Racial disparities in access to liver transplantation in patients with early-stage hepatocellular carcinoma.

BACKGROUND: Orthotopic liver transplantation is the recommended treatment option for patients with early-stage hepatocellular carcinoma and concomitant cirrhosis. Waitlist candidacy can be affected by social determinants of health that vary across races and ethnicities. Our study sought to evaluate whether racial/ethnic disparities exist in access to orthotopic liver transplantation in patients with hepatocellular carcinoma. METHODS: The National Cancer Database participant use file was used to analyze data between 2004 and 2020. Patients 18-70 years of age with TNM clinical stage I and II hepatocellular carcinoma who received either orthotopic liver transplantation or liver directed/nonsurgical therapies were included. Baseline demographic variables and treatment modalities were collected. Patients were assigned fixed categories on the basis of race and ethnicity. Descriptive statistics, multivariable logistical regressions, effects modification analysis, and propensity matching were used. RESULTS: There were 23,313 non-Hispanic White, 5,215 non-Hispanic Black, 5,581 Hispanic, and 2,768 other patients included in this analysis. Significant socioeconomic variation was observed across races. Non-Hispanic White patients were more likely to undergo orthotopic liver transplantation than non-Hispanic Black patients. The proportion of patients insured by Medicare was the same between non-Hispanic White and non-Hispanic Black patients. There was a graeter proportion of non-Hispanic Black patients with Medicaid compared with non-Hispanic White patients, whereas a lower proportion of non-Hispanic Black patients were insured via private insurance compared with non-Hispanic White patients. Effect modification analysis showed the non-Hispanic Black patients were less likely to undergo orthotopic liver transplantation for those with private and Medicare coverage compared with non-Hispanic White patients. Propensity matching showed a significantly decreased rate of orthotopic liver transplantation in non-Hispanic Black patients compared with non-Hispanic White patients. CONCLUSION: Non-Hispanic Black patients were less likely to undergo orthotopic liver transplantation for early-stage hepatocellular carcinoma, despite adjusting for cancer stage and socioeconomic factors, compared with non-Hispanic White patients. Social determinants of health were associated with the probability of undergoing orthotopic liver transplantation. Understanding disparities related to social determinants of health will help guide health policy changes and improved access to care.

Lobectomy or Total Thyroidectomy-Where Is the Pendulum now for Differentiated Thyroid Cancer?

Thyroid surgery remains an essential treatment of thyroid cancer. The historical one-size-fits-all approach to differentiated (papillary and follicular) thyroid carcinoma of total thyroidectomy with central lymph node dissection has been shown to be overtreatment with associated risk of perioperative complications including nerve palsy and hypoparathyroidism. Furthermore, thyroid lobectomy may obviate life-long thyroid hormone replacement. Low-risk thyroid cancers have a low risk of recurrence and those that do recur can be salvaged with reoperation without compromising prognosis. Perioperative risk stratification for recurrence and death greatly influence the need for total thyroidectomy.

A comparison of NSQIP and CESQIP in data quality and ability to predict thyroidectomy outcomes.

BACKGROUND: The Collaborative Endocrine Surgery Quality Improvement Program tracks thyroidectomy outcomes with self-reported data, whereas the National Surgical Quality Improvement Program uses professional abstractors. We compare completeness and predictive ability of these databases at a single-center and national level. METHOD: Data consistency in the Collaborative Endocrine Surgery Quality Improvement Program and the National Surgical Quality Improvement Program at a single institution (2013-2020) was evaluated using McNemar's test. At the national level, data from the Collaborative Endocrine Surgery Quality Improvement Program and the National Surgical Quality Improvement Program (2016-2019) were used to compare predictive capability for 4 outcomes within each data source: thyroidectomy-specific complication, systemic complication, readmission, and reoperation, as measured by area under curve. RESULTS: In the single-center analysis, 66 cases were recorded in both the Collaborative Endocrine Surgery Quality Improvement Program and the National Surgical Quality Improvement Program. The reoperation variable had the most discrepancies (2 vs 0 in the National Surgical Quality Improvement Program versus the Collaborative Endocrine Surgery Quality Improvement Program, respectively; χ2 = 2.00, P = .16). At the national level, there were 24,942 cases in the National Surgical Quality Improvement Program and 17,666 cases in the Collaborative Endocrine Surgery Quality Improvement Program. In the National Surgical Quality Improvement Program, 30-day thyroidectomy-specific complication, systemic complication, readmission, and reoperation were 13.25%, 2.13%, 1.74%, and 1.39%, respectively, and in the Collaborative Endocrine Surgery Quality Improvement Program 7.27%, 1.95%, 1.64%, and 0.81%. The area under curve of the National Surgical Quality Improvement Program was higher for predicting readmission (0.721 [95% confidence interval 0.703-0.737] vs 0.613 [0.581-0.649]); the area under curve of the Collaborative Endocrine Surgery Quality Improvement Program was higher for thyroidectomy-specific complication (0.724 [0.708-0.737] vs 0.677 [0.667-0.687]) and reoperation (0.735 [0.692-0.775] vs 0.643 [0.611-0.673]). Overall, 3.44% vs 27.22% of values were missing for the National Surgical Quality Improvement Program and the Collaborative Endocrine Surgery Quality Improvement Program, respectively. CONCLUSION: The Collaborative Endocrine Surgery Quality Improvement Program was more accurate in predicting thyroidectomy-specific complication and reoperation, underscoring its role in collecting granular, disease-specific variables. However, a higher proportion of data are missing. The National Surgical Quality Improvement Program infrastructure leads to more rigorous data capture, but the Collaborative Endocrine Surgery Quality Improvement Program is better at predicting thyroid-specific outcomes.

Opioid-Free Thyroid and Parathyroid Operations: Are Patients Satisfied With Pain Control?

BACKGROUND: The aim of this study was to evaluate pain control and patient satisfaction using an opioid-free analgesic regimen following thyroid and parathyroid operations. METHODS: Surveys were distributed to all postoperative patients following total thyroidectomy, thyroid lobectomy, and parathyroidectomy between January and April 2020. After surgery, patients were discharged without opioids except in rare cases based on patient needs and surgeon judgment. We measured patient-reported Numeric Rating Scale (NRS) pain scores and satisfaction categorically as either satisfied or dissatisfied. RESULTS: We received 90 of 198 surveys distributed, for a 45.5% response rate. After excluding neck dissections (n = 6) and preoperative opioid use (n = 4), the final cohort included 80 patients after total thyroidectomy (26.3%), thyroid lobectomy (41.3%), and parathyroidectomy (32.5%).The majority reported satisfaction with pain control (87.5%) and the entire surgical experience (95%). A similar proportion of patients reported satisfaction with pain control after total thyroidectomy (90.9%), thyroid lobectomy (90.5%), and parathyroidectomy (80.8%), indicating the procedure did not significantly impact satisfaction with pain control (P = .47). Patients who reported dissatisfaction with pain control were more likely to receive opioid prescriptions (30% vs 2.9%, P < .01), but the majority still reported satisfaction with their entire operative experience (70%). DISCUSSION: Even with an opioid-free postoperative pain regimen, most patients report satisfaction with pain control after thyroid and parathyroid operations, and those who were dissatisfied with their pain control generally reported satisfaction with their overall surgical experience. Therefore, an opioid-free postoperative pain control regimen is well tolerated and unlikely to decrease overall patient satisfaction.

Selumetinib Plus Adjuvant Radioactive Iodine in Patients With High-Risk Differentiated Thyroid Cancer: A Phase III, Randomized, Placebo-Controlled Trial (ASTRA).

PURPOSE: Selumetinib can increase radioactive iodine (RAI) avidity in RAI-refractory tumors. We investigated whether selumetinib plus adjuvant RAI improves complete remission (CR) rates in patients with differentiated thyroid cancer (DTC) at high risk of primary treatment failure versus RAI alone. METHODS: ASTRA (ClinicalTrials.gov identifier: NCT01843062) is an international, phase III, randomized, placebo-controlled, double-blind trial. Patients with DTC at high risk of primary treatment failure (primary tumor > 4 cm; gross extrathyroidal extension outside the thyroid gland [T4 disease]; or N1a/N1b disease with ≥ 1 metastatic lymph node(s) ≥ 1 cm or ≥ 5 lymph nodes [any size]) were randomly assigned 2:1 to selumetinib 75 mg orally twice daily or placebo for approximately 5 weeks (no stratification). On treatment days 29-31, recombinant human thyroid-stimulating hormone (0.9 mg)-stimulated RAI (131I; 100 mCi/3.7 GBq) was administered, followed by 5 days of selumetinib/placebo. The primary end point (CR rate 18 months after RAI) was assessed in the intention-to-treat population. RESULTS: Four hundred patients were enrolled (August 27, 2013-March 23, 2016) and 233 randomly assigned (selumetinib, n = 155 [67%]; placebo, n = 78 [33%]). No statistically significant difference in CR rate 18 months after RAI was observed (selumetinib n = 62 [40%]; placebo n = 30 [38%]; odds ratio 1.07 [95% CI, 0.61 to 1.87]; P = .8205). Treatment-related grade ≥ 3 adverse events were reported in 25/154 patients (16%) with selumetinib and none with placebo. The most common adverse event with selumetinib was dermatitis acneiform (n = 11 [7%]). No treatment-related deaths were reported. CONCLUSION: Postoperative pathologic risk stratification identified patients with DTC at high risk of primary treatment failure, although the addition of selumetinib to adjuvant RAI failed to improve the CR rate for these patients. Future strategies should focus on tumor genotype-tailored drug selection and maintaining drug dosing to optimize RAI efficacy.

Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA) learning curve: a regression analysis of complication rates and severity.

BACKGROUND: Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA) is a natural orifice transluminal endoscopic surgery that offers a truly scarless approach to thyroidectomy. Introduced in 2008, there is a growing body of literature establishing it as a safe endoscopic approach for thyroid procedures. While it is not yet widely practiced, it is quickly growing in popularity. As more surgeons begin to add this technique to their repertoire the question of the learning curve has to be examined. METHODS: Case series from the initial TOETVA operations of four surgeons at three different hospitals were examined. Binomial and ordinal logistic regression were used to characterize the changes in complication rate and severity as they related to case number in the series. Statistics were performed in Minitab and SAS. RESULTS: Each surgeon performed between 23 and 40 TOETVA operations for a total of 130 cases. Binary logistic regression shows a negative relationship between case number and complication rate (P < 0.001, Odds Ratio: 0.91). Ordinal logistic regression shows a negative relationship between case number and complication severity (P < 0.001, Odds Ratio: 1.07). The maximum slope of improvement of complication rate occurred at case number 12. CONCLUSION: The most significant decrease in complications for TOETVA occurs at case 12. As case number progresses, there is a significant decrease in both the risk of a complication occurring and of the severity of that complication. These results support the previously published data on TOETVA learning curve based on operative time.

Transoral Endoscopic Thyroidectomy Vestibular Approach: A Single-institution Experience of the First 50 Cases.

Background. Transoral endoscopic thyroidectomy vestibular approach (TOETVA) has evolved from a novel procedure to a cosmetically appealing alternative to the traditional open thyroidectomy. TOETVA is limited to only high-volume centers with the hope to expand and demonstrate the safety, reproducibility, and application for the correct patient with thyroid disease. We present our experience with the first 50 TOETVA procedures performed at our institution. Methods. From September 2016 to June 2018, we performed 50 transoral endoscopic thyroidectomies via the vestibular approach for a variety of thyroid pathologies. Outcomes were analyzed from a prospectively maintained database. Patients were treated for a different range of thyroid pathologies. Results. A total of 12 (24%) patients underwent total thyroidectomy, whereas 38 (76%) patients underwent a subtotal thyroidectomy or thyroid lobectomy. The mean surgical time was 149 ± 40.0 (90-256) minutes for lobectomy and 217.6 ± 33.3 (175-276) minutes for total thyroidectomy. Of our 50 patients, 16 (32%) had postoperative transient lower lip numbness with an average time to recovery of 23.8 (.43-48) weeks, with 1 (2%) patient having persistent, but improving, lower lip numbness beyond the 6-month follow-up. There were 13 (26%) patients with transient chin numbness with an average time to recovery of 15.7 (2-48) weeks. Two (4%) patients had transient recurrent laryngeal nerve (RLN) injury with hoarseness, whereas 1 (2%) patient had permanent injury. Conclusion. The TOETVA is a safe and reproducible procedure. For selected patients, this technique is a viable alternative to conventional thyroidectomy.

Post-thyroidectomy emergency room visits and readmissions: Assessment from the Collaborative Endocrine Surgery Quality Improvement Program (CESQIP).

BACKGROUND: This study analyzed independent factors associated with post-thyroidectomy Emergency Room (ER) visits and Hospital Readmissions (HR). METHODS: This is a retrospective review from the CESQIP registry of 8381 thyroidectomy patients by 173 surgeons at 46 institutions. A total of 7142 ER visits and 7265 HR were analyzed. Multivariable logistic regression analysis was performed to determine the risk factors for an ER visit or HR. RESULTS: Within 30-days of surgery, rates of all ER visits were 3.4% (n = 250) and all HR were 2.3% (n = 170). Hypocalcemia was the reason for 21.9% of ER encounters and 36.4% of HR. BMI >40 kg/m2 was a risk factor for both ER visit (OR1.86) and HR (OR1.94). Surgical duration >3 h (OR2.63), and transection of recurrent laryngeal nerve (OR4.58) were risk factors for HR. CONCLUSIONS: Strategies to decrease hypocalcemia and improve perioperative care of patients with BMI >40 kg/m2 may improve post-thyroidectomy outcome.

Correlating the Bethesda System for Reporting Thyroid Cytopathology with Histology and Extent of Surgery: A Review of 21,746 Patients from Four Endocrine Surgery Registries Across Two Continents.

BACKGROUND: The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category. METHODS: Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed. RESULTS: Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31-35 years (52.1%, 95% confidence interval (CI) 37.9-66.2%), aged 36-40 years (55.9%, 95% CI 39.2-72.6%) and aged 41-45 years (46.9%, 95% CI 33-60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males. CONCLUSIONS: These data demonstrate that Bethesda categories 1-4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC.

Transoral Endoscopic Thyroidectomy Vestibular Approach.

BACKGROUND: Remote-access thyroid surgery has gained popularity and has advanced significantly over the past two decades, given the patient desire to avoid cosmetically displeasing scarring. It has only been recently that natural-orifice transluminal endoscopic surgery (NOTES) techniques have been geared for thyroidectomies. The transoral endoscopic thyroidectomy vestibular approach has been categorized as a NOTES procedure-given the approach to the thyroid gland via incisions in the oral cavity. Our aim is to provide a review of the current literature on the transoral endoscopic thyroidectomy vestibular approach (TOETVA), to present the worldwide experience of this novel procedure, and to outline whether individual patients have characteristics that would make the procedure feasible for this technique. METHODS: A literature review was done to compile articles detailing the international experience with TOETVA. Our experience combined with what has been published in the literature was used to establish which pathological and patient characteristics make this particular technique feasible for a thyroidectomy. RESULTS: We detail in the provided tables both feasibility for this surgical technique and the international experience. CONCLUSION: TOETVA represents the latest remote-access endoscopic technique for the excision of the thyroid gland. TOETVA is being performed at various international institutions and multiple hospitals in the United States.

Transoral Thyroid and Parathyroid Surgery Vestibular Approach: A Framework for Assessment and Safe Exploration.

The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a new approach to the central neck that avoids an anterior cervical incision. This approach can be performed with endoscopic or robotic assistance and offers access to the bilateral central neck. It has been completed safely in both North American and, even more extensively, international populations. With any new technology or approach, complications during the learning curve, expense, instrument limitations, and overall safety may affect its ultimate adoption and utility. To ensure patient safety, it is imperative to define steps that should be considered by any surgeon or group before adoption of this new approach.

Lifestyle Intervention and Medical Management With vs Without Roux-en-Y Gastric Bypass and Control of Hemoglobin A1c, LDL Cholesterol, and Systolic Blood Pressure at 5 Years in the Diabetes Surgery Study.

Importance: The Roux-en-Y gastric bypass is effective in achieving established diabetes treatment targets, but durability is unknown. Objective: To compare durability of Roux-en-Y gastric bypass added to intensive lifestyle and medical management in achieving diabetes control targets. Design, Setting, and Participants: Observational follow-up of a randomized clinical trial at 4 sites in the United States and Taiwan, involving 120 participants who had a hemoglobin A1c (HbA1c) level of 8.0% or higher and a body mass index between 30.0 and 39.9 (enrolled between April 2008 and December 2011) were followed up for 5 years, ending in November 2016. Interventions: Lifestyle-intensive medical management intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2 years, with and without (60 participants each) Roux-en-Y gastric bypass surgery followed by observation to year 5. Main Outcomes and Measures: The American Diabetes Association composite triple end point of hemoglobin A1c less than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg at 5 years. Results: Of 120 participants who were initially randomized (mean age, 49 years [SD, 8 years], 72 women [60%]), 98 (82%) completed 5 years of follow-up. Baseline characteristics were similar between groups: mean (SD) body mass index 34.4 (3.2) for the lifestyle-medical management group and 34.9 (3.0) for the gastric bypass group and had hemoglobin A1c levels of 9.6% (1.2) and 9.6% (1.0), respectively. At 5 years, 13 participants (23%) in the gastric bypass group and 2 (4%) in the lifestyle-intensive medical management group had achieved the composite triple end point (difference, 19%; 95% CI, 4%-34%; P = .01). In the fifth year, 31 patients (55%) in the gastric bypass group vs 8 (14%) in the lifestyle-medical management group achieved an HbA1c level of less than 7.0% (difference, 41%; 95% CI, 19%-63%; P = .002). Gastric bypass had more serious adverse events than did the lifestyle-medical management intervention, 66 events vs 38 events, most frequently gastrointestinal events and surgical complications such as strictures, small bowel obstructions, and leaks. Gastric bypass had more parathyroid hormone elevation but no difference in B12 deficiency. Conclusions and Relevance: In extended follow-up of obese adults with type 2 diabetes randomized to adding gastric bypass compared with lifestyle and intensive medical management alone, there remained a significantly better composite triple end point in the surgical group at 5 years. However, because the effect size diminished over 5 years, further follow-up is needed to understand the durability of the improvement. Trial Registration: clinicaltrials.gov Identifier: NCT00641251.

Clinical performance of a next-generation sequencing assay (ThyroSeq v2) in the evaluation of indeterminate thyroid nodules.

BACKGROUND: Molecular testing with the Thyroseq v2 next generation sequencing panel ("Thyroseq") is used to estimate the risk of cancer in indeterminate thyroid nodules. METHODS: We analyzed 156 indeterminate thyroid nodules evaluated with Thyroseq, across 3 institutions. Thyroseq data and surgical pathology were matched via pathologic re-review. A result was considered Thyroseq positive if molecular alterations were annotated on the report with malignancy probability >30%. Performance characteristics were estimated using Bayes theorem. RESULTS: The Thyroseq-negative call rate was 65% (102/156). On surgical pathology, 16% (10/63) of nodules were malignant. The positive predictive value of a Thyroseq-positive result was 22% (8/37; if 2 noninvasive follicular thyroid neoplasm with papillary-like nuclear features are counted as malignant, 27%, 10/37). There was 1 false-negative result (negative predictive value 96%, 22/23). The most common mutation was NRAS (19/37) with a positive predictive value of 7% (1/15). The positive predictive value of all RAS mutations (HRAS, KRAS, NRAS) was 9% (2/22). The second most common mutation, BRAF V600E, had positive predictive value of 100% (3/3). CONCLUSION: We report an external analysis of Thyroseq performance in the evaluation of indeterminate thyroid nodules. These data indicate that Thyroseq is likely to offer high negative predictive value but low positive predictive value. Many genetic alterations appear to be nonspecific for malignancy, and positive results should be interpreted with caution. These findings have implications for the management of indeterminate thyroid nodules profiled with Thyroseq.

Insights into beta cell regeneration for diabetes via integration of molecular landscapes in human insulinomas.

Although diabetes results in part from a deficiency of normal pancreatic beta cells, inducing human beta cells to regenerate is difficult. Reasoning that insulinomas hold the "genomic recipe" for beta cell expansion, we surveyed 38 human insulinomas to obtain insights into therapeutic pathways for beta cell regeneration. An integrative analysis of whole-exome and RNA-sequencing data was employed to extensively characterize the genomic and molecular landscape of insulinomas relative to normal beta cells. Here, we show at the pathway level that the majority of the insulinomas display mutations, copy number variants and/or dysregulation of epigenetic modifying genes, most prominently in the polycomb and trithorax families. Importantly, these processes are coupled to co-expression network modules associated with cell proliferation, revealing candidates for inducing beta cell regeneration. Validation of key computational predictions supports the concept that understanding the molecular complexity of insulinoma may be a valuable approach to diabetes drug discovery.Diabetes results in part from a deficiency of functional pancreatic beta cells. Here, the authors study the genomic and epigenetic landscapes of human insulinomas to gain insight into possible pathways for therapeutic beta cell regeneration, highlighting epigenetic genes and pathways.

National Differences in Remission of Type 2 Diabetes Mellitus After Roux-en-Y Gastric Bypass Surgery-Subgroup Analysis of 2-Year Results of the Diabetes Surgery Study Comparing Taiwanese with Americans with Mild Obesity (BMI 30-35 kg/m2).

BACKGROUND: The purpose of this study is to compare effects of different nations on Roux-en-Y gastric bypass (RYGB) vs. intensive medical management (IMM) in achieving remission of type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Between April 2008 and December 2011, this randomized, controlled clinical trial was conducted at four teaching hospitals in the United States and Taiwan involving 71 participants with mild obesity (BMI 30-35 kg/m2). Thirty-six of 71 participants were randomly assigned to the RYGB group, and the others were in IMM group. Partial or complete remission of T2DM was defined as blood HbA1c < 6.5 % (48 mmol/mol) or <6 % (42 mmol/mol) without any antihyperglycemic medication for at least 1-year duration, respectively. RESULTS: At baseline, Taiwanese participants had a lower BMI, younger age, and shorter duration of T2DM than American participants. At 24 months, weight loss was greater in the RYGB group in both populations than in the IMM group. No IMM participant of either population had partial or complete remission of T2DM. In the RYGB group, a substantial proportion of the subjects achieved complete or partial remission (57 % in Taiwanese and 27 % in American participants, P = 0.08). Logistic regression revealed stimulated C-peptide (Odds ratio 2.22, P = 0.02) but not nationality as a significant predictor of diabetes remission. CONCLUSION: Adding RYGB to lifestyle and medical management was associated with a greater likelihood of remission of T2DM in both Taiwanese and American subjects with mild obesity with type 2 diabetes. Residual beta-cell function at baseline appears to be the major factor predicting remission of T2DM. Trial registry number: clinicaltrials.gov Identifier: NCT00641251.

CD40 Signaling in Graves Disease Is Mediated Through Canonical and Noncanonical Thyroidal Nuclear Factor κB Activation.

CD40, a tumor necrosis factor receptor, is a major immune-modulating susceptibility gene for Graves disease (GD) as well as for a variety of other autoimmune diseases. Its broad association with autoimmunity underscores its paramount role in the development of a normal adaptive immune response, primarily in coordinating effective antigen presentation. The molecular pathways by which CD40 activation in the thyroid induces GD are unknown. In this study, we investigated whether NF-κB, a ubiquitious family of transcription factors, mediates the downstream effects of thyroid-specific CD40 activation. Cultured primary human thyrocytes, from patients with and without GD, underwent CD40 stimulation. Once stimulated, cytokines and transcription factors specific for either the canonical nuclear factor κB (NF-κB)1 pathway [interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α], which primarily recruits cells for innate immunity, or the noncanonical NF-κB2 pathway [B cell-activating factor of the TNF family, CC chemokine ligand (CCL)21], which directs B cell viability, were analyzed. Significant upregulation in the messenger RNA and protein levels of both canonical and noncanonical pathway cytokines was observed. Western blot analyses of the specific transcription factors for the NF-κB1 and NF-κB2 pathways (p65 and p100/p52, respectively) demonstrated that p65 is constitutively expressed. In contrast, CD40 stimulation robustly increased the expression of the NF-κB2 p52 transcription factor, and the upregulation was significantly more profound in the GD tissue than in the normal thyroid tissue. Our data show that CD40 activity in thyrocytes is prominently mediated via NF-κB and furthermore suggest that the NF-κB1 and NF-κB2 pathways both contribute to the triggering and the progression of GD.

Transoral endoscopic thyroidectomy vestibular approach with intraoperative nerve monitoring.

BACKGROUND: Transoral endoscopic thyroidectomy by a vestibular approach (TOETVA) is a novel technique for thyroid gland excision. Compared to the transaxillary endoscopic and bilateral axillo-breast approaches, which require substantial dissection to reach the thyroid gland, TOETVA provides the most direct access to the target organ. METHODS: The aim of this video is to provide a step-by-step overview of TOETVA and demonstrate how to set up and utilize intraoperative nerve monitoring. RESULTS: Three incisions are placed in the vestibular region of the oral cavity just below the lower lip for placement of 2 lateral 5-mm trocars and 1 centrally placed 11-mm trocar. Insufflation to 6 mm Hg is used to maintain the working spacing. Using a 2-handed technique and triangulation, the thyroid gland is mobilized, taking care to identify and preserve the relevant cervical anatomy. CONCLUSION: TOETVA is safe and feasible and provides an excellent cosmetic outcome with the most confidentially compared to the other remote access endoscopic approaches.