Association of Thyrotropin Suppression With Survival Outcomes in Patients With Intermediate- and High-Risk Differentiated Thyroid Cancer.

Importance: Suppression of thyrotropin (often referred to as thyroid-stimulating hormone, or TSH) with levothyroxine used in management of intermediate- and high-risk differentiated thyroid cancer (DTC) to reduce the likelihood of progression and death is based on conflicting evidence. Objective: To examine a cohort of patients with intermediate- and high-risk DTC to assess the association of thyrotropin suppression with progression-free survival (PFS) and overall survival. Design, Setting, and Participants: This cohort study used a multicenter database analysis including patients from tertiary referral centers and local clinics followed up for a mean (SD) of 7.2 (5.8) years. Patients with DTC treated uniformly with total thyroidectomy and radioactive iodine between January 1, 1979, and March 1, 2015, were included. Among the 1012 patients, 145 patients were excluded due to the lack of longitudinal thyrotropin measurements. Exposures: Levothyroxine therapy to target thyrotropin suppression with dose adjustments based on changing thyrotropin goal. Main Outcomes and Measures: The primary outcome measures were overall survival and PFS. A Cox proportional hazards model was used to assess the contribution of age, sex, tumor size, histology, and lymph node and distant metastases at landmarks 1.5, 3.0, and 5.0 years. The patients were divided into 3 groups based on mean thyrotropin score before each landmark: (1) suppressed thyrotropin, (2) moderately suppressed or low-normal thyrotropin, and (3) low-normal or elevated thyrotropin. Results: Among 867 patients (557 [64.2%] female; mean [SD] age, 48.5 [16.5] years) treated with a median (range) cumulative dose of 151 (30-1600) mCi radioactive iodine, disease progression was observed in 293 patients (33.8%), and 34 patients (3.9%) died; thus, the study was underpowered in death events. Thyrotropin suppression was not associated with improved PFS at landmarks 1.5 (P = .41), 3.0 (P = .51), and 5.0 (P = .64) years. At 1.5 and 3.0 years, older age (hazard ratio [HR], 1.06; 95% CI, 1.03-1.08 and HR, 1.05; 95% CI, 1.01-1.08, respectively), lateral neck lymph node metastases (HR, 4.64; 95% CI, 2.00-10.70 and HR, 4.02; 95% CI, 1.56-10.40, respectively), and distant metastases (HR, 7.54; 95% CI, 3.46-16.50 and HR, 7.10; 95% CI, 2.77-18.20, respectively) were independently associated with subsequent time to progression, while at 5.0 years, PFS was shorter for patients with lateral neck lymph node metastases (HR, 3.70; 95% CI, 1.16-11.90) and poorly differentiated histology (HR, 71.80; 95% CI, 9.80-526.00). Conclusions and Relevance: Patients with intermediate- and high-risk DTC might not benefit from thyrotropin suppression. This study provides the justification for a randomized trial.

Comprehensive approach to functional palatomaxillary reconstruction using regional and free tissue transfer: Report of reconstructive and prosthodontic outcomes of 140 patients.

BACKGROUND: Palatomaxillary defects were historically restored with a prosthetic obturator; however, advances in local and free tissue transfer has provided a viable alternative for appropriately selected patients with palatomaxillary defects. METHODS: A retrospective chart review of patients who underwent palatomaxillary reconstruction by the lead author between 1998 and 2016 was conducted. Patients who were restored with a palatal obturator were excluded. RESULTS: One hundred forty patients were reconstructed with a total of 159 local, regional, and free flaps with a 96.7% success rate. Seventy-four patients (52.8%) underwent prosthodontic rehabilitation, with 183 implants placed and an 86% success rate. CONCLUSION: Palatomaxillary reconstruction applying a systematic approach, using a multitude of techniques, is a safe and effective way to restore patients without compromising the ability to maintain surveillance. Prosthodontic rehabilitation can be achieved in a high percentage of patients using dental implants, leading to optimal aesthetic and functional results.

Total lower lip and chin reconstruction with radial forearm free flap: A novel approach.

BACKGROUND: The management of large chin and lower lip defects is challenging due to this facial subunit's tremendous functional and aesthetic importance. Specific methods for total lower lip and mentum reconstruction are not well chronicled. Aesthetic and functional goals of this reconstruction include restoration of oral competence by maintaining lower lip height, vermilion reestablishment, color-matched skin introduction to the chin, sensation restoration, and ideally restoration of dynamic activity to the lower lip. METHODS: Literature review performed. RESULTS: Presentation of novel, two-stage technique for lower lip and chin reconstruction with a submental flap and a radial forearm free flap, suspension of the lower lip and chin with a tensor fascia lata graft, and vermilion reconstruction with a buccal mucosal flap. CONCLUSIONS: This procedure meets all goals of total lower lip reconstruction with the exception of the introduction of dynamic tissue and represents a novel solution to a challenging reconstructive problem.

Pilot Study of a Web-based Decision Tool on Post-operative Use of Radioactive Iodine.

Background: The Thyroid Cancer Care Collaborative developed a web-based clinical decision-making module (CDMM) to inform risk-adjusted decisions on post-thyroidectomy radioactive iodine (RAI) use in papillary thyroid cancer (PTC). Methods: In a pilot study, we evaluated the CDMM in 19 PTC cases representing low- (five), intermediate- (seven) and high-risk (seven) disease. Two PTC experts and 10 PTC physicians reviewed cases and assigned risk level and RAI recommendation. The experts used a standard approach while the others used the CDMM. We assessed agreement between responses using a weighted Kappa. Results: Between experts, risk-assignment was concordant in 100%, 57% and 86% of low-, intermediate- and high-risk cases, respectively. Between CDMM users, risk-assignment was concordant in 100%, 29% and 14% in low-, intermediate- and high-risk cases, respectively (p=0.01). CDMM-assigned risk agreed with the expert-assigned risk in 100%, 25% and 0% of low-, intermediate- and high-risk cases, respectively (Kappa=0.69). For RAI use, the experts agreed in 15 cases while CDMM users agreed in eight. On further analysis, interpretation of extrathyroidal extension and lymph node staging led to discrepancies with the CDMM. Conclusions: For a web-based CDMM to accurately inform appropriate use of RAI in PTC, standard pathological and surgical reports are necessary.

Improving the adoption of thyroid cancer clinical practice guidelines.

OBJECTIVES/HYPOTHESIS: To present an overview of the barriers to the implementation of clinical practice guidelines (CPGs) in thyroid cancer management and to introduce a computer-based clinical support system. DATA SOURCES: PubMed. REVIEW METHODS: A review of studies on adherence to CPGs was conducted. RESULTS: Awareness and adoption of CPGs is low in thyroid cancer management. Barriers to implementation include unfamiliarity with the CPGs and financial concerns. Effective interventions to improve adherence are possible, especially when they are readily accessible at the point of care delivery. Computerized clinical support systems show particular promise. The authors introduce the clinical decision making modules (CDMMs) of the Thyroid Cancer Care Collaborative, a thyroid cancer-specific electronic health record. These computer-based modules can assist clinicians with implementation of these recommendations in clinical practice. CONCLUSION: Computer-based support systems can help clinicians understand and adopt the thyroid cancer CPGs. By integrating patient characteristics and guidelines at the point of care delivery, the CDMMs can improve adherence to the guidelines and help clinicians provide high-quality, evidence-based, and individualized patient care in the management of differentiated thyroid cancer. Laryngoscope, 126:2640-2645, 2016.

ACTIVE SURVEILLANCE FOR PAPILLARY THYROID MICROCARCINOMA: NEW CHALLENGES AND OPPORTUNITIES FOR THE HEALTH CARE SYSTEM.

OBJECTIVE: The dramatic increase in papillary thyroid carcinoma (PTC) is primarily a result of early diagnosis of small cancers. Active surveillance is a promising management strategy for papillary thyroid microcarcinomas (PTMCs). However, as this management strategy gains traction in the U.S., it is imperative that patients and clinicians be properly educated, patients be followed for life, and appropriate tools be identified to implement the strategy. METHODS: We review previous active surveillance studies and the parameters used to identify patients who are good candidates for active surveillance. We also review some of the challenges to implementing active surveillance protocols in the U.S. and discuss how these might be addressed. RESULTS: Trials of active surveillance support nonsurgical management as a viable and safe management strategy. However, numerous challenges exist, including the need for adherence to protocols, education of patients and physicians, and awareness of the impact of this strategy on patient psychology and quality of life. The Thyroid Cancer Care Collaborative (TCCC) is a portable record keeping system that can manage a mobile patient population undergoing active surveillance. CONCLUSION: With proper patient selection, organization, and patient support, active surveillance has the potential to be a long-term management strategy for select patients with PTMC. In order to address the challenges and opportunities for this approach to be successfully implemented in the U.S., it will be necessary to consider psychological and quality of life, cultural differences, and the patient's clinical status.

Reconstruction of expanding tracheoesophageal fistulae in post-radiation therapy patients who undergo total laryngectomy with a bipaddled radial forearm free flap: Report of 8 cases.

BACKGROUND: Our surgical approach describes a bipaddled radial forearm free flap (RFFF) for closure of chronic tracheoesophageal fistulae (TEF) in patients who underwent total laryngectomy. The desired functional results were achieved. METHODS: Eight patients underwent the procedure. The surgical approach includes exposure and resection of the fistula tract, and a bipaddled RFFF transfer. Key surgical maneuvers include: circumferential dissection and mobilization of the trachea; partial sternal resection in select cases; inset of flap's distal paddle into the anterior esophageal wall; and inset of the proximal skin paddle to the posterior tracheal wall and cervical skin. RESULTS: Successful reconstruction of all 8 cases was done to restore a normal diet and a widely patent tracheal opening. One patient developed a delayed esophageal stricture, which was successfully managed with home dilation. CONCLUSION: Several TEF treatment approaches have been reported. Our 87.5% esophageal lumen preservation success rate, reestablishment of adequate airway, and uncomplicated postoperative courses demonstrates the reliability of this surgical approach. © 2015 Wiley Periodicals, Inc. Head Neck 38: E172-E178, 2016.

Size distribution of metastatic lymph nodes with extranodal extension in patients with papillary thyroid cancer: a pilot study.

BACKGROUND: Extranodal extension (ENE) is a documented negative prognostic factor in patients with papillary thyroid cancer (PTC). ENE is presumed to manifest in larger lymph nodes. Yet, to date, no study has proven this. This is a pilot study that specifically examines the size distribution of positive lymph nodes manifesting ENE in patients with PTC. METHODS: An Institutional Review Board approved review examined the size of all lymph nodes demonstrating ENE in postoperative PTC patients that underwent surgery for PTC under the care of a single surgeon between 2004 and 2014. All patients in the study had regional metastatic lymph nodes with ENE. Analysis of the size distribution for all lymph nodes with ENE was performed. RESULTS: A total of 47% of lymph nodes with ENE were ≤10 mm. CONCLUSIONS: RESULTS indicate that clinically nonevident, small lymph nodes are at risk of harboring aggressive disease biology reflected in ENE. A total of 47% of all nodes fell within Randolph et al.'s classification of "small" lymph nodes, while 59% of the nodes with ENE were <1.5 cm-the threshold size that was deemed to be prognostically significant by Ito et al. It is apparent that clinically nonevident regional lymph nodes can have adverse histologic features and that the previous presumption that nodes with ENE only appear in clinically evident, macroscopic nodes is flawed.

Very delayed cervical lymph node metastases from hyalinizing clear cell carcinoma: report of 2 cases.

BACKGROUND: Hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland neoplasm most often found in the oral cavity. Although it is generally a low-grade malignancy that is treated with wide local excision, there is a growing body of evidence pointing toward the potential for more aggressive behavior. METHODS: We reviewed available records of patients with delayed cervical lymph node metastases from HCCC. RESULTS: Two patients who were treated with wide local resection for HCCC and remained disease-free at the primary site were diagnosed with cervical lymph node metastases 10 and 14 years later. We treated both with neck dissection, and 1 patient received adjuvant radiation therapy. CONCLUSION: These cases illustrate the risk for occult nodal metastases from HCCC with delayed presentation. Clinician awareness of the presence of subclinical metastases in the neck requires thorough long-term surveillance and potential intervention should nodal disease become manifest.

Intrathyroidal tumors presenting with extranodal extension: what are we missing?

Extranodal extension (ENE) is an indicator of poor prognosis in well-differentiated thyroid cancer (WDTC). We have demonstrated that extrathyroidal extension (ETE) predicts ENE in patients with positive lymph nodes, indicating concordance between primary tumor and lymph node biology. In an effort to determine if there were other histologic features of the primary tumors that indicated an aggressive biology, we examined a subset of patients with intrathyroidal (T1/T2) disease whose lymph nodes had ENE. A review was conducted from January 2004 to March 2013. The histologic features of ETE-negative/ENE-positive tumors (group A, 12 cases) were compared with a random sample of ETE-negative/ENE-negative node-positive patients (group B, 27 cases). Cases were reviewed for size, capsule presence, infiltration, sclerosis, lymphocytic thyroiditis (LT), psammoma bodies, lymphovascular invasion (LVI), perineural invasion (PNI), architecture/cytomorphology, and focality. Size was compared using the Mann-Whitney test, while the remaining features were compared using a Fischer exact test. The breakdown of pathologic features of groups A/B were as follows: 2.28 cm/1.46 cm mean tumor size, 90 %/67 % unencapsulated, 100 %/89 % infiltrative, 100 %/89 % sclerotic, 60 %/52 % LT, 30 %/59 % positive psammoma bodies, 0 %/11 % LVI, 0 %/4 % PNI, 90 %/96 % classic architecture, 50 %/44 % multifocal. Neither size (p = 0.072) nor the other nine histologic features examined reached statistical significance. None of the histologic features appeared to significantly predict ENE. Further examination of intrathyroidal tumors at a molecular level is necessary to determine if there are any identifiable features of intrathyroidal tumors that predict ENE and thus a more aggressive phenotype.

Striving toward standardization of reporting of ultrasound features of thyroid nodules and lymph nodes: a multidisciplinary consensus statement.

BACKGROUND: The use of high-resolution ultrasound (US) imaging is a mainstay of the initial evaluation and long-term management of thyroid nodules and thyroid cancer. To fully capitalize on the diagnostic capabilities of a US examination in the context of thyroid disease, many clinicians consider it desirable to establish a universal format and standard of US reporting. The goals of this interdisciplinary consensus statement are twofold. First, to create a standardized set of US features to characterize thyroid nodules and cervical lymph nodes accurately, and second, to create a standardized system for tracking sequential changes in the US examination of thyroid nodules and cervical lymph nodes for the purpose of determining risk of malignancy. SUMMARY: The Thyroid, Head and Neck Cancer (THANC) Foundation convened a panel of nine specialists from a variety of medical disciplines that are actively involved in the diagnosis and treatment of thyroid nodules and thyroid cancer. Consensus was achieved on the following topics: US evaluation of the thyroid gland, US evaluation of thyroid nodules, US evaluation of cervical lymph nodes, US-guided fine needle aspiration (FNA) of thyroid nodules, and US-guided FNA of cervical lymph nodes. CONCLUSION: We propose that this statement represents a consensus within a multidisciplinary team on the salient and essential elements of a comprehensive and clinically significant thyroid and neck US report with regards to content, terminology, and organization. This reporting protocol supplements previous US performance guidelines by not only capturing categories of findings that may have important clinical implications, but also delineating findings that are clinically relevant within those categories as specifically as possible. Additionally, we have included the specific features of diagnostic and therapeutic interventions that have not been previously addressed.

Transtracheal approach to repair of a tracheo-colonic fistula 44 years after colonic interposition.

BACKGROUND: We present a case report of a trachea-colonic fistula and demonstrate our unique approach to repair, which was efficient and effective. METHODS: The patient was a 50-year-old man who had a congenital tracheoesophageal fistula repair with colonic interposition as a child who now developed a fistula between his colon and trachea. RESULTS: We performed a transtracheal approach, with primary closure of redundant colon mucosa as well as direct repair of the trachea. An inferiorly based sternocleidomastoid muscle flap was interposed between these 2 layers to augment the repair. The patient had an uneventful recovery with an effective reconstitution of the alimentary tract and the airway. CONCLUSION: Tracheo-colonic fistula is an extremely rare pathology, and the scarring that develops after a prior esophagectomy makes a traditional lateral approach very difficult. The transtracheal approach is an effective method to obtain needed exposure in order to carry out the repair.