My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida.
I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016.
Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida.
Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.
👉The parathyroid glands arise from the 3rd (inferior) and 4th (superior) pharyngeal pouches and follow distinct paths as they descend into their normal locations. A thorough knowledge of the anatomy and embryology of the parathyroid glands is crucial to the parathyroid surgeon and will guide the search for ectopic glands when aberrant anatomy is encountered.
👉For example, when a missing inferior gland is noted, the thymus is a common ectopic location that should be investigated, as this structure also arises from the 3rd pouch. In addition to the thymus, ectopic parathyroids may be found high in the neck (undescended), in the chest, embedded in the thyroid gland or in the sheath surrounding the carotid artery and jugular vein.
Diagnosis of a breast cancer during pregnancy requires:
A complex treatment plan with multiple multidisciplinary providers:
From both oncology and obstetrics:
Coordinating the timing of cancer treatment and the delivery of a high-risk pregnancy
Gestational or pregnancy-associated breast cancer:
Refers to any breast cancer diagnosed:
During pregnancy or within the first year after childbirth
This is a rare diagnosis:
Yet remains the most common cancer in pregnant women:
Affecting approximately 15 to 35 women per 100,000 deliveries:
Approximately 0.05%
The majority of pregnancy-associated breast cancers are:
Ductal in origin
More likely to be poorly-differentiated
ER negative or PR negative and HER2-positive compared to non-pregnant women
Present at advanced stages
Evaluation of a dominant breast mass should include:
Ultrasound and mammogram with fetal shielding, and core biopsy:
Interpretation of mammography can be difficult:
In the highly dense tissue of pregnant women
Use of MRI during pregnancy is both contraindicated and unhelpful:
Gadolinium contrast may cause fetal harm during the first trimester and is typically avoided
Although the majority (approximately 80%) of breast biopsies in pregnant women will be benign:
It is critical that malignancy be ruled out
Fine needle aspiration during pregnancy is associated with a higher rate of false positive and false negative results:
Without receipt of tumor markers:
Therefore core biopsy is recommended
Staging should be performed in women with advanced disease, and in those with symptoms concerning for metastases:
This should include:
Chest radiograph with fetal shielding, liver ultrasound or MRI without contrast, and “low-dose” radionuclide bone scans
When possible, treatment of pregnancy-associated breast cancers:
Should follow similar guidelines to non-pregnant patients, and if at all possible, the pregnancy should be carried to term
Systemic treatment of breast cancer during pregnancy involves special consideration of both the mother and baby
Surgery is safe at all stages
Chemotherapy can be delivered from:
14 weeks of gestation following completion of organogenesis through 35 weeks, when it should be stopped to avoid leukopenia in preparation for delivery
Data from a single-institution prospective study indicates that:
FAC chemotherapy (5-FU, doxorubicin, and cyclophosphamide) is safe during the second and third trimesters:
With fetal malformations approximating 1%
Experience with taxanes remained limited:
But the National Comprehensive Cancer Network (NCCN) guidelines recommend weekly paclitaxel if warranted
Methotrexates are contraindicated due to teratogenic side effects
Although, 20% of pregnancy-associated breast cancers are HER2-positive:
Anti-HER2 therapy including trastuzumab has not been proven safe during pregnancy and is best delivered in the adjuvant setting
MotHER, a prospective U.S. registry:
Is evaluating women exposed to trastuzumab +/- pertuzumab during pregnancy or within 6 months of conception and following pregnancy outcomes and infants for the first month of life
Current recommendations suggest that targeted anti-HER2 therapy be delayed until after delivery
Breast conservation is not recommended if radiation would be timed during pregnancy because this is contraindicated:
However, it can be performed if radiation falls after delivery
Axillary lymph node dissection was previously recommended:
But sentinel lymph node biopsy is feasible and should be offered
Hormone therapy should be postponed until after childbirth
Chemotherapy during pregnancy can cause concerns for the fetus which depend on the timing of drug administration:
Congenital malformations can occur in the first trimester
In the second and third trimesters:
Prematurity, low birth weight and myelosuppression are the greatest concerns
Among approved chemotherapy agents, long-term outcomes of children with in-utero exposure demonstrate normal development, cognition, and school performance when prematurity is controlled for
References
Macdonald HR Pregnancy associated breast cancer. Breast J. 2020 Jan 14. doi: 10.1111/tbj.13714. [Epub ahead of print]
Goidescu I, Nemeti G, Caracostea G, Eniu DT, Chiorean A, Pintican R, Cruciat G, Muresan D. The role of imaging techniques in the diagnosis, staging and choice of therapeutic conduct in pregnancy associated breast cancer. Med Ultrason. 2019 Aug 31;21(3):336-343. doi: 10.11152/mu-1958. Review.
👉Rodrigo Arrangoiz MS, MD, FACS is the first thyroid surgeon in Mexico to utilize this test in the management of a thyroid nodule.
👉He is now a member of Center for Advanced Surgical Oncology in Miami
👉ThyroSeq Genomic Classifier (GC) is a test for the pre-operative assessment of thyroid nodules with indeterminate cytology:
👉Which offers accurate assessment of cancer probability in a given nodule and additionally provides information on cancer prognostication, helping to select the most optimal patient management.
👉ThyroSeq incorporates all major scientific advances in thyroid cancer genetics and has more than 10-years’ experience serving physicians and their patients with thyroid nodules and cancer.
👉The first version of ThyroSeq was launched for clinical use at the University of Pittsburgh Medical Center as a seven-gene panel (ThyroSeq v0) in April of 2007.
👉Until recently, the test was offered as ThyroSeq v2. Today, ThyroSeq v3 is available for clinical use.
👉ThyroSeq v3 is also based on next-generation sequencing of DNA and RNA. However, it is expanded to analyze 112 genes, providing information on greater than 12,000 mutation hotspots and greater than 150 gene fusion types(Nikiforova MN et al. 2018).
👉The test detects four classes of genetic alterations: (i) mutations (SNVs, indels); (ii) gene fusions; (iii) gene expression alterations; and (iv) copy number variations (CNVs).
👉The test utilizes a proprietary Genomic Classifier (GC) based on the algorithmic analysis of all detected genetic alterations to report the test result as Positive or Negative.
👉ThyroSeq test consists of several steps:
It starts with the assessment of the FNA sample cellularity:
This is a quality assurance (QA) step that determines if the provided sample has sufficient number of cells to proceed with the analysis.
If the number of cells is below the required limit, the test is cancelled and no charges are posted.
Next, cellular composition of the sample is evaluated:
This step assures that the provided sample has an adequate proportion of thyroid follicular cells.
It also allows accurate detection of c-cells (MTC), parathyroid cells, and other non-thyroidal cells.
Then, the generated next generation sequencing data on 112 genes are processed using an in-house bioinformatic pipeline that applies a complex algorithm to estimate cancer probability in the tested nodule:
The algorithm was built based on cancer probability associated with each genetic alteration and their combination and validated in a prospective, multicenter, double-blind study.
Next, the test results and findings are reviewed by a board-certified pathologist who verifies all findings and releases the test report.
ThyroSeq test report is provided in a user-friendly format that states the probability of cancer in the patient’s nodule, suggests potential patient management, and also lists specific genomic alterations that are relevant to the individual patient.
You can expect results within 2 weeks from the time your specimen is received.
The Clinical Response to Neoadjuvant Endocrine Therapy Correlates with the Duration of Treatment
In the preoperative setting, chemotherapy is typically recommended to:
Improve breast cancer operability or downstage the axilla among medically fit patients:
However, neoadjuvant endocrine therapy (NET) is a good option for:
Post-menopausal women with ER+ breast cancers:
When aiming for improved candidacy for breast conservation or
In patients in whom chemotherapy will not be safely tolerated
Studies evaluating NET have demonstrated:
Similar rates of clinical and radiographic response and breast conservation therapy (BCT) to those reported from studies using neoadjuvant chemotherapy
When neoadjuvant chemotherapy (four cycles of doxorubicin and paclitaxel) was compared directly to NET (12 weeks of aromatase inhibitors; exemestane or anastrozole):
NET was associated with:
Comparable clinical response
Higher rates of breast conservation:
33% vs. 24%
No difference in local recurrence at approximately three years
Meta-analysis and clinical trial data support use of aromatase inhibitors (letrozole or anastrozole) over tamoxifen:
Higher clinical and radiographic response rates:
55% vs. 36%
Improved rates of BCT:
45% versus 35%
The ACOSOG Z10316 trial:
Demonstrated comparable effectiveness of exemestane, letrozole and anastrozole for 16 to 18 weeks before surgery
NET requires a longer duration of treatment than preoperative chemotherapy and depends on the patient’s individual eligibility for breast conservation
NET is typically recommended for:
Three to six months prior to surgery:
However, extended treatment for up to 12 months has been safe and is associated with a greater response to treatment
Although tumor progression is rare on NET:
Continued surveillance is important for women with an intact primary breast tumor taking endocrine therapy, and cancer growth would be an indication for surgery
The majority of clinical trials for NET have focused on postmenopausal women:
In that younger patients often have:
Higher-risk tumor biology and are likely candidates for chemotherapy:
Thus, data on the use of NET in premenopausal patients are limited to phase II trials and include ovarian suppression plus aromatase-inhibitors (i.e., exemestane + goserelin)
References
Semiglazov VF, Semiglazov VV, Dashyan GA, Ziltsova EK, Ivanov VG, Bozhok AA, et al. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer. 2007;110(2):244-254.
Ellis MJ, Ma C. Letrozole in the neoadjuvant setting: the P024 trial. Breast Cancer Res Treat. 2007;105(suppl 1):133-143.
Eiermann W, Paepke S, Appfelstaedt J, Llombart-Cussac A, Eremin J, Vinholes J, et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter trial. Ann Oncol. 2001;12(11):1527-1532.
Smith IE, Dowsett M, Ebbs SR, Dixon JM, Skene A, Blohmer JU, et al. Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol. 2005;23(22):5108-5116.
Cataliotti L, Buzdar AU, Noguchi S, Bines J, Takatsuka Y, Petrakova K, et al. Comparison of Anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer: the pre-operative “arimidex” compared to tamoxifen (PROACT) trial. Cancer. 2006;106(10):2095-2103.
Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, et al. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM5-based intrinsic subtype—ACOSOG Z1031. J Clin Oncol. 2011;29(17):2342-2349.
👉The management of thyroid cancer has undergone a lot of changes over the last 10+ years. The 2015 American Thyroid Association (ATA) management guidelines for thyroid nodules and thyroid cancer recommend a patientcentered approach to evaluating the risk of thyroid cancer recurrence and overall prognosis for each individual patient. This has led to a decrease in total thyroidectomies (removal of the entire thyroid) and an increase in the removal only of the lobe containing the cancer (lobectomy), keeping the other lobe intact. Partially due to this change in surgical approach, there has been a marked decrease in the use of radioactive iodine therapy after surgery for thyroid cancer. There has been discussion in the greater nuclear medicine community regarding some of these recommendations and two prominent nuclear medicine organizations, the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI), declined to endorse the guidelines. In order to promote better understanding of differences in perspective and to reach a more collaborative and consistent, evidence-based set of recommendations, or at least of guiding principles, representatives from the ATA and the European Thyroid Association (ETA) met with representatives from the EANM and the SNMMI to draft a consensus paper. This paper aims to support cooperation among medical societies, to define the goals radioactive iodine therapy, to acknowledge that the published literature is lacking with regard to the best dose of radioactive iodine therapy to use and to better improve the definition of thyroid cancer that is no longer responding to radioactive iodine therapy.
CONCLUSION:
1) The best thyroid cancer management requires cooperation between endocrinologists, surgeons and nuclear medicine physicians. 2) The goal of radioactive iodine therapy should be specifically defined as (a) destroying remaining normal thyroid tissue, (b) treatment of suspected microscopic cancer remaining after surgery or (c) treatment of known visible cancer. 3) Proper patient selection for radioactive iodine therapy requires assessment of postoperative cancer status and not simply preoperative staging. 4) Evaluation of postoperative cancer status should be standardized in terms of blood tests and imaging tests. 5) Proper patient selection for radioactive iodine therapy also requires evaluation of multiple factors, including patient preference, potential side effects, and availability and quality of medical resources. 6) The best administered radioactive iodine therapy cannot be determined from the available literature, favoring more individualized dosing decisions. 7) Identification of cancers that are unlikely to respond to radioactive iodine therapy should not to exclude them from consideration of radioactive iodine therapy. 8)Criteria used to identify cancers that are unlikely to respond to radioactive iodine therapy will continue to evolve, especially with progress in evidence-based studies and better imaging. 9) Prospective studies are needed to address knowledge and evidence gaps with regard to radioactive iodine therapy.
Refers to the delivery of systemic treatment prior to surgery
Preoperative chemotherapy was initially utilized in women with locally advanced or inflammatory breast cancers:
To improve operability
Among women with early-stage breast cancers:
The NSABP B-18 and B-27 randomized clinical trials:
Demonstrated no difference in:
Disease-specific or overall survival:
Between those who received neoadjuvant versus adjuvant chemotherapy
Neoadjuvant chemotherapy:
Improved rates of breast conservation:
68% versus 60%
More recent observational data have demonstrated:
No increased risk in surgical complications among women who underwent neoadjuvant chemotherapy
NAC has more recently been used to:
Downstage the axilla in patients with biopsy-proven lymph node involvement with hopes to avoid completion lymphadenectomy and decrease the risk of lymphedema
Additionally, NAC has been used in women with operable breast cancers:
To theoretically treat micro-metastatic disease prior to local therapy and to allow assessment of the in vivo tumor response to certain chemotherapy regimens
Notably, results from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis included:
Patient-level data from 4,756 women enrolled in clinical trials 1983 to 2002:
Results demonstrated a higher risk of in-breast recurrence after neoadjuvant chemotherapy:
At 15 years, women treated with NAC had a 21% risk of local recurrence (vs. 16% in the surgery-first patients):
This was attributed to a higher rate of breast conservation, but with no difference in distant recurrence or breast cancer-specific overall survival
Among women with operable breast cancers at the time of diagnosis:
Neoadjuvant chemotherapy (NAC) is increasingly used to gain information about the tumor’s response to treatment:
With pathologic response rates correlating with long-term prognosis
Doxorubicin and cyclophosphamide followed by a taxane
Higher risk HER2-negative breast cancers (node-positive hormone-receptor positive patients and triple-negative patients) typically receive:
Anthracycline and taxane-based regimens with or without carboplatin
Notably, results from the CALGB 406034 trial:
Suggested that for triple-negative breast cancer:
The addition of carboplatin to NAC resulted in a 14% increase in eligibility for breast conservation
References
Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16(8): 2672-2685.
Boughey J, Peintinger F, Meric-Bernstam F, Perry AC, Hunt KK, Babiera GV, et al. Impact of preoperative versus postoperative chemotherapy on the extent and number of surgical procedures in patients treated in randomized clinical trials for breast cancer. Ann Surg. 2006;244(3):464-470.
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomized trials. Lancet Oncol. 2018;19(1):27-39.
Fayanju OM, et al. The Clinical Significance of Breast-only and Node-only Pathologic Complete Response After Neoadjuvant Chemotherapy. Annals of Surgery. 2018; 268(4): 591-601.
von Minckwitz, G et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. NEJM. 2018; 380(7): 617-628.
Masuda N, et al. Adjuvant Capecitabine for Breast Cancer After Preoperative Chemotherapy. NEJM. 2017; 376:2147-59.
Golshan M, et al. Impact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer on eligibility for breast-conserving surgery and breast conservation rates: surgical results from CALGB 40603 (Alliance). Annals of Surgery. 2015; Sep; 262(3):434-9.
👉Ogilvie’s syndrome presents as acute large bowel obstruction.
👉Abdominal radiographs show evidence of colonic obstruction, with marked caecal distension being a common feature. Indeed, caecal perforation is a well recognised complication
Recent, more selective use of radioactive iodine (RAI) has led to reevaluation of the clinical importance of achieving complete total thyroidectomy with minimal residual normal thyroid tissue. We utilize the improved localization by post‐RAI remnant ablation, single photon emission computerized tomography‐computed tomography (SPECT‐CT) to define specific anatomic sites of residual RAI‐uptake foci after total thyroidectomy for differentiated thyroid cancer (DTC) and to provide a novel classification system relating uptake to thyroid anatomy and preservation of adjacent neural structures.
Radioactive iodine‐uptake foci in thyroid bed were localized by SPECT/CT imaging at the time of RAI remnant ablation in 141 DTC patients undergoing total thyroidectomy.
Results Minimal residual RAI uptake (median 0.32% at 24 hours) in the thyroid bed was detected by diagnostic planar whole body scans in 93% and by posttherapy SPECT/CT imaging in 99% of subjects. Discrete RAI uptake foci were identified on the SPECT/CT imaging at Berry’s ligament (87%), at superior thyroid poles (79%), in paratracheal‐lobar regions (67%), in isthmus‐region (54%), and in pyramidal lobe (46%). Despite the residual foci, the nonstimulated thyroglobulin (Tg) prior to remnant ablation (with a median thyroid‐stimulating hormone of 0.36 m IU/L) was < 0.6 ng/mL in 53% and < 1 ng/mL in 73% of cases.
Conclusion
After extracapsular total thyroidectomy, highly sensitive detection tools identify microscopic residual RAI avid foci in thyroid bed in the majority of patients. These foci can be classified as 1) neural‐related and 2) capsule‐related. These common residual foci have no relationship to postoperative Tg, suggesting that attempts at radical removal of thyroid tissue in these locations may not be warranted.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 