Justin Practice Questions 2022 Flashcards
Which pathway is TGF-beta part of
SMAD or PI3K/AKT or RAS/RAF/MEK
Apoptosis
Which is not in a proliferation pathway?
BAX (apoptosis gene)
What are G coupled receptors
7 membrane spanning proteins that are activated with GTP then self hydrolyze to GDP and turn off
Transmembrane cell signalling proteins
Proposed mechanism of synergy b/t chemo and angiogenesis inhibitors
Normalization theory - anti-angiogenic agent restores normal blood flow and reduces tumor interstitial fluid pressure favoring the penetration of cytotoxic agents
Most common mechanism of oncogene activation
1) mutation (in promoter)
2) gene amplification (probably this one)
3) chromosome rearrangement
TL: Lit search suggests that gene amplification is the correct answer
Mechanism by which tumor suppressor genes are deactivated
Methylation (think MLH1)
Genes related to apoptosis
- “bcl (b cell lymphoma) - anti-apoptosis
- caspase - programmed cell death including apoptosis (fas pathway), pro apoptosis
- BAX (bcel-2 like protein 4) encoded by BAX gene - pro apoptosis
- TP53
Important: NOT VEGF
Best way to amplify DNA
PCR
Best way to quantitate protein
Mass Spec or ELISA
What are static cells?
Well-differentiated that rarely undergo division as adults (ie neurons, oocytes, striated m, nephrons)
What are expanding cells?
Normally quiescent but grow under stress/injury (ie hepatocytes, vascular endothelium
What are renewing cells
Constantly replicating (ie BM, epidermis, GI
Mechanism of apoptosis (3 phases)
initiation/induction:
—intrinsic pathway = response to internal pro-apoptotic stimuli such as DNA damage
–extrinsic pathway = activated by the binding of ligands
effector: caspase portion
degradation
Morphologically, apoptosis characterized by: condensation of chromatin, nuclear and cytoplasmic blebbing, and cellular shrinkage followed by phagocytic destruction
Oncogene associated with EMCA/lynch syndrome
c-myc… we found kras (maybe wasn’t option?)
Think: M for MMR
diff to find/confirm but looks like similar question last year so trusting their answer (AW)
AS: could be KRAS?
PTEN, MSH2, and TP53 are what type of gene
Tumor suppressor gene
Molecular pathway responsible for epithelial to mesechymal transformation
Wnt/beta-catenin pathway
What is the PD-1 effect on T cells?
PD-1 (expressed on T and B cells) is the negative regulator of T-cell activation.
On T cells, it promotes apopotosis of effector T cells and reduces apoptosis of Treg cells
T cells exhausted and unable to proliferate/secrete IL-2 or kill target cells
PD-1 expressed on: CD4 & CD8 T cells, B cells, monocytes, NK cells, and dendritic cells. Highly expressed on tumor-specific T cells
IL-2 stimulates which cells?
T cells: helper T cells (CD4), cytotoxic T cells (CD8) and Tregs (CD4)
NK cells (in combo with IL-12)
MHC and T cells - which go with which?
Tc/Cytotoxic = MHC1 = CD8 = apoptosis (From beginning to end = MHC1 & CD8)
Th/helper = MHC2 = CD4 (helpers are middle men = MHC2 and CD4)
Both add to 8:
1x8=8
2x4=8
Where are B cells made?
Produced in bone marrow then migrate to lymphoid organs (spleen, LN follicles, GI tract) to mature
What cells are included in innate immunity?
Present at birth. NK, macrophages, dendritic cells
What cells are included in acquired immunity?
T cells and B cells
What cells secrete histamine?
Basophils and Mast cells
What cell / cell line do dendritic cells and macrophages originate from?
Monocytes (myeloid stem cell origin)
Where is MHC I expressed?
MHC class I molecules are ubiquitously expressed on all nucleated mammalian cells including cells of epithelial origin. Platelets too (AW)
(All cells except erythrocytes)
they also had: trophoblast, germ cells ?, neurons?
-expressed on neurons (AW)
-not expressed on spermatogenic cells (AW)
-expression on some types of trophoblasts (AW)…too much to know
Where is MHC II expressed?
MHC class II molecules are selectively expressed on antigen-presenting cells (APC) including dendritic cells (DC), macrophages, and B cells.
Which cells are MHC restricted?
Restrict = T cells
MHC restriction= T cells will only recognize specific Ag on “self” MHC molecule subtype (HLA type) with the correct Ag in combination with it
Prior card had: MHC restriction means that different T cells are restricted to either Class I or Class II MHC antigens. Cytotoxic T cells are restricted to Class I antigens present on nucleated body cells, thus play a role in protecting against virus-infected cells or cancerous cells.
What immune cell secretes IL-1?
Macrophages
(+ monocytes, dendritic cells) (AW)
What does IL-1 do?
Mediates inflammation, fever
Stimulates T cells (cell mediated response)- to make IL-2
Stimulates proliferation of B cells and increase Ab production (Ab mediated response/humoral immunity).
? stimulates Macrophages (inflammatory response) -released by activated macrophage, not sure if it also then acts to further stimulat macrophage (AW)
What do dendritic cells do?
Professional Antigen presenting cells
What do natural killer cells do?
Lymphocyte that destroy tumor cells and cells infected by viruses. Respond to cytokines and interferons. Do not require activation w/receptor (i.e., with MHC1)
Which are the first immune cells to respond?
Polymorphonuclear neutrophils (PMNs)
PMNs=Neutrophils, eosinophils, and basophils
What do CD4 cells do?
recognize MHC II;
Th1 cells stimulate CTLs and macrophages (cellular immune responses)
Th2 cells stimulate antibody responses
Th17 cells mediate autoimmune diseases
What do CD8 cells do
recognize MHC1; secrete cytokines and can defend against tumors by directly killing transformed cells (granuloeoxytosis) or induction of extrinsic apoptosis by activating Fas molecules
What is the function of Immunoglobulins A, D, E, G, M
A = first response: defends mucosal surfaces
D = B cell receptors prior to Ag exposure. Signals B cell activation and is initially coreleased with IgM. Activates basophils and mast cells to produce antimicrobial factors (respiratory immune defense)
E = binds allergans/parasites. Trigger histamine release from mast cell and basophils. involved in hypersensitivity
G = 2nd line Ab; opsonization and neutralization. Crosses placenta
M = 1st line Ab; activates complement. B cell receptor. Used for non-protein Ag. Pentamer
What is the MOA of ipilimumab?
TEST QUESTION
mAb; CTLA4 blockade.
CTLA4 is a receptor on T cells that receives inhibitory signal from dendritic cells/APC (CD80/86 aka B7 molecule).
Ultimately results in Activation of CD4 and CD8 + effector T cells by removing an inhibitory checkpoint on proliferation and function, inhibits Treg activity
Currently used in melanoma
what makes a tumor antigen a good immune (antibody) target?
(Duplicate)
expression on cell surface
What are interleukins?
Interleukins (IL) are a type of cytokine first thought to be expressed by leukocytes alone but have later been found to be produced by many other body cells. They play essential roles in the activation and differentiation of immune cells, as well as proliferation, maturation, migration, and adhesion.
How do you make monoclonal antibodies?
Fuse antibody secreting B cells (spleen cells from mouse immunized with antigen of interest) and myeloma cells —> hybridoma cells.
Select immortal hybridoma that makes specific antibody for antigen of interest
What is a significant limitation of using retroviruses for gene therapy?
Retroviruses (RNA viruses) only infect dividing cells and depend on reverse transcriptive (RNA to DNA) to allow the virus to integrate into the host genome and be continuously produced.
Disadvantage: The ability of retroviruses to integrate into the host cell chromosome also raises the possibility of insertional mutagenesis and oncogene activation. this can lead to leukemia
Which chemo drugs are vesicants?
(Duplicate Q)
Doxorubicin/ Epirubicin/ idarubicin/ daunorubicin
ActinomycinD
Mitomycin C
Nitrogen mustard
Trabectinib
Vinblastine, vincristine, vinorelbine (all vincas)
DAMN TV
Which chemos are S phase specific?
Antimetabolites, Topo 1 (topotecan, irinotecan)
Doxorubicin most cytotoxic in S
“HI 5 The Good Man”= Hydroxyurea,** I**rinotecan, 5-FU, Topotecan, Gem, MTX
Which chemos are M phase specific?
Vinca alkaloids & taxanes: pure M phase
- taxanes: promotes assembly of microtubules and stabilizes them, preventing depolymerization
- vincas: interacts with tubulin w/resulting inhibition of microtubule assembly and cellular division
(Mitotic spindle poisons)
Eribulin, ixabepilone: arrest at G2/M
-Eribulin: inhibitor of microtubule dynamics, binding a small number of high affinity sites at the plus ends of existing microtubules
-Ixabepilone: semi-synthetic analog of epothilone B, like taxol=stabilizes microtubules
Which chemos are G2 phase specific?
- Bleomycin: G2 phase
- Etoposide: G2 (max kill) and S phase
- Eribulin, ixabepilone: causes arrest at G2/M
G2 BE2 or G2 BEE= bleo, etopo, eribulin/ixabepilone
Which Chemos G1 phase specific?
No Chemos specifically act at G1;
MTOR inhibitors, ActD, Tamoxifen - = agree, hormones cited as G1 frequently
Act-D is cell cycle nonspecific with max kill in G1
Which chemos are non-cell cycle specific?
Alkylating: Cyclophosph/ifosf, Altretamine/hexamethylmelamine, ecteinascidin
Platinums
Anti-tumor abx: Doxorubicin, Mitomycin-C, Actinomycin-D
Nitrogen mustards/alk: Melphalan, Chlorambucil
Which chemo leads to amenorrhea in young women?
A. vincristine
B. etoposide
C. mtx
D. cisplatin
Cisplatin
NON CELL CYCLE SPECIFIC ARE MORE LIKELY TO BE GONADAL TOXIC
Chemo induced amenorrhea risk:
Highest risk: Alkylating agents (cyclophosphamide, ifos, busulphan, chlorambucil, melphalan, chlormerthin, procarbazine:
Medium: platinum (cis, carbo); anthracyclines (doxorubicin), taxanes
Low: vincas, bleo, antimetabolites (mtx, 5-FU)
When short-term intensive chemotherapy is used, particularly with antimetabolites, vinca alkaloids, or antitumor antibiotics, injury to the reproductive system is less common. For example, men treated for testicular cancer, children with acute leukemia, and women cured of GTD or ovarian germ cell malignancies usually recover reproductive capacity after therapy
Which chemo don’t have to renally dose?
A Cytoxan
B topo
C gem
D methotrexate
**TEST QUESTION **
Gemcitabine
A BICCC THEMM (ones to renally dose)
ActD
bleo,
ifos,
cis/carbo,
cytoxan,
Capecitabine
topotecan,
hydroxyurea,
etoposide,
mtx/pemetrexed
Melphalan
Which chemos are pro-drugs?
Capecitabine, cyclophosphamide, ifosfamide, gemcitabine
Also the following:
- Oxaliplatin: extensive non-enzymati c conversion to its active metabolize
- Irinotecan: converted to active metabolite SN-38
- MitomycinC
- Cytarabine requires intracellular activation to its phosphorylated derivative
- Temsirolimus
Which of the following agents are cell cycle specific?
A. mtx
B. Taxol
C. Cisplatin
D. carboplatin
E. cyclophosphamide
taxol: M only
- anti-folates (i.e., mtx, pemetrexed): S and G1
Not cell cycle specific:
Alkylating compounds (G1,G2,S): direct DNA damage, DNA adduct formation, free radical production; i.e., radiation, platinum, bleomycin; cyclophosphamide, carboplatin
BAD QUESTION
When is bev held?
Proteinuria >/= 2g in 24h urine (Nephrotic syndrome cutoff is 3.5 g/day) or hypertensive crisis > 180/120 or hypertensive encephalopathy.
package insert says DC not just hold if HTN encephalopathy/PRES or nephrotic range proteinuria (AW)
What toxicity does mtx not have?
A. Cardiotoxicity
B. hepatotoxicity
C. nephrotoxocity
D. hematologic toxicity
Cardiotoxicity
What “rescue” med is available for methotrexate?
Leucovorin - derivative of folic acid (to overcome high dose mtx BM toxicity)
Derivative of tetrahydrofolic acid (reduced by MTX) that is readily converted to other reduced folic acid derivatives which have vitamin activity equivalent to that of folic acid. “rescues” cells by replenishing intracellular reduced folate pools (give within 48 hours of mtx)
FYI can also be used to potentiate anti-tumor activity of 5-FU
What is the most common side effect of amifostine?
(Duplicate)
Hypotension (62%);
Used to protect the kidneys from cisplatin, reduce carbo thrombocytopenia and reduce renal/BM SE from cisplatin and cyclophosphamide
protects salivary glands during radiation tx (decrease dryness in the mouth)
What is the dose limiting toxicity of irinotecan?
Diarrhea > myelosupression
Diarrhea Occuring during infusion- responsive to atropine (anti-cholinergic)
Diarrhea Occuring subacute 2-3 weeks after is not responsive to that, so use anti-motility
Diarrhea Can be life-threatening
What drug characteristics are associated with better IP chemo administration?
ideal IP:
- large molecular weight size
- hydrophilic, ionized compounds.
- high conc in peritoneum
- no need for liver activation
- high volume IP dialysate (low vol increases IP clearance rate rapidly, which is bad)
drugs enter the tumor nodules by passive diffusion
What drug is PPE associated with?
Capecitabine > 5-FU, Doxil, docetaxol (SGO chemo handbook)
(old card had pemetrexed per Chi)
Also Multitargeted tyrosine kinase inhibitors sorafenib, sunitinib
PPE=painful erythema, scaling, swelling, ulceration involving hands/feet
prolonged oral etoposide, weekly and continuous-infusion 5-fluorouracil, capecitabine, PEG-liposomal doxorubicin, prolonged vinorelbine infusions (AW)
What chemo most associated with constipation
Vincristine
Due to autonomic neuropathy: Impaired intestinal motility constipation and upper colon fecal impaction, paralytic ileus
What chemo is primarily renally cleared
**TEST QUESTION ***
Bleomycin (bleo blows out those kidneys)
Bleomycin is eliminated predominantly by the kidney, with 50% of the dose eliminated within 24 hours after administration.
Pemetrexed: About 90% of the drug is excreted unchanged in the urine within 24 hours.
Cisplatin, Carboplatin, oxaliplatin, and Mtx also renally cleared
What chemo causes polymerization of tubulins
Taxol
Unlike other tubulin targeting drugs such as colchicine that inhibits microtubule assembly, paclitaxel stabilizes the microtubule polymers and protects them from disassembly.
What chemo cannot be given IP?
Cyclophosphamide and ifosfamide (are prodrugs that require activation in the liver!)
Capecitabine (oral drug…), cyclophosphamide, ifosfamide
gemcitabine CAN be used as IP chemo (and has been used in pancreatic cancer!)
Some agents are excessively toxic given this route: doxorubicin, mitoxantrone
What are the parameters for carbo calculator
Calvert formula:
Dose (mg) = target AUC (mg/mL x min) x [GFR (mL/min) + 25 (mL/min)]
GFR /CrCl calculated using: Age, creatinine, weight/height, gender
- [(140-age)(wt)(0.85)]/(72xCr)
Use of amifostine
Decrease nephrotox of cisplatin and cytoxan. Prodrug that acts as a free radical scavenger and tends to be selective to non-malignant tissues
Taxol 24 vs. 3 hours
Less neurotoxicity for 24 hours but more BM toxicity
AKA: 3hr= more neurotoxic, 24hr= more myelosuppressive (AW)
Target for aprepitant
**TEST QUESTION **
NK1 receptor (central NS); dominant ligand is substance P
Aprepitant prevents acute and delayed vomiting by inhibiting the substance P/neurokinin 1 (NK1) receptor; augments the antiemetic activity of 5-HT3 receptor antagonists and corticosteroids to inhibit acute and delayed phases of chemotherapy-induced emesis.
Aprepitant is a potent and selective NK-1 tachykinin receptor antagonist that blocks the effects of substance P (SP) in the central nervous system.
Strategies to reduce nephrotoxicity of chemo
Dose reduce, hydration, eliminate other nephrotoxic drugs
Side effect LEAST likely to be minimized when choosing aromatase inhibitor over tamoxifen
**TEST QUESTION **
AI will not Reduce osteoporosis fractures, MSK pain.
Tamox SE: endometrial cancer, vag bleeding, VTE/CVA, hot flashes - anti-est in breast, pro everywhere else (uterus, bone, liver, coagulation system), fatty liver, increased triglycerides, lower LDL, cataracts
AI: hot flashes, osteopenia or osteoporosis, bone pain, diarrhea, heart disease, increase LDL/decrease HDL
Both: hot flashes, sexual dysfunction
Pt on BEP with pulm sx, what do you do first
Stop bleo
Prodrugs: which is not (and list which are common prodrugs)?
A gemzar
B 5FU
C taxotere
D cyclophosphamide
taxotere is not.
True Prodrugs: cyclophosphamide, ifosfamide, capecitabine
Require activation:
- irinotecan - reversible equilibrium with reactive intermediates (SN-38)
- cisplatin, carbo: require activation through irreversible aquation
- others: gemcitabine, 5-FU
Others:
Oxaliplatin: extensive non-enzymatic conversion to its active metabolize
Cytarabine requires intracellular activation to its phosphorylated derivative
Peak level IP vs. IV bioavailability for carbo
A 1:5
B 1:20
C 1:200
D 1:500
(Duplicate)
1:20
Barakat - 18:1 IP vs IV concentration in peritoneal cavity
20:1 cisplatin
1000:1 paclitaxel
Virtually all commonly used drugs administered IP in patients with ovarian cancer have peak or concentration x time product ratio of more than 20.
Most unlikely side effect of bev
A Hypotension
B GI perf
C bleeding
D headache
Hypotension not complication
Hypertension (24% to 42%)
headache (22% to 49%)
Hemorrhage (grades ≥3: ≤7%; including major hemorrhage)
gastrointestinal perforation (≤3%)
Most common sx of GCSF
bone pain
Filgrastin:
Neuromuscular & skeletal: Back pain (15%), ostealgia (3% to 30%)
Pegfilgraststim:
Neuromuscular & skeletal: Ostealgia (31%)
Most emetogenic Chemos
**TEST QUESTION **
Highly emetic (>90%, B&H)
- Cisplatin
- Anthracycline and cyclophosphamide
- Cyclophosphamide >=1500 mg/m²
Most common side effect of megace
A breast tenderness
B weight gain
C hyperglycemia
D hypercholesteremia
weight gain
Hyperglycemia (6%)
gynecomastia (1% to 3%),
weight gain (not attributed to edema or fluid retention)
Most common acute tox of IP chemo
Abdominal pain
Mechanisms of platinum resistance
1) Decreased uptake: Downregulation of CTR1 (Copper transporter 1)
2) Inactivation by glutathione: Elevated levels of enzymes involved in GSH synthesis (gamma-glutamylcystein synthestase) and glutathione S transferase (binds to platinum inactivating it)
3) ** Nuclear excision repair (NER) pathway** : expression of ERCC1 leads to increased repair of platinum-DNA adducts (THIS most common)
4) DNA MMR: loss of function of MMR contributes to developing DNA damage tolerance
5) loss of pro apoptotic factors or over expression of anti-apoptotic factors
Mechanisms of nausea and receptors drugs target/act on
**TEST QUESTION **
Muscarinic - scopolamine
H1 - benadryl, dramamine
D2 - prochlorperazine (compazine, metoclopramie (reglan)
5HT3- zofran, palonsetron
NK-1- aprepitant
GABA - benzos
Mechanism of cisplatin with radiation
Cell repair inhibited.
Cisplatin binds with DNA causing INTRAstand cross-links and DNA adducts that are primarily repaired via NER. Radiation causes single and double strand breaks that are primarily repaired via NHEJ. When these DNA breaks are attempted to be repaired by DNA-protein kinase dependent NHEJ, presence of cisplatin-adducts prevents the repair and leads to cell death.
Increased oxidative stress.
Mechanism of action: topotecan
TEST QUESTION
- Inhibit TOPO-I (a nuclear enzyme that induces reversible SINGLE STAND DNA BREAKS during DNA replication)
- forms topotecan-TOPO-I-DNA complex, preventing religation of ssDNA BREAKS
- Interaction between complex and replication enzymes results in dsDNA breaks and cellular death
S phase
Mechanism of action: methotrexate
Mtx binds to DHF (dihydrofolate reductase) blocking DHF –>THF (tetrahydro-folic acid, active form of folic acid). As a result, thymidylate synthetase and other steps in de novo purine synthesis that require 1-carbon transfer rxn are halted. This arrests DNA, RNA and protein synthesis
S phase specific
Mechanism of action: gemcitabine
**TEST QUESTION **
—> Prodrug metabolized inside cells!!
Metabolized into triphosphate and diphosphate metabolites.
Triphosphate metabolite incorporated into DNA as fradulent base pair, leading to addtl deoxynucleotide at end of DNA.
Replication is terminated (called “MASKED CHAIN TERMINATION) which prevents exonucleases from excising fradulent base pair.
Diphosphate metabolite inhibits ribonucleotide reductase, which depletes deoxynucleotide pools necessary for DNA synth/repair
Primarily S-phase, but also blocks progression through G1 to S.
Gems for short 💎. Gem can be found on a chain around the neck. So it does masked chain termination.
Gems are found in pyramids, so gem-triphosphate is a pyrimidine analog
Mechanism of action: etoposide
Inhibits TOPO-II enzymes (does NOT bind directly to DNA) rather stabilizes transition form of DNA-TOPII.
by stabilizing this it “poisons” TOPOII enzymes which usually helps cells progress out of G2
Cell cycle: S/G2 checkpoint (think more G2)
(JS) also decatenation
Mechanism of action: doxorubicin
Anthracycline antibiotic from Streptomyces peucetius
1) DNA binding and intercalating, inhibiting DNA synthesis (S phase most potent, but not cell cycle specific)
2) Free radical formation - this may be related to the cardiotoxicity (iron chelation)
3) Inhibition of DNA topoisomerase II by inhibiting strand-passing activity of topo-II (acts in G2 phase)
topo II, free radicals (yes), intercalating (yes), DNA adducts
Doxorubicin Limit lifetime dose to what?
Limit dose to 550 mg/m2 cumulative life dose due to cardiac toxicity
From PharmD: Risk for cardiomyopathy increases at cumulative dose 550 over age 18.
Test answer on pharmacy exams is usually 550 but no one ever pushes that high since the recommendation to start dexrazoxane is at 300mg/m2 which is probably why you’re seeing that range!
Cumulative incidence Cardiomyopathy:
450 mg/m2- 3%
550 mg/m2 - 7%
600 mg/m2 - 15%
700 mg/m2 - 40%
Which of the following is the Most leukemogenic chemo?
A etopsoside
B platin
C 5FU
D melphalan
melphalan - 10% risk
Etoposide- 1%
Cisplatin- even less
cyclophos- <1%
Least protein bound chemo?
A doxorubicin
B topotecan
C gem
D carbo
E ifos
Gem / but maybe actually carbo
Chemos low protein bound
gem negligible
Carbo 0%
Ifos negligible
Highly protein bound ie to albumin:
active metab of irinotecan SN-38: ~95%
mtx: 50%
doxorubicin 75%
topotecan 35%
Taxol, docetaxel 90s%
Etoposide 97%
Cis 90%
BIG-CT (least protein bound)
Bleo
Ifos
Gem
Carbo
Topo
Least leukemogenic chemo:
A Cisplatin
B melphalan
C cytoxan
D 5-FU
5-FU
Most leukemogenic: melphalan, cyclophosphamide, etoposide, cisplatin
What are advanced colon adenomas that increase colon cancer risk?
villous or tubulovillous histology (this is the answer), high-grade dysplasia, >/= 1 cm
Changes in apoptosis (two questions)
“not cause inflammation, does cause chromatin condensation (this is the answer)
1) cell shrinkage and rounding due to caspase
2) cytoplasm dense and organelles tightly packed
3) chromatin undergoes condensation against the nuclear envelop (PYKNOSIS)
4) nuclear envelope becomes discontinuous and DNA is fragmented (KARYORRHEXIS)
5) cell membrane buds into blebs
6) cell breaks apart into multiple vesicles called apoptotic bodies - these are phagocytosed”
Least emetogenic chemo?
A Vinca
B carbo
C doxorubicin
D dactinomycin
**TEST QUESTION **
Vinca (vincas don’t vom)
Minimally emetic (<10%)
- Bev
- Bleo
- Nivo, pembro, dostar, durva, ipi
- Trastuzumab
- Vinblastine, vincristine, vinorelbine
Least bone marrow suprresive chemo
Bleomycin (main dose-limiting side effect is pulm tox, 10%; nephrotoxicity)
IP chemo pharmacokinetics
Generally - IP chemo should be LARGER, HYDROPHILIC, IONIZED - b/c clear more slowly from peritoneal cavity and cancer, maintain concentration; penetrate tumor nodules through PASSIVE diffusion (up to 2-3 mm) but that’s why we cytoreduce
Cancer with elevated CA-125 (ovary not a choice)?
Pancreatic, breast, lung cancer), colon, gastric
How does cisplatin augment radiation? (repeat)
Inhibit repair of sublethal damage
Cisplatin sensitizes cancer cells to ionizing radiation via inhibition of non-homologous end joining
Cisplatin pre-treatment increases the number of radiation-induced DNA double-strand breaks
Cellular irradiation induces various forms of DNA damage, with DNA double-strand breaks forming the main cytotoxic lesions.
Most common mutation in mucinous ovarian cancer (p53, KRAS, BRAF, Her2/neu)?
KRAS
Doxil versus doxorubicin
(Duplicate questions)
** TEST QUESTION **
Liposomal bound (aka pegylated) with MPEG methoxypolyethylene glycol to avoid detection by the mononuclear phagocyte system
Results in:
- longer plasma life
- slower plasma clearance,
- reduced volume of distribution
- higher tumor-tissue drug concentrations
- NOT a vesicant
- associated with minimal cardiotox, alopecia, nausea/vomiting
But increased rates of PPE (dose limiting in 25%) and stomatitis
MOA P53 as tumor suppressor
can activate DNA repair, cause G1/S arrest to allow time for repair of DNA damage, maintains genomic stability, initiate apoptosis
Mutation associated with mucinous epithelial ovarian cancer
KRAS, tp53
Mucinous ovarian cancer most common tumor suppressor? Oncogene?
Tumor suppressor: TP53
Oncogene: KRAS
Which pathway is responsible for the Epithelial to mesenchymal transition
WNT/Beta-catenin
Telomerase
Telomeres are “caps” at ends of chromosomes and keep chromosomes from being degraded. Every time cell divides, a few base pairs lost and eventually these “caps” are gone. Telomerase is a protein/DNA complex that lengthens the 3’ telomere end so the cell can divide forever (and thus be immortalized)
Aromatase inhibitors most common side effect
(Duplicate)
**TEST QUESTION **
—> Arthralgia (15-36%) , ? asthenia actually more
vasodilation (25% to 36%)
Endocrine & metabolic: Hot flash (12% to 36%)
Gastrointestinal: Gastrointestinal distress (29% to 34%)
When p53 is activated - what stage of cell cycle does it arrest?
G1 (p53 is the first O.G.) - or apoptosis if defects are large
Relative risk of raloxifene and thrombosis
RR 2.1 (grady 2004, RCT of 7700+ women)
The risk of venous thromboembolic disease (deep venous thrombosis or pulmonary embolism) was 3.1 times higher (95% CI, 1.5-6.2) in women assigned to the raloxifene group than to the placebo group. (Cummings 1999, RCT of 7700+ women)
JS- still lower risk for VTE on raloxifene than tamoxifen
Are psammoma bodies in high grade serous ovary good or bad?
Good/favorable prognosis
What cells make hCG?
Syncytiotrophoblast
What makes up OVA1
CA-125, transthyretin (pre-albumin), Apo A-1, β2 microglobulin, transferrin (5 things)
What stain is used for melanoma?
S100
additionally: SOX10, MelanA, HMB45
What is function of gemzar prodrug
substitutes cytosine that stops replication by “masked chain termination”
anticancer nucleoside is an analog of deoxycytidine. Gemcitabine inhibits thymidylate synthatase, leading to inhibition of DNA synthesis and cell death. Gemcitabine is a prodrug, and once transported into cell, must be phosphorylated by deoxycytidine kinase to an active form. Both gemcitabine diphosphate and gemcitabine triphosphate inhibit processes required for DNA synthesis. Incorporation of gemcitabine triphosphate into DNA is most likely the major mechanism by which gemcitabine causes cell death. After incorporation of gemcitabine nucleotide on the end of the elongating DNA strand, one more deoxynucleotide is added, and thereafter, the DNA polymerases are unable to proceed. This action “masked termination” apparently locks the drug into DNA as the proofreading enzymes are unable to remove gemcitabine from this position
What is least leukomegenic chemo
bleo
Topo vs etoposide (does etopo or topotecan bind topo I or II)
topo – topo I
etop – topo II
(topo t one, etop second letter t two)
Which chemos require adjustment for renal compromise
(Duplicate)
TEST QUESTION
A BICCC THEMM (ones to renally dose)
ActD
bleo,
ifos,
cis/carbo,
cytoxan,
Capecitabine
topotecan,
hydroxyurea,
etoposide,
mtx/pemetrexed
Melphalan
Alkylating
Topoisomerase
Act-D/Bleo
Platinums
Anti-metabolites (excluding 5-FU, gem)
Which chemos requires adjustment for liver compromise?
(Duplicate)
TEST QUESTION
MTV ME 5 CD
methotrexate
Taxanes (docetaxel/ paclitaxel/nab-paclitaxel)
vinkas (vincristine, vinblastine, vinorelbine)
Mitoxantrone
Epirubicin
5-FU
cyclophosphamide
doxorubicin/doxil
Does 3 hr vs 24 hr administration of taxol lead to increase neurotoxicity or decrease in neurotoxicity?
3 hour more neurotoxic, 24 hour more neutropenia
Most common serious side effect of tamoxifen?
A thrombosis
B ut cancer
C vasomotor
D colon cancer
(Duplicate)
Endometrial cancer
Notes say VTE, but…
UTD:
Serious, life-threatening, and fatal events include uterine malignancies, stroke, and pulmonary embolism.
Incidence rates per 1,000 woman-years:
Endometrial adenocarcinoma: 2.20 versus 0.71 for placebo
Stroke: 1.43 for tamoxifen versus 1.00 for placebo.
PE: 0.75 for tamoxifen versus 0.25 for placebo
I confirmed with drug package insert from FDA - jv
Most common overall side effect of tamoxifen?
A thrombosis
B ut cancer
C vasomotor
D colon cancer
Overall: vasomotor (>90%)
What’s the mechanism of action for Topotecan
Traps topoisomerase I on DNA causing unrepaired ssDNA break
Stabilizes the cleavage complex
Acts in G2 phase, but also has some activity in S phase
Pertuzumab mechanism of action
Block HER2 heterodimerization
Pertuzumab is a recombinant humanized monoclonal antibody which targets the extracellular human epidermal growth factor receptor 2 protein (HER2) dimerization domain. Inhibits HER2 dimerization and blocks HER downstream signaling halting cell growth and initiating apoptosis. Pertuzumab binds to a different HER2 epitope than trastuzumab so that when pertuzumab is combined with trastuzumab, a more complete inhibition of HER2 signaling occurs
Which needs renal dosing more (etoposide vs. bleo) - since both are renally cleared
TEST QUESTION
Bleo
Bleo BLOWS out the kidneys
What is Calvert’s formula?
Dose (mg) = target AUC (mg/mL × min) × [GFR (mL/min) + 25 (mL/min)]
The Calvert formula is used to calculate the carboplatin dose accurately in order to obtain a target Area Under the Curve (AUC) by using only the GFR
Crockroft-Gault
Equation used to estimate creatinine clearance
Used in carboplatin dosing calculations
CrCl = 0.85 for female * [(140-age)(weight kg) / (72Cr)]
Unreliable in patients who are at the extremes of body weight or have an abnormally low serum creatinine
Tamoxifen vs. raloxifene
Both anti-est in breast (tamox more effective in breast cancer prevention than raloxifene, but raloxifene less serious side effects [VTE, ut cancer, cataracts])
Both pro-est in the bone
Tamox pro-est in endometrium, but raloxifene is not.
Which is least emetogenic?
A Carbo
B vinca
C doxorubicin
D ifos
**TEST QUESTION **
Vincas
Highly emetic (>90%)
- Cisplatin
- Anthracycline and cyclophosphamide
- Cyclophosphamide >=1500 mg/m²
Minimally emetic (<10%)
- Bev
- Bleo
- Nivo, pembro
- Trastuzumab
- Vinblastine, vincristine, vinorelbine
Which chemo is activated within a tumor cell?
** TEST QUESTION **
Capecitabine
AS: and Gemcitabine
Ideal ROC (receiver operating curve) - AUC
Higher AUC, the more accurate
There are several scales for AUC value interpretation but, in general, ROC curves with an AUC ≤0.75 are not clinically useful and an AUC of 0.97 has a very high clinical value, correlating with likelihood ratios of approximately 10 and 0.1.
AUC varies from 0 to 1. Closer to 1, the higher sensitivity and higher specificity.
What are highly emetogentic chemos
Cisplatin, carbo AUC 4+, doxorubicin >60, Ifos >2
NCCN (>90%)
AC combination defined as any chemotherapy regimen that contains an anthracycline and cyclophosphamide
• Carboplatin AUC ≥4 • Carmustine >250 mg/m2
Cisplatin • Cyclophosphamide >1500 mg/m2 • Dacarbazine • Doxorubicin ≥60 mg/m2 • Epirubicin >90 mg/m2 • Fam-trastuzumab deruxtecan-nxki
Ifosfamide ≥2 g/m2 per dose
• Mechlorethamine • Melphalan ≥140 mg/m2 • Sacituzumab govitecan-hziy • Streptozocin
What are moderately emetogenic chemos
Carbo AUC <4, doxorubicin <60, ifos, oxaliplatin
NCCN (30-90%)
Minimally emetogentic chemos
**TEST QUESTION **
Vincristine, Nivolumab, Bev, Bleo, MTX <50, Pembro
NCCN. <10%:
mAb with emetogenic potential
Olaratumab (anti-platelet derived growth factor)
Withdrawn from the market and used for sarcoma
Anastrozole mechanism
reversible binding to aromatase, blocking extragonadal conversion of androgens to estrogens
inhibiting aromatase thus, the conversion of androstenedione to estrone, and testosterone to estradiol, is prevented. Anastrozole causes an 85% decrease in estrone sulfate levels.
Abraxane (nab-paclitaxel) compared to paclitaxel
Same terminal half life, larger clearance, larger Vd, less allergenic
Paclitaxel is solvent-based and formulated in a mixture of polyoxyethylated castor oil and dehydrated alcohol, while nab-paclitaxel is an albumin-bound nanoparticle formulation of paclitaxel and is free of solvents
Advantage of liposomal doxorubicin over standard
tumor-tissue drug concentration is 4x-16x higher in liposomal formulation
Less cardiotox
gemcitabine mechanism of actions (2)
- Structurally similar to deoxycytidine, gets phosphorylated x3, then incorporated as fradulent base pair, then additional deoxynucleotide added–masked chain termination preventing excision of fradulent base pair–irreparable error that stops synthesis
- Diphosphate version inhibits the enzymeribonucleotide reductase(RNR), which is needed to create new nucleotides. The lack of nucleotides drives the cell to uptake more of the components it needs to make nucleotides from outside the cell, which increases uptake of gemcitabine as well
Chemotx that need dose reduction for hepatic impairment (bili or transaminitis)
TEST QUESTION
MTV ME CD
Mtx
Taxanes
Vinkas
Mitoxantrone
Epirubicin
cyclophosphamide
Doxil/doxorubicin
Doxorubicin MOA
Intercalates DNA inhibiting Topo-II,
Chelates iron
Forms free radicals, active during entire cell cycle, but most active in S
Chemotx causing alopecia
Taxol, ifos, Act-D, etoposide, bleo
alkylating agents (IV cyclophosphamide, ifosfamide, busulfan, thiotepa),
antitumor antibiotics (dactinomycin, doxorubicin, epirubicin, idarubicin),
antimicrotubule agents (paclitaxel, docetaxel, ixabepilone, eribulin),
topoisomerase inhibitors (etoposide, irinotecan at higher doses)
Alopecia is less common or incomplete with:
bleomycin,
low-dose epirubicin or doxorubicin (especially <30 mg/m2),
oral cyclophosphamide,
fluorouracil,
capecitabine,
gemcitabine,
melphalan,
methotrexate,
mitomycin,
mitoxantrone,
platinum agents (oxaliplatin, cisplatin, and carboplatin),
topotecan
weekly low-dose irinotecan
vinca alkaloids (vinorelbine, vincristine, vinblastine).
Most Common side effect of anastrozole
A asthenia
B headache
C increased bone density
D decreased fractures
E Arthralgia
**TEST QUESTION **
Asthenia
AS: Package insert Asthenia 19%, arthralgia 15%, headache 14%, hot flash
Chemo associated with ovarian failure
(Duplicate)
Cyclophosphamide > melphalan, cisplatin, etoposide
Biggest ones are alkylating agents and procarbazine
Also cisplatin, doxorubicin
Drug that will stay in the intraperitoneal cavity the longest?
paclitaxel (large molecule, water insoluble, high cavity to plasma AUC ratio[1000:1])
Not renally cleared chemotherapy
A topotecan
B gemcitabine
C Cyclophosphamide
D methotrexate
TEST QUESTION
Cyclophosphamide: hepatic inactivation appears to be the major mechanism of active drug elimination
Carboplatin, oxaliplatin, Pemetrexed, Bleomycin, Topotecan, gemcitabine, and Mtx also renally cleared
Mechanism of chemotherapy related nausea/vomiting?
** TEST QUESTION **
Acute: Related to 5-HT3
Delayed: substance P
acute CINV, free radicals generated by toxic chemotherapeutic agents stimulate enterochromaffin cells in the gastrointestinal tract, causing the release of serotonin. Subsequently, serotonin binds to intestinal vagal afferent nerves via 5-HT3 receptors, which trigger the vomiting reflex via the nucleus of the solitary tract (NTS) and chemoreceptor trigger zone (CTZ) in the CNS.
delayed CINV. Substance P is principal neurotransmitter. Chemotherapy drugs trigger the release of substance P from neurons in the central and peripheral nervous systems, which then binds to neurokinin-1 (NK1) receptors mainly in the NTS to induce vomiting.
Amongst the agents known to cause secondary leukemia, which is the least likely?
A Ifosfamide
B cyclophosphamide
C altretamine
D carbo/cis
E melphalan
F etoposide
Carbo/cis? (I believe this is wrong, cisplatin has been associated with leukemia)…
Notes said “Ifosfamide (THIS ONE we think)”
But literature review suggests platinum agents are least likely in this list.
- Leukemogenic agents: cyclophosphamide, cisplatin, etoposide, melphalan, cytoxan. Others: chlorambucil, CCNU (Lomustine), BCNU (carmustine), DTIC (dacarbazine), altretamine
AS: B&H -alkylating agents, procarbazine and nutrosoureas are major offenders. Prolonged Etoposide as well
A, B, C, E are alkylating agents + F etoposide
Amongst the agents known to cause secondary leukemia, which is the least likely?
A Ifosfamide
B cyclophosphamide
C altretamine
D carbo/cis
E melphalan
F etoposide
Lowest risk likely platinum agents
- Ifosfamide: listed in UTD
- cyclophosphamide: bolded in UTD
- altretamine discontinued; not listed as AE though is alkylating
- carbo: not listed in UTD
- cis: listed in UTD
- melphalan: listed in UTD
- etoposide: listed in UTD
Most leukemogenic: melphalan > cyclophosphamide > etoposide, cisplatin, procarbazine, and the nitrosoureas
two well defined groups
1) alkylating agents or
2) drugs binding to the enzyme DNA-topoisomerase II.
Call Exner bodies
Granulosa cell tumors
(Call your Granny)
Schiller-Duval
Endodermal sinus tumor (ESS)
its a papillary structure that grows into a cystic space. The papilla is covered by tumor cells and HAS A CENTRAL CAPILLARY region.
Multinucleated giant cells
Dysgerminoma
What cells make hCG?
Syncytiotrophoblast
What makes up OVA1?
CA-125 (upregulated)
transthyretin (pre-albumin)
transferrin
Apo A-1
Beta2 microglobulin (upregulated)
5 things!
*OVA1 is also known as multivariate index assay.
The score ranges from 0 to 10 and interpreted as follows:
Premenopausal patients:
*Low probability of malignancy: OVA1 <5
*High probability of malignancy: OVA1 ≥5
Postmenopausal patients:
*Low probability of malignancy: OVA1 <4.4
*High probability of malignancy: OVA1 ≥4.4
What tumor marker is elevated for PSTT
HPL
- extravillous (intermediate) trophoblast cells, most PSTTs are female and diploid.
- Surgery (hysterectomy with salpingectomy +/- pelvic lymph node biopsy if non metastatic with low risk findings vs. hysterectomy with salpingectomy and excision of mestastic disease + EMA-EP, EP/EMA or BEP for metastatic disease).
Where is Breslow’s depth measured from for melanoma?
From granular layer of surface epithelium to the deepest melanoma
(Background: Breslow is a measure of how deeply a melanoma tumor has grown into the skin)
*Layers of the skin from most superficial to deeper: stratum corneum, stratum lucidum, stratum granulosum, strutum spinosum, stratum basase > dermis.
What are the levels of Breslow?
“Level 1 = in situ
Level 2 = through BM
Level 3 = through papillary dermis
Level 4 = through reticular dermis (survival starts to drop off from 90% or higher to 67%)
Level 5 = through subcutaneous fat (33%)”
Measured from the granular layer of the epidermis to the deepest point of invasion
Tamox least likely to be associated with what benign growth?
answer: ovarian cysts
most likely to be associated with in order of highest association:
benign endometrial polyps
hyperplasia
fibroids/adenomyosis
*also sarcomas and carcinosarcomas
What subunit of HCG is shared with other hormones
Alpha same as LH, FSH, TSH; beta is distinct
- Thyroid work up should be obtained in patients with molar pregnancy or GTD with bHCG > 100,000.
- If features of thyroid storm or impending storm begin immediate treatment with:
Beta blocker – Propranolol preferred.
Thionamide – Propylthiouracil (PTU) preferred.
Iodine – Saturated solution of potassium iodide (SSKI) or Lugol’s solution.
Consider Hydrocortisone if confirmed clinic storm.
Cholestyramine is an additional adjunctive therapy, especially if the patient is allergic to thionamides.
Most common tumor in dysgenetic gonads
Gonadoblastoma (benign)
Most common malignant tumor in dysgenetic gonads
Dysgerminoma
Which growth factors bind to serine-threonine kinase receptor?
Peptide growth factors
*Receptor serine/threonine kinases such as transforming growth factor beta (TGF-beta) receptors contain a single transmembrane domain.
*Hypersignaling via the TGF-β pathway is associated with increased tumor dissemination (immune evasion, promotion of angiogenesis, increased epithelial to mesenchymal transformation) and has been well studied in ovarian cancer.
Location of estrogen receptor and of action mechanism
** TEST QUESTION **
cytosol —> nucleus.
MOA: transcription factor
ERs are ligand-dependent transcription factors
Cancer related to fusion protein
Endometrial stromal sarcomas
(uptodate said: JAZF1-SUZ12 and EPC1/PHF1gene fusion)
*JAZF1-SUZ12 is a carcinogenic fusion related to low-grade ESS. Its fusion frequency is reported to be 75% in endometrial stromal nodule, 50% in low grade ESS, and 15% in high grade ESS, and can be used to distinguish LG-ESS from HG-ESS.
*EPC1-PHF1 is associated with the morphology and clinical features of low-grade ESS.
FOXL2 and ovarian cancer subtypes
adult granulosa cell tumor
EBRT vs brachytherapy: which symptom is shared?
FATIGUE (answer)
-wrong answers: vaginal stenosis, 2 other
Which is a direct (rather than indirect) effect of radiation?
LET (answer)
wrong answers:
photons, gamma rays, hypoxia, chemosens
What radiation is used to treat superficial lesions (aka skin)?
Electrons (answer)
wrong choices: gamma ray, orthovoltage
What is the elemental source for brachytherapy/interstitial?
Iridium-192 (answer)
wrong choice: cesium
What is the depth of dose for 12 MeV in radiation?
4 cm (R90 where beyond <90% of dose is administered)
What is the definition of linear energy transfer (LET)?
The rate of deposition of energy along the path of the radiation beam. Amount of energy transferred to local environment in form of ionizations and excitations. Average energy for a given path length traveled. Average path length for a given deposited energy.
Unit = kEV/um
What is high LET radiation?
OPTIONS:
1. neutrons
2. protons
3. photons
4. Gamma rays
5. alpha particles (I added this option but not in justine’s) “
High LET: alpha particles, neutrons
What is low LET radiation?
electrons, gamma rays, xrays
(both electromagnetic radiation)
What is % dose of XRT 1 cm vs 2 cm from source?
400% because dose is = 1/r squared
*Repeated question
How do you manage severe carboplatin sensitivity if patient is responding to the drug?
Desensitization protocol
We do not recommend rechallenging patients with platinum agents, even with additional premedications. Instead, we advocate referral to an allergist for skin testing. If skin testing is positive, the patient should either avoid any future exposure to the drug or receive it only through a desensitization protocol.
Chemotherapy agents associated with PPE?
Chi: Capecitabine > 5-FU, Doxil, Docetaxol
Also Multitargeted tyrosine kinase inhibitors sorafenib, sunitinib
Factors that increase the rate of PPE with doxil administration?
Higher dose infusion and prior neuropathy
initial doses greater than 40 mg/m2
higher dose and more cycles increased the incidence of several toxicities, including PPE. The use of cooling mechanisms, higher number of PLD cycles, and occurrence of mucositis, neutropenia, and peripheral neuropathy are possible predictors of PPE.
Dose limiting toxicity of Gemcitabine
**TEST QUESTION **
Myelosuppression
Chemo causing ovarian failure
A. cyclophosphamide
B. 5-FU
C. MTX
Cyclophosphamide
EXACTLY why we give taxol before cisplatin/ Carboplatin
( duplicate)
Carboplatinum, cisplatin, cyclophosphamide decrease its clearance and therefore increase myelosuppression so these drugs should be administered after paclitaxel (to decrease myelosuppression)
Mechanism and dose limiting toxicity vinorelbine
Vinka alkaloid derived from vinblastine. It inhibits tubular polymerization, disrupting the formation of tubules during mitosis.
Most of the drug is metabolized in the liver and excreted in the bile.
Dose-limiting toxicity is myelosuppression.
Loss of MSH2 & MSH6 in tumor MMR testing, what next step?
A Tumor genetics
B germline genetics
C methylation testing
**TEST QUESTION **
germline genetics
methylation testing is for Loss of MLH1 and PMS2 —> MLH1 promoter methylation
Which is more important for dosing methotraxate: biliary obstruction or poor renal function, both were choices
Poor renal function
(table 13.11 and 13.9 in Principles and Practice Chi)
confirmed (AW)
Complication with giving carbo as 3rd line for ovary cancer
hypersensitivity
Different side effect between SERM and aromatase inhibitors
** TEST QUESTION **
Tamox SE: endometrial cancer, VTE/CVA, hot flashes
- anti-est in breast, pro everywhere else (uterus, bone, liver, coagulation system) , fatty liver, cataracts, decreased LDL
Ralox: fewer serious side effects than tamoxifen. No increased UtCa risk
AI: hot flashes, osteopenia or osteoporosis, bone pain, diarrhea, heart disease
Both: hot flashes, sexual dysfunction
Which is mTOR inhibitor?
(Duplicate Qs)
the -olimuses not an option.
metformin also inhibits mTOR
Rapalogs:
Rapamycin
Temsirolimus
Everolimus
Deforolimus
Zotarolimus
Diet Derived:
Curcumin
Resveratrol
epigallocatechin gallate (EGCG)
3,3-Diindolylmethane (DIM)
Genistein
Caffeine
Bevacizumab MOA
binds to, and neutralizes, extracellular vascular endothelial growth factor (VEGF) A , preventing its association with endothelial receptors VEGFR1&2
ERBB2 gene encodes
ERBB2 also known as HER2/neu is a gene that encodes for the receptor tyrosine-protein kinase erbB-2.
How is mTOR related to pertuzumab?
Pertuzumab is a monoclonal antibody that binds to her2.
mTOR is downstream from this receptor
Her2 —> PI3K —> PIP3 —> PDK —> AKT —> mTOR
VEGF roles
Causative factor in blood vessel permeability and development
VEGFRs are predominantly found on endothelial cells and bone marrow derived cells
PI3K/AKT/mTOR pathway
PI3K-AKT-mTOR pathway promotes cell growth/survival and inhibits apoptosis and autophagy
- PI3K (phosphatidylinositol-3-kinase) is activated by Growth factor receptor or RAS
- Activated PI3K generates PIP3 (phosphatidylinositol-3-4-5-triphosphate)
- PIP3 activates PDK (phosphoinositide-dependent-kinase)
3.5. [PTEN inhibits PIP3]. - PDK phosphorylates AKT.
- phosphorylated AKT:
6a. Activates mTOR —> synthesis of proteins, needed for cell growth and cell cycle progression
6b. Inhibits Foxo family of transcription factors, responsible for transcription of genes needed for apoptosis and apoptosis cell cycle arrest
How does the HPV vaccine work
Recombinant L1 capsid protein (1 of 2 viral capsid proteins). Forms virus like particles (VLPs) which are combined with adjuvants. Adjuvants stimulate the immune system (aluminum based). VLPs induce humoral response with antbiotides and some cell-mediated immune response
What are HAMAs (human anti-mouse antibodies)?
When patients react to mouse antibodies as if they were a foreign substance, and create a new set of antibodies against the mouse antibodies
A single dose of mouse monoclonal antibodies has the potential to induce an immune response initiating the production on anti-mouse antibodies. However it has been shown that the concentration and IgG isotype of murine antibody used does not influence the production of HAMA [2]. Circulating HAMA has the capability to bind to mouse antibodies that are used in subsequent procedures or treatments. This diminishes the efficacy of the antibody based treatments. The presence of HAMA in patient samples can also be a cause of false positive or false negative immunoassay results, depending on the assay principles and the type of monoclonal antibodies used in the test
Estrogen isoforms created by
Alternative splicing vs. Alternate promoter usage
Pre-mRNA contains both coding regions (exons) that specify the protein sequence and introns that are removed during a process called splicing.
Alternative splicing allows for different combinations of exons to be included in the final mature mRNA, leading to mRNA transcripts that exclude or include specific exons, resulting in isoforms with variations in their protein structure and function.
genes may also have multiple promoters to create different isoforms
Endometrial cancer mutation associated with good prognosis
POLE
Excellent prognosis regardless of grade - high tumor mutation burden, tumor neoantigen production, and tumor infiltrating T cells
Endometrioisis related marker
CA125 is the most common tumor marker associated with endometriosis
ARID1A is the most frequently mutated in gene in endometriosis related ovarian cancer
EGFR (epidermal growth factor receptor) (how it works)
Cell membrane receptors that bind peptide growth factors are composed of an extra cellular ligand-binding domain, a membrane spanning region, and a cytoplasmic tyrosine kinase domain
Binding of a growth factor to the extracellular domain results in dimerization and confirmational shifts in the receptors and activation of the inner tyrosine kinase
The kinase transfers a phosphate group from ATP to a specific tyrosine residue on the growth factor receptor itself (auto phosphorylation) and on molecular targets inside the cell
Describe VEGF proteins and receptors
7 glycoproteins in the family: VEGF A-E and placental growth factor 1-2
- secreted by tumor cells, endothelial cells, stromal cells, leukocytes, platelets
VEGF-A,B,E stimulate angiogenesis via VEGFR1 (A/B) and VEGFR2 (A/E)
VEGFR-C,D activate VEGFR3 and stimulate lymphangiogenesis
ABE12 and CD3
—> high VEGF-D expression is independent poor prognostic factor for epithelial ovarian cancer
Describe HPV cancer pathway
E6/E7 are viral oncogene proteins:
- E6 inactivates p53 leading to its proteosomal degradation,
- E7 inactivates pRb by competing for binding and then frees transcription factor E2F —> expression of S phase genes, uncontrolled cell cycle progression
Cancer vaccines general mechanism
designed to induce antitumor immune responses against specific tumor-associated antigens (TAA). TAAs may be
(i) antigens that are overexpressed in cancers, (ex: Her2/Neu, or mesothelin)
(ii) cancer/germline antigens that are only expressed in germline cells, but can be reexpressed in cancer cells, (ex: MAGE-A1 (melanoma associated antigen), NY-ESO-1, New York esophageal squamous cell carcinoma 1)
(iii) cell lineage differentiation antigens, (ex: tyrosinase and gp100.
Delivery classifications:
i) peptide/protein-based, (ii) cell-based, (iii) DNA/RNA-based, or (iv) glycan-based.
Sipuleucel-T (Provenge) is first therapeutic cancer vaccine for prostate (autologous APCs exposed to cancer antigen, then returned to pt
Cancer risk with Peutz-Jeghers
Also gene?
(Duplicate)
- breast (32 to 54 percent)
- Colorectal – 39 percent
- Stomach – 29 percent
- Small bowel – 13 percent
- Pancreas – >15%
- SCTAT - >10%
**cervix (10 percent) adenoma malignum (minimal deviation adenocarcinoma)
Stk11 (tumor suppressor), autosomal dominant
multiple hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation
Cancer risk with MEN2
Parathyroid hyperplasia (10-25%),
medullary thyroid ca (almost all will get this, avg age 30s),
pheo (~50% will get this),
RET protooncogene
Cancer risk with MEN1
M3 P’s: pancreatic, parathyroid, pituitary.
Pancreatic (~30%, Zollinger-Ellison syndrome, insulinoma),
pituitary adenoma (15-20%),
angiofibroma,
parathyroid hyperplasia (almost 100%),
lipoma,
carcinoid tumors
MEN1 gene
Cancer risk with Li-Fraumeni
Also gene
TP53 mut -
CLASSICALLY: breast (>60%), sarcoma (bone & soft tissue), CNS, ACC (head and neck cancer)
Osteosarcoma most common in kids
Also melanoma, colorectal, gastric, prostate
Cancer risk with Cowden
also gene
PTEN mut
breast (triple neg), endometrial, thyroid (3-38%), CRC, renal cell carcinoma. Also have mucocutaneous lesions, thyroid disease (50%), GI polyps
Breast cancer screening for BRCA
annual MRI 25-29yo; 30-75yo annual mammo + breast MRI/ (NCCN 2/24)
MicroRNA when bind to 3’ UTR (untranslated region) of mRNA - targeted mechanism of action
**TEST QUESTION **
miRNAs regulate gene expression by binding to the 3’ untranslated region (3’UTR) of messenger RNA (mRNA), using mechanisms such as Translational repression (most common) and mRNA Cleavage (less common) to silence a gene by preventing translation (medium complementarity), faster degradation (low complementarity) or cleavage (perfect complementarity).
Complementarity = matching
Least recommended colon ca screening for lynch/HNPCC
**TEST QUESTION **
Sigmoidoscopy aka flex sig (majority right sided tumors prior to splenic flexure)
BRCA1 most common type of breast cancer & histologic characteristics
(Duplicate)
** TEST QUESTION **
Triple negative, poorly differentiated invasive ductal carcinoma MC
higher proportion of medullary carcinomas (13%)
more frequently estrogen receptor- and progesterone receptor-negative, and p53-positive
low frequency of HER2 expression.
High grade, and had exceptionally high mean mitotic counts, a syncytial growth pattern, pushing margins, and confluent necrosis. Atypical medullary carcinoma was overrepresented in BRCA1 mutation carriers.
Equal LVSI to wild type
BRCA1 cancer risks
breast (>60% absolute risk),
male breast cancer (0.2%–1.2%)
ovary (39%–58%),
pancreas (≤5%),
prostate (7%–26%),
Uterine serous
BRCA2 cancer risks
breast (>60% absolute risk),
male breast cancer (1.8%–7.1%),
ovary (13%–29%),
pancreas (5%–10%)
prostate (19%–61%),
uveal melanoma (BRCA2),
melanoma ( BRCA2)
stomach/biliary (maybe in BRCA2?), JD: Cannot confirm this….
BRCA 2 - most common type of breast cancer
A ductal ER+
B lobular ER+PR+
C phyllodes ER+
ductal ER+
70% to 80% ER+ PR+
higher grade than sporadic age-matched controls.
Usually her2 -
Invasive ductal carcinoma is the most common histological type in BRCA2 breast tumors. There is no agreement about whether there is any special histological type with a higher frequency among BRCA2-mutation carriers.
Poss higher incidence of tumors belonging to a “tubular lobular group” including invasive lobular, tubular, and cribriform carcinomas in BRCA2 patients.
Pleomorphic lobular carcinomas and extensive intraduct carcinomas were more common in BRCA2 mutation carriers.
JD: All I can find is that ductal is most common (searched B&H, UTD, Gemini, google search), lobular is increased, up to 10% but still not close to as common
BRAF mutations common in what cancers?
Oncogene commonly mutated in Type 1 ovarian cancers (low grade serous cancers, endometrioid and clear cell cancers, and mucinous cancers). But rare in recurrent low grade serous. KRAS more common in borderline tumors, both activate MAP kinase pathway
Best med for anticipatory chemo-induced nausea
A 5HT3 antagonist
B benzo
C steroid
D NK1R antagonist
benzo
Best criteria to diagnose HNPCC
A MSI
B Amsterdam
C MLH1 methylation
D MMR gene alterations
**TEST QUESTION **
MMR gene alterations
at what age do you start HNPCC screening
20-25 for HNPCC genes MLH1, MSH2/EPCAM
30-35 for PMS2/MSH6
….or 2-5yr prior to earliest familial CRC
Age 10-15y for APC mutation (Famililal adenomatous polyposis)
Age 18 for STK11 (PJS)
Ascites and ovarian cancer - which VEGF/ VEGF-R?
VEGFR2 by VEGF-A has major permeability enhancing effect
(Hint: VEGF-A “A for ascites” VEGF-R2 “2 much ascites”
Ang-1, Ang-2 (Angiopoietin 1/2) targets
A hypoxia-inducible factor 2-alpha
B TIE 1
C FGF
Tie1.
Angiopoietin ligands (ANG1–ANG4) and the TIE (TIE1 and TIE2) receptor tyrosine kinases form an endothelial signalling pathway that is necessary for embryonic cardiovascular and lymphatic development. In adults, this system regulates vascular homeostasis, and controls vessel permeability, inflammation and angiogenic responses.
AW: I think this should be TIE2…Tie1 and Tie2 are highly homologous proteins both part of the angiopoietin/Tie signaling axis. Tie2 is the main signal-transducing receptor, while Tie1 modulates Tie2 signaling
Tie2 can bind to all four known angiopoietins, while Tie1 cannot bind to any of them.
AMG386 (Trebananib)- target
A placental growth factor
B hypoxia-inducible factor 2-alpha
C VEGF, Tie1
D angiopoieten 1/2
** TEST QUESTION **
AMG386 aka trebananib is angiopoietin (Ang) 1 and 2 neutralizing peptibody with anti-angiogenic activity
Trebananib is a peptide-Fc fusion protein that targets the Ang1/Ang2/Tie2 pathway and inhibits angiogenesis by blocking the interaction between Ang1/Ang2 with the Tie2 receptor.
JD: would add - “Anti-angiogenesis agent”
3 ways that oncogenes are activated, which is not?
A mutation in promoter region regulating inactivation
B amplification
C hypermethylation
D chromosome rearrangement
hypermethylation
BRCA1 chromosome location
(Duplicate)
17q21
(Same chromosome as TP53)
TP53 chromosome location
17p13
(Same chromosome as BRCA1)
BRCA2 chromosome location
(Duplicate)
13q12
(Same chromosome as RB)
PTEN chromosome location
10q23
Rb gene location
13q14
(Same chromosome as BRCA2)
What are the three BRCA1/2 founders mutations?
BRCA1 185delAG
BRCA1 5382insC
BRCA2 6174delT
What gene is encodes the CSF (colony stimulating factor) receptor?
The c-fms proto-oncogene (expressed on myeloid cells) encodes a receptor mononuclear phagocyte colony stimulating factor, CSF-1 (M-CSF)
most common mutation location p53
Exons 5-8
What are null cells?
a lymphocyte in the blood that does not have on its surface the receptors typical of either mature B cells or T cells
NK cells are part of a group of lymphocytes originally called null cells (through this is an outdated term). Unlike other lymphocytes, such as T and B cells, they do not have to find their specific match to identify an invader. Similarly, they do not depend on memory of past pathogen infections to attack a cell.
Difference between adenovirus and retrovirus as vector for gene therapy
Adenoviruses (DNA viruses) not incorporated into host DNA
Not replicated when cell divides, so requires re-administration
gamma retroviruses integrated into host genome. These resulted in a lower likelihood that adjacent genes will be activated, a better ability to transduce nondividing cells, and a shorter culture period… but oncogenic/leukemogenic
Which PARP do PARPi’s inhibit?
PARP1 and 2; however Rucaparib inhibits PARP1-3
Olaparib, Rucaparib–PARP-1,2,3
(JS) Niraparib, Veliparib–PARP-1,2
Reminder Rucaparb elevated Cr due to MATE1/2 inhibition
purine bases
adenine & guanine
(pure As Gold)
pyrimidine bases
cytosine, thymine, uracil
Cytosine is found in both DNA and RNA,
thymine is present only in DNA,
uracil is present only in RNA
Pyramids CUT
CUT the Py 🥧
What inherited syndromes merit breast cancer screening with MRI
BRCA, Li-Fraumeni, Cowden/Bannayan–Riley–Ruvalcaba syndrome, PJS
NCCN 6/23:
Recommend: BRCA1/2, PALB2, STK11, TP53, PTEN
Consider: ATM, BARD1, CDH1, CHEK2, NF1, RAD51C/D
Which is most consistent with BRCA2:
A 40yo with ovary cancer
B 45yo with breast cancer
C 65yo with ovary
D woman with pancreatic cancer.
Think answer is pancreatic: https://www.nature.com/articles/gim201785
Notes said: “45yo with breast cancer (later peak incidence with BRCA2)” = we think too
“The peak incidence of breast cancer was seen in women 41–50 years old for BRCA1 mutation carriers and those 51–60 years old for BRCA2 mutation carriers.”
VUS in BARD1 gene found age 40
What to do?
A Routine mammogram
B MRI
C tamoxifen
D risk reduction surgery
Routine mammogram
BRIP=normal breast screening, RRSO “RIP=ovary, like IP chemo”
BARD=MRI/mammo, no ovary “BAD BREAST”
Endo cancer with medullary thyroid and hamartomas, what is genetic mutation
** TEST QUESTION**
Cowden’s syndrome; PTEN mutation
Cardiac SE with taxol
** TEST QUESTION**
asymptomatic bradycardia
trastuzumab MOA.
MAb binds to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER-2); blocks downstream signaling
ErbB2 (Her2Neu) part of EGRF family. HER2 does not directly bind ligand-activation results from heterodimerization with another ERBB member or by homodimerization when HER2 concentration are high
it mediates antibody-dependent cellular cytotoxicity by inhibiting proliferation of cells (MAPK, PIK3 pathway inhibition) which overexpress HER-2 protein.
most common G3-4 tox with olaparib
(Duplicate)
anemia (21%)
next closest=neutropenia at 6%
Growth factor associated with endometrial cancer
** TEST QUESTION **
Insulin Like Growth Factor -1 (IGF1)
Describe the WNT/beta-catenin pathway
Beta-catenin (CTNNB1 gene) involved with cadherins in cell-cell adhesion junctions and plays a role in inhibiting excessive growth when cells contact one another (cytoplasmic function)
Nuclear target genes promote cell proliferation such as c-myc, cyclin D1 (nuclear function)
Beta-catenin regulated by the WNT pathway:
WNT extracellular ligands bind frizzled cell surface receptor –> Frizzled activates intracellular dishevelled which breaks up destruction complex —> increased accumulation of beta -catenin. Saturates cytoplasmic sites first then translocates to the nucleus.
Disheveled accomplishes this by inhibiting protein complex (axin, GSK-3 beta, APC) that normally proteolyticly degrades beta-catenin
Describe epithelial to mesenchymal transition
A series of events that progress epithelial tumor cells along a mesenchymal like continuum and up regulates survival and invasion signals promoting single cell autonomy
- down regulation of proteins that promotes homotypic cell attachment, such as E-cadherin.
- Upregulation proteins that promote heterotypic cell adhesion, such as P and N cadherin
An epithelial-mesenchymal transition (EMT) is a biologic process that allows a polarized epithelial cell, which normally interacts with basement membrane via its basal surface, to undergo multiple biochemical changes that enable it to assume a mesenchymal cell phenotype, which includes enhanced migratory capacity, invasiveness, elevated resistance to apoptosis, and greatly increased production of ECM components (1). The completion of an EMT is signaled by the degradation of underlying basement membrane and the formation of a mesenchymal cell that can migrate away from the epithelial layer in which it originated.
Which of the following has the Least cumulative effect on bone marrow?
A cisplatin
B cytoxan
C carbo
D taxol
Taxol (AW)
Chi: Radiation, alkylating agents (e.g., melphalan, carboplatin), and other DNA-damaging agents (e.g., nitrosoureas, mitomycin C), can have cumulative long-term effects on bone marrow reserve. Most other agents, including taxanes and topotecan, show no evidence of cumulative toxicity and can be administered for multiple cycles without dose modification, once a tolerable dose is established.
cisplatin - dose limiting is renal, neurop, tinnitus; myelosupp is mild (occurs in 25-30%)
cytoxan (myelosuppression is dose limiting, leukopenia),
carbo - dose limiting is myelosuppression (thrombocytopenia)
taxol (notes say we chose taxol) - dose limiting is neutropenia
Prior card: they thought cisplatin
Most lethal impact of radiation
DOUBLE STRANDED BREAKS
other options: single stranded break, 2 other choices
Most common risk factor for radiation enteritis
Chemorads
Answer choices:
**chemorads (this one?) **= yes (AW)
Prior abd surgery
age (higher risk if older)
cervical cancer
higher obesity (no, higher risk in skinny people)
Pubmed - Summary of RF for GI RT injury:
*RT: tx volume, total dose, fractionation dose, schedule
*Combined modality therapies: surgery, chemo (particularly concurrent)
*Med co-morbidities: vascular disease, connective tissue disease, IBD, HIV
*Genetic susceptibility: single nucleotide polymorphism, ataxia telangiectasia
Predisposing risk factors: previous abdominal surgery, PID, thin body habitus, HTN, and DM
Most common organ with toxicity in HDR (or any pelvic radiation)
Rectum HDR
terminal ileum WPRT
Main differences between HDR and LDR
LDR is 0.4-2.0 Gy per hour vs HDR is >12 Gy per hour.
HDR: LESS TX TIME- technically more fractions and higher fraction dose for HDR (lower overall dose-60% with HDR vs LDR). Less time for tissue repair. higher fx size = More late toxicities. Lose out on “bioradiologic advantage” of LDR.
LDR: Less fractions and dose - better tissue repair esp for “late responding tissues”. Exposure of staff. less optimal positioning and higher risk of device moving.
LDR where radioactive source (Cs) positioned inside for a few days vs HDR (Ir) temporary placement of radioactive source; more precise
Just completed radiation, perforated sigmoid and feculent
choices:
Loop ileostomy
end ileostomy
rectosigmoidectomy with end stoma (this one??)
How to reduce small bowel complications with radiation?
Answer: tx with full bladder
wrong choices:
prone position
decubitus position
How had addition of chemosensitizers affect radiation outcomes
Mortality (THIS ONE)
Wrong answers:
enterocolitis
noninfectious bladder cystitis
fistula formation
TL: In meta-analysis 2010 / HR death 0.69 or 10% absolute improvement, HR recurrence 0.66 (13% absolute improvement, OR 1.98 gr 3/4 esp GI tox)
Increased OS and dx control with chemoRT. Also get more morbidity but worth it (AW)
Dose of brachy after hyst for endometrial cancer is dosed to where
0.5cm deep and 0.5cm wide; 5mm!
NCCN: 7 Gy x 3 fractions prescribed at a depth of 0.5 cm from the vaginal surface is a regimen used by many
Direct and indirect radiation/xrt mechanisms
Direct = causes direct DNA break.
Indirect = electron interacts with water and makes a free radical which produces oxidative stress and DNA damage
Cervical cancer pt s/p RT presents with fever, diarrhea, imaging with collapsed bowel, thick walls, dilated bowel
Thumb printing (thickening of haustral folds) = cdiff due to edema
UTD: findings consistent with toxic megacolon include small bowel dilatation, air-fluid levels (mimicking an intestinal obstruction or ischemia), and “thumb printing” (scalloping of the bowel wall) due to submucosal edema
Advantage of HDR vs LDR?
Less treatment time (this one)
*repeated question
Wrong answers
-Less treatment
-Less toxicity
-More effective
Notes from Justine: HDR has higher acute tox, more treatments, lower dose overall (each fx larger, more fractions), may lose radiobiologic advantage of LDR, tx faster
Advantage of HRD over LDR?
Answer: less exposure to staff to radiation for prolonged periods of time
Other wrong answers: less treatments, less toxicity
What effect does ionizing radiation have on DNA that results in largest impact (double strand break, single strand break, base alteration, one other choice)
DS Breaks
this is the lethal kill of ionizing radiation
What’s the half life of Cesium?
30 years
seize the day in your 30s
20 years after chemoRT, which risk factor led to lumbosacral radiculopathy?
answer: increased dose per fraction
- lumbosacral radiculopathy is associated with intracavity and intraop radiation
Wrong answers: cisplatin, 5-FU cream
longest half life radio isotopes?
cesium (30 years)
*This question has been repeated multiple times!
Remember - Radium has the longest half life 1,600 years. Guessing Radium was not an answer choice in this question.
-Iridium192: 74 days
-Colbalt60: 5 years
Superior border EBRT
answer: L4-5 interspace
wrong: L4 vertebral body, L5 vertebral body
Chi: superior border of the pelvic fields is S1–L5 interspace for early-stage disease (i.e., nonbulky IB or IIA) or at the L4–5 interspace for more advanced disease
for lower PA nodes radiate up to L2, for full PA field radiate up to T12-L1.
What phase of the cell cycle is most radio-resistant?
S (late) and early G1
reminder: S= synthesizing DNA that can be used as a template for repair; G1= long and quiescent
Most radiosensitive phase(s) of cell cycle?
G2 and M
reminder: G2 = short and cell is proliferating; M = chromosomes lined up in spindle and does not stop to repair
At what energies do certain radiotherapy principles dominate?
- Photo electric effect 10-25 kEV
- Compton scattering 25kEV - 25mEV
- Pair production (does not start until 1.02 MeV, dominant >30 mEV)
What affects response/sensitivity to radiation? (4 R’s)
1.Repair (if fractionated, time for recovery of sublethal injury)
2.Repopulation (growth of cells between fractors)
3.Redistribution (depending what part of the cell cycle)-give time to get into more sens G2/M
4.Reoxygenation (oxygenated cells are 3x more sensitive to radiation)”
Advantage of high LET (alpha and neutrons)?
Does not depend on O2 so effective for hypoxic tumors (oxygen enhancement ratio = 1)
Majority of effect is due to direct effect
What organ is most sensitive to radiation?
Kidney
(JS) Lowest RT tolerances:
Kidney/Lung: 1500-2000 cGy
Liver:2000-3000 cGy
Ovary: 2000 cGy (as little as 500cGy in postmenopausal women)
Dose to sterilize ovaries?
Age dependent, BUT:
B&H: 20 Gy (as little as 5-10Gy in older premenopausal women)
Chi says a single dose of 4-8 Gy or fractionated doses of 12-20 Gy
Prior card says 2-6 (unfractionated), 6-10 (fractionated)
How to calculate energy to get to certain depth
Depth in cm x 3 = amount of energy in MeV
*internet:MeV means one mega electron volt, or one million electron volts
12mEV dose = 4 cm depth…4cmx3=12
How to decrease acute effects of radiation
Decrease total dose and treatment time –> affects mucosal cells
How to decrease chronic effects of radiation
Decrease DOSE PER FRACTION –> affects endothelial cells
What does the shoulder of the cell survival curve represent?
Sublethal damage that is repaired
What is the minimum amt of energy to cause ionization?
35 eV
Max dose small bowel?
45 Gy
(that’s why dose for cervix is that.. And required to sterilize occult dz for adjv radiation)
Max dose for bladder and rectum and lower 1/3 vagina?
75 Gy
Name the mm/cm
1.Vaginal cancer - intracavitary alone
2.Add interstitial threshold
3.Add EBRT threshold
- <5 mm
- > 5mm
- > 2 cm
Radiation proctitis? Name treatment
All 4 are answers
Steroid suppositories
Low residue diet
Anti-motility drugs
Hydration
Chronic radiation enteritis treatment?
can try cholestryamine
(JS) UTD diet, hydration, antidiarrheals, bile acid sequestrants, abx for bacterial overgrowth)
What radiation particle is decay of radioactive isotope
Gamma rays originate within the nucleus, emitted from radioisotope
What type of radiation is caused by deceleration of high energy electrons?
X-rays originate outside of nucleus and produced by bombardment of target with high speed electrons
Alpha particle
Two protons and two neutrons (i.e. He nucleus)
Beta particle
high speed electrons
B- = electron
B+ = positron
What is Gompertzian tumor growth?
Doubling time increases as the tumor size increases
y axis: tumor size log scale
x axis: time
What shifts the cell survival curve to the left?
Left = less radiation needed
Oxygen and higher energy radiation
(JS) Increased temp, decreased pH, increased 2,3-DPG (enzyme that helps release O2 to tissue)
^isn’t this for RBC’s? JD -yes it’s for both. Whatever shifts O2 curve right shifts cell survival curve left
What shifts the cell survival curve to the left?
“Left = less radiation needed
Oxygen and higher energy radiation”
What is max fetal dose of radiation during pregnancy?
10 Gy
What is dose of EBRT for breast cancer?
50Gy, if adjuvant only 10-15 Gy
(JS)- I think this is old news. NCCN states hypofractionated WBRT (39–42.9 Gy in single fractions of 2.6–3.3 Gy) compared to
standard 50 Gy in single fractions of 2 Gy were equivalent.
First order cell kill kinetics?
Constant FRACTION of cells killed with each treatment
When is LET best used?
necrotic tumor
IMRT differs from 4-field radiation in all ways except:
Delivers same dose
*repeated question
Most common site affected in whole pelvic XRT?
answer: ileum
wrong options: rectum, bladder, ureter
Which has highest LET?
alpha particle
Order of highest to lowest:
alpha, neutron, proton
MLH: Think it’s alpha then neutron
(Hi! LET the APrN do the work! (alpha, proton, neutron))
Cobalt decay produces what radiation?
This emits high intensity gamma rays
Cobalt 60 half life?
5.26 year half life
Iridium 192 half life?
74 days
Cesium 137 half life
30 years!
*This is asked multiple times
How is WPRT targeted?
Targeted areas include primary tumor and areas of suspected microscopic disease
(JS) Chi says:
GTV: clinical/radiographically evident tumor
CTV: where microscopic disease likely to spread aka lymph nodes
How are LET and OER related?
INVERSELY; Higher LET (linear energy transfer) is associated with lower OER (oxygen enhancement ratio)
Most important factor to determine the dose of HDR delivered?
Source dwell time
HDR is performed using a single tiny (1mm x 3 mm) highly radioactive source of Iridium-192 that is laser welded to the end of a thin, flexible stainless steel cable. The source is housed in a device called an afterloader. The computer-guided afterloader directs the source into the treatment catheters placed in and around the prostate by the brachytherapy physician. The source travels through each catheter in 5 mm steps, called “dwell” positions. The distribution of radiation and dose is determined by the dwell positions the source stops at and the length of time it dwells there. This ability to vary the dwell times is like having an unlimited choice of source strengths. This level of dose control is possible only with HDR.
What are the disadvantages of HDR?
answer: potential late tissue effects w HDR
wrong answers: Lower therapeutic ratio, labor intense, need for sedation
Chi: loss of the radiobiologic advantage of LDR, decreased time for normal tissue repair, potential increase in late tissue effects with large fraction sizes, an increase in number of implants (more labor-intensive), need for sedation
What is the most important determinant of HDR dose?
Chi: source dwell time
answer: Length of the source
wrong choices: age of the source, shape of the source
What clinical scenario is most likely to be a factor in oxygen enhancement ratio?
answer: 6 cm cervical mass bc necrotic so less oxygen so more radio resistant by 2 - 3 x more.
other options:
Tx of groins in vulvar ca, adjuvant tx to Pa nodes
notes: Reoxygenation: hypoxic tumor cells get better oxygen during fractionated RT, this increase response of the tumor
Oxygen is the MOST effective known radiation sensitizer.
The sensitivity of fully oxygenated cells to low oxygen cells is 3X better
Oxygen Enhancement Ratio (OER): ratio btw dose needed to achieve a given level of cell death under O2 vs hypoxic conditions
How to protect vulva SKIN during radiation?
answer: frog leg all the way baby
wrong choices: antifungal, estrogen cream, dilite H2O2, cold something
Brachytherapy side effect that doesn’t occur with EBRT?
vaginal atrophy
Treatment of acute cystitis due to radiation?
answer: ditropan (oxybutynin)
wrong answers:
fulguration (tx for hemorrhagic cystitis)
Fluid restruction
Bladder irrigation (tx for hemorrhagic cystitis)
LET relationship to OER
inverse!
High LET: OER is diminished
LET: linear energy transfer - rate of energy deposition along the path of a radiation beam
OER: oxygen enhancement ratio - ratio btw dose needed to achieve a given level of cell death under O2 vs hypoxic conditions
What has the highest linear energy transfer (LET)?
alpha particle
What is the least likely complication associated with extensive terminal ileum resection?
A. intrinsic factor deficiency
B. Vit B12 def
C. Vit K def
D. fat malabsorption
E. iron
answer: intrinsic factor deficiency (made in gastric cells, so plenty in system)
notes:
1.B12 just not absorbed if resection >100 cm
2. bile acid deficiency b/c bile acid losses exceed compensatory increase in hepatic bile acid production
this exacerbates absorption of fat and fat-soluble vitamins
disruption of fluid absorption so cannot tolerate large bolus feedings or high osmolarity (i.e., simple carbs)
3. fat soluble vitamins (vitamin A,D,E,K)”
Blind Loop Syndrome complication
small bowel bacterial overgrowth
What is the cause of refractory hypokalemia in setting of K replacement?
answer: hypoMag
wrong options: bicarb, phosphorus, calcium
Notes: Patients with hypokalemia may also have hypomagnesemia due to concurrent loss with diarrhea or diuretic therapy or, in patients with hypomagnesemia as the primary abnormality, renal potassium wasting. Such patients can be refractory to potassium replacement alone
What is the advantage of protons over electrons in radiation?
Dose stops at precise place due to Bragg peak
(electrons are less precise; most of the dose is delivered 0.5-3 cm from patient’s skin and then gradually loses energy until reaches its target; affecting the non-target tissues)
The Bragg peak is a pronounced peak on the Bragg curve which plots the energy loss of ionizing radiation during its travel through matter.
What cancer type has the least acute radiation effects?
answer: vagina
wrong choices: ovary, bladder, small intestine
Tx of HYPERmagnesemia
answer: Fluids and loop diuretic (i.e., lasix)
wrong answer: calcium, other choices
(JS) UTD says IV calcium only if severe/symtpomatic
Treatment of cystitis during xrt
Oxybutinin (anti-cholinergic, antagonizes M1, M2, M3 receptors of Ach receptor)
Oxybutinin aka Ditropan
What are Point A and
Point B?
hint: Manchester system
Point A = 2 cm lateral to central canal of uterus and 2 cm from external os/lateral fornix in axis of uterus (where ureter crosses uterine artery, avg point from which to assess dose in paracervical region)
Point B = 5 cm from midline at level of point A aka 3 cm lateral to point A (correspond to obturator nodes)
Most common TPN risk?
hyperGLYCEMIA
Most common reason for hyperkalemia postop?
**TEST QUESTION **
renal dysfunction
Most calories from TPN come from…
answer: Glucose (40-80%)
choices: fat (15-60%), protein
Earliest lab value to measure in nutrition progress?
answer: pre albumin
other options: albumin
Which of the following is associated with steatosis aka fatty liver in TPN?
CHOICES:
1. excess calories from glucose
2. excess calories from protein
3. excess calories from fat
4. excess calories from any source
5. insufficient fat soluble vitamins;
6. insufficient calories from fat”
answer: excess calories from glucose (dextrose)
This is known as overfeeding syndrome.
Which is not associated with blind loop syndrome?
choices:
1.overgrowth of bacteria
2.fat malabsorption
3.Fe deficiency
4.diarrhea
5.vitamin b12 deficiency
answer: Fe deficiency
*Blind loop syndrome arises when the bacterial colonies residing in the upper gastrointestinal tract grow out of control altering the physiological processes of the small intestine. Leads to: vitamin B12 deficiency, fat malabsorption and steatorrhea, nausea, flatulence, fat-soluble vitamin deficiencies (ADEK) and intestinal wall injury.
How much ileum resection will result in B12 deficiency?
60 cm
How much ileum resection will disrupt bile salt/fat malabsorption?
100 cm
*Unabsorbed bile salts enter the colon and stimulate fat and water secretion, which results in diarrhea.
What is refeeding syndrome?
Glu load leads to insulin productions with cells shifting P and K into cells > can lead to life threatening hypoP and hypoK
*malnourished patients receiving artificial refeeding (whether enterally or parenterally) are high risk for refeeding syndrome
Most common ELECTROLYTE abnormality with TPN?
Hypophosphatemia
*add 15 to 30 mEq
UTD: 20-40mmol/d
Angela’s: 10-15 mEq to each 1L
What is associated with zinc deficiency?
answer: alopecia and dry skin
wrong choices (but all correct): growth retardation, decrease taste/smell, depression, impaired wound healing, arrhythmia
Technically all are correct. Other source asked question of what def associated with alopecia and dry skin= zinc
Where is zinc absorbed?
small intestine
What is associated with selenium deficiency?
all of these: CHF, cardiomyopathy, muscle degeneration, white nail beds
- critical in converting thyroid hormone thyroxine (T4) into its more active counterpart triiodothyronine, therefore can lead to hypothyroidism
What vitamin is part of glutathione peroxidase?
Selenium (this is mineral) > (Selena has good gluts.)
*Vitamin E ,C and B6 and B12 are all listed as possibly being inolved.
*Glutathione peroxidase protect the organism from oxidative damage and inflammation, preventing ROS-mediated initiation of cancer (well studied in breast cancer).
Where is copper absorbed?
Stomach and Small Intestines
What percentage of copper is bound to ceruloplasmin?
90%
*Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism.
What is associated with copper deficiency?
all of these: anemia, neutropenia, muscle weakness, ataxia, depigmentation, neurologic abnormalities
NOT: bloody diarrhea
Which is worse - micropapillary or microinvasion in borderline tumors?
micropapillary
*Micropapillary is associated with higher recurrence rate, microinvasions and invasive implants.
What is pathognomic for endodermal sinus tumors?
Schiller duval bodies
Essential fatty acids?
Omega 6 (linoleic acid) and Omega 3 (alpha-linoleic acid)
What is the half life of pre-albumin?
3 days
What is the half life of albumin?
20 days or 3 weeks
Calorie requirement based on weight for TPN?
30 kcal/kg/day
What affects HDR?
applicator, distance and source (all 3)
Source Dwell time May be most important
How to reduce PPE sx
Cold packs, emoillents, B6, dose reduction, vitamin E
What to do if recognized pancreatic injury during debulk
A Repair injury
B pancreatectomy
C splenectomy
D place pelvic drain
pancreatectomy (this one if option is distal?)
place drain near site - not pelvic
What preop abx is most assciated with cdiff
Options cefotetan (2nd gen, this one), ertapenem, two other choices
From UTD:
Fluoroquinolones
Clindamycin
Penicillins and combinations (broad spectrum)
Cephalosporins (2nd/3rd/4th generation)*
Carbapenems
- Use of 1 to 2 doses of a first-generation cephalosporin (cefazolin) for surgical antibiotic prophylaxis does not confer significant risk for C. difficile infection.
What is the LEAST appropriate palliative intervention in a woman with a 12 cm cecum and malignant sigmoid lesion?
A. pain management with tincture of opium
b. loop colostomy
c. gastric tube
d. tube through the cecum
e. colorectal stent
Gastric tube (too proximal)
What is better 6 month long term Laparoscopic vs. Laparotomy endom ca staging
Quality of life and body image
Notes say: LSC - physical function, QOL, scar, pain
Better QoL
Lace trial: https://pubmed.ncbi.nlm.nih.gov/20638899/
Better body image
GOG 2222: https://pubmed.ncbi.nlm.nih.gov/19805678/
Pain better @ 6 weeks, but same @ 6 months
Temporary clamp on ureter, what to do
Stent
Rectosigmoid - distal stenosis after radiation, mgmt
A Progressive dilation
B loop colostomy
C LAR with Hartman’s pouch
A Progressive dilation
Pancreatic leak seen postoperatively, how to manage
Percutaneous drain
Old lady died after unvaccinated and splenectomy done, likely cause?
Strep pneumo
Most likely to have ureteral obst. Pt w hx of:
A pelvic Radiation + extrafascial hyst
B rad hyst + pelvic Radiation
C pelvic Radiation
D rad hyst
rad hyst + pelvic Radiation (this one)
Most common cause not seeing SBO on x-ray?
A NGT drainage
B High/proximal obst
C intestinal perforation
High/proximal obst (MLH can’t verify)
perforation (would see free air)
Lit Review:
the accuracy of plain radiographs in the diagnosis of bowel obstruction ranges from only 50 to 80%.
Plain radiographs are poor at identifying closed loop or strangulated obstructions in the setting of SBO
Most common cause incorrect surgical count
A multiple surgeries
B Change RN staff
C long operation
D obesity
multiple surgeries
Literature review:
Items being dropped, not initially counted, large case, packing issue, change in procedure
Most common complication of transverse loop colostomy?
A Retraction
B stricture
C parastomal hernia
D prolapse
Prolapse (this one most common)
#1 is skin irritation if choice
vs retraction for end colostomy
Most common complication continent ileal conduit?
A stone formation
B leaking
C Can’t cath
Stones (5-35%) based on UTD
notes say: Can’t cath aka stomal stricture (2-14%, THIS ONE)
leaking (short term 2-10%)
stone formation (3% upper tract, 5-35% pouch calculi).
infection 5%.
Mgmt of ureteral injury at ureterovesical junction?
A ureteroneocystotomy
B Boari flap
C ureteroureterostomy
D transureterureterostomy
E nephrostomy
F nephrectomy
Ureteroneocystotomy
Lower ureter 90% (ureteroneocystotomy), psoas hitch ureteral reimplantation helps if cannot do either of the prior w/o tension).
Middle ureter 7% (Boari flap, transureterureterostomy).
Upper ureter 2% (nephrostomy, nephrectomy, autotransplation, ileal or appendiceal interposition graft)
Patient with history of Left hemicolectomy and needs diversion. What procedure to do?
Ileostomy on notes.
MLH not verified
Least thermal injury
A pure coag
B blend cut & coag
C pure cut
D spray
pure unblend cut
Highest risk for VRAM flap complications?
A Prior surgery
B smoking
C obesity
Obesity per lit review (AW-agree)
preop RT, obesity increase risk of wound complications/ deep SSI.
https://pubmed.ncbi.nlm.nih.gov/30113449/ says no risk in failure for pts w proper abdominal surgery
Notes said: Prior surgery (this one - prior Maylard?), smoking, obesity
For elective hyst pt with recent cardiac stent what should you do first?
Find out when/type of stent,
If bare metal stent, wait minimum 4-6wk or 90d, if drug eluting wait 12 months
“bare-metal stents should delay having elective surgery for at least 6 weeks after stent placement, and those who receive a drug-eluting stent should put off elective procedures for at least a year”
Bowel injury during L/S no bowel prep, 1 cm, what do you do
Primary repair (answer if < = 1 cm)
Biggest risk factor for LAR anastomosis leak
A no bowel prep
B only one dose of abx
C Tension
D hand sewn anastomosis
E presence of ileostomy
Tension (this one),
Distance of anastomosis from anal verge (if LAR <6cm from anal verge, highest risk i.e., 19% per Morrow) or this one if an option
B&H: The most important variables in the anastomotic leak rate are the distance from the anus to the anastomosis, the vascularity of the cut ends, the tension on the anastomotic line, and the elimination of the pelvic cavity
Associated with decreased SSI with rectosigmoid resection?
A Chlorhexadine bath
B normothermia
C mechanical and antibiotic prep
mechanical and antibiotic prep (this one)
Not Normothermia: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3398839/
Lit Review: Definitely antibiotic prep; just still out on added benefit of mechanical w/oral abx:
https://www.sciencedirect.com/science/article/abs/pii/S0090825822019175
Risk factors for anastomotic leak
A Increasing ascites >4L
B albumin <2
C smoking
if tension and <5-6 cm from small verge are not options…
albumin <3.5
Cite: https://jamanetwork.com/journals/jamasurgery/fullarticle/600912
? smoking: : Kwak et al. reported habitual smoking to be significantly associated with AL (OR 6.529, p = 0.007)
(ASA) score of ≥ 3 (P < 0.001), smoking (P = 0.001), diabetes (P = 0.035), a preoperative serum albumin level of < 4 g/dl (P = 0.030),
https://onlinelibrary.wiley.com/doi/full/10.1111/codi.13476
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700187/#B33-diagnostics-11-02382
How do you diagnose Abdominal compartment syndrome
Measurement of bladder pressure (not imaging!)
UTD: Intra-abdominal pressure can be measured indirectly using intragastric, intracolonic, intravesical (bladder), or inferior vena cava catheters [78]. The wall of the hollow viscus or vascular structure acts as a membrane to transduce pressure.
Sustained intra-abdominal pressure >20 mmHg (with or without APP <60 mmHg) associated with new organ dysfunction
How do you manage Abdominal compartment syndrome
Conservative mgmt: avoiding positive fluid balance after initial resuscitation, evac intraluminal contents, evac space-occupying lesions (i.e., ascites, hematoma), improve abdominal wall compliance, decrease tidal volume/paralyze.
Surgical mgmt: abdominal decompression if pressure >25 mmHg (possibly 15-25 mmHg) and end organ damage; with temporary wall closure.
proper positioning, improving abdominal wall compliance (eg, pain control, sedation, paralysis, mechanical ventilation), and reducing intra-abdominal volume
Distal obstruction due to malignant disease with Cecum 12 cm. Best treatment option?
A Transcutaneous gastrostomy
B Percutaneous cecostomy
C Transverse colostomy
D stent
transverse colostomy
Woman who is 12 months s/p rad hyst with unilateral leg swelling no erythema what is the best test to order to diagnose
LE DOPPLER
What nerve injury is associated with numbness over the thigh after a pelvic LND?
genfem
What are the phases of wound healing?
Wound healing is classically divided into 4 stages:
(A) hemostasis / coagulation (mast cells, histamines, fibrin clot, vasoconstriction)
(B) inflammation: release of PMNs, macrophages
(C) proliferation / Fibroplasia (collagen deposition)
(D) remodeling
Tensile strength at 10% for PDS
56 days / 8w
Tensile strength at 10% for polyglycolic acid (vicryl)
28 days / 4w
Tensile strength at 10% for chromic catgut
14 days / 2w
also seen 21-28 days listed (excel detroit sheet says 28d, Justin says 14d)
Tensile strength at 10% for catgut
5 days / 1w
What is max total local lido dose (mg) w/o epi? With epi?
300 mg WITHOUT epi
500 mg WITH epi
What is max total local lido dose (mg/kg) w/o epi? With epi?
4.5 mg/kg WITHOUT epi
7 mg/kg WITH epi
Tx for lidocaine tox
Duplicate
Usually supportive - use benzos for seizures
Dialysis is not useful
EKG changes with HYPERmag
prolongation of the PR interval
increase in QRS duration
increase in QT interval.
Complete heart block and cardiac arrest may occur at a plasma magnesium concentration above 15
Which drug increases platelets
A bactrim
B vanco
C GCSF
D heparin
E IL-11
IL-11 (THIS ONE)- tx and ppx against thrombocytopenia!
bactrim, vanco, GCSF, heparin - the others all may lower
What are acceptable options for colon cancer screening for those at average risk per ACOG?
Colorectal cancer screening for average-risk* women:
-begin at age 45 years.
-stopping routine screening at age 75 years.
Screening test options:
- Colonoscopy (gold standard) every 10 years
- CT colonography (virtual colonoscopy) every 5 years
- Flexible sigmoidoscopy every 5 years
- Fecal immunochemical test (FIT) annually
- Guaiac-based fecal occult blood test (gFOBT) annually
- Multi-targeted stool DNA test (mt-sDNA or Cologuard) every 3 years
What is associated with increasing opiate dose
Tolerance associated with increasing dose (THIS ONE)
Other option included dependence, 2 other choices
Sx of HYPERmag
(think of pre-e)
4-6: nausea, HA, drowsy/lethargy, diminished DTR, flushing
6-10: somnolence, hypocalcemia, absent DTR, bradycardia, hypotension; ECG changes (prolonged PR interval, increased QRS, increased QT interval)
>10: flaccid quadriplegia, apnea, resp failure, cardiac arrest, complete heart blck (resp failure precedes cardiac collapse)
Risk factors for lymphedema
UTD:
- obesity, esp BMI >50
- lymphadenectomy + postoperative radiotherapy > lymphadenectomy alone
- # LN removed
- postoperative infections following lymph node dissection
- Cellulitis
- DVT
Notes also say, but cannot verify: extent of surgery, postop DVT 20% in pt with hyst + LND; higher for inguinal LND 30%?
Chi: Lymphedema starts to appear within weeks of surgery.
Obesity, the number of lymph nodes removed, the extent of surgery, postoperative infection, radiation therapy, and postoperative DVT increase the risk of developing lymphedema.
Pseudomonas UTI - which does NOT cover?
A zosyn
B Amox
C cipro
D meropenem
E aztreonam
Amox (this one).
Pseudomonas coverage: zosyn, ceftazidime or cefepime, aztreonam, cipro (not as much other fluroquinolones), levo, meropenem/doripenem (not as much imipenem), aminoglycosides
AG but need dual therapy (except for tx of UTI).
Oral: pick cipro (or levofloxacin but levo’s additional spectrum of coverage is usually unnecessary)
What antibiotics can be used to treat pseudomonas?
IV First Line Choices:
●Antipseudomonal penicillins + beta-lactamase inhibitor:
*Piperacillin-tazobactam
●Cephalosporins with antipseudomonal activity include:
*Ceftazidime
*Cefepime
●Monobactam: Aztreonam
●Fluoroquinolones:
*Ciprofloxacin (Levofloxacin has no advantage due to additional spectrum; potentially harmful. NOT moxifloxacin
●Carbapenems: Meropenem (preferred over imipenem due to resistance)
Aminoglycosides (tobramycin favored over gentamicin; amikacin) are active against P. aeruginosa but are generally not used as single agents because of inadequate clinical efficacy at most sites.
- can be single agent for treatment of lower urinary tract infections (cystitis).
PO antibiotics — Fluoroquinolones are the only antibiotic class with oral formulation that is reliably active against P. aeruginosa. Ciprofloxacin > levofloxacin.
Do not use moxifloxacin or fosfomycin
How do you treat a pt with a PE postop with renal failure (CrCl 20)?
A IVC filter
B LMWH
C heparin
HEPARIN
UTD: “Renal failure — IV UFH is our preferred anticoagulant in those with severe renal failure (eg, CrCl <30 mL/minute) since renal adjustment is not required for therapeutic anticoagulation.”
enoxaparin would be ok w/ CrCl <30 @ 1mg/kg/day. Just not ok on dialysis
Other anticoagulants acceptable at this CrCl:
Apixaban
Edoxaban
Warfarin
argatroban
Not recommended:
Dalteparin
Dabigatran
Rivaroxaban
Notes Say: heparin (THIS ONE). LMWH (can dose 1 mg/kg daily rather than 1 mg/kg BID or 1.5 mg/kg daily but not if <30)
PE on anticoagulation. Treatment?
Are they actually therapeutic?
Switch to lovenox if on warfarin
Increase lovenox dose.
Consider IVC filter.
Anti-Xa and direct thrombin inhibitors is unstudied in this population
UTD: increase heparin dose if on UFH.
If on LMW heparin, factor Xa or direct thrombin inhibitors in whom subtherapeutic anticoagulation suspected but unconfirmed, or those subtherapeutic on warfarin, switching to a rapid–acting anticoagulant that can be followed (eg, unfractionated heparin) may be prudent while investigations are ongoing. (AW)
What is first line Outpatient treatment for neutropenic fever?
NCCN 1/24:
Outpatient PO options:
- Ciprofloxacin plus amoxicillin/clavulanate (category 1) - (use clinda if PCN allergy)
- Levofloxacin
- Moxifloxacin (category 1)
Inpatient therapy:
- Cefepime (category 1)
- Imipenem/cilastatin (category 1)
- Meropenem (category 1)
- Piperacillin/tazobactam (category 1)
- Ceftazidime (category 2B)
Most sensitive/specific test for cdiff
Stool cell culture cytotoxicity assay- gold standard
two-step approach: enzyme immunoassay (EIA) test first for glutamate dehydrogenase (GDH), followed by a toxin test and/or a nucleic acid test (NAAT)
Most sensitive test finding to r/o CHF in woman with dyspnea postop?
A BNP <100
B normal CXR
C physical exam with no LE edema
D low CVP
BNP <100 (this one)
BNP levels below 100 pg/mL and those above 500 pg/mL have, respectively, a 90% negative predictive value (NPV) and positive predictive value (PPV)
In patients with dyspnea at rest, the negative predictive value of a normal plasma NP level is high. NP levels are often (but not exclusively) elevated in patients with HFrEF, but may be normal in a substantial number of patients with HFpEF.
CXR limitations - especially HFpEF, where the sensitivity of cardiomegaly is 24 percent and pleural effusion is only 9 percent. In contrast, the same study found that specificity for these findings is excellent (96 and 98 percent, respectively)
specificity / sensitivity edema (72 and 53 percent)
A decrease in cardiac output either due to decreased heart rate or stroke volume (e.g., in ventricular failure) results in blood backing up into the venous circulation (increased venous volume) as less blood is pumped into the arterial circulation. The resultant increase in thoracic blood volume increases CVP.
Most predictive of pulmonary infection after surgery
A Pulm edema
B low vertical incision
C EBL
D nutrition
nutrition (low albumin associated with post-op PNA)
Also:
Increased age, chronic obstructive pulmonary disease, emergency surgery, postoperative reduced albumin, prolonged ventilation, and longer duration of bed rest were identified as significant
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304902/
What are risk factor for postop pulm complications?
UTD:
Definite risk factors include [1,3,7]:
●Upper abdominal, thoracic (open), aortic, head and neck, neurosurgical, and abdominal aortic aneurysm surgery
●Emergency surgery
●Age >65 years
●Surgery lasting greater than three hours
●Poor general health status, ASA class >2
●Heart failure
●Serum albumin <3 g/dL
●Chronic obstructive lung disease
●Cigarette use within the previous eight weeks
●Intraoperative long acting neuromuscular blockade
●Functional dependence
●Obstructive sleep apnea
●Recent lower respiratory tract infection
●Frailty
Probable risk factors include:
●General anesthesia (compared with spinal, epidural anesthesia, or other regional anesthetic techniques)
●Arterial tension of carbon dioxide (PaCO2) >45 mmHg (5.99 kPa)
●Abnormal chest radiograph
●Current upper respiratory tract infection
●Postoperative nasogastric tube placement
Most likely means to transmit cdiff
Not washing hands b/t patients
Most likely complication from subclavian line placement
Arrhythmias
Cardiac complications are one of the immediate complications which occur during subclavian line placement. Most common is the onset of arrhythmias (premature atrial and ventricular contractions) which occur when guidewire comes in contact with the right atrium. [9]These arrhythmias can be easily managed by slightly removing the guidewire.
Notes say: NEJM 1994 misplacement (6%), arterial puncture (3.7%), PTX (1.5%), mediastinal hematoma (0.6%)
(JS) can’t find arrhythmias as the MOST common. UTD says below are the immediate complications of all central venuos access, but PTX more common in subclavian:
Immediate complications:
Bleeding
Arterial puncture
Arrhythmia
Air embolism
Thoracic duct injury (with left SC or left IJ approach)
Catheter malposition
Pneumothorax or hemothorax
Delayed Complications
Infection
Venous thrombosis, pulmonary emboli
Venous stenosis
Catheter malfunction
Catheter migration
Catheter embolization
Myocardial perforation
Nerve injury
H&H
Pneumothorax and subclavian venous thrombosis are the most common catheter-related complications for temporary and permanent central venous catheters (CVCs)
Detroit excel lists Pneumothorax (Gemini supports) (AW)
Most common complication of HIT
A Thrombosis
B hypersplenism
C ARF
Thrombosis (this one)
UTD:
Thrombocytopenia (platelet <150,000/microL) most common; 85 to 90%
Thrombosis occurs in up to 50 percent
bleeding was seen in approximately 6 percent
—> Complications of thrombosis: death (most commonly due to pulmonary embolism), skin necrosis, limb gangrene (sometimes requiring amputation), and organ infarction
Mechanism of action for bisphosphonates
Inhibit osteoclastic bone resorption (primary) – also reduce decreased osteoclast progenitor development and recruitment by promoting osteoclast apoptosis
Manifestations of hypoMg
Neuromuscular hyperexcitability (tremor, tetany, sz, weakness, apathy, delirium, up to coma),
CV (widened QRS and peaked t-waves with moderate magnesium depletion, and widening of the PR interval, diminution of T waves, and atrial and ventricular arrhythmias with severe depletion.
JS - similar sxs of hypocalcemia
Which of the following is Inappropriate abx for neutropenic fever?
A Meropenem
B Piperacillin/tazobactam
C Ciprofloxacin plus amoxicillin/clavulanate
D Ceftriaxone
E Levofloxacin
Ceftriaxone (3rd gen without pseudomonas coverage)
Ceftazidine only 3rd generation with P. aeruginosa coverage
4th Generation - Adds Pseudomonas Coverage
NCCN 6/24:
Inpatient therapy:
- Cefepime (category 1)
- Imipenem/cilastatin (category 1)
- Meropenem (category 1)
- Piperacillin/tazobactam (category 1)
- Ceftazidime (category 2B)
Outpatient PO options:
- Ciprofloxacin plus amoxicillin/clavulanate (category 1)
- Levofloxacin
- Moxifloxacin (category 1)
How to tx DVT if renal failure (CrCl <10)
anticoagulants acceptable at this CrCl and for dialysis
Apixaban
Warfarin
argatroban (makes sense bc used in HIT, which can have renal failure)
Heparin ok as treatment, but only if no suitable alternative.
*UTD says enoxaparin would be ok <30 @ 1mg/kg/day. This would not be ok on dialysis
Not recommended:
Dalteparin
Dabigatran
Rivaroxaban
Edoxaban
Notes say: Don’t use lovenox –> can use coumadin or argatroban or heparin or apixiban
(JS) UTD: recommends UFH followed by warfarin titration inpatient if dialysis dependent.
Hyponatremia - most concerning sx
confusion
Symptoms:
●Nausea and malaise, which are the earliest findings, may be seen when the serum sodium concentration falls below 125 to 130 mEq/L.
●Headache, lethargy, obtundation and eventually seizures, coma, and respiratory arrest can occur if the serum sodium concentration falls below 115 to 120 mEq/L. Noncardiogenic pulmonary edema has also been described.
Euvolemic Hyponatremia with high urine sodium (>40)
High urine Na >40, high urine osmolality >300 = SIADH
Euvolemic Hyponatremia with low urine sodium (<25)
Low urine Na <25, low urine osm <100 = primary polydipsia, malnutrition, potomania, or surreptitious diuretic use
What’s the difference between HIT I and HIT II?
Type I HIT, also known as heparin-associated thrombocytopenia (HAT), is a non-immune mediated reaction. Type I HIT is much more common than type II and can occur as early as day 1 of therapy. This is a mild reaction, it is not associated with any complications, and platelet counts will spontaneously normalize even if heparin is continued.
—> HIT 1 can happen on day 1
Type II HIT is an immune, antibody-mediated reaction. Because it takes time for the antibodies to form, this reaction usually occurs after 5 to 14 days of receiving heparin. However, if a patient has been exposed to heparin within the last 100 days, antibodies may remain in the system, causing this reaction to manifest as soon as day one of re-exposure to heparin. This is a very serious reaction that causes a hypercoagulable state and can lead to life-threatening complications.
—> HIT II (looks like 11) happens on day 11 ish
(classic HIT as we know it)
Esophageal doppler vs. conventional monitoring intraop for fluid resuscitation
A Lower mortality
B less ICU stays
C Faster return of bowel function
D lower MAP
E lower CO
FASTER RETURN OF BOWEL FUNCTION
less ICU stays (THIS ONE) - disagree
Lit review: shorter LOS
Notes say: Less/shorter ICU stay would be my answer. Found association with higher CO.
i found this: Intraoperative oesophageal Doppler guided fluid management associated w/a 1.5-day median reduction in postoperative hospital stay. Patients recovered gut function significantly faster and suffered significantly less gastrointestinal and overall morbidity (AW)
EPO known risks
**BOXED WARNING: Erythropoiesis-stimulating agents (ESAs) ** increase the risk of death, MI, stroke, venous thromboembolism, thrombosis of vascular access. ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence
- death risk (in CKD when used to target a hemoglobin level of greater than 11 g/dL.)
This drug DOES reduce allogeneic RBC transfusion preop
Can cause hypertension
Epo DOES NOT improve quality of life, fatigue, or patient well-being.
Define obesity hypoventilation syndrome
Obesity (body mass index ≥30-35 kg·m2)
daytime/awake hypercapnia (arterial carbon dioxide tension ≥45 mmHg) and sleep disordered breathing.
rule out other disorders that may cause alveolar hypoventilation
COPD greatest preop eval risk
HAVING COPD=FEV1/FVC <70
COPD is an independent predictor for postoperative pneumonia (OR 1.71, 95% CI 1.59-1.83), reintubation (OR 1.54, 95% CI 1.42-1.66), and failure to wean from the ventilator (OR 1.45, 95% CI 1.35-1.56), in addition to non-pulmonary adverse outcomes
there appears to be no prohibitive level of pulmonary function below which surgery is absolutely contraindicated.
preoperative spirometry was not predictive of complications following abdominal surgery. PFTs should not be performed routinely in patients undergoing nonresectional surgery. The degree of physiologic impairment (eg, FEV1 or FVC) does not correlate with the risk of postoperative pulmonary complications.
Complication of cdiff
Toxic megacolon
●Megacolon should be suspected in patients with severe systemic toxicity together with radiographic evidence of large bowel dilatation (>6 cm diameter in the colon and/or >12 cm diameter in the cecum). Megacolon may be complicated by bowel perforation; manifestations include abdominal rigidity, involuntary guarding, diminished bowel sounds, rebound tenderness, and severe localized tenderness in the left or right lower quadrants; abdominal radiographs may demonstrate free abdominal air
(JS) tx same as fulminant colitis -> supportive care until pushed to operate, then TOTAL colectomy (not partial)
Colon cancer screening recs
for Average risk (no history of IBD, no family history) starting at age 45yo per NCCN, USPSTF, and ACS:
1) Colonoscopy q10 years (preferred)
2) Stool-based test (guaiac-based testing or Fecal immunochemical test (FIT) testing) q1yr –> if pos then scope
3) Multitargeted stool DNA (mt-sDNA)–based testing q3yr, aka cologuard
3) flex sig q5-10 years (+/- FIT)
4) CT colonosgraphy q5years
Least helpful: MD digital rectal exam
Best way to check for PE
A V/Q
B CT pulmonary angiography
C Lower-extremity ultrasound with Doppler
D Magnetic resonance pulmonary angiography
E Catheter-based pulmonary angiography
CT pulmonary angiography
FYI: normal chest radiograph is usually required prior to V/Q scanning
Catheter-based pulmonary angiography: contrast is injected under fluoroscopy via a catheter introduced into the right heart, was the historical gold standard for the diagnosis of PE. less accurate than CTPA
Best imaging to identify brain mets
MRI
Contrast-enhanced MRI is the preferred imaging study for the diagnosis of brain metastases [36-39]. Contrast-enhanced MRI is more sensitive than either nonenhanced MRI or CT scanning in detecting lesions in patients suspected of having cerebral metastases and in differentiating metastases from other central nervous system (CNS) lesions
Best abx for Klebsiella
Notes say: Ceftazidime (this one), imipenem and clinda, vanc and gent
From emedicine: 3rd gen cephalosporins, carbapenemas (ie: imipenem), AG (gent), quinolones
Lit review:
- third or fourth-generation cephalosporin as monotherapy
- respiratory quinolone as monotherapy
- either 3/4 G cephalosporin or respiratory quinolone + aminoglycoside.
- If penicillin-allergic: aztreonam or a respiratory quinolone
- If nosocomial: carbapenem monotherapy
Appearance of radiation enteritis on imaging
Diffuse bowel wall thickening
The ileum is the most frequently injured segment of the small intestine because of its location in the pelvis. Submucosal edema and fibrosis are seen at barium examinations as thickening and straightening of small-bowel folds and separation of adjacent loops. CT can directly reveal bowel wall thickening related to submucosal edema (Fig. 4A,4B). Fluoroscopic evaluation may show single or multiple areas of stenosis and small-bowel obstruction. Altered peristalsis may also be encountered. Fibrotic changes in the mesentery may cause fixation of bowel loops; in this condition, the loops appear angulated and tethered at small-bowel follow-through examination. Increased density in the mesentery may be evident at CT [5].
Least likely reason for afib
A hypoxia
B electrolyte imbalance,
C Anemia
D PE
Anemia (this one)
Lit review: all can cause afib… but our discussion suggests anemia is likely correct
What element is required in RBC production?
Copper
What is a normal ventilator tidal volume setting based on weight?
6-8 cc/kg (more than 10cc/kg associated with lung injury)
What is a normal A-a gradient?
5-10 mmHg
What does PCWP approximate?
LA pressure
Definition of acute renal failure
KDIGO guidelines define AKI as follows
●Increase in serum creatinine by ≥0.3 mg/dL (≥26.5 micromol/L) within 48 hours, or
●Increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days, or
●Urine volume <0.5 mL/kg/hour for six hours
Which diuretics may lead to HYPERKALEMIA
Duplicate
Potassium-sparing diuretics such as spironolactone, amiloride, and triamterene
Which hyperK tx affect serum but not total K levels
Duplicate
Things that push into cells - B2 agonist, glucose/insulin, bicarb
FYI: IV calcium is administered for myocardium membrane stabilization and does not promote the intracellular shift or elimination of potassium
Which hyperK tx affect both serum and total K levels
Duplicate
K-binding agents: Kayexalate (sodium polystyrene sulfonate), Lokelma (sodium zirconium cyclosilicate). Dialysis, loop or thiazide diuretic
When placing Swan ganz- where are you if you see dicrotic notch
Past the PULMONARY VALVE and into the pulmonary artery
the location of the catheter can be determined by viewing the pressure measured from the tip of the catheter.
- right atrium (RA), the pressure usually averages <5 mmHg and fluctuates a few mmHg.
- right ventricle (RV), the systolic pressure increases to ~25 mmHg and the diastolic pressure remains similar to right atrial diastolic pressure.
- pulmonary artery (PA), the systolic pressure normally is similar to the right ventricular systolic pressure, but the diastolic pressure increases to about 10 mmHg because of pulmonic valve closure at the beginning of diastole.
- balloon Inflated occludes the PA branch. the pressure in the distal port rapidly falls, reaches a stable lower value that is similar to left atrial pressure (mean pressure normally 8-10 mmHg). The pressure recorded during balloon inflation approximates left atrial pressure because the occluded vessel and its distal branches that eventually form the pulmonary veins act as an extension of the catheter.
See: https://cvphysiology.com/heart-failure/hf008
Which blood product cannot transmit CMV?
FFP (b/c no leukocytes)
Frozen components, including fresh frozen plasma (FFP) and cryoprecipitate, have not been shown to transmit CMV
How long can you store RBC
42 days (6 weeks) due to current Anticoagulant-preservative (A-P) solutions
Which coagulation factors are the following
Fibrinogen
Prothrombin
Thrombin
Fibrinogen = factor I (think F1brinogen)
Prothrombin = factor II (think proThrOmbin)
Thrombin = factor IIA (pro means before so this must be 2A)
Which component of the clotting cascade does PTT measure?
Intrinsic
“PTT=play table tennis, Inside”
Intrinsic
Which component of the clotting cascade does PT measure?
Extrinsic \
“PT= play tennis, outside”
JS- the only way out of the hospital is after PT eval (exit via PT)
Most common organisms line infection
Coag neg staph, staph aureus, Enterococcus
Most frequently isolated BSI organisms include coagulase-negative staphylococci (31%), Staphylococcus aureus — either methicillin sensitive or resistant (20%), enterococci (9%), Escherichia coli (6%), Klebsiella species (5%), and Candida species (9%).
AS: UTD says Coag neg staph 16.4%, S. aureus 13.2%, Enterococcus 15.2%, Candida 13.3% as most common
Tx of SVT
Adenosine
What does labeling index do?
Measures proliferation and cells that have COMPLETED S phase
Example: Ki-67 proliferative index
What lab or vital sign abnormality is First and most sensitive to blood loss?
Pulse/tachycardia
What to give if patient has low fibrinogen?
Cryoprecipitate
What does FISH measure?
Fluorochrome-labelled DNA probe is hybridized to specific base pair sequence in metaphase chromosomes or interphase nuclei. Detects recurring numerical or structural chromosomal abnormalities
What is ELISA?
Enzyme-linked immunosorent assay. Ab bound to plate to capture the antigen; also attached to enzyme that can convert some chemical into something that can be measured by color
What is a southern blot?
Measures DNA
“DNA is bigger/heavier, things are bigger in the south”
What is a northern blot?
Measures RNA
What is malignant hyperthermia?
Justines answer: reaction to anesthesia, tx with dantrolene, develop rhabdo. RYR1 mutation
Which are vitamin K dependent coag factors?
II, VII, IX, X (2+7=9 and 10)
What to do if suspect air embolism after Swan Ganz?
Answer: Left lateral and t-burg
Wrong answer: try to aspirate
Describe nec fasc
Gray margins, irregular borders, erythema, pain out of proportion, crepitus, fever
AS: lymphangitis often = for erysipelas (group A strep)
What is the risk of reinfarction <3 months and >6 months after MI?
Less than 3 months after MI: risk for reinfraction is 30%
Greater than 6 months after MI - risk is 1-2%
What abx for high risk endocarditis undergoing dental procedure?
Ampicillin
Ideal time to stop smoking before surgery?
4 weeks
at least 4-6wk
Which does not cause an increased A-a gradient?
hypoventilation
wrong answers: shunting, V/Q mismatch
Which is least likely to affect A-a gradient?
Hypoventilation
wrong answers: ARDS, PNA, PE, pulmonary edema
*Repeated question
Best test for aneuploidy
answer: flow cytometry for propidium iodide
background information: Flow cytometry (FCM) provides a fast and precise method for determination of DNA-aneuploidy index.
*Aneuploidy was diagnosed previousy by counting the metaphase chromosomes under the microscope, with difficulties in precision/accuracy, long processin time and handling of strong acids (difficult for large scale use).
*Flow cytometry surpasses the above barriers by quantifying the amount of DNA rather the counting the number of chromosomes, it has low level of variation coefficient of the DNA peaks, an equal proportion of cells in each peak, and a small difference in DNA of the sample and internal reference. It is now widely used to identify aneuploidy in cancers.
OR is closer to RR if prevalence is high or low?
Low
Which flap lowest failure?
Any RAM flap is flap of choice for gynecologic defects lower failure rate than gracillis
Based on morrow
Based on UTD for anterolateral thigh flaps: donor site morbidity, including skin separation and lymphocele, are recognized complications of flap harvest.
What is the diff between assist control, intermittent mandatory ventilation, and pressure controlled ventilation?
assist control–Triggered with patient’s resp effort but if not initiated will deliver a breath at pre-specified interval, patient can over-breathe the vent.
intermittent mandatory ventilation–Initiates breath at prespecified intervals if patient doesn’t (but not triggered by patient breath), can lead to increased work of breathing.
Pressure-controlled ventilation: ventilate a patient with a maximal peak pressure. In contrast to volume-controlled ventilation, pressure-control involves the selection of an inspiratory pressure instead of a tidal volume target. The setting of an inspiratory pressure, as well as an associated positive end-expiratory pressure (PEEP), will allow a provider to control the peak pressure, thereby protecting from barotrauma.
What is the pathophysiology of nausea and vomiting induced by uremia, hyperCa, and some medications?
Duplicate
High plasma concentrations of emetogenic substances (opioids, selective serotonin reuptake inhibitors, urea, and calcium) trigger nausea and vomiting by stimulating dopamine D2 receptors located in the chemoreceptor trigger zone.
The best treatment would be a dopamine antagonist, such as haloperidol, which is the most potent of dopamine receptor blockers, and metoclopramide.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426995/
What is the relationship between adjusted PCWP and ARDS vs CHF?
Adjusted PCWP < 44 mmHg below colloid oncotic pressure - likely ARDS (answer)
Adjusted PCWP > 44 mmHg above colloid oncotic pressure - likely CHF (I’m not sure if this statement is correct - it was not highlighted in red)
- I could not find these specific numbers. On UPTD, the following is mentioned: pulmonary edema occurs at pulmonary artery capillary pressures as low as 18 mmHg. By contrast, patients with chronic heart failure have an increased lymphatic capacity and do not develop pulmonary edema until much higher pulmonary capillary pressures (eg, >25 mmHg) are reached.
What is the goal of phase I, II, III, IV trials?
I = defines max tolerated dose
*Ia trials will provide a single dose of the drug to each participant to determine the MTD within one treatment arm.
*Phase Ib trials run multiple arms simultaneously to test more than one dose of the drug.
II = defined biologic activity > effectiveness in a certain type of cancer and side effects
*Phase 2A studies are typically more preliminary and can address issues such as dosing and safety, while phase 2B studies are generally ‘mini-phase 3’ studies that provide data on efficacy.
III = usually RCT > confirm efficacy compared to standard treatments
*3a studies take place before FDA approval.
*3b studies are conducted after. Post-approval studies may further research how the treatment impacts quality of life, for example.
IV = large scale to see if can translate to larger population, post market studies.
How would you approach the nutritional support for a patient following an uncomplicated debulking with moderately impaired nutritional status
A partial parenteral nutrition (PPN)
B TPN,
C isotonic fluids with addition of D5
D enteral feeding
enteral feeding
Best opioid for renal issues
Dilaudid (most likely because Fentanyl was not a choice. Fentanyl is preferred but it was most likely not listed on the exam)
transdermal buprenorphine, transdermal fentanyl, and oral hydromorphone are the most tolerable opioids in these patients;
hydrocodone, oxycodone, and methadone are useful but require careful monitoring
tramadol, codeine, morphine, and meperidine should be avoided due to risk of accumulation and adverse events
What is the relationship between standard deviation and variance?
Standard deviation = square root of variance
SD = “how far datapoint is from measured mean”. Variance = “how variable datapoints are from each other”
What is smaller than the standard deviation? How do you calculate it?
Standard error of the mean
standard error of the mean = SD / square root of n
Doing multiple t-tests results in more of what type of error?
Type I (false positive aka erroneously rejecting null hypothesis)
Is chi-square parametric or non-parametric?
Non parametric
*used to examine whether two categorical variables are independent in influencing the test statistics. if ≤ 20% of expected cell counts are less than 5, then use the chi-square test; if > 20% of expected cell counts are less than 5, then use Fisher’s exact test. Both methods assume that the observations are independent.
Most likely EKG finding in post op MI
Characteristic ECG changes of periop MI include new T-wave inversion and ST-segment depression = NSTEMI most likely postop
- Could not confirm this, based on UTD changes would be based on whether is a STEMI (ST segment elevation changes noted) vs. NSTEMI (above) with changes on EKG which may follow a sequence based on time of onset.
Most likely EKG finding in post op MI
Characteristic ECG changes of periop MI include new T-wave inversion and ST-segment depression.
- UTD changes would be based on whether is a STEMI (ST segment elevation changes noted) vs. NSTEMI (above).
What is the heparin induced thrombocytopenia 4 T score?
Scoring system consisted of four criteria, each of which was worth 0, 1, or 2 points. Study used ≤3 points to define low probability group (≤5%) for HIT, 4-5 points for intermediate and 6-8 points for high.
*The 4 Ts score should be used as a guide for clinicians and should not substitute for clinical judgment.
*Based on UTD, HIT antibody testing or presumptive treatment for HIT is not pursued with scores ≤3 (eg, we do not discontinue heparin or start a non-heparin anticoagulant) because the risk of HIT is low and presumptive treatment carries risks (eg, bleeding).
See pic
ERAS style intraop fluid management most likely to cause what detrimental effect?
Cause AKI
https://www.sciencedirect.com/science/article/abs/pii/S009082582100651X
Insulin and endometrial cancer mechanism
Notes say: insulin is an anabolic hormone that stimulates cell proliferation via MAPK, PI3K, PTEN/atk pathways
Lit review:
estrogen + insulin promotes proliferation endometrial cancer cells compared with estrogen or insulin alone
estrogen and IGF-1 can synergistically promote the development of tumors in mice by activating MAPK and AKT signaling pathways > *activate mTOR, p70S6 kinase, and GSK-3-beta, which are important for stimulation of protein synthesis and glucose transport. This pathway is also important for IGF-1 stimulation of cell motility, inhibition of apoptosis, and stimulation of cellular differentiation.
estrogen may bind to IGF-1R and exert non-genetic transcriptional effects through the Ras/MAPK signaling pathway
Most significant valve issue in elderly
aortic stenosis
*According to a table on UTD mitral regurgitation prevalence is 9.3% versus 2.8% prevalence of aortic stenosis in elderly above the age of 75.
Utility of FE Urea
- Results > 50 to 65 percent common in acute tubular necrosis (ATN)
- Results < 35 percent in prerenal disease
- FEUrea is more reliable on patients taking diuretics then FENa (which can be be falsely high in patients taking a diuretic).
Similar to FeNa, a larger value is more indicative of ATN
- Fractional Exceretion of Urea = Uur X Pcreat / Ucreat X Pur · 100%
Uur = Urine urea
Pcreat = Plasma creatinine
Ucreat = Urine creatinine
Pur = Plasma urea
ICU- cystatin C (if neither option, uninfluenced)
What lab testing exists for HIT
Solid-phase ELISA immunoassay that detects the presence of anti-platelet factor 4 (PF4)/heparin antibodies in patient serum
- most widely used laboratory test for HIT.
- fast but more false +.
- sensitivity and specificity 97.5% and 83.4%
- NPV of 99.6%, PPV 44.4%
Functional assays (Serotonin release assay)
- gold standard
- disadvantages: high cost, use of radioactive material, technical demands of the assay, delay in obtaining results due to lack of routine availability at most institutions.
- Ticagrelor: interfere with functional assays for HIT, leading to false negative tests.
What is timing of HIT
Occurs 5-10 days after heparin exposure, or within 24hrs if antibodies already present
How to monitor enoxaparin
factor Xa inhibition (anti-factor Xa activity): Target levels for BID enoxaparin are between 0.5 and 1 measured 4-6 hours after dose, starting after 3rd-4th dose
Routine monitoring of anti-factor Xa activity is not required but has been utilized in patients with obesity, kidney insufficiency and pregnancy
given changes in pharmacokinetic parameters and renal clearance.
For patients >144 kg, if anti-factor Xa monitoring is available, adjusting dose based on anti-factor Xa activity is recommended
Dose of lovenox for obese patients
treatment:
BMI ≥30 kg/m2: usual dosing range: 0.7 to 1 mg/kg every 12 hours - actual body weight
BMI ≥50 kg/m2: lower end of the usual dosing range
Extreme BMI (~114 kg/m2), doses below usual may be indicated. anti-factor Xa monitoring is recommended
Ppx
BMI 30 to 39 kg/m2: standard dosing
BMI ≥40 kg/m2: fixed or weight-based dosing - 40 mg twice daily or 0.5 mg/kg twice daily (based on actual body weight)
BMI >50 kg/m2: 60 mg twice daily or 0.5 mg/kg twice daily (based on actual body weight). target anti-factor Xa level.
Renal Dose reduction of lovenox
CrCl >=30: No dose adjustment necessary
CrCl <30mL/min: 30mg daily prophylaxis, 1mg/kg once daily for therapeutic
Standard dose of lovenox
Ppx: 40mg daily
Treatment: 1 mg/kg every 12 hours (preferred) or 1.5 mg/kg once every 24 hours.
How do hemodynamic parameters change with trendelenburg and pneumoperitoneum?
- increase CVP, MAP, SVR, PCWP and pulmonary arterial pressures
- decrease cardiac output and stroke volume per UTD
what opiate causes prolonged QT and torsades
methadone
70 yo with DM, HTN, AFIB sp TLH/BSO what anti coag post op
lovenox
was there a difference in QOL during or after IP chemotherapy for ovarian cancer?
worse during through 6 weeks after , but no different 1 year later (GOG172)
Medicine class most associated with delirium in elderly post-operative patients?
Benzos
Others: cimetidine, corticosteroids, diphenhydramine, belladonna, promethazine, warfarin, narcotics, benzodiazepines, and antiparkinsonian drugs
Most common complication after splenectomy?
A Transient bacteremia with encapsulated organisms
B left atelectasis
C abscess
D pancreatic leak
left atelectasis (THIS ONE in Bristow text)
During inguinal LND, use of fibrin sealants increases risk of?
A lymphedema
B Infection
C drainage from site
D wound separation
Infection
https://www.gynecologiconcology-online.net/article/S0090-8258(08)00198-4/fulltext
What is least likely complication of premenopausal BSO?
A anxiety/depression
B CV dz
C Kidney stones
D metabolic syndrome
Kidney stones (This one),
Though does increase risk of
- Chronic kidney disease
- dementia
- CV disease
- all cause mortality
- Parkinson’s
- anxiety and depression
- glaucoma
- osteoporosis
- sexual dysfunction
Most common injury L/S
urinary tract of option and specific for gyn
Otherwise Bowel slightly higher than vascular
Bowel: 0.03 to 0.65% undergoing laparoscopic surgery
Vascular: 0.01 to 0.64% of laparoscopies
urinary tract 0.03 to 1.7% of laparoscopic gyn surgeries
Up to one-half of complications occur at the time of abdominal access for camera or port placement
ABG for PE
Respiratory alkalosis (tachypnic),
decreased CO2 and PaO2;
elevated A-a gradient
What is Erythropoietin production stimulated by?
Decreased O2 in the renal artery
Erythropoietin (EPO) is a glycoprotein hormone, naturally produced by the peritubular cells of the kidney, that stimulates red blood cell production.
Renal cortex peritubular cells produce most EPO in the human body. PO2 directly regulates EPO production. The lower the pO2, the greater the production of EPO”
If Swan-ganz will not wedge, what value most closely corresponds?
PA diastolic pressure
pulmonary artery (PA) diastolic pressure is similar to the pulmonary artery wedge pressure and is similar to left atrial pressure (mean pressure normally 8-10 mmHg).
- accurate as long as no pulmonary HTN exists
See: https://cvphysiology.com/heart-failure/hf008
What is contraindication to PA catheter placement
Notes say: LBBB
Absolute contraindications:
●Infection at the insertion site
●The presence of a right ventricular assist device
●Insertion during cardiopulmonary bypass
●Lack of consent
Relative contraindications:
- coagulopathy (INR >1.5), thrombo (<50k) - risk hemorrhage
- hypo- /hyper-K, -Mg, -Na, -Ca) - risk life-threat arrhythmias
- pH <7.2 or >7.5 - risk life-threatening arrhythmias
High risk
- severe pulmonary HTN (risk pulmonary artery rupture)
- Eisenmenger’s syndrome (risk pulmonary artery rupture)
- right or left bundle branch block (risk CHB)
- defibrillator or pacemaker (risk of displacement)
- prosthetic or stenotic tricuspid / pulm valve (diff cath adv)
- latex allergy (most catheters have latex)
- persistent L SVC (misplacement to the left atrium)
- right atrial or ventricular masses (diff cath advancement).
Best predictor of weaning off vent
Rapid shallow breathing index (RR/TV);
Successful weaning predicted if RSBI <105
Weaning failure predicted if >=105
What is nec fasc type I and type II?
Type I: (polymicrobial) immunocompromised pts (often DM, elderly). anaerobic/aerobic bacteria (eg., Staphylococcus aureus, Haemophilus, Vibrio, Escherichia coli, Bacteroides fragilis).
Think DM Type1 are immune compromised
Type II: (monomicrobial) immunocompetent patients w history of trauma (sometimes minor). S. pyogenes (GAS /other beta hemolytic strep) +/-Staphylococcus aureus
What changes occur with short bowel syndrome to intestinal villi
- Epithelial hyperplasia
- lengthening of remaining villi
- remnant bowel will dilate and elongate, resulting in increased intestinal weight and protein content.
- Villus lengthening
- microvilli proliferation
-Total enterocyte number is increased - Hypertrophy of the muscle layers —> increase in bowel wall thickness.
- ileum demonstrates more adaptive capacity than the jejunum.
Which is not a tx for short bowel syndrome?
A anti motility agents
B nutritional support
C octreotide
D B12 supplementation
Notes say: octreotide (this one - b/c stomach) <— unsure of stomach comment, but correct as it has a lot of negative effects
Octreotide — The use of octreotide should be reserved for patients with intravenous fluid requirements that are greater than 3 L per day and only after the period of maximal intestinal adaptation
Typical candidates include patients with SBS and a high-output end-jejunostomy.
Octreotide increases small bowel transit time and reduces fluid losses, but tachyphylaxis often develops.
Octreotide diminishes splanchnic protein synthesis, which can interfere with the process of adaptation
predisposes patients to the development of gallstones for which patients with SBS are at high risk
Also avoid growth hormone, cholestyramine, and glutamine
—
Fat soluble vitamins (A, D, E, and K), vitamin B12, folate, calcium, magnesium, zinc, iron, copper, and selenium are the main micronutrients at risk for deficiency
JD: yeah, octreotide only for >3L and developes tachy. Bad. The rest are all neccessary.
Calcium correction for albumin
Corrected Calcium mg/dL = (0.8 * (Normal Albumin - Pt’s Albumin)) + Serum Ca
JD: Corrected Ca mg/dL = Measured Ca + (0.8* (4 - measured Alb))
Indications for dialysis
These are “urgent indications”.
A (acidosis <7.1)
E (electrolytes, hyperK >6.5)
I (intoxication, methanol, ethanol, lithium, ASA)
O (volume overload)
U (uremia, encephalopathy/pericarditis)
Most common lab abnormality in DIC
D-dimer elevation is most sensitive and specific and probably correct answer
Also in the decreasing order of frequency are thrombocytopenia, elevated fibrin degradation products (FDPs), prolonged PT, aPTT and a low fibrinogen
JD: I cannot confirm the above, and think likely thrombocytopenia
https://emcrit.org/ibcc/dic/
Is dialysis useful for lidocaine overdose
No
Not dialyzable
How often should splenectomy patients get vaccinated?
Every 5 years
JD: MenB every 2-3 yrs (new as of 2019 ACIP reccomendation)
PPSV23 and MenACWY every 5 years
For transureteroureterostomy - where should it run in relation to IMA
and great vessels
In front of great vessels can be in front of or behind IMA
“This is achieved by tunneling the donor ureter through the sigmoid colon mesentery superior to the inferior mesenteric artery to avoid kinking.”
BB: online textbook says inferior to IMA
MLH: Also saw pics of this above IMA online
Bottom line: IMA relationship probably depends on ureter length
JD: “ preferably cephalad to the IMA. If there is enough ureteral length that the ureter can be readily passed caudal to the IMA across to the contralateral side, then the patient is likely a candidate for ureteroneocystostomy.” Hinmans atlas of urologic surgery
Most common cause not seeing SBO on x-ray?
A NGT drainage
B perforation
C High/proximal obst
High/proximal obst (this one),
Unable to verify in lit review
JD: unable to verify this as well
Risk factors for unplanned retained foreign object in surgery:
The most common root cause of URFOs reportd to the Joint Commission are:
- absence of policies/procedures,
- failure to comply with policies/procedures,
- problems with hierarchy and intimidation,
- failure in communication with physicians,
- failure of staff to communicate relevant patient information
JD: In a retrospective study that used malpractice insurance files and identified 61 retained surgical items, a multivariate analysis identified three factors that were associated with a significantly increased risk: an emergency procedure (risk ratio [RR] 8.8, 95% CI 2.4-31.9), unplanned change in the procedure performed (RR 4.1, 95% CI 1.4-12.4), and increased body mass index (RR per one-unit increment 1.1, 95% CI 1.0-1.2)
Ultimately mixed data depending on what study you look at….. but:
Emergency surgical procedures, Unexpected change in the course of the surgical procedure, obesity, Involvement of two or more surgical teams, Procedures involving one or more open body cavities, Prolonged surgical procedures, use of an unusually large number of instruments, Absence of the attending surgeon at final closure were all associated.
Trainees involved are LESS associated.
What bowel diversion is best to do following a left hemicolectomy?
Ileostomy
Estrogen receptor expression can help distingish:
A LMS vs GIST
B small cell cervix vs endometrial carcinoma
C mucinous ovarian primary vs metastatic mucinous GI cancer
D metastatic breast cancer and primary ovarian cancer
Answer: Small cell cervix (0%) vs endometrioid (80%),
FYI: info from pathology outlines
LMS (42%) vs GIST (0%): No
mucinous ov (0%) vs metastatic mucinous GI cancer
- colon 0%
met breast (lobular 97%) and prim ov (HGSOC 97%)
JD: Should be B.
LMS is not 100%, (25-60% cited in PMID 25018868), Leito et al GynOnc 2012 with an LMS case series with 42%ER+.
ECG Changes by electrolyte imbalance
HyperK and HyperMg
- Increase PR and QTc
- Prolonged QRS
- Peaked T waves and flattened p waves
- Bradycardia
HypoMg
- Prolonged PR
- Prolonged QT
HypoK
- Prolonged PR
- T wave flattening/inversion
- U wave
HyperCa
- shortened QT
- J waves
HypoCa
- prolonged ST segment (causing longer QT)
