A systematic review and meta-analysis on the outcomes of type I thyroplasty in the irradiated neck.

BACKGROUND: Type I thyroplasty has been well-documented as a safe and effective treatment modality for vocal fold motion impairment, as well as other select cases of persistent glottic insufficiency. However, history of prior radiation to the neck has traditionally been viewed as a relative, if not formal contra-indication to this procedure. The objective of this systematic review was to analyze all available data in the literature on type I thyroplasty in previously irradiated patients and perform a meta-analysis assessing whether complications and revision rates are significantly different between radiated and non-irradiated patients. Secondary outcomes were to compare voice outcomes between these cohorts. METHODS: Several databases were screened for relevant citations using the PICO process. The quality of studies and risk of bias were evaluated using the MINORS scoring system. Main endpoints for analysis in this study were complication rate and revision rate. Secondary endpoint was reported voice outcome. RESULTS: Three articles were included in the analysis. Zero major complications were reported, including no instances of implant extrusion or explantation. There was an 11.8 % rate of minor complications. There were similar rates of revision between radiation and control groups. There was no significant difference in voice outcomes between groups. The average MINORS score of the studies suggested a high risk of bias. CONCLUSIONS: Based on limited quality evidence, this review suggests that type I thyroplasty is safe and feasible in carefully selected irradiated patients, with comparable complication and success rates as their non-irradiated cohorts. Further large-scale studies are warranted.

de Quervain's thyroiditis: A review of experience with surgery.

BACKGROUND: de Quervain's thyroiditis is an inflammatory condition of the thyroid mostly treated medically, rarely requiring surgical treatment. We intend to review the surgical experience with de Quervain's thyroiditis at a tertiary cancer center over a period of 22years. METHODS: A retrospective review of medical records from 1992 to 2014 at a tertiary cancer center was performed and all patients with a histopathological diagnosis of de Quervain's thyroiditis were included. RESULTS: Ten patients with a histopathological diagnosis of de Quervain's thyroiditis were included in the study. One patient in the study presented with dysphagia due to the goiter. The remaining patients presented with thyroid nodules. None presented with typical symptoms of the disease. Seven of the ten patients that had been evaluated for a goiter at an outside facility underwent fine needle aspiration cytology. Of the seven patients, one patient was suspected to have medullary carcinoma of the thyroid, two had follicular neoplasia, and the others had indeterminate nodules. Eight of the ten patients underwent surgery for suspected malignancy, with eight receiving a total thyroidectomy and two patients getting a thyroid lobectomy with isthmusectomy. Two patients had an abnormally hard gland to palpate during surgery with the others not having any suspicious findings. Seven of the ten of the patients had lymph node sampling from level 6 and all were benign on final pathology. The mean duration of post-operative follow-up was 15months. There was no morbidity associated with surgery in any of these patients with eight of the ten patients requiring thyroid hormone replacement. None of the patients needed further neck surgery for thyroid disease. CONCLUSION: de Quervain's thyroiditis is an inflammatory condition of the thyroid that is rarely treated surgically. However when presentation is atypical and the FNAC is inconclusive or is suspicious for a malignancy, patients receive surgery putting them at a risk for morbidity. Good clinical assessment with combined use of ultrasound with FNAC especially read by an experienced cytopathologist has the potential to reduce unnecessary operative intervention.

SCCRO3 (DCUN1D3) antagonizes the neddylation and oncogenic activity of SCCRO (DCUN1D1).

The activity of cullin-RING type ubiquitination E3 ligases is regulated by neddylation, a process analogous to ubiquitination that culminates in covalent attachment of the ubiquitin-like protein Nedd8 to cullins. As a component of the E3 for neddylation, SCCRO/DCUN1D1 plays a key regulatory role in neddylation and, consequently, cullin-RING ligase activity. The essential contribution of SCCRO to neddylation is to promote nuclear translocation of the cullin-ROC1 complex. The presence of a myristoyl sequence in SCCRO3, one of four SCCRO paralogues present in humans that localizes to the membrane, raises questions about its function in neddylation. We found that although SCCRO3 binds to CAND1, cullins, and ROC1, it does not efficiently bind to Ubc12, promote cullin neddylation, or conform to the reaction processivity paradigms, suggesting that SCCRO3 does not have E3 activity. Expression of SCCRO3 inhibits SCCRO-promoted neddylation by sequestering cullins to the membrane, thereby blocking its nuclear translocation. Moreover, SCCRO3 inhibits SCCRO transforming activity. The inhibitory effects of SCCRO3 on SCCRO-promoted neddylation and transformation require both an intact myristoyl sequence and PONY domain, confirming that membrane localization and binding to cullins are required for in vivo functions. Taken together, our findings suggest that SCCRO3 functions as a tumor suppressor by antagonizing the neddylation activity of SCCRO.

Membranous Vocal Fold Lesions in Patients With Chronic Cough: A Case Series.

OBJECTIVES: Trauma related to chronic cough and forceful glottal closure has been associated with lesions of the vocal process; however, there is limited description of cough leading to membranous vocal fold lesions. We present a series of mid-membranous vocal fold lesions in a cohort of patients with chronic cough, with a proposed mechanism of lesion formation. METHODS: Patients treated for chronic cough with membranous vocal fold lesions affecting phonation were identified. Presentation, diagnosis, treatment strategies (behavioral, medical, and surgical), patient-reported outcome measures (PROMs), and videostroboscopy were reviewed. RESULTS: Five patients are included (four females, one male, aged 56±16 years). Mean cough duration was 2.6±3.5 years. All patients were on acid suppressive medications for existing gastroesophageal reflux disease (GERD) prior to referral. All lesions were identified at the mid-membranous vocal folds and morphologically encompassed a wound healing spectrum between ulceration and/or granulation tissue (granuloma) formation. Patients were treated in an interdisciplinary fashion with behavioral cough suppression therapy, superior laryngeal nerve block, and neuromodulators. Three had persistent lesions requiring procedural intervention (one office-based steroid injection and two surgical excisions). At the completion of treatment, all five patients had improvement in Cough Severity Index with an average decrease of 15.2±4.8. All but one patient had improvement in their Voice Handicap Index-10 with an average decrease of 13.2±11.1. One patient undergoing surgical intervention was noted to have a persistent lesion on follow-up. CONCLUSION: Mid-membranous vocal fold lesions in patients with chronic cough are uncommon. When they do occur, they represent epithelial change arising in context of shear injury and are distinct from phonotraumatic lesions in the lamina propria. An interdisciplinary approach including behavioral cough suppression therapy, neuromodulators, superior laryngeal nerve block, and acid suppression are reasonable for initial management, reserving surgical intervention for refractory lesions once the inciting source of injury has been controlled.

Parathyroidectomy in First Trimester of Pregnancy.

Primary hyperparathyroidism is not commonly diagnosed during pregnancy. For pregnant women with mild, asymptomatic disease, surgery can be avoided unless the degree of hypercalcemia becomes more severe or they develop complications. However, there are no evidence-based guidelines to assist clinicians regarding the management of primary hyperparathyroidism during pregnancy. When surgery is deemed necessary during pregnancy, the second trimester is generally considered to be the optimal time. We report the case of a 31-year-old female G1P0 who presented at 6 weeks gestation with symptoms of nausea, vomiting, polyuria, and corrected calcium of 14.8 mg/dL. Due to the extreme degree of hypercalcemia and refractory to medical treatment, it was decided that surgery could not be delayed until the second trimester. At 7w3d gestational age the patient had resection of a 37 gram, 5 × 4 × 3 cm right inferior parathyroid adenoma.

Previous External Beam Radiation Treatment Exposure Does Not Confer Worse Outcome for Patients with Differentiated Thyroid Cancer.

BACKGROUND: Radiation exposure, especially in childhood, is known to increase the risk for the development of thyroid cancer. However, the prognosis of patients with thyroid cancer with a history of radiation treatment exposure remains unclear. METHODS: One hundred and sixteen patients with a previous history of radiotherapy in the head and neck region were identified from an institutional database of 3664 patients with differentiated thyroid cancer treated between 1986 and 2010. Using the Kaplan-Meier method, disease-specific survival and recurrence-free survival were compared between patients with (RT; n = 116) and without (No RT; n = 3509) a prior history of radiation exposure. RESULTS: The median ages of the RT and No RT cohorts were 52 and 47 years. The median follow-up for both groups was 54 months. Patients who had a prior history of radiation treatment exposure were more likely to be male (38.8% vs. 26.9%; p = 0.005) and older than 45 years of age (67.2% vs. 53.9%; p = 0.005). Other patient, tumor, and treatment characteristics were similar between the groups. There was no difference in the five-year disease-specific survival of the RT and No RT patients (97.4% vs. 98.7%; p = 0.798). The five-year recurrence-free survival was also similar between the RT and No RT patients (97.8% vs. 94.9%; p = 0.371). CONCLUSION: The findings suggest that differentiated thyroid cancer patients with a history of prior radiation treatment exposure have similar outcomes to those with no history of head and neck radiation exposure.

Oncogenic function of SCCRO5/DCUN1D5 requires its Neddylation E3 activity and nuclear localization.

PURPOSE: To determine mechanisms by which SCCRO5 (aka DCUN1D5) promotes oncogenesis. EXPERIMENTAL DESIGN: SCCRO5 mRNA and protein expression were assessed in 203 randomly selected primary cancer tissue samples, matched histologically normal tissues, and cell lines by use of real-time PCR and Western blot analysis. SCCRO5 overexpression was correlated with survival. The effect of SCCRO5 knockdown on viability was assessed in selected cancer cell lines. Structure-function studies were performed to determine the SCCRO5 residues required for binding to the neddylation components, for neddylation-promoting activity, and for transformation. RESULTS: In oral and lung squamous cell carcinomas, SCCRO5 mRNA levels corresponded with protein levels and overexpression correlated with decreased disease-specific survival. Knockdown of SCCRO5 by RNAi resulted in a selective decrease in the viability of cancer cells with high endogenous levels, suggesting the presence of oncogene addiction. SCCRO5 promoted cullin neddylation while maintaining conserved reaction processivity paradigms involved in ubiquitin and ubiquitin-like protein conjugation, establishing it as a component of the neddylation E3. Neddylation activities in vitro required the potentiating of neddylation (PONY) domain but not the nuclear localization sequence (NLS) domain. In contrast, both the NLS domain and the PONY domain were required for transformation of NIH-3T3 cells. CONCLUSIONS: Our data suggest that SCCRO5 has oncogenic potential that requires its function as a component of the neddylation E3. Neddylation activity and nuclear localization of SCCRO5 are important for its in vivo function.