VN during thyroid and parathyroid procedures. Different electrode types vary in their ability to record amplitudes and latencies. Bilateral orientation improves EMG responses in all electrode types. Additional validation of cutaneous electrodes as an alternative noninvasive method to monitor the VN is needed.
Currently, the only approved treatments for gastrointestinal stromal tumor (GIST) are tyrosine kinase inhibitors (TKI), which eventually lead to the development of secondary resistance mutations in ...KIT or PDGFRA and disease progression. Herein, we identified G protein-coupled receptor 20 (GPR20) as a novel non-tyrosine kinase target in GIST, developed new GPR20 IHC, and assessed GPR20 expression in cell lines, patient-derived xenografts, and clinical samples from two institutes (United States and Japan). We studied GPR20 expression stratified by treatment line, KIT expression, GIST molecular subtype, and primary tumor location. We produced DS-6157a, an anti-GPR20 antibody-drug conjugate with a novel tetrapeptide-based linker and DNA topoisomerase I inhibitor exatecan derivative (DXd). DS-6157a exhibited GPR20 expression-dependent antitumor activity in GIST xenograft models including a GIST model resistant to imatinib, sunitinib, and regorafenib. Preclinical pharmacokinetics and safety profile of DS-6157a support its clinical development as a potential novel GIST therapy in patients who are refractory or have resistance or intolerance to approved TKIs. SIGNIFICANCE: GPR20 is selectively expressed in GIST across all treatment lines, regardless of
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genotypes. We generated DS-6157a, a DXd-based antibody-drug conjugate that exhibited antitumor activity in GIST models by a different mode of action than currently approved TKIs, showing favorable pharmacokinetics and safety profiles.
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The optimized synthesis of 5-oxo-4,4-diphenylimidazolidin-2-ylidenecyanamide, which is known as 2-cyanoguanidinophenytoin (CNG-DPH) (3), and (imidazo4,5-dimidazole-2,5-diylidine)dicyanamide (4) has ...been reported in the present work. Furthermore, new Mannich bases derived from CNG-DPH were synthesized via its reaction with formaldehyde and using the corresponding amines, piperidine (base 5), and morpholine (base 6). Also, the antimicrobial activity and X-ray crystal structures for CNG-DPH and their Mannich bases were studied. The bases 3 and 6 crystallized in a monoclinic system; the crystal structure of 3 containing four molecules in the unit cell with a P21/c space group. The unit cell of 6 has eight molecules with a C2/c space group. The inter and intra hydrogen bond contacts packed and stabilized both of the structures. The morpholine ring of base 6 demonstrated a distinctive chair configuration. Mannich bases 5 and 6 showed promising antimicrobial effects. base 4 has a greater percentage for in vitro cytotoxicity (IC50) against normal cells, whereas 3 has the lowest ratio.
Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of ...URCS patients.
URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres were retrospectively identified. Based on molecular assessment, cases were classified as follows: (1) CIC-rearranged round cell sarcomas, (2) BCOR::CCNB3-rearranged round cell sarcomas, (3) unclassified URCSs. Treatment, prognostic factors and outcome were reviewed.
In total, 148 patients were identified 88/148 (60%) CIC-rearranged sarcoma (median age 32 years, range 7–78), 33/148 (22%) BCOR::CCNB3-rearranged (median age 17 years, range 5–91), and 27/148 (18%) unclassified URCSs (median age 37 years, range 4–70). One hundred-one (68.2%) cases presented with localised disease; 47 (31.8%) had metastases at diagnosis. Male prevalence, younger age, bone primary site, and a low rate of synchronous metastases were observed in BCOR::CCNB3-rearranged cases. Local treatment was surgery in 67/148 (45%) patients, and surgery + radiotherapy in 52/148 (35%). Chemotherapy was given to 122/148 (82%) patients. At a 42.7-month median follow-up, the 3-year overall survival (OS) was 92.2% (95% CI 71.5–98.0) in BCOR::CCNB3 patients, 39.6% (95% CI 27.7–51.3) in CIC-rearranged sarcomas, and 78.7% in unclassified URCSs (95% CI 56.1–90.6; p < 0.0001).
This study is the largest conducted in URCS and confirms major differences in outcomes between URCS subtypes. A full molecular assessment should be undertaken when a diagnosis of URCS is suspected. Prospective studies are needed to better define the optimal treatment strategy in each URCS subtype.
•Undifferentiated small round cell sarcomas (URCS) represent a therapeutic challenge.•Pathological, clinical and molecular data of these ultra-rare sarcomas are provided.•CIC-rearranged tumours have poor survival compared to BCOR:CCNB3/unclassified URCS.•Translational research and RNA-seq findings are discussed.
Objectives/Hypothesis
During intraoperative neuromonitoring in thyroid surgery, two different kinds of stimulator probes, monopolar and bipolar, are commonly used to stimulate the laryngeal nerves. ...We explore the unique characteristics of both of these probes as they relate to intraoperative laryngeal nerve mapping.
Methods
Twenty‐one patients undergoing neuromonitored thyroidectomy by a single surgeon were enrolled. Electromyography (EMG) amplitude and latency measurements were prospectively recorded concurrently from 1 mA stimulation of vagus nerve (VN) and inferior/superior recurrent laryngeal nerve before (with and without fascia) and after thyroid resection using bipolar and monopolar stimulator probes.
Results
Significantly higher amplitudes were obtained with monopolar stimulator probes as compared to bipolar probes, in several stimulation scenarios such as at right VN pre‐resection (carotid sheath intact), right VN pre‐resection (carotid sheath dissected), right VN post‐resection and left VN (carotid sheath dissected). No significant differences were found between amplitudes and latency values in all other stimulation scenarios.
Conclusions
According to this study, both probes are reliable and safe for neural mapping. The kind of probe used during neural monitoring is based on surgical situations and surgeon preference.
Level of Evidence
3 (According to Oxford Centre for Evidence‐Based Medicine 2011 Levels of Evidence) Laryngoscope, 131:E2718–E2726, 2021
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