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• The use of an aromatase inhibitor (letrozole) with an inhibitor of the cyclin dependent kinases 4 and 6 (ribociclib):
  • Was compared with an aromatase inhibitor alone in postmenopausal women with hormone receptor positive HER2-negative metastatic breast cancer:
    • In the MONALEESA-2 study
• MONALEESA-2 Trial:
  • Results showed an improvement with the addition of ribociclib to letrozole alone in:
    • Progression-free survival (PFS):
      • From 42.2% to 63%
    • Overall response rate:
      • From 37.1% to 52.7%
  • This regimen was also investigated in premenopausal women with advanced, hormone receptor-positive breast cancer, and improved PFS compared with placebo plus endocrine therapy
• References
  • Hortobagi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med.2016;375(18)1738-1748.
  • Tripathy D, Im SA2, Colleoni M3, Franke F4, Bardia A5, Harbeck Nm et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19(7):904-915.

• Calcium:
  • Is the most abundant cation in the human body
• As much as 99% of calcium:
  • Is stored in the musculoskeletal system
• The remainder is present in serum and exists in three forms:
  • 45% is bound to albumin and is biologically inert
  • 50% is ionized and metabolically active
  • A small percentage is complexed with citrate and is also biologically inactive
• Hypoalbuminemia means:
  • That more of the total serum calcium will be free and metabolically active
• Although total serum calcium may be low:
  • The patient may not be metabolically hypocalcemic
• Ionized calcium levels:
  • Are inversely affected by the pH of blood:
    • A one-unit rise in pH:
      • Will decrease the ionized calcium level by 0.36 mmol/L
• Hypoventilation:
  • Would cause a drop in pH and thus a subsequent rise in the ionized calcium level

#Arrangoiz #ParathyroidSurgeon #ParathyroidExpert #CalciumHemostasis #HeadandNeckSurgeon #MSMC #MountSinaiMedicalCenter #Miami #Mexico #EndocrineSurgery

• A mandibulotomy can be performed in one of three locations:
  • Lateral:
    • Through the body or angle of the mandible
  • Midline
  • Paramedian
• A lateral mandibulotomy has several disadvantages:
  • First, the muscular pull on the two segments of the mandible is unequal:
    • Putting the mandibulotomy site under significant stress and causing a delay in healing:
      • For this reason, intermaxillary fixation may be required
  • Second, the ability to gain access to the suture line to maintain cleanliness following surgery in the oral cavity is hampered as a result of intermaxillary fixation leading to poor oral hygiene and the potential risk for sepsis of the suture line
  • Third, a lateral mandibulotomy poses several anatomic disadvantages including:
    • Denervation of the teeth distal to the mandibulotomy site and the skin of the chin:
      • As a result of transection of the inferior alveolar nerve
    • A lateral mandibulotomy also causes devascularization of the distal teeth and the distal segment of the mandible:
      • From its endosteal blood supply
    • The exposure provided by a lateral mandibulotomy:
      • Is limited
    • If the patient needs postoperative radiation therapy:
      • Delayed healing can lead to complications at the site of the mandibulotomy
  • For these reasons, a lateral mandibulotomy:
    • Is not recommended
• By placing the mandibulotomy in the anterior midline:
  • All the disadvantages of a lateral mandibulotolotomy:
    • Are avoided
  • However, splitting the mandible in the midline:
    • Requires extraction of one central incisor tooth:
      • To avoid exposure of the roots of both central incisor teeth:
        • Which are at risk of extrusion
      • Extraction of one central incisor tooth alters the aesthetic appearance of the lower dentition
    • In addition, a midline mandibulotomy requires:
      • Division of muscles arising from the genial tubercle, that is:
        • The geniohyoid and genioglossus:
          • Leading to a delayed recovery of the functions of mastication and swallowing
  • Therefore a median mandibulotomy:
    • Also is not preferred for these reasons
• A paramedian mandibulotomy:
  • On the other hand, avoids all the disadvantages of a lateral mandibulotomy and the sequelae of a midline mandibulotomy
  • It offers significant advantages, such as:
    • Wide exposure
    • Preservation of the geniohyoid and genioglossus muscles:
      • Leading to preservation of the hyomandibular complex
    • The only muscle requiring division is the mylohyoid muscle:
      • Which leads to minimal swallowing difficulties
  • A paramedian mandibulotomy:
    • Does not cause denervation or devascularization of the skin of the chin or the teeth and mandible
  • Fixation at the mandibulotomy site is easy
  • The site of the mandibulotomy is able to withstand radiation therapy if the patient needs postoperative treatment
• Thus at present a paramedian mandibulotomy:
  • Remains an optimal surgical approach for access to posteriorly located larger lesions of the oral cavity and tumors of the oropharynx and parapharyngeal space

#Arrangoiz #CancerSurgeon #HeadandNeckSurgeon #SurgicalOncologist #MountSinaiMedicalCenter #MSMC #Miami #Mexico

• The latest National Comprehensive Cancer Network (NCCN) clinical practice guidelines:
  • Have added fluoroestradiol F18 (FES) PET scan to its list of considerations for patients with recurrent or metastatic ER breast cancer
• The NCCN guideline now recommends clinicians consider the use of FES PET for ER-positive disease during work-up of patients with recurrent or metastatic breast cancer
• The guideline update follows the publication of the Society of Nuclear Medicine and Molecular Imaging’s appropriate use criteria statement on ER-targeted PET imaging in March of 2023:
  • Which noted that FES PET is appropriate when a clinician is considering endocrine therapy and assessing ER status at initial diagnosis of metastatic breast cancer, when the disease progresses after endocrine therapy, when lesions are challenging or dangerous to biopsy, and / or when other tests evaluating ER status are inconclusive
• The addition to FES PET in the NCCN guidelines in addition to fluorodeoxyglucose gives clinicians an opportunity to assess ER function in all tumor sites in patients with ER-positive metastatic breast cancer
• FES was approved by the FDA for use as an adjunct to biopsy in patients with recurrent or metastatic breast cancer in May 2020 and is currently the only imaging agent approved by the agency for that indication:
  • This is a helpful tool for diagnostic confirmation and may have the ability to aid in prognosis and prediction of clinical benefit from endocrine based therapies, including with CDK 4/6 inhibitors
  • We have many endocrine options now, and FES PET may identify patients who remain ER+ and thus potentially benefit from endocrine based therapy
• References: 
  • https://www.gehealthcare.com/about/newsroom/press-releases/ge-healthcare-announces-fes-pet-imaging-recommendation-in-nccn-clinical-practice-guidelines-in-oncology-nccn-guidelines

• The current indications for a segmental mandibulectomy include:
  • Gross invasion by an oral cavity cancer
  • Invasion of the inferior alveolar nerve or canal by the tumor
  • Massive soft-tissue disease adjacent to the mandible
  • A primary malignant tumor of the mandible
  • A tumor that has metastasized to the mandible

• The CREATE-X trial:
  • Randomly assigned 910 patients:
    • With HER2 negative breast cancer and residual disease after undergoing neoadjuvant chemotherapy:
      • To standard postsurgical treatment and capecitabine or placebo
• The primary end point:
  • Was disease-free survival (DFS)
• Secondary end points included:
  • Overall survival (OS)
• DFS was longer in the capecitabine group than in the control group (placebo):
  • 74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years
• Among patients with triple-negative disease:
  • DFS was 69.8% in the capecitabine group versus 56.1% in the control group
• OS rate was 78.8% versus 70.3%
• There is no role for tamoxifen or anastrozole in triple negative breast cancer
• Residual disease after completion of neoadjuvant chemotherapy:
  • Is associated with worse outcomes

References

1. Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Eng J Med. 2017;376(22):2147-2159.

2. Symmans WF, Wei C, Gould R, Yu X, Zhang Y, Liu M, et al. Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol. 2017;35(10):1049-1060.

• The omission of adjuvant regional nodal irradiation did not appear to increase the risk for recurrence or death among patients with breast cancer whose disease converted from lymph node-positive to lymph node-negative after neoadjuvant chemotherapy, according to research presented at the 2023 San Antonio Breast Cancer Symposium
• There is no standard of care in place for patients with breast cancer for whom neoadjuvant chemotherapy has eliminated lymph node involvement, the researchers explained
• The researchers performed a phase 3 clinical trial of 1,641 patients with lymph-node positive, nonmetastatic breast cancer who were found to have no lymph node involvement after neoadjuvant chemotherapy and surgery
• They randomly assigned patients to two different regimens:
  • One group was assigned to skip regional nodal irradiation after undergoing mastectomy or whole breast irradiation and breast-conserving surgery
  • The other group was assigned to continue with chest wall irradiation and regional nodal irradiation following mastectomy or whole-breast irradiation plus regional nodal irradiation and breast-conserving surgery
• Median follow-up was 59.5 months, and patients were a median of 52 years old
• Seventy-eight percent had experienced a complete breast pathological response
• In the “no regional nodal irradiation group,” 91.8% of patients were invasive breast cancer-recurrence free at 5 years compared with 92.7% of those who did undergo regional nodal irradiation
• In both groups, 93.4% of patients were reported to be distant-recurrence free at 5 years
• Overall survival was 94% in patients who were assigned to skip regional nodal irradiation and 93.6% in those who did not skip the therapy, according to the researchers
• The researchers are planning a longer-term follow-up to further examine their findings, and a 10-year analysis time point was reached this past year
• There findings suggest that downstaging cancer-positive regional lymph nodes with neoadjuvant chemotherapy can allow some patients to skip adjuvant regional nodal irradiation without adversely affecting oncologic outcomes
  • Follow-up of patients for long-term outcomes continues
• Reference: 
  • Mamounas, E. Loco-regional irradiation in patients with biopsy-proven axillary node involvement at presentation who become pathologically node-negative after neoadjuvant chemotherapy: Primary outcomes of NRG Oncology/NSABP B-51/RTOG 1304. Abstract GS02-07. SABCS 2023

• In women with hormone receptor positive (HR+), HER2-negative early breast cancer, the 21-gene signature score:
  • Provides prognostic information that is independent of clinicopathological features
• A high score (on a scale of 0 to 100) indicates:
  • A higher rate of distant recurrence and is predictive of chemotherapy benefit
• The prospective Trial Assigning Individualized Options for Treatment (TAILORx);
  • Showed that endocrine therapy alone was noninferior to adjuvant chemotherapy plus endocrine (chemoendocrine) therapy:
    • In women with HR+, HER2-negative, axillary node-negative breast cancer and a 21-gene recurrence score of 11 to 25
  • An exploratory analysis indicated some benefit of chemotherapy:
    • In women 50 years of age or younger who had a recurrence score of 16 to 25
    • In this analysis there was a small (~1.6%) chemotherapy benefit in distant disease-free survival for patients with recurrence score results from 16 to 20, and a modest (~6.5%) chemotherapy benefit for patients with recurrence score results from 21 to 25

References

1. Sparano JA, Gray RJ, Ravdin PM, Makower DF, Pritchard KI, Albain KS, et al. Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer. New Engl J Med. 2019;380(25):2395-2405.

2. Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. New Engl J Med. 2018;379(2):111-121.

• Overview:

  • The tongue is a mass of muscle:

    • That is almost completely covered by a mucous membrane:

    • It occupies most of the oral cavity and oropharynx

  • It is known for its role in taste:

    • But it also assists with:

      • Mastication (chewing)

      • Deglutition (swallowing)

      • Articulation (speech)

      • Oral cleansing

  • Five cranial nerves:

    • Contribute to the complex innervation of this multifunctional organ

  • The embryologic origins of the tongue:

    • First appear at 4 weeks’ gestation:

    • • The body of the tongue forms from derivatives of the first branchial arch:

      • • These gives rise to two lateral lingual swellings and one median lingual swelling (known as the tuberculum impar):

        • • The lateral lingual swellings slowly grow over the tuberculum impar and merge:

          • • Forming the anterior two thirds of the tongue

    • Parts of the second, third, and fourth branchial arches give rise to the base of the tongue

  • Occipital somites:

    • Give rise to myoblasts:

    • • Which form the intrinsic tongue musculature

• Gross Anatomy:

  • From anterior to posterior:

    • The tongue has three surfaces:

      • Tip

      • Body

      • Base

  • The tip:

    • Is the highly mobile, pointed anterior portion of the tongue

  • Posterior to the tip lies the body of the tongue:

    • Which has dorsal (superior) and ventral (inferior) surfaces

  • The median sulcus of the tongue:

    • Separates the body into left and right halves

  • The terminal sulcus, or groove:

    • Is a V-shaped furrow:

      • That separates the body from the base of the tongue:

    • • • At the tip of this sulcus is the foramen cecum:

          • A remnant of the proximal thryoglosal duct

  • The base of tongue contains the lingual tonsils:

    • The inferior most portion of Waldeyer’s ring

• Lingual papillae:

  • The surface of the body of the tongue (dorsum):

    • Derives its characteristic appearance from the presence of lingual papillae:

    • • Which are projections of lamina propria covered with epithelium

  • The four types of lingual papillae are as follows:

    • Vallate (circumvallate)

    • Foliate

    • Filiform

    • Fungiform

  • The vallate papillae (circumvallate):

    • Are flat, prominent papillae that are surrounded by troughs:

    • • In humans, there are 8 to 12 vallate papillae:

        • Located directly anterior to the terminal sulcus:

      • • • The ducts of the lingual glands of von Ebner secrete lingual lipase into the surrounding troughs:

        • • • To begin the process of lipolysis

  • The foliate papillae:

    • Are small folds of mucosa (short vertical folds) located along the lateral surface of the tongue:

    • • They are located on the sides at the back of the tongue:

      • • Just in front of the palatoglossal arch of the fauces:

        • • The foliate papillae appear as a series of red colored, leaf–like ridges of mucosa

    • There are four or five vertical folds, and their size and shape is variable

    • They are covered with epithelium, lack keratin and so are softer, and bear many taste buds:

      • Approximately 1000 taste buds:

        • Taste buds:

          • The receptors of the gustatory sense:

            • Are scattered over the mucous membrane of their surface

    • They are usually bilaterally symmetrical:

    • • Sometimes they appear small and inconspicuous, and at other times they are prominent

    • Because their location is a high risk site for oral cancer, and their tendency to occasionally swell:

      • They may be mistaken as tumors or inflammatory disease

    • Serous glands drain into the folds and clean the taste buds

    • Lingual tonsils:

      • Are found immediately behind the foliate papillae and, when hyperplastic, cause a prominence of the papillae

  • The filiform papillae:

    • Are the most numerous of the lingual papillae

    • They are fine, small, cone-shaped papillae:

      • Covering most of the dorsum of the tongue:

    • • • They cover most of the front two-thirds of the tongue’s surface

    • They appear as very small, conical or cylindrical surface projections, and are arranged in rows which lie parallel to the sulcus terminalis:

      • At the tip of the tongue, these rows become more transverse

    • They are responsible for giving the tongue its texture and are responsible for the sensation of touch

    • Unlike the other kinds of papillae:

      • Filiform papillae do not contain taste buds

  • The fungiform papillae:

    • Are mushroom shaped (generally red in color) and are dispersed most densely along the tip and lateral surfaces of the tongue:

    • • Humans have approximately 200 to 300 fungiform papillae

  • Each vallate, foliate, and fungiform papilla contains taste buds (250, 1000, and 1600 taste buds, respectively):

    • Each taste bud is innervated by several nerve fibers

    • In humans:

      • All taste buds can perceive the five different taste qualities:

        • Salt

        • Sweet

        • Bitter

        • Acid

        • Umami

• Each taste bud consists of:

  • Taste receptor

  • Basal cell

  • Edge cell

• When a taste molecule binds to a taste receptor, the receptor cell depolarizes:

  • Causing an influx of Ca++:

    • Which results in the release of an unknown neurotransmitter

  • Following depolarization, the afferent neural pathway depends on the location of the taste bud that was stimulated:

    • In the anterior two thirds of the tongue:

      • The chorda tympani branch of the facial nerve (cranial nerve VII) is stimulated

    • The lingual-tonsillar branch of the glossopharyngeal nerve (cranial nerve IX) relays taste information:

      • From the posterior third of the tongue (base of the tongue)

• Taste fibers from the anterior two thirds of the tongue:

  • First travel with the lingual nerve and then are relayed to the chorda tympani nerve:

  • • This nerve enters the temporal bone from the infratemporal fossa:

    • • Where it joins the facial nerve and travels to the geniculate ganglion:

      • • Where its pseudounipolar cell bodies are located

  • From the geniculate ganglion:

    • The taste fibers travel in the nervus intermedius to the nucleus of the solitary tract located in the medulla oblongata

• Similarly:

  • Taste fibers from the posterior one third of the tongue travel with the lingual-tonsillar nerve:

    • To the inferior glossopharyngeal ganglion and then to the nucleus of the solitary tract located in the medulla oblongata

• Second-order neurons:

  • Then project taste fibers to the parabrachial nucleus of the pons

• The central tegmental tract:

  • Carries taste sensation from the pons to the thalamus

• The pathway ends in the:

  • Frontal operculum and insular cortex

 

Rodrigo Arrangoiz MS, MD, FACS a head and neck surgeon and is amember of Center for Advanced Surgical:

He is first author on some publications on oral cavity cancer:

• Oral Tongue Cancer: Literature Review and Current Management

  • https://www.oatext.com/pdf/CRR-2-153.pdf

• Understand Cancer: Research and Treatment Oral Cavity Cancer: Literature Review and Current Management.

  • https://www.researchgate.net/publication/303366031_Understand_Cancer_Research_and_Treatment_Oral_Cavity_Cancer_Literature_Review_and_Current_Management

Training:

• General surgery:

• Michigan State University:

• 2004 al 2010

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• Fox Chase Cancer Center (Filadelfia):

• 2010 al 2012

• Masters in Science (Clinical research for health professionals):

• Drexel University (Filadelfia):

• 2010 al 2012

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• IFHNOS / Memorial Sloan Kettering Cancer Center:

• 2014 al 2016

 

 

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#Mexico #Miami

• Fibroadenomas:Are benign, solid neoplasms of the breast:Consisting of fibroepithelial elements
  • Their size is hormonally influenced:As evidenced by fluctuation in size with the menstrual cycle and regression in postmenopausal women
  • Fibroadenomas are often solitary masses:But in approximately 25% of patients present with multiple lesion’s
  • They have a characteristic clinical presentation: Rubbery, mobile, and firm:Despite this, previous reports have indicated that diagnosis by clinical examination:Is accurate in only 50% to 75% of patient’s

• One of the clinical dilemmas facing both surgeons and patients is the concern that the mass is something more ominous than a fibroadenoma:Both benign and malignant phylloides tumors may mimic fibroadenomas
  • Additionally, published reports have described adenocarcinoma and ductal carcinoma in situ:Arising within fibroadenomas or misdiagnosed as fibroadenomas
• Because of the potential for more aggressive pathology masquerading as fibroadenomas:Management has been debated and recommendations changed several times in recent decades:Until the mid-1980s:Standard practice was excision of all fibroadenomas
  • • Subsequent studies in the 1980s and 1990s:Demonstrated the safety of observing the presumed fibroadenomas:In women under age 35:Who had a fine-needle aspirate biopsy that did not contain malignant or suspicious cells
    • More recently, the question has been asked whether biopsy is even necessary:Smith and Burrows concluded:That patients under the age of 25 with benign ultrasound findings:Could be safely observed without a biopsy

• Criteria for excision of suspected fibroadenomas of the breast: Patients with an age greater than 35 years
  • Immobile or poorly circumscribed mass
  • Size greater than 2.5 cm
  • Biopsy not definitive for fibroadenoma

• Fibroadenomas:Son neoplasias benignas y sólidas de la mama que consisten en elementos fibroepiteliales.
  • Su tamaño está influenciado hormonalmente: Como lo demuestra la fluctuación en el tamaño con el ciclo menstrual y regresión en mujeres posmenopáusicas.
  • Los fibroadenomas son a menudo tumores solitarios: Pero en aproximadamente el 25% de los pacientes presentan lesiones múltiples
  • Tienen una presentación clínica característica: Gomoso, móvil y firme: A pesar de esto, informes anteriores han indicado que el diagnóstico mediante examen clínico: Es preciso en solo 50% a 75% de los pacientes
  • Uno de los dilemas clínicos que enfrentan los cirujanos y los pacientes es la preocupación de que la tumoración sea algo más siniestra que un fibroadenoma: Los tumores filoides benignos y malignos pueden simular fibroadenomas:Además, los informes publicados han descrito el adenocarcinoma y el carcinoma ductal in situ: Surgen dentro de fibroadenomas o se diagnostican erróneamente como fibroadenomas.
  • Debido al potencial de una patología más agresiva disfrazada de fibroadenomas: El manejo ha sido debatida y las recomendaciones cambiaron varias veces en las últimas décadas:Hasta mediados de la década de 1980: La práctica estándar fue la escisión de todos los fibroadenomas.
    • • Estudios posteriores en las décadas de 1980 y 1990: Demostró la seguridad de observar los presuntos fibroadenomas: En mujeres menores de 35 años que tuvieron una biopsia por aspiración con aguja fina que no contenía células malignas o sospechosas
    • • Más recientemente, se ha preguntado si la biopsia es necesaria: Smith y Burrows concluyeron: Que los pacientes menores de 25 años con hallazgos benignos de ultrasonido: Podría observarse con seguridad sin una biopsia.