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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_901_Библиотеки_им_академика_М_И_Перельмана
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322
S. C. Wimann et al.
Types of immunotherapies
Type Characteristics Indications Side effects
Cancer vaccines Generate a T cell response
Checkpoint
inhibitor
immunotherapy
Combination
immune
checkpoint
blockade
strategies
T cell adoptive
therapy
Anti-PD-1 and PD ligand 1/2
(pembrolizumab,
nivolumab)
Ipilimumab and tremelimumab
(CTLA-4 blockade)
Concurrent PD-1 and CTLA-4
blockade (e.g., nivolumab +
ipilimumab)
Tumor-inltrating lymphocytes
are effector T cells that are able
to induce tumor regression
Better tolerated than
ipilimumab as a rst line
therapy for metastatic
cancers, including
melanoma and renal cell
cancer. However, this is not
yet approved as adjuvant
therapy for melanoma
Ipilimumab ➔ approved for
metastatic melanoma and as
adjuvant therapy
Metastatic melanoma,
non-small cell lung cancer,
renal cell carcinoma, colon
cancer
The most signicant results
have been achieved in
melanoma (lymphocytic
receptors can be directed
against specic tumor
antigens, such as
NY-ESO-1in melanoma
and synovial sarcoma)
Fatigue and rash
Diarrhea; colitis; skin rash;
hepatitis; and endocrine
toxicities (hypophysitis,
hypothyroidism, and adrenal
insufciency)
Chemotherapy
Mechanism of action
Mechanisms by which
cancer cells develop
resistance
Cytotoxic drugs ➔ cancer cell death
Cytostatic drug ➔ arrest of cancer cell growth
Most chemotherapeutic agents destroy cancer cells during DNA replication in the S
phase of mitosis
Cancer cells can modify cell surface transport protein ➔ inhibit the amount of drug
entering the cell and increase the amount of drug exiting the cell
Cancer cells can induce increased metabolism or breakdown of chemotherapeutic drugs
Cancer cells can alter cell surface target proteins ➔targeted therapies can no longer bind
the target for which it was developed
10 Breast andOncology
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Common chemotherapeutic agents
Class Agent Mechanism of action Toxicity
Anthracyclines Doxorubicin Topoisomerase II inhibitor Heart toxicity
323
Taxanes Paclitaxel Disruption of microtubule
function
Platinum compounds Oxaliplatin Cross-link DNA strands,
thereby inhibiting DNA
synthesis and function. If
the DNA is damaged
enough, the cell will
undergo apoptosis
Cisplatin Prevent repair of the DNA
leading to DNA damage
Carboplatin Attach alkyl groups to the
nucleotides, leading to the
formation of monoadducts,
and DNA fragmenting
Antimetabolites 5-uorouracil Inhibits thymidylate
synthetase
Gemcitabine Inhibit DNA synthesis and
repair
Methotrexate Inhibits DHFR Mucositis, diarrhea,
Topoisomerase
inhibitors
Etoposide Inhibits topoisomerase Alopecia and gastrointestinal
Bone marrow suppression,
peripheral neurotoxicity, and
mucositis
Peripheral sensory neuropathy,
neutropenia, thrombocytopenia
Nephrotoxic, neurotoxic,
ototoxic
Myelosuppression, peripheral
neuropathy
Mucositis, neurotoxicity,
myelosuppression
Diarrhea, myelosuppression
myelosuppression, neurotoxicity
toxicity
Irinotecan Inhibits topoisomerase Neutropenia, diarrhea, nausea,
vomiting, alopecia, and fatigue
Antibiotics Bleomycin Oxidatively damages DNA Pulmonary brosis
Mitomycin C Inhibits DNA synthesis Bone marrow toxicity
Hemolytic uremic syndrome
Targeted therapies
Therapy Characteristic Uses Side effect
Trastuzumab Humanized monoclonal
antibody that inhibits HER2
dimerization with HER3
Pertuzumab Binds to an extracellular
domain of HER2
First line choice for HER2/
neu–positive breast cancer, in
addition to chemotherapy
Fever, nausea, vomiting
Oral sores, weakness,
anemia, muscle aches
324
S. C. Wimann et al.
Targeted therapies
Therapy Characteristic Uses Side effect
Bevacizumab Vascular endothelial growth
factor (VEGF) is the target
of bevacizumab, which
directly binds to VEGF to
inhibit angiogenesis
Cetuximab Chimeric monoclonal
antibody directed against
epidermal growth factor
(EGF) receptor
Imatinib Imatinib targets epidermal
growth factor receptor
Tyrosine kinase inhibitor
Sunitinib Targets broblast growth
factor, platelet-derived
growth factor, and VEGF
receptors
Sorafenib Inhibits VEGFR2, fms-like
tyrosine kinase 3 (FLT3),
PDGFR, and broblast
growth factor receptor
(FGFR)-1
Rituximab Chimeric monoclonal
antibody
When given with uorouracil
and oxaliplatin or irinotecan,
has achieved good response
rates in metastatic colon
cancer
Approved for the treatment for
colorectal cancer in association
with chemotherapy. It is also
indicated for squamous cell
head and neck cancer in
association with radiotherapy
Imatinib and sunitinib are
commonly used for
gastrointestinal stromal tumors
Imatinib and sunitinib are
commonly used for
gastrointestinal stromal tumors
Used for hepatocellular
carcinoma
Used in non-Hodgkin
lymphoma, achieving good
response and survival rates
without signicant toxicity
Increase the risk of
anastomotic leak. More
common side effects
include fatigue, nausea,
poor appetite, constipation,
and leukopenia.
Skin reaction most
prominent on hands and feet
in rst 2weeks, weakness,
fatigue, weight loss,
anorexia
Edema, anemia and
leukopenia, nausea,
myalgias, and rash.
Fatigue, nausea, vomiting,
abdominal pain, hand-foot
syndrome, taste change
Diarrhea, fatigue, hand-foot
skin reaction, and
hypertension
Febrile neutropenia,
pyrexia, pneumonia, and
anemia
Radiation therapy
Mechanism of
action
Types
Radiation therapy delivers energy to kill malignant cells through DNA damage
External beam radiation therapy (EBRT)➔ delivers radiation from a source outside the patient
EBRT ➔produces ionizing radiation to target tumor and damages the DNA of rapidly
dividing tumor cells
Intraoperative radiation therapy (IORT) ➔ delivers radiation at the time of the surgery
IORT allows exclusion of structures by operative mobilization or direct shielding of these
structures
Brachytherapy ➔ radioactive seed is implanted into a target area
The radiation emitted is active over only a short distance➔ advantage of brachytherapy is the
ability to deliver high doses of radiation to the tumor
10 Breast andOncology
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Radiation therapy
The side effects depend upon the anatomic area of treatment and are related to treatment
factors
Tissues swell during the RT ➔ acute side effects (abdominal radiation ➔ nausea and
Radiation side
effects
vomiting; head and neck irradiation ➔ mouth and throat sores, thoracic irradiation
➔esophagitis, pelvic radiation ➔ urinary symptoms and bowel changes)
Long-term side effects of radiation therapy are largely related to the irradiated tissue brosis
Infertility ➔ pediatric and young adult cancer patients (ovaries and testicles are highly
sensitive to radiation)
Cardiac toxicity ➔ number of malignancies, including breast cancer, Hodgkin lymphoma, in
which the heart receives some irradiation
Second cancers have an established relationship with prior radiation therapy
Radiation therapy for mantle cell irradiation➔ increases the risk of breast cancer
Radiation therapy for breast cancer ➔increases the risk of secondary angiosarcoma
Radiation-induced enteritis or colitis can occur any time following radiation damage to the
small bowel or colon➔ supportive care
Radiation-induced proctitis involves damage to the rectum and anal canal➔ treatment with
formalin irrigation
325
Microscopic colitis consists of two types, including collagenous colitis and lymphocytic
colitis➔ treatment with budesonide
Genetic Susceptibility
Genetic susceptibility
Type Mechanism Example
Oncogene
Tumor
suppressor
genes
DNA mismatch
repair
Mutation of proto-oncogenes ➔
gain of function mutation
Mutation in tumor suppressor
gene ➔ loss of function
Cells have two copies of any
given tumor suppressor gene ➔
both alleles must be inactivated➔
to result in a cancer
Mutations in genes involved in
repair of errors in DNA
replication
RAS (colorectal, neuroblastoma, pancreas, bladder, leukemia),
HER2/neu (breast, ovarian), and MYC (cervix, colon, breast,
lung, stomach)
Rb (retinoblastoma) and TP53 (colon, breast, lung, sarcoma,
leukemia, lymphoma)
Hereditary nonpolyposis colorectal cancer (HNPCC)
326
Biomarkers for cancer
Biomarker Characteristics
S. C. Wimann et al.
Carcinoembryonic antigen (CEA)
CA 19-9
CA-125
AFP Hepatocellular cancer and non- seminomatous germ cell tumors
PSA
β-hCG
Colon cancer ➔detection of recurrence and prognosis
Pancreatic and biliary tract adenocarcinoma ➔ detection and monitoring
Ovarian cancer ➔detection and monitoring
Prostate cancer ➔ monitor progression of disease
Germ cell tumors
Endocrine
parath
yroglossal
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HassanHashmi andKepalPatel
Thyroid
Anatomy
Embryology
Ventral portion of the fourth pharyngeal pouch →
lateral thyroid lobes
Fourth and fth branchial pouches → ultimobranchial
bodies containing neural crest cells → parafollicular
(C cells)
The thyroglossal duct descends from the pharynx at
the foramen cecum of the tongue → pyramidal lobe. If
the duct remains patent → thyroglossal duct cyst
External
yroid
gland (III)
Thymus
11
Foramen
cecum
I
II
III
IV
V
Th
duct
Internal
parathyroid
gland (IV)
Thymus
H. Hashmi (*)
General Surgery Residency, NYU Long Island
School of Medicine, NYU Langone—Long Island
Hospital, Mineola, NY, USA
K. Patel
NYU Langone Health, New York, NY, USA
e-mail: kepal.patel@nyulangone.org
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
H. Ajouz et al. (eds.), The ABSITE Blueprints, https://doi.org/10.1007/978-3-031-32643-1_11
327
328
Superior thyroid
Th
vian
trunk
Right internal
brachiocephalic
vena cava
brachiocephalic
e
e
Lar
Anatomy
H. Hashmi and K. Patel
Arterial supply
Superior thyroid artery (branch of external carotid)
Inferior thyroid arteries (branch of thyrocervical trunk)
Thyroid Ima artery is anatomic variant found in 10%
of patients
Venous drainage
Superior and middle thyroid veins drain into internal
jugular vein
Inferior thyroid vein drain into brachiocephalic vein
External
carotid
artery
Thyroid ima
artery
yrocervical
trunk
Right
subclavian
artery
Brachiocephalic
jugular vein
Thyroid plexus
of veins
Right
Inferior
thyroid
artery
vein
Superior
artery
Arch of
aorta
Isthmus of
thyroid gland
Left common
carotid artery
Left subcla
artery
Superior
thyroid vein
Internal
jugular vein
Middle
thyroid
vein
Inferior
thyroid veins
Left
vein
Anterior to the thyroid the strap muscles
(sternothyroid ➔thyrohyoid➔ sternohyoid)
Nerves of the thyroid
Nerve Anatomy Function Injury
Superior
laryngeal
nerve
(SLN)
Arises from the vagus nerve as it exits
the skull base
Courses with the superior thyroid
artery until 1cm before the artery
enters the superior pole capsule
Superior Laryngeal Nerv
Internal branch
Superior Laryngeal Nerv
External branch
Recurrent
yngeal Nerve
External branch
→ motor
function
➔innervates the
inferior
constrictor and
cricothyroid
muscles
Internal
branch➔sensory
External branch of the superior laryngeal
nerve is the most injured nerve following
a total thyroidectomy due to its close
proximity to the superior thyroid artery
Injury leads to the loss of voice projection
particularly at high pitches and increased
fatiguability of the voice
Injury can increase the risk of aspiration
Right subcla
ry
ior
11 Endocrine
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Nerves of the thyroid
Nerve Anatomy Function Injury
329
Ascends in the tracheoesophageal
groove and crosses the inferior thyroid
artery; courses through the ligament of
berry and enters the larynx via the rst
tracheal ring
Recurrent
laryngeal
nerve
(RLN)
Left: Originates from the left vagus at
the level of aortic arch; courses
posterior to the aorta at the
ligamentum arteriosum
Right: Originates from the right vagus;
courses posterior to the subclavian
artery and ascends superiorly
Nonrecurrent nerve (1–2%) caused
by a vascular anomaly, may occur on
the right when the right subclavian
artery arises directly from the aortic
arch, passing between the trachea and
esophagus
Six major nodal regions in the neck
Level Name Borders
I Submental Mandible, hyoid bone, and the
posterior edge of the
submandibular gland
II Superior
cervical
III Middle
cervical
Anteriorly bound by the lateral
margin of the sternohyoid muscle
and the posterior edge by the
SCM from the base of the skull to
the level of the hyoid bone
Anteriorly bound by the lateral
margin of the sternohyoid muscle
and the posterior edge by the
SCM between the level of the
hyoid bone to the inferior border
of the cricoid cartilage
Responsible for
sensory and
motor function
of larynx (all
muscles except
the cricothyroid)
Provides vocal
cord abduction
and adduction
Carotid
artery
Spinal
accessory
nerve
Sternocelidomastoid
The right RLN is more susceptible to
injury because it (1) has a more variable
course than the left and (2) is more likely
to be nonrecurrent than the left
Unilateral injury➔ dysphonia
Bilateral injury➔ bilateral cord paresis,
air way obstruction, and severe aspiration
Hyoid bone
Right vagus
nerve
Right common
carotid artery
vian
artery
Right recurrent
laryngeal nerve
Jugular
vein
IIB
VA
VB
Trachea
Aorta
Submandibular
gland
IIA
III
VI
IV
IB
Thyroid cartilage
Thyroid gland
Inferior laryngeal
nerve
Left subclavian arte
Left recurrent
laryngeal nerve
IA
Hyoid
bone
Cricoid
cartilage
Left vagus
nerve
Left common
carotid artery
Anter
digastic
IV Inferior
cervical
Anteriorly bound by the lateral
margin of the sternohyoid muscle
and the posterior edge by the SCM
from the inferior border of the
cricoid cartilage to the clavicle
V Posterior
triangle
Anteriorly by the SCM,
posteriorly by the anterior margin
of the trapezius, and inferiorly by
the clavicle.
VI Central From left carotid to right carotid
and from hyoid to innominate vein
First echelon nodal basin for PTC
330
Physiology
H. Hashmi and K. Patel
Thyrotropin (Thyroidstimulating hormone
(TSH)
T3 & T4
Calcitonin
Pathophysiology of
hyperthyroidism
Pathophysiology of
hypothyroidism
Released from the anterior pituitary in response to decreased levels of T3 and increase
in thyrotropin-releasing hormone (TRH)
TSH regulates iodide uptake as well as the production and storage of T4 and T3
Most of the thyroid hormone released from the thyroid is in the form of T4
T4 is then converted to the more active form (T3) by deiodination in peripheral tissues.
A large portion of this conversion occurs in the liver, which is one of the larger
regulators of T3
T3 has much greater biologic activity and shorter half-life than T4
T4 and T3 are bound to thyroglobulin within the thyroid gland
T4 and T3 are present in the blood either unbound or bound to thyroxine-binding
globulin
Only free unbound thyroid hormone has biological activity
Released from the parafollicular cells
Opposes the effects of parathyroid hormone by reducing serum calcium levels
Primary hyperthyroidism: Elevated free T4 and T3 ➔ suppressed TSH
Subclinical hyperthyroidism: Normal thyroid hormone levels, TSH suppressed
Primary hypothyroidism: High TSH concentration and low serum free T4
Subclinical hypothyroidism: Normal T4 concentration, elevated TSH levels
Secondary (central) hypothyroidism: Low T4 levels and a lack of appropriate TSH
elevation (occur at the level of the hypothalamus or the pituitary gland)
Ultrasound ofThyroid
Ultrasound of thyroid
Depth penetration is inversely related and resolution is directly related to the frequency of the
ultrasound ➔ For the thyroid, a high-resolution linear array transducer (10–15mHz) is optimal
Characteristics
Image gain adjusts the overall amplication of the returning reections displayed on the
ultrasound image
Limited ability to evaluate deep tissues (large goiters) because high frequency has low penetration
Limitations
Image distortion by air-lled structures such as the trachea and calcic deposits in the thyroid and
bone
Non-visualization of portions of the thyroid gland that lie substernally (probe can be angulated to
optimize the image of the surrounding area)
11 Endocrine
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Features of benign and malignant thyroid nodules
Common Criteria The most widely used criteria for evaluating thyroid nodules are the American
Thyroid Association (ATA) and the Thyroid Imaging Reporting and Data
System (TI-RADS) standards
331
Features of benign thyroid
nodule
Features suspicious of
malignancy in thyroid nodule
Suspicious lymph nodes Long axis: Short axis<2, hypoechoic, loss of central fatty hilum, eccentric (vs.
Cystic, spongiform, anechoic or hyperechoic, wider-than-tall, smooth borders,
comet-tail artifacts, and macrocalcications
Hypervascular, hypoechoic, taller than wide, solid, irregular margin; punctate
calcications
concentric) thickening of cortex; cystic, size >10mm, round shape, presence of
microcalcications, or ill-dened capsular margins
Research
Reference Findings
Tessler FN, Middleton WD, Grant EG, etal. ACR
Thyroid Imaging, Reporting And Data System
(TI-RADS): white paper of the ACR TI-RADS
Committee. J Am Coll Radiol 2017;14:587–595
The thyroid imaging, reporting, and data system
(TI-RADS) reporting system from the American
College of Radiology assigns a point system for
features and then sums the features for a point total that
ranges from TR1 (benign) to TR5 (high suspicion of
malignancy)
Hyperthyroidism
Surgical causes of hyperthyroidism
Causes Characteristics Management
Most common cause of
hyperthyroidism
Exophthalmos, pretibial edema,
Graves’ disease
(70%)
Toxic
multinodular
goiter (TMN
goiter) (25%)
weight loss, palpitations
Elevated TSH receptor antibodies
(TRAb) that mimic TSH
Thyroid scintigraphy ➔diffuse
homogenous uptake
Women>men
Age>50years
Hyperthyroidism symptoms, airway
compromise
Thyroid scintigraphy➔
heterogenous uptake
Antithyroid medications (ATMs)➔ 25% cure rate
Radioactive iodine (RAI)➔ 75% cure rate;
contraindications: pregnancy or lactation, children,
smokers (increased eye disease)
Risk: hypothyroidism
Surgery➔ 99% cure rate; recommended for patients
with concurrent nodular thyroid disease or large goiters,
and severe cases of thyrotoxicosis
Risk: RLN injury; hypoparathyroidism
Antithyroid medications (ATMs) are not effective
long-term management
Surgery is the preferred management
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