Biologics for Psoriasis.

Biologic therapies targeting tumor necrosis factor alpha (TNF-α) (infliximab, adalimumab, certolizumab, etanercept), the p40 subunit shared by IL-12 and IL-23 (ustekinumab), the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab), IL-17A (secukinumab, ixekizumab), IL-17-RA (brodalumab) and both IL-17A and IL-17F (bimekizumab) have revolutionized the treatment of psoriasis. In both the short and long term, risankizumab had highest Psoriasis Area and Severity Index 90 scores compared to other oral and injectable biologics. IL-23 inhibitors had lowest rates of short-term and long-term adverse events and most favorable long-term risk-benefit profile compared to IL-17, IL-12/23, and TNF-α inhibitors.

Molecular Genetics Augment Cytopathologic Evaluation and Surgical Planning of Pediatric Thyroid Nodules.

PURPOSE: Molecular genetic testing in conjunction with cytopathology may improve prediction of malignancy in thyroid nodules, particularly those with indeterminate cytology (Bethesda III/IV). Though now commonplace in adults, pediatric data are limited. This study examines molecular genetics of pediatric nodules with correlation to cytologic and histologic classification at time of surgery and the distribution of mutations. METHODS: Retrospective chart review of 164 patients <22 years who underwent surgical resection of a thyroid nodule between 2002 and 2020 with molecular testing on fine-needle aspiration biopsy (FNA) or final histopathology. RESULTS: 85 (52 %) of 164 patients undergoing thyroid resection had available molecular genetic testing. BRAF V600E testing was performed on the FNA samples of 73 (86 %) patients and on 15 (18 %) surgical specimens; 31 (37 %) were positive. Of the remaining 54 patients, 21 had additional mutation/fusion testing. In 17 (81 %) cases, an alternate mutation/fusion was identified including 8 gene fusions, 3 DICER1 mutations, 4 NRAS mutations, one BRAF variant, and one unknown variant. BRAF, DICER1 mutations, and gene fusions predicted malignancy. Greater than 95 % of BRAF mutations were in Bethesda V/VI lesions and associated with classic variant PTC whereas fusions and DICER1 mutations clustered in Bethesda IV nodules. Bethesda III nodules harbored BRAF and NRAS mutations. In Bethesda IV nodules, a gene fusion or DICER mutation altered the surgical decision-making (upfront thyroidectomy rather than lobectomy) in 70 % of nodules submitted for genetic testing. CONCLUSION: Expanded molecular genetic testing on FNA of pediatric thyroid nodules, particularly Bethesda III/IV, may improve prediction of malignancy and augment surgical decision-making. LEVEL OF EVIDENCE: III.

Tall cell variant papillary thyroid carcinoma impacts disease-free survival at the 10 % cut-point on multivariate analysis.

INTRODUCTION: The diagnosis of tall cell variant papillary thyroid carcinoma (TCV-PTC) corresponds to the feature of "aggressive histology" within the framework of the American Thyroid Association (ATA) Risk of Recurrence (ROR) guidelines. Using the current World Health Organization (WHO) definition for TCV-PTC (tall cells with height at least twice the width, distribution ≥ 30 %), we examined the impact of this diagnosis on disease-free survival (DFS). METHODS: The study cohort consisted of 347 patients treated for primary papillary thyroid carcinoma (PTC). Current ATA guidelines were followed for the extent of surgery and the administration of adjuvant radioiodine therapy. Clinical surveillance included ultrasound examination and biochemical parameters according to ATA standards. The outcome was measured as time from surgery to first disease recurrence (DR) versus time from surgery until the last documented disease-free encounter (no evidence of disease, NED). Disease-free patients with fewer than 6 months of follow-up were excluded from this cohort. Structural recurrences are documented by histology or cytology whereas biochemical recurrences are documented by rising serum thyroglobulin in the absence of structural disease. All slides on all patients were examined by two pathologists with the substantial interobserver agreement (Kappa = 73 %). The primary tumors are categorically classified either as (1) TCV-PTC (definition above), (2) Papillary thyroid carcinoma with tall cell features (PTC-TCF) (≥ 10 % < 30 % tall cells), or (3) Control (< 10 % tall cells). Tumor size is categorized as either (1) ≤ 10 mm, (2) 11-29 mm, or (3) ≥ 30 mm. Degree of ETE is categorized as either intrathyroidal, microscopic ETE, histologic spread to strap muscles, or pT4 disease. RESULTS: 185 patients are classified as TCV-PTC (≥ 30 % tall cells), 62 as PTC-TCF (≥ 10 % < 30 % tall cells), and 100 as control group (< 10 % tall cells). TCV-PTC is associated with ≥ 30 mm size (p = .0246) and invasion of strap muscles and/or pT4 (p = .0325). There was no relationship between TCV-PTC and aggressive lymph node (ALN) status defined by ATA. Overall follow-up ranged from two months (one patient death) to 203 months (mean 40.8, median 33.0). DR occurred in 61 patients (mean 31.4 months, range 0 -184, 59 structural recurrences, 2 biochemical recurrences). Three models for TCV-PTC were examined: Model 1 - Tall cells ≥ 10% versus control, Model 2 - TCV-PTC versus TCF-PTC versus control, and Model 3 - TCV-PTC versus control. Kaplan Meier curves demonstrated decreased DFS with ALN status (p = .0001), ETE (p = .0295), and TCV-PTC (Model 1, p = .041). On multivariate analysis, TCV-PTC (Model 1) remained significantly predictive when adjusted for ALN (p = .0059). ETE dropped out of the model. CONCLUSION: TCV-PTC is significantly associated with larger tumors and a greater degree of ETE. The diagnosis of TCV-PTC significantly impacts DFS at the 10 % cut-point on multivariate analysis.

The anatomical basis for preserving the blood supply to the parathyroids during thyroid surgery, and a review of current technologic advances.

BACKGROUND: Devascularization of the parathyroid glands is generally accepted as the most common mechanism for iatrogenic hypocalcemia, a frequently seen complication of both total and completion thyroidectomy procedures. Much has been written about iatrogenic hypoparathyroidism, but few papers have precisely delineated the arterial supply of the parathyroid glands and the common anatomical variations that may impact parathyroid preservation during thyroid surgery. METHODS: We offer an illustrated review and discussion of the only two anatomic studies published in the medical literature focusing on parathyroid vasculature. In addition, we examine current techniques of parathyroid identification, preservation, and classification. FINDINGS: A surgical technique that preserves the parathyroid arteries is vital to preserving the viability of the parathyroid gland(s) during thyroid surgery. In 1907, Halsted and Evans described a technique of ligating the distal branches of the thyroid arteries beyond the origin of the parathyroid arteries, a technique termed ultra-ligation. In 1982, Flament et al.. reported three distinct anatomical variations of the parathyroid arteries which place the parathyroid blood supply at risk for devascularization during thyroid surgery. Our review also highlights novel techniques that aid surgeons in identification and assessment of the parathyroid glands. CONCLUSIONS: Recognition of the variations of parathyroid anatomy and their potential to lead to devascularization aids thyroid surgeons in their pursuit of parathyroid preservation. An awareness of the variety of novel parathyroid identification and preservation techniques can assist surgeons to achieve this goal.

Diagnosis and management of pharyngoesophageal stenosis: A comprehensive approach to prophylactic, endoscopic, and reconstructive treatment options.

BACKGROUND: Pharyngoesophageal stenosis (PES) is a serious complication that substantially impacts functional outcomes and quality of life (QOL) for up to a third of head and neck cancer patients who undergo radiotherapy. Dysphagia is often multifactorial in nature and is a devastating complication of treatment that impacts patients' QOL, general health and overall wellbeing. The authors detail the clinical presentation, risk factors, imaging characteristics, preventive measures, and multimodality treatment options for PES. METHODS: The authors present a comprehensive management algorithm for PES, including treatment by dilation, stenting, spray cryotherapy and dilation, and reconstructive treatment options utilizing different pedicled and free flaps. RESULTS: The authors advocate for a thorough assessment of the extent and degree of pharyngoesophageal involvement of PES to determine the optimal management strategy. CONCLUSIONS: The development of post treatment dysphagia requires appropriate imaging and biopsy, when indicated, to rule out the presence of persistent/recurrent cancer. Multidisciplinary management by a team of physicians well-versed in the range of diagnostic and therapeutic interventions available for PES is critical to its successful management.

Extraskeletal Ewing sarcoma of the buccal space.

Extraskeletal Ewing sarcoma (EES) is a rare soft tissue tumor, and EES of the head and neck is particularly rare. Radiographic imaging of these lesions is crucial given their anatomical complexity and infrequent incidence. Conventional EES imaging features include a large, hyperintense, heterogeneously enhancing lesion, with frequent invasion of local structures. In this case report, a 19-year old male presented with left facial swelling and pain. He underwent sclerotherapy and bleomycin treatment for a presumed lymphatic malformation. Initial imaging demonstrated a rim-enhancing lesion within the left buccal space with no muscle invasion or bony erosion present. Two years later, imaging identified an enlarging buccal mass with destruction of the zygomatic arch and inferolateral orbital wall. The patient underwent surgical resection of the mass. Pathology confirmed the mass to be a small round blue cell tumor and FISH testing confirmed the presence of the EWSR1 gene arrangement that is consistent with EES. The patient tolerated the procedure well and underwent chemoradiation therapy. At three years postoperatively, the patient remains disease free. The presented case demonstrates an unusual presentation of a buccal space EES as a rim-enhancing, centrally hypointense mass with no bony erosion or muscular invasion. The location and atypical imaging appearance of this case offer insight for future diagnosis of EES.

Multifocal Parotid Oncocytic Cystadenomatosis: A Rare Process that Can Mimic Malignancy.

Multifocal cystic oncocytosis (MCO) is a rare, benign process accounting for approximately 0.1% of salivary gland lesions. Salivary oncocytosis is characterized by multiple unencapsulated solid nodules of oncocytic cells derived from transformed striated ducts. MCO is a variant of salivary oncocytosis which manifests as cystically dilated striated ducts. It is difficult to obtain a definitive preoperative diagnosis of MCO; therefore, these lesions are commonly treated with surgery. We report the unique case of a 66-year-old male who previously underwent a superficial left parotidectomy for a pleomorphic adenoma. Four years later, he presented with clinical and radiographic suspicion of a multifocal recurrent pleomorphic adenoma. The patient subsequently underwent a revision parotidectomy. However, final pathology confirmed a diagnosis of MCO. Although MCO is commonly treated with surgery due to lack of a definitive preoperative diagnosis, surgery is unnecessary outside of diagnostic, functional or cosmetic considerations. Thus, if a patient with parotid oncocytosis treated by superficial parotidectomy develops disease re-manifestation in the residual deep lobe, further surgery is not indicated. There is no risk of malignant progression in this process. We report on this unusual entity as it may mimic salivary malignancy or, as in this case, recurrence of benign disease.

Impact of ADHD on Household Chores.

Objective: To assess the relationship between ADHD and performance of household chores. Method: A 72-question online questionnaire was developed to collect demographic/clinical information as well as parents' assessment of their child's performance of self-care (SC) and family-care (FC) chores. Results: The sample consists of 797 primary caregivers of children with ADHD. The overwhelming majority of parents believed that ADHD to some extent affected their child's ability to independently and satisfactorily complete SC and FC chores. An inverse relationship was noted between parent ratings of a child's ability to do chores independently and satisfactorily and the likelihood they believed ADHD affected chore performance. There was no difference in chore performance between children with or without co-morbid oppositional defiant disorder. Conclusion: Given that household routines, including chores, play an important role in children's development and psychosocial adjustment, clinicians must be sensitive to the adverse impact that ADHD may have in this regard.

Stair-step tracheal repair: Surgical technique.

Typical surgical treatment for invasive thyroid carcinoma at the level of the cricoid substantially reduces surrounding cartilaginous support and risks damage to the recurrent laryngeal nerve (RLN). We present a novel tracheal reconstructive technique that minimizes this injury risk. A 72-year-old man with recurrent invasive thyroid carcinoma underwent cricotracheal resection and reconstruction using a stair-step approach. Diseased cartilage was removed by a left hemitracheal and hemicricoid resection. A portion of normal trachea was also resected on the contralateral right side, removing the third and fourth hemitracheal rings, to close the defect with a sliding tracheoplasty and avoid dissection near the right cricothyroid joint on the side of the functioning RLN. The trachea was elevated superiorly and reanastomosed to the cut margin of the cricoid. This novel stair-step approach to tracheal reconstruction offers reduced risk of injury to the contralateral RLN while still establishing a patent airway.

Management of orbital complications in palatomaxillary reconstruction: A review of preemptive and corrective measures.

BACKGROUND: Reconstruction of orbit-sparing palatomaxillary defects requires consideration of globe dystopia, orbital volume, eyelid position and function, and the nasolacrimal system to preserve and optimize vision, globe protection, and appearance. We describe the fundamentals of orbital and eyelid anatomy, common orbital complications related to palatomaxillary reconstruction, and preemptive and corrective surgical techniques to be utilized during and after globe-sparing palatomaxillary reconstruction. METHODS: We present a review of the literature supplemented by clinical case examples. RESULTS: We advocate for the use of preemptive and corrective techniques to ensure optimal aesthetic and functional outcomes for patients with orbital defects. CONCLUSIONS: Recognition and anticipation of problems in patients undergoing midface ablative and reconstructive procedures are vital to the implementation of corrective measures. Incision choice, orbital volume restoration, appropriate orbital floor reconstruction, and permanent or temporary lower eyelid suspension during the primary surgery can all significantly impact the development of long-term orbital complications.

The role of molecular testing in the diagnosis of medullary thyroid cancer: A case report of oncocytic medullary thyroid carcinoma and review of the literature.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a somewhat rare, particularly aggressive form of thyroid cancer. The authors present what we believe to be the first case of MTC diagnosed solely on the basis of molecular testing, as well as a review of the literature concerning this topic and oncocytic variants of MTC. CASE DESCRIPTION: A 30-year-old female patient with a 1.1 cm thyroid nodule underwent a fine-needle aspiration biopsy showing a Bethesda IV Hurthle cell neoplasm. Molecular testing of the specimen identified a RET M918 T mutation. The patient underwent a total thyroidectomy and bilateral central neck dissection. Initial pathologic analysis yielded a diagnosis of Hurthle cell adenoma. Based on the patient's known RET mutation, immunohistochemistry for calcitonin was performed and yielded a positive result. The final diagnosis was amended to an oncocytic variant of medullary thyroid carcinoma. DISCUSSION: Had this patient undergone fine-needle aspiration (FNA) biopsy without molecular testing or serum calcitonin measurement, the patient's disease would have been diagnosed as a Hurthle cell adenoma. Despite the lack of characteristic features of malignancy and the rarity of oncocytic MTC, the diagnostic pitfall in this oncocytic lesion was avoided due to molecular testing at the time of FNA biopsy. CONCLUSION: This case draws attention to the unique clinical value of molecular testing in the diagnosis of MTC. The authors believe this case supports the consideration for molecular testing to prevent missed diagnoses in cases of rare benign-appearing disease.

A novel radial forearm free flap design to treat pharyngoesophageal stenosis in combination with the posterior wall of the trachea.

Pharyngoesophageal stenosis (PES) is a common and serious complication of head and neck cancer treatments such as radiation therapy, chemotherapy, tracheoesophageal puncture placement, and total laryngectomy surgery. Dilation-resistant stenosis requires surgical reconstruction, often with a radial forearm free flap (RFFF). With the present technique, the authors refine their previous bipaddled free flap design used to reconstruct a persistent tracheoesophageal fistulae (TEF) in combination with PES. Accordingly, we present a novel bipaddled triangular RFFF design ideally suited to address the shape of the defect in the posterior tracheal wall that results when the TEF is opened and the esophageal and tracheal components are restored.