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• Papillary thyroid cancer (PTC):
  • Has a high predilection for spread to locoregional lymph nodes (LNs):
    • Occurring in up to 40% to 90% of cases:
      • When prophylactic nodal dissection is performed:
      • Though such high rates of metastatic disease may prove enticing to recommend routine prophylactic node dissection:
        • Recurrence-free survival is not effected by the removal of sonographically normal, microscopically diseased nodes
      • Instead, prophylactic central neck dissection may be individually considered for those patients with:
        • T3 or T4 tumors, or in the presence of lateral neck metastases
      • Clinically suspicious or biopsy-proven nodal disease warrants a “therapeutic” dissection of the involved compartments
        • “Berry picking,” or selective removal of suspicious LN metastases, is not recommended:
          • As it is associated with significantly higher recurrence rates and does not lower the rate of postoperative complications compared with systematic compartmental dissections
• The risk of surgical complications with nodal dissection should be weighed against the benefit of LN removal:
  • Central neck dissections may result in temporary or permanent injury to the RLN and hypoparathyroidism
  • Surgeon case volume predicts patient outcomes:
    • Those performing less than 10 cases compared with those performing more than 100 cases per year had complications in 24% and 14.5% of cases, respectively
  • Although dissection of the lateral neck is less often associated with adverse events:
    • Injury to the spinal accessory nerve may occur with dissection of level II or V
  • Similarly, chyle leaks may be seen after removal of nodes in level IV:
    • Particularly on the left side

• Historically:
  • Almost all patients were given thyroid hormone:
    • To fully suppress serum thyroid-stimulating hormone (TSH)
  • The rationale for this approach:
    • Was based on the theory that TSH is a stimulant for thyroid cell proliferation and suppression of thyrotropin will inhibit tumor growth:
      • Indeed, early studies supported the role of TSH suppression in reducing the likelihood of disease progression and improving survival:
        • Particularly in those with high-risk disease
      • More recent analyses, however, have failed to demonstrate a benefit of such suppressive therapy in those with low-risk tumors:
        • In fact, such treatment may prove harmful
      • A long-term observational study showed a three-fold increased risk of cardiovascular death for each ten-fold reduction in mean TSH level
      • Patients with subclinical thyrotoxicosis:
        • Are also at increased risk of atrial fibrillation, ventricular hypertrophy, diastolic dysfunction, and impaired cardiac reserve
        • Additionally, bone turnover may be adversely affected by suppressive doses of levothyroxine:
          • Higher rates of osteoporosis may be seen in thyroid cancer patients:
            • There is an increased risk of fracture when suppressive doses of levothyroxine are used
  • As a consequence of the myriad negative effects of excess levothyroxine:
    • The target TSH range should be determined on an individual basis
    • It is also worthy of note that lowering TSH to undetectable levels probably does not confer additional benefit beyond that seen with less aggressive suppression below 0.1 mU/L
    • The optimal TSH range should consider the initial risk for recurrence, the response to therapy, and the risk for thyrotoxicosis-related morbidities in the individual patient
    • Furthermore, this target TSH for the individual patient may evolve over time, depending on the response to therapy

• Excellent Response to Therapy:
  • Patients with no biochemical (unstimulated serum thyroglobulin (Tg) < 0.2 or stimulated Tg < 1.0 ng/mL) or radiographic evidence of disease are classified as having an excellent response to therapy
  • Patients with an initial low to intermediate risk of recurrence who meet these criteria:
    • Are recommended to have serum Tg monitored every 12 to 24 months
  • Patients with initially high-risk disease:
    • Should continue to have a serum Tg measurement at least every 6 to 12 months
• Biochemical Incomplete Response to Therapy:
  • Patients who have undergone total thyroidectomy and remnant ablation and have an unstimulated serum Tg > 1 ng/mL or a stimulated Tg > 10 ng/mL or a rising thyroglobulin antibody (TgAb) titer with negative imaging:
    • Are classified as having a biochemical incomplete response to therapy
  • Such patients should undergo imaging with sonography of the neck:
    • If the disease is unable to be located:
      • Cross-sectional imaging of the neck and chest should be performed
  • Serum Tg should be followed at least every 6 to 12 months.
• Structural Incomplete Response to Therapy:
  • Those patients with structurally or functionally (on diagnostic whole-body scan [DxWBS] or 18(FDG-PET) evident disease are classified as:
    • Having a structural incomplete response to therapy
  • Unfortunately, the majority of patients in this category will have persistent disease in spite of additional treatments
  • Disease-specific death rates are high in this group:
    • 11% with locoregional metastases
    • 50% with distant metastases
• Indeterminate Response to Therapy:
  • Patients with biochemical or structural findings that cannot be confidently classified as either excellent response or persistent disease:
    • Are deemed as having an indeterminate response to therapy
  • Such patients may be carefully followed with biochemical testing and serial imaging to better delineate which category is ultimately appropriate
  • It is estimated that up to 20% of these patients will eventually develop conclusive evidence of disease requiring additional therapy

• Invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC):
  • Is now considered a separate entity and no longer a subtype of PTC
• IEFVPTC has a RAS-like mutational and transcriptomic profile:
  • Similar to that of follicular adenoma (FA) and follicular thyroid carcinoma (FTC) (Figure):
    • Whereas classic PTC and the infiltrative follicular subtype of PTC:
      • Have BRAF V600E-like molecular profiles
• IEFVPTCs:
  • Have a fibrous capsule or well-defined border and lack the histologic features of infiltrative follicular PTC
• Like FTC:
  • IEFVPTC can invade vessels in the capsule and develop distant metastasis

• Risk stratification in differentiated thyroid cancer has traditionally used a relatively small set of clinical and pathological factors to create models that predict disease-specific mortality or overall survival:
  • Although clinically useful, these models provided static estimates of risk with information available within the first few months of initial therapy and demonstrated suboptimal, long-term outcome predictions for any individual patient

• Over the last decade, additional models have been developed that provide predictive information with regard to other clinically relevant outcomes, such as:
  • The risk of having persistent disease after initial therapy
  • The risk of structural or biochemical disease recurrence
  • The likelihood of going into remission following initial therapy in adult patients with thyroid cancer

• Furthermore, rather than using information that is only available at one particular point in time, these new models emphasize the importance of dynamic risk assessment:
  • Where the initial risk assessment is modified over time as new data become available
• These dynamic risk assessments allow us to:
  • Integrate response to therapy assessments with the underlying individual tumor biology:
    • To provide real-time risk assessments at any point in the course of the patient’s disease
• Thus, the modern view of risk stratification begins with:
  • The identification of a suspicious nodule (peri-diagnostic period) and continues through the phases of:
    • Diagnosis
    • Treatment
    • Adjuvant therapy
    • Follow-up

#Arrangoiz #ThyroidSurgeon #CancerSurgeon #HeadandNeckSurgeon #SurgicalOncologist #Teacher #Miami #MountSinaiMedicalCenter

• Asymptomatic, small thyroid nodules (usually ≤ 1 cm maximal diameter, 1 cm³, or 1 mL volume) confined to the thyroid and surrounded by normal thyroid parenchyma:
  • Can be followed with active surveillance:
    • With or without cytologic confirmation:
      • In patients who value their normal thyroid function and who desire avoidance of thyroid surgery
• Patients who demonstrate tumors larger than 1.5 to 2.0 cm; tumors in subcapsular locations adjacent to important structures, such as the trachea and recurrent laryngeal nerve; or tumors with documented growth rate doubling times of < 2 years:
  • Are generally considered inappropriate for observation and would be considered to have actionable disease
• If the tumor growth rate is unknown at the time of nodule detection:
  • Then this can be established with serial ultrasound evaluations done approximately every 6 months for 1 to 2 years
• The frequency of ultrasound evaluations and long-term follow-up:
  • Depends on the tumor size, location, and established growth rate
• With the use of this paradigm:
  • Active surveillance continues until:
    • There is a 3-mm increase in tumor diameter:
      • Which corresponds to a 100% increase in tumor volume
    • Identification of metastatic disease
    • Direct invasion into surrounding structures of the thyroid
    • A decision to discontinue active surveillance based on patient preference
• This risk-stratified, minimalistic management approach to very low-risk thyroid cancers has been shown to be safe and effective over 5 to 10 years of follow-up in studies from Japan, Korea, and the United States:
  • In the first 10 years of active surveillance follow-up:
    • Only 2% to 8% of papillary microcarcinomas:
      • Increase ≥ 3 mm in maximum diameter
    • 12% to 14% demonstrate an increase in tumor volume of > 50%:
      • The smallest change in nodule volume that can be reproducibly measured
    • Novel lymph node metastases:
      • Are detected in 2% to 4%
  • The likelihood of disease progression is higher in younger patients than in older patients
• Importantly, at the time of disease progression:
  • Deferred surgical intervention is quite effective with excellent outcomes and no disease-specific mortality
• References:
  • Ito Y, Miyauchi A. Active surveillance as first-line management of papillary microcarcinoma. Annu Rev Med. 2019;70:369–379.
  • Ito Y, Miyauchi A, Kudo T, Oda H, Yamamoto M, Sasai H, Masuoka H, Fukushima M, Higashiyama T, Kihara M, Miya A.. Trends in the implementation of active surveillance for low-risk papillary thyroid microcarcinomas at Kuma Hospital: gradual increase and heterogeneity in the acceptance of this new management option. Thyroid. 2018;28(4):488–495.
  • Tuttle RM, Zhang L, Shaha A. A clinical framework to facilitate selection of patients with differentiated thyroid cancer for active surveillance or less aggressive initial surgical management. Expert Rev Endocrinol Metab. 2018;13(2):77–85. 
  • Tuttle RM, Fagin JA, Minkowitz G, Wong RJ, Roman B, Patel S, Untch B, Ganly I, Shaha AR, Shah JP, Pace M, Li D, Bach A, Lin O, Whiting A, Ghossein R, Landa I, Sabra M, Boucai L, Fish S, Morris LGT. Natural history and tumor volume kinetics of papillary thyroid cancers during active surveillance. JAMA Otolaryngol Head Neck Surg. 2017;143(10):1015–1020. 
  • Tuttle RM, Zhang L, Shaha A. A clinical framework to facilitate selection of patients with differentiated thyroid cancer for active surveillance or less aggressive initial surgical management. Expert Rev Endocrinol Metab. 2018;13(2):77–85.
  • D’Agostino TA, Shuk E, Maloney EK, Zeuren R, Tuttle RM, Bylund CL. Treatment decision making in early-stage papillary thyroid cancer. Psychooncology. 2018;27(1):61–68.
  • Groopman J, Hartzband P.. Your Medical Mind. How to Decide What Is Right for You. New York, NY: Penguin Books.
  • Ito Y, Miyauchi A. Prognostic factors and therapeutic strategies for differentiated carcinomas of the thyroid. Endocr J. 2009;56(2):177–192.

• The 2015 ATA guidelines:
  • Now accept a minimalistic surgical approach (thyroid lobectomy without neck dissection):
    • To treat intrathyroidal papillary thyroid carcinomas < 4 cm in properly selected patients
  • Careful peri-diagnosis, preoperative, and intraoperative risk stratification:
    • Are the keys to successful use of thyroid lobectomy:
      • Without having to perform an unacceptable rate of early-completion thyroidectomies
• Patients classified as being ideal for lobectomy:
  • Would have papillary microcarcinomas:
    • That appeared to be confined to the thyroid in the setting of an otherwise normal thyroid ultrasound and clinical N0 neck
• We classify patients as appropriate for lobectomy:
  • If the tumor is 1 to 4 cm in maximum dimension, if the contralateral lobe is normal, or if there are other abnormalities on the ultrasound, such as thyroiditis or benign-appearing nodules (again, in the setting of the clinical N0 neck)
• Patients with extrathyroidal extension, clinical N1 disease, or distant metastasis:
  • Would be considered inappropriate for thyroid lobectomy as initial therapy
• In addition to the relevance of peri-diagnostic and preoperative risk stratification with respect to the selection of thyroid lobectomy as initial therapy:
  • It is important to recognize that there are intraoperative findings that should alter that recommendation and lead to an immediate total thyroidectomy:
    • We encourage patients to find a surgeon who they trust and to empower the surgeon to make a final decision in the operating room regarding the extent of initial surgery that should be performed, which can vary from lobectomy to total thyroidectomy, with or without neck dissection
    • However, even with appropriate preoperative and intraoperative risk stratification:
      • As many as 6% to 20% of patients will have unexpected findings on the final pathology report:
        • That may lead to a completion thyroidectomy and usually, radioactive iodine
      • An additional 5% to 10% may require completion thyroidectomy:
        • At some later point during follow-up for diagnostic or therapeutic purposes
          
      • The rate of early-completion thyroidectomy, performed following review of the initial pathology report, will vary, depending on how aggressive each management team is with regard to the use of radioactive iodine for either remnant ablation or adjuvant treatment
      • If minor factors, such as minor extrathyroidal extension, very small-volume lymph node metastasis, or small tumors with aggressive histologic features usually lead to radioactive iodine therapy, then the completion thyroidectomy rate may be as high as 20%
      • In our hands, the completion thyroidectomy rate is much lower, as we have a much more restricted use of radioactive iodine:
        • The most common reason for completion thyroidectomy in our hands is unanticipated, extensive vascular invasion documented on the pathology report that obviously could not be visualized preoperatively or intraoperatively
• Thus, patients need to understand that the final determination of whether a thyroid lobectomy is the appropriate initial therapy can only be achieved by:
  • The integration of preoperative, intraoperative, and postoperative risk stratification
• Patients who are uncomfortable with this approach will often choose a total thyroidectomy as initial therapy
• Patients motivated to keep part of the thyroid will often accept that uncertainty, recognizing that the final decision regarding the completeness of initial therapy cannot be completely known until several weeks after the surgery is completed when more complete risk stratification can be accomplished
• References:
  • Tuttle RM, Zhang L, Shaha A. A clinical framework to facilitate selection of patients with differentiated thyroid cancer for active surveillance or less aggressive initial surgical management. Expert Rev Endocrinol Metab. 2018;13(2):77–85. 
  • Carty SE, Doherty GM, Inabnet WB III, Pasieka JL, Randolph GW, Shaha AR, Terris DJ, Tufano RP, Tuttle RM; Surgical Affairs Committee Of The American Thyroid Association. American Thyroid Association statement on the essential elements of interdisciplinary communication of perioperative information for patients undergoing thyroid cancer surgery. Thyroid. 2012;22(4):395–399.

Beahrs Triangle or Riddle’s triangle

• This is one of the most important triangles in relation with thyroid surgery
• This triangle is named after O.H. Beahrs:
  • Its synonymous with Riddle’s triangle
• Baehr’s triangle is bounded by:
  • Base:
    • Common carotid artery
  • Superior:
    • Inferior thyroid artery
  • Medial:
    • Recurrent laryngeal nerve
• The triangle lies:
  • Posterior to the thyroid gland:
    • In the tracheo-esophageal groove
• Boundaries of Baehr’s triangle:
  • Can be identified after retracting the ipsilateral thyroid lobe medially:
    • To safe guard the recurrent laryngeal nerve

• RLN Triangle:
  • This is an inverted triangle with:
    • Apex formed inferiorly by:
      • Thoracic inlet
    • Medially:
      • Trachea
    • Lateral Margin:
      • The medial edge of retracted strap muscles
    • The superior border is:
      • The lower edge of the inferior pole of the gland
• Recurrent laryngeal nerve exits as a single trunk here at thoracic inlet
• Triangle of Concern:
  • The commonest site for bleeding in thyroidectomy:
    • Is the ‘triangle of concern’, comprising the:
      • Trachea medially
      • RLN nerve laterally
      • With the thyrothymic ligament and loose fat above the sternum at the base
      • Berry’s ligament at the apex
• This triangle has the small branches of the inferior thyroid artery that require meticulous hemostasis with in the vicinity of RLN, which can cause injury to nerve

• Classically, the RLN is identified intraoperatively in Simon’s triangle, which  is formed by:
  • The common carotid artery laterally
  • The esophagus medially
  • The inferior thyroid artery superiorly
• The recurrent laryngeal nerve  crosses the triangle