Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• Is a randomized phase III trial:
  • That established trastuzumab deruxtecan (T-DXd) as the preferred therapy for patients with HER2-positive metastatic breast cancer:
    • Previously treated with trastuzumab emtansine (T-DM1)
• Population:
  • HER2-positive unresectable or metastatic breast cancer
  • Prior therapy:
    • Trastuzumab + taxane and T-DM1
  • Randomization: T
    • DXd vs Investigator’s choice (trastuzumab + capecitabine or lapatinib + capecitabine)
  • Primary endpoint:
    • Progression-free survival (PFS, BICR)
  • Key secondary endpoints:
    • Overall survival (OS), ORR, duration of response, safety
• Mechanism of Action (Why T-DXd Is Different):
  • Trastuzumab deruxtecan is a next-generation antibody–drug conjugate (ADC) with:
    • High drug-to-antibody ratio (≈8:1)
    • Cleavable linker membrane-permeable topoisomerase I payload bystander effect:
      • Enabling killing of adjacent tumor cells with heterogeneous HER2 expression:
        • This design explains its activity after T-DM1 failure, where resistance commonly develops.
• Efficacy Results:
  • Progression-Free Survival (Primary Endpoint):
    • Median PFS:
      • T-DXd:
        • ~17.8 months
      • Control:
        • ~6.9 months
      • Hazard ratio:
        • ~0.36
      • Risk reduction:
        • ~64% reduction in progression or death
    • Clinically transformative improvement in disease control
  • Overall Survival:
    • Median OS:
      • T-DXd:
        • ~39.2 months
      • Control:
        • ~26.5 months
      • Hazard ratio:
        • ~0.66
    • Statistically significant and clinically meaningful OS benefit, uncommon in heavily pretreated HER2-positive MBC trials
  • Objective Response Rate:
    • T-DXd:
      • ~69%
    • Control:
      • ~29%
    • Complete responses:
      • Observed with T-DXd
• Safety Profile:
  • Common Adverse Events (T-DXd):
    • Nausea
    • Fatigue
    • Alopecia
    • Vomiting
    • Neutropenia
    • Anemia
    • Interstitial Lung Disease (ILD) / Pneumonitis:
      • Any-grade ILD:
        • ~10%
      • Grade ≥3 ILD:
        • ~1–2%
      • Fatal events:
        • Rare but reported
• Key clinical takeaway:
  • Early recognition, prompt drug interruption, and steroid initiation are essential
  • Patient education and routine symptom monitoring are mandatory
• How DESTINY-Breast 02 Changed Practice:
  • Before DESTINY-Breast 02:
    • Post-T-DM1 options relied on capecitabine-based combinations:
      • Limited durability and modest survival benefit
  • After DESTINY-Breast 02:
    • T-DXd is the standard of care after T-DM1:
      • Supported by PFS + OS superiority:
        • Endorsed by NCCN, ASCO, ESMO
  • Represents a paradigm shift in the HER2-positive metastatic sequence
• Treatment Sequencing (Current Standard):
  • First line:
    • Trastuzumab + pertuzumab + taxane
  • Second line:
    • T-DXd
  • Later lines:
    • Tucatinib-based regimens
    • Clinical trials
    • Other HER2-targeted agents
• Surgical and Multidisciplinary Relevance:
  • Durable systemic control increases:
    • Consideration of local therapies for oligoprogression
    • Delayed need for palliative surgery
  • Highlights importance of:
    • Early referral to medical oncology
    • Coordinated surveillance for pulmonary toxicity
• Key Take-Home Messages:
  • DESTINY-Breast 02 firmly establishes T-DXd as best-in-class post-T-DM1 therapy:
    • Demonstrates both PFS and OS benefit in a refractory population
  • ILD monitoring is critical to safe delivery
  • Confirms the power of ADC engineering in overcoming resistance

When a thyroid nodule is suspected or discovered, high-resolution thyroid ultrasound is the single most important diagnostic study.

🔍 What does a thyroid ultrasound tell us?

Ultrasound allows us to evaluate:

Size and exact location of the nodule Composition (solid, cystic, or mixed) Margins (smooth vs irregular) Echogenicity and calcifications Vascularity (with Doppler imaging) Cervical lymph nodes

➡️ These features are far more predictive of cancer risk than symptoms or blood tests.

📊 Risk stratification matters

Using ultrasound findings, nodules are categorized with validated systems such as:

ATA risk patterns ACR TI-RADS

These systems help determine:

✔️ Which nodules need biopsy

✔️ Which nodules can be safely observed

✔️ Appropriate follow-up intervals

🧪 Important clarification

Blood tests do not diagnose thyroid cancer CT scans and MRIs are NOT first-line tests for thyroid nodules Ultrasound provides real-time, radiation-free, highly accurate evaluation

🦋 Why this matters for patients

Proper ultrasound evaluation:

Prevents unnecessary biopsies and surgeries Ensures early diagnosis of clinically significant thyroid cancer Guides personalized management

👨‍⚕️ Rodrigo Arrangoiz, MD

Surgical Oncologist – Thyroid, Head & Neck, Breast

Mount Sinai Medical Center

📌 Take-home message:

Not all ultrasounds are equal.

Expert, high-resolution thyroid ultrasound makes all the difference.

📚 References

Haugen BR et al. ATA Guidelines for Thyroid Nodules. Thyroid Tessler FN et al. ACR TI-RADS. Radiology Russ G et al. EU-TI-RADS. European Journal of Endocrinology

Thyroid Awareness Month – Day 3

Who Is at Risk for Thyroid Nodules?

Thyroid nodules can occur in anyone, but certain factors make them more likely.

👥 Common Risk Factors

Age: Nodules become more common as we get older Female sex: Women develop thyroid nodules 3–4 times more often than men Iodine imbalance: Both deficiency and excess can play a role Family history: Thyroid nodules or thyroid cancer in first-degree relatives Autoimmune thyroid disease: Hashimoto’s thyroiditis increases nodule prevalence

☢️ Higher-Risk Situations

Radiation exposure to the head and neck, especially during childhood Prior radiation therapy for acne, tonsils, or cancer (historical treatments) Certain genetic syndromes (rare, but important)

🧠 Important clarification

Having risk factors does not mean a thyroid nodule is cancer.

➡️ Even in higher-risk individuals, most nodules are benign.

🔍 What matters most?

Risk factors help guide how closely we evaluate, but ultrasound findings ultimately determine:

Cancer risk Need for biopsy Follow-up strategy

📌 Key point for patients:

A thyroid nodule should never be ignored — but it should also never cause unnecessary fear. Proper, evidence-based evaluation is the answer.

👨‍⚕️ Rodrigo Arrangoiz, MD

Surgical Oncologist – Thyroid, Head & Neck, Breast

Mount Sinai Medical Center

📚 References

Haugen BR et al. ATA Guidelines for Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid Guth S et al. Very high prevalence of thyroid nodules. Thyroid Gharib H et al. Evaluation and Management of Thyroid Nodules. Endocrine Practice

Thyroid nodules can occur in anyone, but certain factors make them more likely.

👥 Common Risk Factors

Age: Nodules become more common as we get older Female sex: Women develop thyroid nodules 3–4 times more often than men Iodine imbalance: Both deficiency and excess can play a role Family history: Thyroid nodules or thyroid cancer in first-degree relatives Autoimmune thyroid disease: Hashimoto’s thyroiditis increases nodule prevalence

☢️ Higher-Risk Situations

Radiation exposure to the head and neck, especially during childhood Prior radiation therapy for acne, tonsils, or cancer (historical treatments) Certain genetic syndromes (rare, but important)

🧠 Important clarification

Having risk factors does not mean a thyroid nodule is cancer.

➡️ Even in higher-risk individuals, most nodules are benign.

🔍 What matters most?

Risk factors help guide how closely we evaluate, but ultrasound findings ultimately determine:

Cancer risk Need for biopsy Follow-up strategy

📌 Key point for patients:

A thyroid nodule should never be ignored — but it should also never cause unnecessary fear. Proper, evidence-based evaluation is the answer.

👨‍⚕️ Rodrigo Arrangoiz, MD

Surgical Oncologist – Thyroid, Head & Neck, Breast

Mount Sinai Medical Center

📚 References

Haugen BR et al. ATA Guidelines for Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid Guth S et al. Very high prevalence of thyroid nodules. Thyroid Gharib H et al. Evaluation and Management of Thyroid Nodules. Endocrine Practice

Most thyroid nodules cause no symptoms at all and are found incidentally on imaging or routine exams.

🔹 Common scenario: You feel well — the nodule is discovered on ultrasound

🔹 Important fact: Lack of symptoms does NOT mean the nodule is dangerous (or benign)

👀 When can symptoms occur?

Symptoms are more likely when nodules are large or strategically located:

A visible or palpable lump in the neck Difficulty swallowing or a sensation of food “getting stuck” Hoarseness or voice changes (uncommon, but important) Neck pressure or fullness, especially when lying flat Rarely, shortness of breath

⚠️ Hormone-related symptoms (less common)

A small percentage of nodules produce excess thyroid hormone (“hot” nodules), which may cause:

Palpitations Weight loss Heat intolerance Tremors or anxiety

🚨 When should you seek evaluation?

You should be evaluated if you notice:

✔️ A new or growing neck lump

✔️ Persistent hoarseness

✔️ Difficulty swallowing or breathing

✔️ A personal history of radiation exposure or family history of thyroid cancer

🔍 Bottom line:

Symptoms alone cannot determine whether a nodule is benign or malignant.

➡️ High-resolution ultrasound is essential for proper evaluation.

👨‍⚕️ Rodrigo Arrangoiz, MD

Surgical Oncologist – Thyroid, Head & Neck, Breast

Mount Sinai Medical Center

📌 Take-home message:

Most thyroid nodules are silent.

Don’t rely on symptoms — rely on proper imaging and expert evaluation.

📚 References

Haugen BR et al. ATA Guidelines for Thyroid Nodules. Thyroid Gharib H et al. Evaluation and Management of Thyroid Nodules. Endocrine Practice Durante C et al. JAMA

What Are Thyroid Nodules?

Thyroid nodules are very common in the general population.

🔹 With modern high-resolution ultrasound, thyroid nodules are detected in up to 50–60% of adults

🔹 More than 90% are benign

🔹 Most people have no symptoms and feel completely well

👉 The key is not panic — it’s proper evaluation.

🔍 How should thyroid nodules be evaluated?

The most important first step is a high-resolution thyroid ultrasound, which allows us to:

Accurately measure and characterize nodules Assess features associated with cancer risk Use validated risk-stratification systems (ATA / TI-RADS) Decide whether a biopsy is actually necessary

🧪 A key fact for patients

Only 5–10% of thyroid nodules are cancer.

When thyroid cancer is detected early, cure rates are excellent.

👨‍⚕️ Rodrigo Arrangoiz, MD

Surgical Oncologist – Thyroid, Head & Neck, Breast

Mount Sinai Medical Center

📌 Take-home message:

Having a thyroid nodule is common.

Having it evaluated correctly by an experienced team makes all the difference.

📚 References

Haugen BR et al. ATA Guidelines for Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid Durante C et al. Long-term surveillance of benign thyroid nodules. JAMA Gharib H et al. Fine-needle aspiration biopsy of thyroid nodules. Endocrine Practice

Thyroid Nodules

– Thyroid nodules are very common in the general population. With modern high-resolution ultrasound, nodules can be detected in up to 50% to 60% of adults.

👉 The good news: more than 90% of thyroid nodules are benign.

🔍 What is the best way to evaluate a thyroid nodule?

The first and most important test is a high-resolution thyroid ultrasound. It allows us to:

Accurately characterize the nodule (size, margins, echogenicity, calcifications) Stratify cancer risk using validated systems (such as ATA or TI-RADS) Determine whether a biopsy is necessary

🧪 When is a biopsy needed?

If the ultrasound shows suspicious features, a ultrasound-guided fine-needle aspiration biopsy (FNAB) is recommended.

✔️ This is a safe, minimally invasive, outpatient procedure that provides highly accurate information to determine whether a nodule is benign or malignant, helping avoid unnecessary surgery.

📊 Key facts (evidence-based)

Thyroid nodules are found in up to 60% of adults on ultrasound Only 5% to 10% of nodules are malignant Ultrasound-guided FNAB has high diagnostic accuracy and a very low complication rate

🏥 Experience you can trust

👨‍⚕️ Dr. Rodrigo Arrangoiz

Surgical Oncologist | Thyroid, Head & Neck, and Breast Surgery

Mount Sinai Medical Center

📌 Take-home message: Early detection and proper evaluation of thyroid nodules make a real difference—protecting patients from unnecessary treatments while identifying cancer early when it is most curable.

📚 References

Haugen BR et al. 2015 ATA Guidelines for Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. Russ G et al. European Thyroid Association Guidelines for Ultrasound Malignancy Risk Stratification (EU-TI-RADS). Eur J Endocrinol. Gharib H et al. Fine-Needle Aspiration Biopsy of Thyroid Nodules. Endocrine Practice. Durante C et al. Long-term Surveillance of Benign Thyroid Nodules. JAMA.

• The Cernea classification:
  • Is used during thyroid surgery to predict the risk of injury to the external branch of the superior laryngeal nerve (EBSLN):
    • Based on its anatomical relation to the superior thyroid artery and the upper pole of the thyroid
  • It includes three types:
    • Type I:
      • The EBSLN crosses more than 1 cm above the upper edge of the thyroid superior pole:
        • The artery-nerve intersection is > 1 cm above the gland
      • Minimal risk during ligation of the superior thyroid vessels
    • Type IIa:
      • The nerve crosses within 1 cm above the superior pole:
        • Distance < 1 cm but above the pole
      • Moderate risk, as it’s close to vascular pedicle
    • Type IIb:
      • The EBSLN crosses below the upper edge of the superior pole:
        • Under the pole
      • Highest risk:
        • Nerve lies within the ligation field
• Clinical Significance:
  • Intraoperative studies show Type IIa + IIb:
    • Account for ~ 65% of cases:
      • Emphasizing the high chance of encountering the nerve near or below the vascular pedicle
  • Type IIb alone:
    • Occurs in up to 48% of cases in some series 
  • Risk of EBSLN injury rises with more inferior nerve trajectories (IIa / IIb):
    • Injuries lead to altered voice quality:
      • Reduced pitch, vocal fatigue, and weakened projection
• Surgical Implications:
  • Routine identification:
    • Especially for Type II subtypes:
      • Is key during superior pole dissection
  • Intraoperative neuromonitoring (IONM) helps detect and preserve the EBSLN:
    • Reducing morbidity
  • Transection of overlying muscles (e.g., sternothyroid):
    • Can improve visualization of the nerve

• The vagus nerve:
  • Also known as the 10th cranial nerve
  • Gives rise to the superior laryngeal nerve (SLN) and recurrent laryngeal nerve (RLN) in the neck
  • After descending toward the larynx:
    • The SLN divides into:
      • The internal laryngeal nerve (ILN)
      • External laryngeal nerve (ELN)

• The RLN innervates all of the intrinsic muscles of the larynx:
  • Except the cricothyroid muscle:
    • This muscle, tenses the vocal cords and adducts the vocal cords:
      • Is innervated by the ELN
• The other branch of the SLN, the ILN:
  • Provides sensory innervation to the laryngeal mucosa
• There are many exceptions to the normal innervation of the laryngeal muscles:
  • Which can influence the interpretation of laryngoscopy results or voice changes after thyroid surgery
• A neural anastomosis:
  • That provides additional motor innervation to the muscles of the larynx normally innervated by the injured nerve:
    • Can contribute to an incorrect interpretation of injury during laryngoscopy or stroboscopy
• According to recent clinical studies:
  • Electrical stimulation of the RLN can cause contraction of the cricothyroid muscle:
    • This suggests that extra-laryngeal branches and or other communications of the RLN:
      • Can sometimes contribute to innervation of this muscle
• The laryngeal nerves:
  • Can form a great variety of anastomoses:
    • These various connections among the ILN, ELN, and RLN have been investigated by many anatomists over the centuries
• Claudius Galen:
  • Was the first to describe the communication between the ILN and RLN
  • Currently, Galen’s anastomosis:
    • Is most commonly defined as:
      • The direct communication between the posterior branches of the ILN and the RLN
    • It can occur as:
      • A single trunk
      • A double trunk
      • A plexus

• Besides Galen’s anastomosis, other communications have been observed and described as follows:
  • The arytenoid plexus:
    • Which links the anterior branch of the RLN with the arytenoid branch of the ILN

• The cricoid communication:
  • Which connects branches originating bilaterally from the RLNs with the superior branch from the deep portion of the arytenoid plexus
• The thyroarythenoid communication:
  • Which is formed by the ascending branch of the RLN and the descending branch from the anterior branch of the ILN

• The communication between the ELN and RLN:
  • Human communicating nerve
• The communication between the ILN and ELN
• The communication between the RLN and the sympathetic trunk

• Despite progress in the development of new techniques:
  • Such as intra-operative nerve monitoring:
    • Which help to reduce the risk of iatrogenic injuries during thyroid surgeries and other procedures conducted in close proximity to the laryngeal nerves:
      • The laryngeal muscles are often paralyzed postoperatively due to iatrogenic injury to the laryngeal nerves
• In view of the complexity and variability of the anatomy in this region:
  • Detailed anatomical knowledge is crucial if surgery is to be both successful and safe, and to reduce the risk of nerve injury
• Observing an intra-laryngeal anastomosis during laryngeal surgery or an extra-laryngeal communication between laryngeal nerves during thyroid surgery:
  • Can lead to confusion, misidentification, and an increased risk of iatrogenic injury
• A thorough understanding of the complex anastomoses between the laryngeal nerves is crucial in patients with laryngeal muscle paralysis
  • Paralyzed laryngeal muscles can be spontaneously reinnervated from an anastomosis between laryngeal nerves
  • Additionally, in cases in which surgical reinnervation is required, some of the nerves that form anastomoses can be used as grafts to restore damaged nerve connections
  • On the other hand, variations in the normal anatomy of the laryngeal nerves can disrupt selective surgical laryngeal reinnervation:
    • A procedure based on the assumption that each laryngeal muscle is supplied by only one nerve branch originating from the RLN
  • Anastomoses among laryngeal nerves can result in exceptions to this rule
  • Such anastomoses have been widely described in the literature:
    • However, there is still no consensus about their prevalence and functionality
  • The significant heterogeneity among studies reporting data on anastomoses between the laryngeal nerves is noteworthy:
    • For example, the reported prevalence of the most common communication, Galen’ s anastomosis:
      • Ranges from 25% to 100%
• Prevalence of Galen’s anastomosis:
  • A total of 14 studies (n = 890 hemilarynges) presented data on the prevalence of Galen’s anastomosis
  • The overall pooled prevalence rate:
    • Was 76.7% (95% confidence interval [CI]: 59.0– 90.0)
  • Subgroup analysis revealed no significant difference in the prevalence of Galen’s anastomosis between the right and left sides
  • Subgroup analyses by gender (males vs females) and geographical origin, and the sensitivity analysis, also revealed no significant differences:
    • However, although the difference was not significant:
      • The prevalence of the anastomosis was highest in Europeans (88.2%) and lowest in North Americans (44.8%)
  • Analysis of the different types of Galen’s anastomosis (two studies, n = 261 anastomoses):
    • Showed a significant difference in the prevalence between single versus double trunk and plexus formation
    • But no significant difference between double trunk and plexus formation
    • The most common type of Galen’s anastomosis was a single trunk:
      • With a pooled prevalence rate 92.3% (95% CI: 84.1–97.5)
    • This was followed by the double trunk anastomosis type:
      • With a pooled prevalence of 4.2% (95% CI: 0.5– 10.7)
    • The plexus formation type with a pooled prevalence of 3.5% (95% CI: 0.2–9.5) (I2: 70.4%, 95% CI: 0–93.3; Co- chran’s Q, P value = 0.066
• Prevalence of a communication between the ELN and RLN
  • A total of eight studies (n = 639 hemilarynges) provided data on the prevalence of the communication between the ELN and RLN
  • The overall meta-analysis revealed that this communication was present in:
    • 21.3% of hemilarynges (95% CI: 3.8–46.0)
  • A subgroup analysis showed no significant difference between left and right sides
  • Although the difference was not statistically significant:
    • The pooled prevalence rate calculated for the North American subgroup (32.0%) was twice that for the European subgroup (14.4%)
• Prevalence of the arytenoid plexus:
  • Five studies (n = 478 hemilarynges) included data on the prevalence of the arytenoid plexus:
    • The pooled prevalence rate was 79.7% (95% CI: 41.1–100)
  • In the European subgroup:
    • The arytenoid plexus was observed in 96.9% of hemilarynges (95% CI: 83.6–100)
  • Subgroup analysis revealed no significant difference with respect to side
• Prevalence of the cricoid communication:
  • Two studies (n = 120 hemilarynges) reported prevalence data for the cricoid communication:
    • The pooled prevalence rate was 19.7% (95% CI: 0–100)
  • There was no significant difference in sub- group analysis based on side
• Prevalence of the thyroarytenoid communication:
  • A total of three studies (n = 430 hemilarynges) presented data on the prevalence of the thyroarytenoid communication:
    • The overall pooled prevalence was 6.3% (95% CI: 0.4–16.9)
  • In subgroup analysis, there was no significant difference in pooled prevalence between the right and left sides:
    • The calculated pooled rate for the left side (15.9%) was almost twice that for the right side (8.8%)
• Communication between the ILN and ELN:
  • A total of two studies (n = 280 hemilarynges) reported data on a communication between the ILN and ELN
    • The pooled prevalence estimate of this communication in hemilarynges was 8.8% (95% CI: 0–35.3; I2 97.0%, 95% CI: 92.2–98.8; Cochran’s Q, P value <0.001)
• References:
  • Journal of Voice, Vol. 31, No. 4, 2017

#Arrangoiz #HeadandNeckSurgeon #CancerSurgeon #ThyroidSurgeon #ParathyroidSurgeon #ThyroidExpert #ParthyroidExpert #Teacher #Miami #Mexico

• In 1984 Göran Åkerström, on the basis of 503 necropsies, analysed the location of the parathyroid glands:
  • Together with the work of Gilmour (n=478) and Wang (n=160), they form the foundations of our current knowledge on the subject
• Dr. Juan M. Rangone modified the diagrams from Åkerström’s original publication to come up with the percentages of location of the “normodescended” parathyroid glands:
• A. Percentages of the different locations of the superior parathyroid glands:
  • 80% corresponds to the midglandular variant
  • 12% to the cricopharyngeal variant
  • Usually located 1 cm higher than the crossing of the recurrent laryngeal nerve and the inferior thyroid artery
• B. Percentages of the different locations of the inferior parathyroid glands:
  • Roughly 90% are located at the level, or no more than 1 cm below the inferior pole of the thyroid gland
• Image:
  • 1- External carotid artery.
  • 2- Superior thyroid artery.
  • 3- Inferior thyroid artery.
  • 4- Upper thyroid pole.
  • 5- Lower thyroid pole.
  • 6- Inferior laryngeal nerve (recurrent laryngeal).
  • 7- Pharynx.
  • 8- Cervical trachea.
  • 9- Larynx (thyroid cartilage).
• Recommended Bibliography:
  • Åkerström G, Malmaeus J, Bergström R. (1984) Surgical anatomy of human parathyroid glands. Surgery 95(1):14-21.
  • Wang C (1976) The anatomic basis of parathyroid surgery. Ann Surg. 183(3): 271–275.
  • Gilmour JC (1938) The gross anatomy of the parathyroid glands. J Pathol Bacteriol. 46(1): 133-149.