Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• Management of euthyroid patients with positive thyroid antibody titers:
  • Can typically be monitored without the institution of thyroid hormone replacement therapy:
    • However, there are some data that pregnant patients with positive thyroid antibody titers may have improved pregnancy outcomes and reduced complications with the institution of LT4 replacement therapy
• In non-pregnant patients with hypothyroidism:
  • There are standard recommendations for treatment and monitoring:
    • This usually consist of LT4 therapy and TSH and FT4 monitoring every 6 weeks with adjustments in LT4 dosing until the TSH is within the goal range (typically 1 to 3 uIU/mL) although a higher target range is considered
      acceptable in the elderly patients

• Stavros has proposed the following BIRADS categories for breast ultrasound (see Table)

• The American College of Radiology classification:
  • Subdivides category 4 into:
    • BIRADS 4a:
      • Which has a 2% to 10 % risk of malignancy
    • BIRADS 4b:
      • Which has a 10% to 50 % risk of malignancy
    • BIRADS 4c:
      • Which has a 50% to 95% risk malignancy
  • BIRADS 5:
    • Has 95% or greater chance of malignancy
• In evaluating a solid sonographic nodule:
  • One should first look for any of the 10 signs of malignancy, and if even 1 of them is present:
    • The lesion cannot be considered BIRADS 3
  • The signs of malignancy are:
    • Shadowing
    • Hypoechoic echotexture
    • Spiculation
    • Angular margins
    • Thick echogenic halo
    • Microlobulation
    • Taller than wide
    • Duct extension
    • Branching pattern
    • Calcifications
• Note that Stavros compares the echogenicity of lesions to that of breast fat, not breast parenchyma:
  • Therefore, a lesion with hypoechoic echotexture would be very hypoechoic if breast parenchyma is used as the reference

• The hypoechoic lesion in the image does not have smooth margins but appears microlobulated
• Regardless of whether the classification of Stavros or the American College of Radiology is used:
  • The risk of the lesion in this patient is not low enough to be considered BIRADS 3 nor high enough risk to warrant BIRADS 5:
    • Thus, it falls somewhere in the BIRADS 4 range:
      • Biopsy is required
• References:
  • D’Orsi CJ, Sickles EA, Mendelson EB, Morris EA. ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System. 5^th ed. Reston, VA: American College of Radiology; 2013
  • Jales RM, Sarian LO, Torresan R, Marussi EF, Alvares BR, Derchain S. Simple rules for ultrasonographic subcategorization of BI-RADS®-US 4 breast masses. Eur J Radiol. 2013;82(8):1231-1235.
  • Stavros AT. Breast Ultrasound. Philadelphia, PA: Lippincott Williams & Wilkins; 2004.

• Toboggans technique for retrosternal goitre a valuable technique to protect RLN:
  • The surgery of retrosternal goiter is at increased risk for iatrogenic recurrent laryngeal nerve lesion
• Charles Proye:Described a surgical technique to avoid this lesion
• To have a better exposition, resection of the prethyroid muscles can be considered:Particularly if it is a voluminous and / or recurrent goiter. 
• The approach starts with:The thyroid isthmus liberation that is dissected free from the anterior part of the trachea and transected
• Then:The middle thyroid vein is divided and the superior pole vessels are divided
• The superior pole is then mobilized laterally:And the recurrent laryngeal nerve is searched for at its entry point into the larynx
• The nerve function can be verified by the neuromonitoring:Which also helps to find it in this vessel-rich area
• The dissection continues between the nerve and the posterior part of the thyroid:Progressively from top to bottom:Descending as on a toboggan
• After the recurrent nerve dissection:The goiter can usually be extracted without difficulty:Dividing the last vessels holding the goiter inside

https://www.liebertpub.com/doi/full/10.1089/ve.2014.0009

Rodrigo Arrangoiz MS, MD, FACS

Surgical Training:

• General Surgery
• Michigan State University:
• 2005 to 2010• Complex Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:
• Fox Chase Cancer Center (Filadelfia):
• 2010 to 2012• Masters in Science (Clinical research for health care professionals):
• Drexel University (Filadelfia):
• 2010 to 2012• Head and Neck Surgery and Oncology
• IFHNOS / Memorial Sloan Kettering Cancer Center:
• 2014 to 2016

• Patients with HT:
  • May present in a:
    • Euthyroid state:
      • With normal thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels
    • Subclinical hypothyroidism:
      • With mild TSH elevations (5 to 10 uIU/
        mL), and a paucity of symptoms
    • Significant / overt hypothyroidism:
      • With TSH > 10 uIU/mL
• Although a goiter may be noted during a
  physical examination:
  • Thyroid morphology associated with HT varies widely and ranges from:
    • Atrophic, barely palpable glands to slightly
      enlarged glands to very large goiters
• The gland texture:
  • May be smooth as in“simple” goiters or contain numerous nodules as seen with multinodular goiters
• Although the euthyroid state may persist
  for many years:
  • About 4% to 5% of initially euthyroid patients with HT will develop hypothyroidism each year:
    • The rate of progression is somewhat dependent on the intensity of the inflammatory reaction and the concomitant rate of induced thyroid follicle destruction
• HT is usually not associated with any neck discomfort:
  • But there are instances where individuals will present with anterior neck pain or tenderness:
    • So HT should be considered in the differential diagnosis of patients with neck discomfort
• Episodes of more acute thyroiditis:
  • With the development of transient thyrotoxicosis have been reported
    and been referred to as Hashitoxicosis
• Changes from HT noted by thyroid ultrasound, such as:
  • Heterogeneous parenchyma:
    • May become evident before the ability to measure thyroid antibody titers in the patient’s serum
• Although thyroid nodules certainly can be present in the context of HT:
  • Focal inflammatory changes due to HT may give the false impression of thyroid nodules:
    • The term pseudonodule refers to instances where there is the appearance of a thyroid nodule in at least one ultrasound view, but it cannot be reproduced on the additional complementary views:
      • Such lesions may not be evident upon future imaging at a later point in time
    • Therefore in patients with HT, the possibility of a pseudonodule should be considered before proceeding with FNA sampling
• Thyroid enlargement associated with HT:
  • May regress with LT4 therapy:
    • Particularly if TSH elevation is present at the time of diagnosis:
      • However, some goiters associated with HT will persist or even grow whether or not LT4 suppression is used:
        • If such patients exhibit progressive goiter growth or develop compressive type symptoms thyroidectomy may need to be considered
  • If the goiter is large and especially if
    tracheal deviation or substernal extension is present:
    • Then preoperative imaging with computed tomography (CT) of the neck is warranted to
      better define the anatomy and help plan the surgical approach
• Histopathology is typically notable for:
  • Prominent lymphocytic infiltration, foci of lymphoid germinal centers, and follicle destruction.
• Controversy exists if HT patients have an increased risk for thyroid cancer and, if so, whether or not HT is associated with a more aggressive disease pattern

• The recommended workup and staging of DCIS includes:
  • History and physical examination
  • Bilateral diagnostic mammography
  • Pathology review
  • Determination of tumor estrogen receptor (ER) status
  • MRI as indicated is special situations
• For pathology reporting:
  • The NCCN panel endorses the College of American Pathologists Protocol:
    • For both invasive and noninvasive carcinomas of the breast
• The NCCN panel recommends testing for ER status:
  • In order to determine the benefit of adjuvant endocrine therapy or risk reduction
• Although the tumor HER2 status is of prognostic significance in invasive cancer, its importance in DCIS has not been elucidated:
  • To date, studies have either found unclear or weak evidence of HER2 status as a prognostic indicator in DCIS
  • The NCCN Panel has concluded that knowing the HER2 status of DCIS does not alter the management strategy and is not required DCIS
• The role of MRI in management of DCIS remains unclear:
  • MRI has been prospectively shown to have a sensitivity of up to 98% for high-grade DCIS
  • In a prospective, observational study of 193 women with pure DCIS who underwent both mammography and MRI imaging preoperatively:
    • 93 (56%) women were diagnosed by mammography and 153 (92%) were diagnosed by MRI (P < .0001)
    • Of the 89 women with high-grade DCIS:
      • 43 (48%) who were not diagnosed by mammography:
        • Were diagnosed by MRI alone
  • However, other studies suggest that MRI can overestimate the extent of disease:
    • Therefore, surgical decisions should not be not be solely based on MRI results especially when mastectomy is being contemplated
  • If MRI findings suggest more extensive disease than is seen on mammography such that a markedly larger resection is required for complete excision:
    • The findings should be verified histologically through MRI-guided biopsy of the more extensive enhancement
  • Studies have also been performed to determine whether the use of MRI reduces re-excision rates and decreases local recurrence in women with DCIS:
    • No reduction in re-excision rates was seen in women undergoing lumpectomy following MRI compared with those who did not undergo preoperative MRI
  • The NCCN Panel recommends only performing breast MRI for DCIS in select circumstances where additional information is warranted during the initial workup, noting that the use of MRI has not been shown to increase likelihood of negative margins or decrease conversion to mastectomy for DCIS
• Primary Treatment for DCIS:
  • The goal of primary therapy for DCIS:
    • Is to prevent progression to invasive breast carcinoma
  • Management strategies for DCIS treatment include:
    • Surgery:
      • Mastectomy or lumpectomy
    • Radiation therapy
    • Adjuvant endocrine therapy:
      • To reduce risk of recurrence
  • Surgery:
    • Excision of DCIS using a breast-conserving approach (lumpectomy) with or without whole breast radiation therapy (WBRT) or alternatively, mastectomy:
      • Are the primary treatment options for individuals with DCIS:
        • The choice of local treatment does not impact overall disease-related survival:
          • Therefore, the individual patient’s acceptance of the potential for an increased risk of local recurrence must be considered
• Post-excision mammography:
  • Is valuable in confirming that an adequate excision of DCIS has been performed particularly for DCIS patients who initially present with microcalcifications
• Mastectomy:
  • Patients with DCIS and evidence of widespread disease (ie, disease involving two or more quadrants) on diagnostic mammography or other imaging, physical examination, or biopsy:
    • May require mastectomy
• Mastectomy permanently alters the lymphatic drainage pattern to the axilla:
  • So that future performance of a sentinel lymph node biopsy (SLNB) is not technically feasible
    • Therefore, for DCIS patients who intend on treatment with mastectomy, or alternatively, for local excision in an anatomic location that could compromise the lymphatic drainage pattern to the axilla (eg, tail of the breast):
      • A SLNB procedure should strongly be considered at the time of definitive surgery to avoid necessitating a full axillary lymph node dissection for evaluation of the axilla
• Complete axillary lymph node dissection (ALND):
  • Is not recommended unless there is pathologically documented invasive cancer or axillary lymph node metastatic disease in patients (by either biopsy or SNLB)
  • However, a small proportion of women (about 25%) with seemingly pure DCIS on initial biopsy:
    • Will have invasive breast cancer at the time of the definitive surgical procedure and thus will ultimately require ALN staging
• Lumpectomy plus Whole Breast Radiation Therapy (WBRT):
  • Breast conserving therapy (BCT) includes lumpectomy to remove the tumor with negative surgical margins followed by WBRT to eradicate any residual microscopic disease
  • Several prospective randomized trials of pure DCIS have shown that the addition of WBRT after lumpectomy:
    • Decreases the rate of in-breast disease recurrence, or distant metastasis-free survival
  • In the long term follow-up of the RTOG 9804 trial, at 7 years:
    • The local recurrence rate was:
      • 0.9% (95% CI, 0.0%–2.2%) in the radiation therapy arm versus 6.7% (95% CI, 3.2%–9.6%) in the observation arm (HR, 0.11; 95% CI, 0.03– 0.47; P < .001)
    • In the subset of patients with good-risk disease features:
      • The local recurrence rate was low with observation but was decreased significantly with the addition of radiation therapy
    • A meta-analysis of four large multicenter randomized trials:
      • Confirms the results of the individual trials, demonstrating that the addition of WBRT after lumpectomy for DCIS:
        • Provides a statistically and clinically significant reduction in ipsilateral breast events (HR [hazard ratio], 0.49; 95% CI; 0.41–0.58, P < .00001)
        • However, these trials did not show that the addition of RT has an overall survival benefit
    • The long-term follow-up of the NSABP B-17 showed that at 15 years:
      • Radiation therapy resulted in a 52% reduction of ipsilateral invasive recurrence compared with excision alone (HR, 0.48; 95% CI, 0.33–0.69, P < .001)
      • However, overall survival (OS) and cumulative all-cause mortality rates through 15 years were similar between the two groups (HR for death, 1.08; 95% CI, 0.79–1.48)
    • Similar findings were reported by a large observational study of the SEER database that included 108,196 patients with DCIS:
      • In a subgroup analysis at 10 years, of 60,000 women treated with breast-conserving therapy, with or without radiation therapy:
        • Radiation therapy was associated with a 50% reduction in the risk of ipsilateral recurrence (adjusted HR, 0.47 [95% CI, 0.42–0.53]; P < .001), however, breast cancer-specific mortality was found to be similar (HR, 0.86 [95% CI, 0.67–1.10]; P = .22)
  • More recently, in a population-based study, the use of WBRT in patients with higher-risk DCIS:
    • Higher nuclear grade, younger age, and larger tumor size:
      • Was demonstrated to be associated with a:
        • Modest, but statistically significant improvement in survival
• RT Boost:
  • The use of RT boost has been demonstrated to provide a small but statistically significant reduction in IBTR risk (4% at 20 years):
    • In all age groups for invasive breast cancer
  • Recently, a pooled analysis of patient-level data from ten academic institutions evaluated outcomes of pure DCIS patients:
    • All treated with lumpectomy and WBRT (n = 4131) who either received RT boost with a median dose of 14 Gy (n = 2661) or received no boost (n = 1470):
      • The median follow-up of patients was nine years
        • A decrease in IBTR was seen in patients who received boost compared with those who did not at:
          • 5 years (97.1% vs 96.3%)
          • 10 years (94.1% vs 92.5%)
          • 15 years (91.6% vs 88.0%)
            • P = .0389 for all
      • The use of RT boost was associated with significantly decreased IBTR across the entire cohort of patients (hazard ratio [HR], 0.73; 95% CI, 0.57-0.94; P = .01)
      • In a multivariate analysis that took into account factors associated with lower IBTR, including grade, ER positive status, use of adjuvant tamoxifen, margin status, and age:
        • The benefit of RT boost still remained statistically significant (hazard ratio, 0.69; 95% confidence interval [CI], 0.53 – 0.91; P < .010)
        • Even in patients considered very low risk based on negative margins status (defined as no ink on tumor as per National Surgical Adjuvant Breast and Bowel Project definition, or margins 10 mm or no tumor on re-excision in 48 % of patients)
        • Although the rate of IBTR were acceptably low for the low-/intermediate grade group at the 5 years, at a median follow-up time of 12.3 years, the rates of developing an IBTR were 14.4% for low/intermediate-grade and 24.6% for high grade DCIS (P = .003)
        • This suggests that IBTR events may be delayed but not prevented in the seemingly low-risk population
        • Therefore, the NCCN panel concluded that for DCIS patients treated with lumpectomy alone (without radiation), irrespective of margin width:
          • The risk of IBTR is substantially higher than treatment with excision followed by whole breast radiation therapy (even for predefined low-risk subsets of DCIS patients)

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #DCIS #BreastCancer #CASO #Miami #CenterforAdvancedSurgicalOncology

• A genetic predisposition for HT:
  • Is evident in about 75% of cases
• Certain HLA class II antigens:
  • Such as ARG74 in DR3:
    • Carry an increased risk for the development of several autoimmune disorders that
      include HT:
      • With cytotoxic T-lymphocytes antigen-4 (CTLA-4) also playing a role
• A growing number of environmental factors:
  • Have been implicated in the etiology of HT as well
• Interestingly, iodine supplementation programs in areas of iodine deficiency:
  • Have been associated with rising rates of HT and associated hypothyroidism
• The element selenium (Se++):
  • Is an integral component of the selenoprotein deiodinase enzymes
  • Deiodinases are present in the thyroid as well as various peripheral tissues:
    • Regulating deiodination of thyroxine (T4) and
      triiodothyronine (T3)
  • Reduced serum Se++ levels:
    • Have been noted with cases of HT
  • Although some reports indicate benefits of selenium replacement therapy to reduce the occurrence of HT and the development of hypothyroidism:
    • This has not yet been fully proven
• Remarkably, tobacco and moderate alcohol use:
  • Which have other negative effects:
  • Appear to be associated with a reduced risk of
    autoimmune related hypothyroidism
• Although the development of some autoimmune conditions has been reportedly related to previous infectious exposures:
  • No such association has been noted with
    HT
• Although radiation exposure:
  • Potentially increases the risk of developing thyroid malignancy:
    • It remains to be proven if this predisposes to the development of thyroid autoimmunity
• Other studies have reported a connection between vitamin D deficiency and increased risk of autoimmunity:
  • As well as vitamin D supplementation reducing TPOAb titers in patients with HT on LT4 replacement therapy
• In other autoimmune conditions such as Graves’ disease:
  • Stress has been identified as a potential promoting factor:
    • Albeit available data has not proven any effect on TPOAb production or development
      of hypothyroidism
• Endogenous factors contributing to the risk for
  HT include:
  • Female gender:
    • 7:1 female:male ratio
  • Sex hormones such as:
    • Estrogen, postpartum thyroiditis (PPT), pregnancy, and the presence of fetal microchimerism
• Patients with Down’s and Turner’s syndromes:
  • Also display an increased propensity toward development of autoimmune hypothyroidism

• Phyllodes of the breast:
  • Is a rare lesion
• Phyllodes are classified into three groups:
  • Benign
  • Borderline
  • Malignant
• Borderline and malignant phyllodes:
  • Have a higher incidence of local recurrence:
    • Therefore, historically management was a mastectomy without nodal assessment
  • Recently, more patients are undergoing lumpectomy for this lesion
  • Researchers believe that local recurrence rates are similar for borderline and malignant phyllodes tumors
  • Local recurrence is lower with negative margins:
    • Historically, 1 cm margins have been recommended for malignant and borderline phyllodes tumors and continue to be recommended in the current 2024 NCCN guidelines:
      • The guidelines however note that while narrow margins are associated with an increased risk for local recurrence they are not an absolute indication for mastectomy
    • Newer data may suggest a smaller margin is adequate:
      • Spanheimer et al identified local recurrences in 16% of 71 patients with borderline or malignant phyllodes tumors undergoing breast-conserving surgery
      • Some of these patients had a positive or close (< 1 mm) margin
      • When the subset of patients with a margin > 1 mm was considered, the local recurrence rate was 12%
• In addition, radiation may play a role in decreasing the risk of local recurrence:
  • In a prospective, multi-institutional study, 46 patients (30 with malignant phyllodes tumors and 16 with borderline phyllodes tumors) underwent margin-negative resections followed by radiation therapy:
    • Eight of these patients had margins < 2 mm
    • After 10 years of observation for all patients, none had developed a local recurrence
  • In another study using data from the National Cancer Database, Gnerlich et al. showed that adjuvant radiation therapy decreased the risk of local recurrence after resection of phyllodes tumors by more than half (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.19–0.95)
• References:
  • Tan, BY, Acs, G, Apple, SK, et al. Phyllodes tumor of the breast: a consensus review. Histopathology. 2016;68(1):5-21.
  • Spanheimer P, Murray M, Zabor E, et al. Long term outcomes after surgical treatment of malignant/borderline phyllodes tumors of the breast. Ann Surg Oncol.2019;26(7):2136-2143.
  • Barth R, Wells W, Mitchell S, Cole B. A prospective, multi-institutional study of adjuvant radiation therapy after resection of malignant phyllodes tumors. Ann Surg Oncol. 2009;16(8):2288-2294.
  • Gnerlich J, Williams R, Yao K, Jaskowiak N, Kulkarni S. Utilization of radiotherapy for malignant phyllodes tumors: analysis of the National Cancer Database 1998–2009. Ann Surg Oncol. 2014;21(4):1222-1230

• The Society of Surgical Oncology / American Society for Radiation Oncology (SSO / ASTRO) 2014 Consensus Guidelines:
  • Regarding margins of resection for invasive carcinoma of the breast:
    • Recommend the use of “no ink on tumor” as the standard
  • Patients with invasive cancer:
  • Even with associated ductal carcinoma in situ (DCIS), are treated according to these guidelines
• In a meta-analysis of 33 studies including 32,363 patients:
  • Odds of local recurrence were associated with margin status of positive vs. negative:
    • But not decreased with increasing margin distance for patients with invasive carcinoma
  • The study reported that rates of in-breast tumor recurrence are twice as high with positive margins:
    • Regardless of tumor biology, radiation boost, or endocrine therapy:
• There was no evidence that wide margins reduce recurrence, even in patients with extensive intraductal component
  • However, the American Society of Clinical Oncology (ASCO) guidelines recommend consideration of post-excision mammography to document adequate resection in patients with microcalcifications
• References:
  • Moran MS, Schnitt SJ, Giuliano AE, et al. SSO-ASTRO consensus guideline on margins for breast-conserving surgery with whole breast irradiation in stage I and II invasive breast cancer. Int J Radiat Oncol Biol Phys. 2014;88(3):553-564.
  • Houssami N, Macaskill P, Marinovich ML, Morrow M. The association of surgical margins and local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy: a meta-analysis. Ann Surg Oncol. 2014;21(3):717-730.
  • Buchholz TA, Somerfield MR, Griggs JJ, et al. Margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer: American Society of Clinical Oncology endorsement of the Society of Surgical Oncology/American Society for Radiation Oncology consensus guideline. J Clin Oncol.2014;32(14):1502-1506.

Sentinel Lymph Node Surgery After Neoadjuvant Chemotherapy in Patients With Node-Positive Breast Cancer / The ACOSOG Z1071 (Alliance) Clinical Trial

• According to the ACOSOG Z1071 study for patients who had positive nodes pre-chemotherapy and then had a sentinel node biopsy the false-positive rate was less than 10%:
  • If dual tracer was used
  • Greater than two sentinel nodes were removed
  • Any clipped nodes were included
• If only one lymph node was removed:
  • The false-negative rate was unacceptably high and further axillary surgery was needed
• Until the Alliance 11202 trial is completed:
  • The standard treatment remains an axillary dissection for positive nodes after chemotherapy
• References
  • Boughey JC, Suman VJ, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: The ACOSOG Z1071 (Alliance) Clinical Trial. JAMA. 2013; 310(14): 1455-1461. doi: 10.1001/jama.2013.278932.

• Of all autoimmune disorders, chronic lymphocytic thyroiditis, also known as Hashimoto’s thyroiditis:
  • Is by far the most prevalent
• The eponym Hashimoto’s thyroiditis (HT):
  • Relates to Dr. Hashimoto, from Japan, who, in 1912:
    • First reported a connection between goiter and intrathyroidal lymphocytic inflammation:
      • Referring to it as“struma lym-
        phomatosa”
• HT is understood to be an autoimmune condition:
  • In which activation of the immune system against the thyroid:
    • Leads to increased presentation of thyroid antigens and a rise in Th-1 T-cell cytotoxic action:
      • Mediated by ICAM-1-mediated CD8+ cells:
        • Thereby causing the disruption of thyroid follicles and cell apoptosis
• Typically, thyroid peroxidase antibodies (TPOAb) and / or thyroglobulin antibodies (TgAb):
  • Can be measured in the serum of patients with active HT
• In the general population, up to 20% of adults may have measurable thyroid antibody titers, which occur more often in the elderly and women