Evaluating the Rising Incidence of Thyroid Cancer and Thyroid Nodule Detection Modes: A Multinational, Multi-institutional Analysis.

Importance: 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. Objectives: 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. Design, Setting, and Participants: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.

Trends in Diagnosis of Noninvasive Follicular Thyroid Neoplasm With Papillarylike Nuclear Features and Total Thyroidectomies for Patients With Papillary Thyroid Neoplasms.

Importance: Increasing detection of early-stage papillary thyroid neoplasms without improvements in mortality has prompted development of strategies to prevent or mitigate overtreatment. Objective: To determine adoption rates of 2 recent strategies developed to limit overtreatment of low-risk thyroid cancers: (1) a new classification, noninvasive follicular thyroid neoplasm with papillarylike nuclear features (NIFTP), and (2) hemithyroidectomy for selected papillary thyroid carcinomas (PTCs) up to 4 cm in size. Design, Setting, and Participants: This is a cross-sectional analysis of 3368 pathology records of 2 cohorts of patients from 18 hospitals in 6 countries during 2 time periods (2015 and 2019). Participating hospitals were included from the US (n = 12), Canada (n = 2), Denmark (n = 1), South Korea (n = 1), South Africa (n = 1), and India (n = 1). The records of the first 100 patients per institution for each year who underwent thyroid-directed surgery (hemithyroidectomy, total thyroidectomy, or completion thyroidectomy) were reviewed. Main Outcomes and Measures: Frequency of diagnosis of NIFTP, PTCs, and thyroidectomies during the study period. Results: Of the 790 papillary thyroid neoplasms captured in the 2019 cohort, 38 (4.8%) were diagnosed as NIFTP. Diagnosis of NIFTP was observed in the US, South Africa, and India. There was minimal difference in the total proportion of PTCs in the 2015 cohort compared with the 2019 cohort (778 [47.1%] vs 752 [44.5%]; difference, 2.6% [95% CI, -16.9% to 22.1%]). The proportion of PTCs eligible for hemithyroidectomy but treated with total thyroidectomy in the 2 cohorts demonstrated a decreasing trend from 2015 to 2019 (341 of 453 [75.3%] vs 253 of 434 [58.3%]; difference, 17.0% [95% CI, -1.2% to 35.2%]). Conclusions and Relevance: Results of this cohort study showed that the 2 mitigation strategies for preventing overtreatment of early-stage thyroid cancer have had mixed success. The diagnosis of NIFTP has only been applied to a small proportion of thyroid neoplasms compared with expected rates. However, more patients eligible for hemithyroidectomy received it in 2019 compared with 2015, showing some success with this deescalation strategy.

Intraoperative acupuncture for posttonsillectomy pain: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES/HYPOTHESIS: To evaluate the effect of intraoperative acupuncture on posttonsillectomy pain in the pediatric population. STUDY DESIGN: Prospective, double-blind, randomized, placebo-controlled trial. METHODS: Patients aged 3 to 12 years undergoing tonsillectomy were recruited at a tertiary children's hospital between February 2011 and May 2012. Participants were block-randomized to receive acupuncture or sham acupuncture during anesthesia for tonsillectomy. Surgeons, staff, and parents were blinded from treatment. Tonsillectomy was performed by one of two surgeons using a standard technique (monopolar cautery), and a single anesthetic protocol was followed. Study endpoints included time spent in the postanesthesia care unit, the amount of opioids administered in the perioperative period, and pain measures and presence of nausea/vomiting from postoperative home surveys. RESULTS: Fifty-nine children aged 3 to 12 years were randomized to receive acupuncture (n = 30) or sham acupuncture (n = 29). No significant demographic differences were noted between the two cohorts. Perioperative data were recorded for all patients; 73% of patients later returned home surveys. There were no significant differences in the amount of opioid medications administered or total postanesthesia care unit time between the two cohorts. Home surveys of patients but not of parents revealed significant improvements in pain control in the acupuncture treatment-group postoperatively (P = 0.0065 and 0.051, respectively), and oral intake improved significantly earlier in the acupuncture treatment group (P = 0.01). No adverse effects of acupuncture were reported. CONCLUSIONS: This study demonstrates that intraoperative acupuncture is feasible, well tolerated, and results in improved pain and earlier return of diet postoperatively. LEVEL OF EVIDENCE: 1b.

Clinician-performed thyroid ultrasound-guided fine-needle aspiration.

Fine needle aspiration biopsy (FNA) is the key step in selecting most patients with thyroid nodules for or against surgery. Accurate acquisition of cytologic samples from suspicious lesions is achieved by adding ultrasound guidance to optimize targeting as well as to enable sampling from nonpalpable lesions. This article discusses the indications, variations, and technical details of ultrasound-guided FNA.

Validation of a grading system for lateral nasal wall insufficiency.

This study was designed to validate a grading scheme for lateral nasal wall insufficiency with interrater and intrarater reliability measures. Representative endoscopic videos depicting varied degrees of lateral nasal wall insufficiency were collated into a 30-clip video (15 clips in duplicate). This was rated by five reviewers for a total of 150 observations. Interrater and intrarater reliability were determined using Fleiss kappa and intraclass correlation coefficient (ICC) statistics, respectively. Good agreement was established between reviewers (interrater reliability), with a Fleiss kappa of 0.7733 (p < 0.01). Analysis of intrarater variability with the ICC revealed a very strong agreement (ICC = 0.88; p < 0.01). The proposed grading system is shown to have good interrater and intrarater reliability. It provides a reliable instrument for assessing lateral wall insufficiency.

Single-operator flexible nasolaryngoscopy-guided transthyrohyoid vocal fold injections.

OBJECTIVES: A number of laryngeal injection techniques have been described for performing vocal fold medialization or delivery of medications, including peroral and percutaneous approaches. Although flexible nasolaryngoscopy-guided injection (FNGI) improves visualization and patient tolerance over rigid endoscopy, the technique requires an assistant to manipulate the laryngoscope. The efficacy and patient tolerance of a novel, single-operator technique for FNGI are evaluated. METHODS: Patients who required laryngeal injection for vocal fold medialization or for administration of cidofovir or steroids were included in this study. Indications included vocal fold paresis or paralysis, sulcus deformities, recurrent respiratory papillomatosis, vocal fold polyps, and laryngeal granulomas. All procedures were performed in the office setting with topical and local anesthesia with the patient awake. The surgeon performed flexible nasolaryngoscopy with the nondominant hand while using the dominant hand to perform transthyrohyoid injection with a 25-gauge needle with proximal and distal bends. RESULTS: Twenty-six patients underwent a total of 42 single-operator FNGI procedures; 19 unilateral and 23 bilateral injections were performed. All but 1 of the procedures were completed with adequate visualization and placement of injectant and good patient tolerance. CONCLUSIONS: Single-operator FNGI via a transthyrohyoid approach is a viable and versatile laryngeal injection technique for a variety of indications. It provides access to the anterior, middle, and posterior parts of the larynx. It eliminates the need for an assistant experienced in nasolaryngoscopy and allows the surgeon to adjust and optimize visualization in a fashion analogous to endoscopic sinus surgery.

Impact of positron emission tomography/computed tomography surveillance at 12 and 24 months for detecting head and neck cancer recurrence.

BACKGROUND: In head and neck cancer (HNC), 3-month post-treatment positron emission tomography (PET)/computed tomography (CT) reliably identifies persistent/recurrent disease. However, further PET/CT surveillance has unclear benefit. The impact of post-treatment PET/CT surveillance on outcomes is assessed at 12 and 24 months. METHODS: A 10-year retrospective analysis of HNC patients was carried out with long-term serial imaging. Imaging at 3 months included either PET/CT or magnetic resonance imaging, with all subsequent imaging comprised of PET/CT. PET/CT scans at 12 and 24 months were evaluated only if preceding interval scans were negative. Of 1114 identified patients, 284 had 3-month scans, 175 had 3- and 12-month scans, and 77 had 3-, 12-, and 24-month scans. RESULTS: PET/CT detection rates in clinically occult patients were 9% (15 of 175) at 12 months, and 4% (3 of 77) at 24 months. No difference in outcomes was identified between PET/CT-detected and clinically detected recurrences, with similar 3-year disease-free survival (41% vs 46%, P = .91) and 3-year overall survival (60% vs 54%, P = .70) rates. Compared with 3-month PET/CT, 12-month PET/CT demonstrated fewer equivocal reads (26% vs 10%, P < .001). Of scans deemed equivocal, 6% (5 of 89) were ultimately found to be positive. CONCLUSIONS: HNC patients with negative 3-month imaging appear to derive limited benefit from subsequent PET/CT surveillance. No survival differences were observed between PET/CT-detected and clinically detected recurrences, although larger prospective studies are needed for further investigation.

Complications of esophagoscopy in an academic training program.

OBJECTIVE: To assess the efficacy and safety of flexible versus rigid esophagoscopy in an academic training setting. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic training center. SUBJECTS AND METHODS: A retrospective medical record review was performed on all adult patients undergoing esophagoscopy from 2002 to 2007. RESULTS: A total of 546 procedures were performed with flexible (n = 276) or rigid (n = 270) endoscopes. Seven esophageal perforations (2.6%) occurred, all in association with rigid endoscopy and all in patients with a history of head and neck cancer. Esophageal perforation rates were associated with attending level of experience. There were no deaths. No synchronous esophageal cancers were found in any patient undergoing panendoscopy for the evaluation of a head and neck cancer. CONCLUSION: The 2.6 percent esophageal perforation rate observed in this study is higher than that typically reported for rigid esophagoscopy. When performed as part of routine panendoscopy, no synchronous esophageal tumors were found, questioning the value of esophagoscopy in this setting. All perforations occurred in patients with a history of head and neck cancer and were associated with the level of the surgeon's experience in performing rigid endoscopy.

Purified hematopoietic stem cell allografts reconstitute immunity superior to bone marrow.

Antigen-specific immune responses are impaired after allogeneic hematopoietic cell transplantation (HCT). The events contributing to this impairment include host hematolymphoid ablation and donor cell regeneration, which is altered by pharmacologic immune suppression to prevent graft-versus-host disease (GVHD). A generally accepted concept is that graft T cell depletion performed to avoid GVHD yields poorer immune recovery because mature donor T cells are thought to be the major mediators of protective immunity early post-HCT. Our findings contradict the idea that removal of mature donor cells worsens immune recovery post-HCT. By transplantation of purified hematopoietic stem cells (HSC) compared with bone marrow (BM) across donor and recipient pairs of increasing genetic disparity, we show that grafts composed of the purified progenitor population give uniformly superior lymphoid reconstitution, both qualitatively and quantitatively. Subclinical GVHD by T cells in donor BM likely caused this lympho-depleting GVHD. We further determined in the major histocompatibility complex (MHC)-mismatched pairs, that T cell restricted proliferative responses were dictated by donor rather than host elements. We interpret these latter findings to show the importance of peripheral antigen presentation in the selection and maintenance of the T cell repertoire.

Foramen magnum meningioma: Dysphagia of atypical etiology.

INTRODUCTION: We present a case of a foramen magnum meningioma that highlights the importance of the neurologic exam when evaluating a patient with dysphagia. A 58-year-old woman presented with an 18-month history of progressive dysphagia, chronic cough and 30-pound weight loss. Prior gastroenterologic and laryngologic workup was unrevealing. RESULTS: Her neurologic examination revealed an absent gag reflex, decreased sensation to light touch on bilateral distal extremities, hyperreflexia, and tandem gait instability. Repeat esophagogastroduodenoscopy was normal, whereas laryngoscopy and video fluoroscopy revealed marked hypopharyngeal dysfunction. Brain magnetic resonance imaging demonstrated a 3.1 x 2.7 x 2.9 cm foramen magnum mass consistent with meningioma. The patient underwent neurosurgical resection of her mass with near complete resolution of her neurologic symptoms. Pathology confirmed diagnosis of a WHO grade I meningothelial meningioma. CONCLUSION: CNS pathology is an uncommon but impressive cause of dysphagia. Our case demonstrates the importance of a thorough neurologic survey when evaluating such a patient.

The independent effect of drug resistance on T cell activation in HIV infection.

OBJECTIVE: Antiretroviral-treated individuals with drug-resistant HIV experience slower CD4 cell count declines than untreated individuals, independent of degree of viremia. As immune activation independently predicts disease progression, we hypothesized that patients with drug-resistant viremia would have less immune activation than patients with wild-type viremia, independent of plasma HIV RNA levels and that these differences would not be explained by a direct drug effect of protease inhibitors. METHODS: Percentages of activated (CD38/HLA-DR) T cells were compared between untreated participants with wild-type viremia and antiretroviral-treated participants with drug-resistant viremia, after adjusting for plasma HIV RNA levels among other factors associated with T cell activation. Changes in T cell activation were also assessed in subjects discontinuing protease inhibitors while continuing other antiretroviral medications. RESULTS: Twenty-one untreated participants with wild-type viremia and 70 antiretroviral-treated participants with drug-resistant viremia were evaluated. Relative to untreated participants, those with drug-resistant viremia had 29% fewer activated CD4 (P = 0.051) and CD8 (P = 0.012) T cells after adjustment for plasma HIV RNA levels among other factors. There was no evidence for an early change in T cell activation among 13 subjects with drug-resistant viremia interrupting protease inhibitors while continuing other antiretroviral medications, but a significant increase in T cell activation with complete or partial emergence of wild-type sequences in protease. CONCLUSIONS: Antiretroviral-treated patients with drug-resistant viremia have less T cell activation than untreated patients, independent of plasma HIV RNA level. Decreased ability of drug-resistant variants to cause T cell activation likely contributes to slower CD4 cell count declines among patients with drug-resistant viremia.