Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• Assist Control (AC):
  • Is a commonly used mode of ventilation:
    • Is one of the safest modes of ventilation:
      • In the Emergency Department
  • Patients receive:
    • The same breath, with the same parameters:
      • As set by the clinician, with every breath
    • They may take additional breaths, or over-breathe:
      • But every breath:
        • Will deliver the same set parameters
    • Assist control can be:
      • Volume-targeted:
        • Volume control, AC/VC:
          • Where the clinician sets a desired volume, or
      • Pressure-targeted:
        • Pressure control, AC/PC:
          • Where the clinician selects a desired pressure
• Synchronized Intermittent Mandatory Ventilation (SIMV):
  • Is a type of intermittent mandatory ventilation, or IMV
  • The set parameters are similar to those in AC, and the settings can be:
    • Volume controlled (SIMV-VC) or
    • Pressure controlled (SIMV-PC)
  • Similar to AC:
    • Each mandatory breath in SIMV:
      • Will deliver the identical set parameters:
        • However, with additional spontaneous breaths:
          • The patient will only receive pressure support or CPAP:
            • For example:
              • In SIMV-VC we can set a TV, and as long as the patient is not breathing spontaneously:
                • Each delivered mechanical breath will achieve this tidal volume
              • However, spontaneous breaths in this mode of ventilation:
                • Will have more variable tidal volumes:
                  • Based on patient and airway factors
• Pressure Regulated Volume Control (PRVC):
  • Is a type of assist-control (AC):
    • That combines the best attributes of:
      • Volume control and
      • Pressure control
  • The clinician selects:
    • A desired tidal volume:
      • The ventilator gives that tidal volume with each breath:
        • At the lowest possible pressure:
          • If the pressure gets too high and reaches a predefined maximum level:
            • The ventilator will stop the air flow and cycle into the exhalation phase:
              • To prevent excessive airway pressure and resulting lung injury
  • In this mode of ventilation:
    • The pressure target is adjusted:
      • Based on lung compliance:
        • To help achieve the set tidal volume
• Pressure Support:
  • Is a partial support mode of ventilation:
    • In which the patient receives a constant pressure (the PEEP):
      • As well as a supplemental, “supporting” pressure:
        • When the ventilator breath is triggered
  • In this mode:
    • The clinicians can set the PEEP and
    • The additional desired pressure over the PEEP
      • However:
        • The peak inspiratory airflow, the respiratory rate, and the tidal volume:
          • Are all dependent variables:
            • Determined by the patient’s effort
          • The patient triggers every breath, and when the patient stops exerting effort:
          • The ventilator stops administering the driving pressure, or the desired pressure over PEEP:
            • Therefore, patients placed on this mode of ventilation:
              • Must be able to take spontaneous breaths
• Non-invasive positive pressure ventilation (NIPPV):
  • Refers to two non-invasive modes of ventilation:
    • In which the patient’s airway is not secured with an endotracheal tube:
      • Rather, these modes of ventilation are delivered through:
        • A tight-fitting facemask or nasal prongs
  • There are several indications, and clear contraindications to these modes of ventilation:
    • Both CPAP and BPAP are non-invasive modes of ventilation
• Continuous Positive Airway Pressure (CPAP):
  • Is a partial support mode of ventilation:
    • In which the patient received a constant airway pressure throughout the respiratory cycle
  • The peak inspiratory airflow, respiratory rate, and tidal volume are:
    • All dependent variables and determined by the patient’s effort:
      • Therefore:
        • The patient must be awake, minimally sedated, and able to take spontaneous breaths during this mode of ventilation
• Bilevel Positive Airway Pressure (BPAP or BiPAP):
  • Is a partial support mode of ventilation:
    • In which the patient receives two levels of airway pressure throughout the respiratory cycle:
      • A high inspiratory pressure (iPAP):
        • Is similar to the peak airway pressure setting
      • The lower expiratory pressure (ePAP):
        • Similar to PEEP:
          • Is clinically apparent at the end of expiration and helps maintain alveolar distention
  • The patient must be awake, minimally sedated, and able to take spontaneous breaths during this mode of ventilation
• Unconventional Modes of Ventilation:
  • There are other modes of ventilation occasionally used in specific circumstances in ICUs, including:
    • Airway Pressure Release Ventilation (APRV):
      • Also referred to as:
        • Bi-Level or Bi-vent
    • High-frequency Oscillatory Ventilation
    • Proportional Assist Ventilation (PAV), and
    • Neurally Adjusted Ventilator Assist (NAVA)
      • But these modes are not appropriate in the ED without expert consultation

#Arrangoiz #Surgeon #Teacher #Doctor

Thyroid cancer (TC) represents the most common endocrine malignancy, accounting for 3.4% of all cancers diagnosed annually.

The transformation of the thyroid follicular cells may result in differentiated or undifferentiated TC, through a multistep process that is the most accepted theory of follicular cell carcinogenesis.

In this model, distinct molecular alterations have been associated with specific stages, driving progression from well-differentiated to undifferentiated follicular-derived thyroid carcinomas.

More recently, the cancer stem-like cells theory has been proposed, according to which phenotypically different cancer cells could be generated by a small subpopulation of stem cells after genetic and epigenetic transformations.

Differentiated TC, accounting for more than 90% of thyroid malignancies, comprises papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC).

Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are rare tumors (5 and 1%, respectively) associated with aggressive behavior and short median time of survival (5 years and 6 months, respectively).

Differently, medullary thyroid carcinoma (MTC), representing 5% of TC, arises from parafollicular C cells.

In the last 30 years, the availability of the genome sequence has produced much progress in elucidating the molecular mechanisms underlying TC.

TC is a relatively simple genetic disease with a relatively low somatic mutation burden in each tumor.

Driver mutations, i.e., mutations that provide a selective growth advantage thus promoting cancer development, are identified in more than 90% of TC.

The molecular pathogenesis of the majority of TC involves dysregulation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K)/AKT signaling pathways.

MAPK activation is considered to be crucial for PTC initiation, through point mutations of the BRAF and RAS genes or gene fusions of RET/PTC and TRK.

On the other hand, PI3K/AKT activation is thought to be critical in FTC initiation and can be triggered by activating mutations in RAS, PIK3CA, and AKT1 as well as by inactivation of PTEN, which negatively regulates this pathway.

TC progression and dedifferentiation to PDTC and ATC involves a number of additional mutations affecting other cell signaling pathways, such as p53 and Wnt/β-catenin.

More recently, TERT promoter mutations have been described in all the histological TC type, with a significantly higher prevalence in aggressive and undifferentiated tumors, indicating their role in TC progression.

Mutations in the RET (Rearranged during transfection) proto-oncogene account for most MTC cases and can occur sporadically or as inherited germline events in the multiple endocrine neoplasia type 2A (MEN2A) and 2B (MEN2B) syndromes.

A minority of sporadic MTC are caused by H-, K-, and N-RAS mutations.

#Arrangoiz #ThyroidSurgeon #ThyroidExpert #ThyroidCancer #CancerSurgeon #SurgicalOncologist #HeadandNexkSurgeon

• As part of routine surveillance of patients diagnosed with breast cancer, the following is recommended according to the NCCN guidelines:
  • History and physical exam:
    • 1 to 4 times per year:
      • As clinically appropriate, for 5 years, and then annually
  • Educate, monitor, and refer for lymphedema management
  • Mammography every year
  • In the absence of symptoms:
    • There is no evidence to support laboratory or imaging studies:
      • For metastatic screening
  • Women on tamoxifen:
    • Should have annual gynecologic screening
  • Women on aromatase inhibitor therapy:
    • Should have monitoring of bone health and density at baseline and periodically thereafter
  • Assess and encourage adherence to adjuvant endocrine therapy
  • Evidence suggests that active lifestyle and achieving and maintaining an ideal body weight (20 to 25 BMI):
    • May lead to optimal breast cancer outcomes
• The American Society of Clinical Oncology (ASCO) and the American Cancer Society convened a multidisciplinary expert panel and published:
  • The Breast Cancer Survivorship Care Guidelines in 2016
  • A multidisciplinary panel that included primary care, gynecology, surgical oncology, medical oncology, and radiation oncology physicians in conjunction with nursing agreed upon these guidelines
  • Together, they reviewed more than 1000 articles and ultimately included 237 of them as the basis for their recommendations
  • In essence, their conclusions mirror those in the current NCCN guidelines:
    • Supporting regular surveillance for breast cancer recurrence, which includes a:
      • Cancer-related history and physical examination
      • Routine imaging screening with mammography for new primary breast cancer
      • The panel agrees routine laboratory or additional imaging is not necessary in asymptomatic patients to evaluate for recurrence
      • The panel stresses the importance of maintaining a healthy lifestyle

REFERENCES

1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines for Oncology: Breast Cancer. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp Published January 2016. Accessed January 29, 2017.
2. Runowicz CD, Leach CR, Henry NL, et al. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. J Clin Oncol. 2016;34(6):611-635.

#Arrangoiz #Surgeon #CancerSurgeon #BreastSurgeon #SurgicalOncology #Teacher

• NSABP B-17:
  • A Phase III Randomized Study of:
    • Postoperative Radiotherapy Following Segmental Mastectomy and Axillary Dissection in Patients with:
      • Noninvasive Intraductal Adenocarcinoma of the Breast:
  • Compared lumpectomy alone to lumpectomy plus breast irradiation:
    • In 818 patients with localized DCIS
  • This trial concluded:
    • That radiotherapy significantly decreases the rate of invasive cancer and DCIS in the ipsilateral breast by:
      • Approximately 50%

#Arrangoiz #BreastSurgeon #SurgicalOncologist #Teacher #Surgeon #BreastCancer

• NSABP B-23:
  • Was developed in an attempt to determine whether:
    • Tamoxifen was effective:
      • In patients with ER-negative tumors:
        • By randomizing them to:
          • Four cycles of adjuvant doxorubicin and cyclophosphamide (AC) or
          • Six cycles of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF):
            • With or without tamoxifen
  • The results of B-23 demonstrated:
    • No significant improvement in:
      • Disease-free survival (DFS) or OS:
        • With tamoxifen added to chemotherapy in patients with ER-negative tumors:
          • DFS:
            • CMF – 83%
            • CMF plus tamoxifen – 83%
            • AC – 83%
            • AC plus tamoxifen – 82%
          • OS:
            • CMF – 89%
            • CMF plus tamoxifen – 89%
            • AC – 90%
            • AC plus tamoxifen – 91%
  • Additionally:
    • NSABP B-23 confirmed the results of NSABP B-15:
      • That four cycles of AC are equivalent to 6 cycles of CMF:
        • In terms of DFS and OS

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #Teacher

• The CALGB 9343 trial:
  • Enrolled 647 patients:
    • From 1994 until 1999
  • Long-term follow-up data:
    • Were published in 2013:
      • With a median follow-up of:
        • 12.6 years
  • Women age 70 years or older:
    • With clinical stage I:
      • cT1, cN0, cM0
    • ER-positive breast cancer
    • Treated by lumpectomy
  • Were randomly assigned to receive:
    • Tamoxifen plus radiation therapy (TamRT) or
    • Tamoxifen alone (Tam)
  • At 10 years:
    • 98% of women:
      • Receiving TamRT were free from local and regional recurrences
    • Compared to 91% of those receiving Tam
  • The 10-year estimates of overall survival (OS) were:
    • 67% (95% confidence interval [CI], 62–72%) in the TamRT group versus
    • 66% (95% CI, 61%–71%) in the Tam group:
      • But the difference was not statistically significant
  • In addition to concluding that:
    • While RT (in addition to Tam):
      • Reduces locoregional recurrence:
        • The authors noted that “the impact of breast cancer in this select group of older women is much smaller than that of comorbid conditions:
          • Only 3% of women in study have died as a result of breast cancer whereas 49% have died as a result of other causes

REFERENCES

1. Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013;31:2382-2389.

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #BreastCancer

• The ACOSOG Z1071 trial:
  • Was designed to determine the false negative rate (FNR) of:
    • Sentinel lymph node (SLN) surgery after chemotherapy:
      • In women initially presenting with cN1 disease
  • It enrolled women from 136 institutions:
    • Who had clinical:
      • T0 through T4
      • N1 through N2
      • M0 breast cancer
        • Who received neoadjuvant chemotherapy
  • Patients enrolled had:
    • Pre-chemotherapy axillary nodal disease confirmed by:
      • Fine-needle aspiration or
      • Core needle biopsy
  • Following chemotherapy:
    • Patients underwent:
      • Both SLN surgery and axillary lymph node dissection
  • Sentinel lymph node surgery:
    • Using both:
      • Blue dye (isosulfan blue or methylene blue) and a radiolabeled colloid mapping agent:
        • Was encouraged
  • Rates of detection of at least:
    • One SLN were:
      • 92.9% in patients:
        • With cN1 disease and
      • 89.5% in patients:
        • With cN2 disease
  • Overall the FNR of SLN after neoadjuvant chemotherapy was:
    • 12.6%:
      • 90% Bayesian Credible Interval, 9.85%–16.05%
  • Bivariable analyses found that:
    • The likelihood of a false-negative SLN finding was significantly decreased:
      • When the mapping was performed:
        • With the combination of blue dye and radiolabeled colloid:
          • P=.05; FNR:
            • 10.8% combination vs 20.3% single agent and
        • By examination of at least 3 SLNs:
          • P=.007; FNR:
            • 9.1% for ≥3 SLNs vs 21.1% for 2
  • While the study overall did not meet the predetermined acceptability threshold of:
    • Postneoadjuvant SLN biopsy FNR being 10% or less:
      • The authors concluded that:
        • Changes in approach and
        • Patient selection:
          • That result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to axillary lymph node dissection in this patient population

REFERENCES

1. Boughey JC, Suman VJ, Mittendorf EA, et al; Alliance for Clinical Trials in Oncology. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310:1455-1461.

#Arrangoiz #BreastSurgeon #BreastSurgery #CancerSurgeon #SurgicalOncologist #BreastCancer

• NSABP B-14:
  • Randomized patients after surgery to:
    • Five years of tamoxifen or
    • 5 years of placebo:
      • To determine if there was a:
        • Significant survival advantage with the addition of endocrine therapy to:
          • ER-positive tumors
  • After 10 years of follow-up:
    • A statistically significant DFS benefit was derived:
      • With the use of tamoxifen for 5 years:
        • 69% vs 57%
          • P<0.0001
    • With a 37% reduction:
      • In the rate of contralateral breast cancer (P=0.007)
    • The most recent update of this trial:
      • Continues to demonstrate this survival benefit at 15 years:
        • Irrespective of age
        • Menopausal status, and
        • Tumor ER concentration
    • A follow-up question to protocol B-14:
      • Asked the recommended duration of tamoxifen therapy beyond 5 years:
        • The same patient population was then re-randomized to:
          • Five additional years of tamoxifen or
          • Five years of placebo
        • There was a significant disadvantage in:
          • DFS:
            • 86% vs 92%, P= 0.003 and
          • Distant DFS:
            • 90% vs 96%, P=0.01:
              • For patients who continued tamoxifen for more than 5 years versus those who took it for only 5 years
                • The lack of benefit with additional tamoxifen use was independent of patient age

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #Teacher

👉One of the pioneers in thyroid surgery in the twentieth century, Thomas Peel Dunhill, began his work on the problems of goiter and thyrotoxicosis in Melbourne in 1910 had performed 312 operations, 200 of which were for exophthalmic goiter.

Dunhill adopted a technique of total lobectomy on one side and subtotal on the other side after reading Frank Harley’s paper which was published in 1907.

👉He used his technique under local anesthesia at first and later under light general anesthesia. At that time the mortality for this operation was 30% in hospitals in London and with his method, he achieved a mortality of less than 3%, despite accepting the most severely ill patients suffering from uncontrolled atrial fibrillation.

👉The technique that he adopted — total lobectomy by a pericapsular dissection technique
— is even now considered by many surgeons the optimal method of resection.

👉He also described later operation on retrosternal goiter by splitting the sternum and in 1920 he produced his outstanding paper in an early issue of British Journal of Surgery.

👉In the same year, Sistrunk described his radical operation for the thyroglossal tract that included the resection of the middle third of hyoid at the base of the tongue.

#Arrangoiz #ThyroidSurgeon #ThyroidExpert

• Breast cancers during pregnancy:
  • Are often locally advanced due to delays in diagnosis, and many of these young patients will require chemotherapy
• Systemic treatment of breast cancer during pregnancy:
  • Involves special consideration of both the mother and the baby
• Data from a single-institution prospective study:
  • Reported on 40 pregnant women initially and updated their series years later to include 57 women:
    • Treated with FAC chemotherapy (5-FU, doxorubicin, and cyclophosphamide):
      • During the second and third trimesters
  • Investigators concluded:
    • This regimen to be safe as fetal malformations occurred only 1.3% of the time:
      • Which was similar to the rate of malformations seen in fetuses not exposed to chemotherapy
• Methotrexate is contraindicated in all trimesters:
  • As its method of action is as an antimetabolite and anti-folate agent
• Although limited data exist on taxane-based therapies:
  • The NCCN recommends that if needed:
    • It should be given with weekly dosing
• Anti-HER2 therapy with either trastuzumab or pertuzamab:
  • Is contraindicated during pregnancy:
    • With case reports associating oligohydramnios or anhydramnios with therapy
• First-trimester chemotherapy:
  • Is contraindicated based on:
    • An increased risk of:
      • Fetal malformation
      • Stillbirth
      • Miscarriage
• Second- and third-trimester chemotherapy:
  • Appears to be safe:
    • But may be associated with:
      • Intrauterine growth retardation
      • Prematurity
      • Low birth weight
• Chemotherapy:
  • Should not be given after 35 weeks’ gestation or within 3 weeks of planned delivery:
    • The median gestational age is 38 weeks with more than 50% of babies born by vaginal delivery
• Breastfeeding while on chemotherapy:
  • Is contraindicated due to excretion of drugs into breast milk

REFERENCES

1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines for Oncology: Breast Cancer. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp Published January 2016. Accessed January 29, 2017.
2. Amant F, Deckers S, Van Calsteren K, et al. Breast cancer in pregnancy: Recommendations of an international consensus meeting. Eur J Cancer. 2010;46:3158-3168.
3. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. A Reference Guide to Fetal and Maternal Risk. 6th ed. Philadelphia, Pa: Lippincott Williams and Wilkins; 2006.
4. Gwyn K, Theriault R. Breast cancer during pregnancy. Oncology (Williston Park). 2001; 15(1):39-46.
5. Hahn KM, Johnson PH, Gordon N, et al. Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero. Cancer. 2006:107(6):1219-1226.

#Arrangoiz #Surgeon #CancerSurgeon #SurgicalOncologist #BreastSurgeon #BreastCancer #Teacher