Justin Practice Questions 2022 Flashcards

1
Q

Which pathway is TGF-beta part of

A

SMAD or PI3K/AKT or RAS/RAF/MEK

Apoptosis

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2
Q

Which is not in a proliferation pathway?

A

BAX (apoptosis gene)

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3
Q

What are G coupled receptors

A

7 membrane spanning proteins that are activated with GTP then self hydrolyze to GDP and turn off

Transmembrane cell signalling proteins

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4
Q

Proposed mechanism of synergy b/t chemo and angiogenesis inhibitors

A

Normalization theory - anti-angiogenic agent restores normal blood flow and reduces tumor interstitial fluid pressure favoring the penetration of cytotoxic agents

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5
Q

Most common mechanism of oncogene activation

A

1) mutation (in promoter)
2) gene amplification (probably this one)
3) chromosome rearrangement

TL: Lit search suggests that gene amplification is the correct answer

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6
Q

Mechanism by which tumor suppressor genes are deactivated

A

Methylation (think MLH1)

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7
Q

Genes related to apoptosis

A
  1. “bcl (b cell lymphoma) - anti-apoptosis
  2. caspase - programmed cell death including apoptosis (fas pathway), pro apoptosis
  3. BAX (bcel-2 like protein 4) encoded by BAX gene - pro apoptosis
  4. TP53

Important: NOT VEGF

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8
Q

Best way to amplify DNA

A

PCR

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9
Q

Best way to quantitate protein

A

Mass Spec or ELISA

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10
Q

What are static cells?

A

Well-differentiated that rarely undergo division as adults (ie neurons, oocytes, striated m, nephrons)

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11
Q

What are expanding cells?

A

Normally quiescent but grow under stress/injury (ie hepatocytes, vascular endothelium

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12
Q

What are renewing cells

A

Constantly replicating (ie BM, epidermis, GI

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13
Q

Mechanism of apoptosis (3 phases)

A

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

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14
Q

Oncogene associated with EMCA/lynch syndrome

A

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?

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15
Q

PTEN, MSH2, and TP53 are what type of gene

A

Tumor suppressor gene

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16
Q

Molecular pathway responsible for epithelial to mesechymal transformation

A

Wnt/beta-catenin pathway

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17
Q

What is the PD-1 effect on T cells?

A

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

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18
Q

IL-2 stimulates which cells?

A

T cells: helper T cells (CD4), cytotoxic T cells (CD8) and Tregs (CD4)
NK cells (in combo with IL-12)

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19
Q

MHC and T cells - which go with which?

A

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

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20
Q

Where are B cells made?

A

Produced in bone marrow then migrate to lymphoid organs (spleen, LN follicles, GI tract) to mature

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21
Q

What cells are included in innate immunity?

A

Present at birth. NK, macrophages, dendritic cells

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22
Q

What cells are included in acquired immunity?

A

T cells and B cells

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23
Q

What cells secrete histamine?

A

Basophils and Mast cells

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24
Q

What cell / cell line do dendritic cells and macrophages originate from?

A

Monocytes (myeloid stem cell origin)

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25
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) ## Footnote 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
26
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.
27
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 ## Footnote 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.
28
What immune cell secretes IL-1?
Macrophages (+ monocytes, dendritic cells) (AW)
29
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)*
30
What do dendritic cells do?
Professional Antigen presenting cells
31
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)
32
Which are the first immune cells to respond?
Polymorphonuclear neutrophils (PMNs) | PMNs=Neutrophils, eosinophils, and basophils
33
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
34
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
35
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
36
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
37
what makes a tumor antigen a good immune (antibody) target? (Duplicate)
expression on cell surface
38
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.
39
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
40
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
41
Which chemo drugs are vesicants? (Duplicate Q)
Doxorubicin/ Epirubicin/ idarubicin/ daunorubicin ActinomycinD Mitomycin C Nitrogen mustard Trabectinib Vinblastine, vincristine, vinorelbine (all vincas) DAMN TV
42
Which chemos are S phase specific?
Antimetabolites, Topo 1 (topotecan, irinotecan) Doxorubicin most cytotoxic in S "HI 5 The Good Man"= **H**ydroxyurea,** I**rinotecan, **5**-FU, **T**opotecan, **G**em, **M**TX
43
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
44
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
45
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
46
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
47
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
48
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
49
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
50
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 ## Footnote BAD QUESTION
51
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. ## Footnote package insert says DC not just hold if HTN encephalopathy/PRES or nephrotic range proteinuria (AW)
52
What toxicity does mtx not have? A. Cardiotoxicity B. hepatotoxicity C. nephrotoxocity D. hematologic toxicity
Cardiotoxicity
53
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
54
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)
55
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
56
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) ## Footnote drugs enter the tumor nodules by passive diffusion
57
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 ## Footnote prolonged oral etoposide, weekly and continuous-infusion 5-fluorouracil, capecitabine, PEG-liposomal doxorubicin, prolonged vinorelbine infusions (AW)
58
What chemo most associated with constipation
Vincristine Due to autonomic neuropathy: Impaired intestinal motility constipation and upper colon fecal impaction, paralytic ileus
59
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
60
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.
61
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
62
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)
63
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
64
Taxol 24 vs. 3 hours
Less neurotoxicity for 24 hours but more BM toxicity AKA: 3hr= more neurotoxic, 24hr= more myelosuppressive (AW)
65
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.
66
Strategies to reduce nephrotoxicity of chemo
Dose reduce, hydration, eliminate other nephrotoxic drugs
67
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
68
Pt on BEP with pulm sx, what do you do first
Stop bleo
69
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
70
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.
71
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%)
72
Most common sx of GCSF
bone pain Filgrastin: Neuromuscular & skeletal: Back pain (15%), ostealgia (3% to 30%) Pegfilgraststim: Neuromuscular & skeletal: Ostealgia (31%)
73
Most emetogenic Chemos **TEST QUESTION **
Highly emetic (>90%, B&H) - Cisplatin - Anthracycline and cyclophosphamide - Cyclophosphamide >=1500 mg/m²
74
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)
75
Most common acute tox of IP chemo
Abdominal pain
76
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
77
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
78
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.
79
Mechanism of action: topotecan **TEST QUESTION**
1. Inhibit TOPO-I (a nuclear enzyme that induces reversible SINGLE STAND DNA BREAKS during DNA replication) 2. forms topotecan-TOPO-I-DNA complex, preventing religation of ssDNA BREAKS 3. Interaction between complex and replication enzymes results in dsDNA breaks and cellular death S phase
80
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
81
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**
82
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
83
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**
84
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! ## Footnote Cumulative incidence Cardiomyopathy: 450 mg/m2- 3% 550 mg/m2 - 7% 600 mg/m2 - 15% 700 mg/m2 - 40%
85
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%
86
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) **B**leo **I**fos **G**em **C**arbo **T**opo
87
Least leukemogenic chemo: A Cisplatin B melphalan C cytoxan D 5-FU
5-FU Most leukemogenic: melphalan, cyclophosphamide, etoposide, cisplatin
88
What are advanced colon adenomas that increase colon cancer risk?
villous or tubulovillous histology (this is the answer), high-grade dysplasia, >/= 1 cm
89
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"
90
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
91
Least bone marrow suprresive chemo
Bleomycin (main dose-limiting side effect is pulm tox, 10%; nephrotoxicity)
92
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
93
Cancer with elevated CA-125 (ovary not a choice)?
Pancreatic, breast, lung cancer), colon, gastric
94
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.
95
Most common mutation in mucinous ovarian cancer (p53, KRAS, BRAF, Her2/neu)?
KRAS
96
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
97
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
98
Mutation associated with mucinous epithelial ovarian cancer
KRAS, tp53
99
Mucinous ovarian cancer most common tumor suppressor? Oncogene?
Tumor suppressor: TP53 Oncogene: KRAS
100
Which pathway is responsible for the Epithelial to mesenchymal transition
WNT/Beta-catenin
101
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)
102
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%)
103
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
104
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
105
Are psammoma bodies in high grade serous ovary good or bad?
Good/favorable prognosis
106
What cells make hCG?
Syncytiotrophoblast
107
What makes up OVA1
CA-125, transthyretin (pre-albumin), Apo A-1, β2 microglobulin, transferrin (5 things)
108
What stain is used for melanoma?
S100 ## Footnote additionally: SOX10, MelanA, HMB45
109
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
110
What is least leukomegenic chemo
bleo
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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)
112
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 ## Footnote Alkylating Topoisomerase Act-D/Bleo Platinums Anti-metabolites (excluding 5-FU, gem)
113
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
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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
115
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
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Most common overall side effect of tamoxifen? A thrombosis B ut cancer C vasomotor D colon cancer
Overall: vasomotor (>90%)
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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
118
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
119
Which needs renal dosing more (etoposide vs. bleo) - since both are renally cleared **TEST QUESTION**
Bleo | Bleo BLOWS out the kidneys
120
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
121
Crockroft-Gault
Equation used to estimate creatinine clearance Used in carboplatin dosing calculations CrCl = 0.85 for female * [(140-age)*(weight kg) / (72*Cr)] Unreliable in patients who are at the extremes of body weight or have an abnormally low serum creatinine
122
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.
123
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
124
Which chemo is activated within a tumor cell? ** TEST QUESTION **
Capecitabine | AS: and Gemcitabine
125
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.
126
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
127
What are moderately emetogenic chemos
Carbo AUC <4, doxorubicin <60, ifos, oxaliplatin NCCN (30-90%)
128
Minimally emetogentic chemos **TEST QUESTION **
Vincristine, Nivolumab, Bev, Bleo, MTX <50, Pembro NCCN. <10%:
129
mAb with emetogenic potential
Olaratumab (anti-platelet derived growth factor) Withdrawn from the market and used for sarcoma
130
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.
131
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
132
Advantage of liposomal doxorubicin over standard
tumor-tissue drug concentration is 4x-16x higher in liposomal formulation Less cardiotox
133
gemcitabine mechanism of actions (2)
1. 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 2. Diphosphate version inhibits the enzyme ribonucleotide 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
134
Chemotx that need dose reduction for hepatic impairment (bili or transaminitis) **TEST QUESTION**
MTV ME CD Mtx Taxanes Vinkas Mitoxantrone Epirubicin cyclophosphamide Doxil/doxorubicin
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Doxorubicin MOA
Intercalates DNA inhibiting Topo-II, Chelates iron Forms free radicals, active during entire cell cycle, but most active in S
136
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).
137
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
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Chemo associated with ovarian failure (Duplicate)
Cyclophosphamide > melphalan, cisplatin, etoposide Biggest ones are alkylating agents and procarbazine Also cisplatin, doxorubicin
139
Drug that will stay in the intraperitoneal cavity the longest?
paclitaxel (large molecule, water insoluble, high cavity to plasma AUC ratio[1000:1])
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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
141
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.
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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
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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.
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Call Exner bodies
Granulosa cell tumors (Call your Granny)
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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.
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Multinucleated giant cells
Dysgerminoma
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What cells make hCG?
Syncytiotrophoblast
148
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
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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).
150
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.
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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%)" ## Footnote Measured from the granular layer of the epidermis to the deepest point of invasion
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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
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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.
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Most common tumor in dysgenetic gonads
Gonadoblastoma (benign)
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Most common malignant tumor in dysgenetic gonads
Dysgerminoma
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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.
156
Location of estrogen receptor and of action mechanism ** TEST QUESTION **
cytosol —> nucleus. MOA: transcription factor ERs are ligand-dependent transcription factors
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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.
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FOXL2 and ovarian cancer subtypes
adult granulosa cell tumor
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EBRT vs brachytherapy: which symptom is shared?
FATIGUE (answer) -wrong answers: vaginal stenosis, 2 other
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Which is a direct (rather than indirect) effect of radiation?
LET (answer) wrong answers: photons, gamma rays, hypoxia, chemosens
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What radiation is used to treat superficial lesions (aka skin)?
Electrons (answer) wrong choices: gamma ray, orthovoltage
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What is the elemental source for brachytherapy/interstitial?
Iridium-192 (answer) wrong choice: cesium
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What is the depth of dose for 12 MeV in radiation?
4 cm (R90 where beyond <90% of dose is administered)
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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
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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
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What is low LET radiation?
electrons, gamma rays, xrays (both electromagnetic radiation)
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What is % dose of XRT 1 cm vs 2 cm from source?
400% because dose is = 1/r squared *Repeated question
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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.
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Chemotherapy agents associated with PPE?
Chi: Capecitabine > 5-FU, Doxil, Docetaxol Also Multitargeted tyrosine kinase inhibitors sorafenib, sunitinib
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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.
171
Dose limiting toxicity of Gemcitabine **TEST QUESTION **
Myelosuppression
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Chemo causing ovarian failure A. cyclophosphamide B. 5-FU C. MTX
Cyclophosphamide
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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)
174
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.
175
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
176
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) ## Footnote confirmed (AW)
177
Complication with giving carbo as 3rd line for ovary cancer
hypersensitivity
178
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
179
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
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Bevacizumab MOA
binds to, and neutralizes, extracellular vascular endothelial growth factor (VEGF) A , preventing its association with endothelial receptors VEGFR1&2
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ERBB2 gene encodes
ERBB2 also known as HER2/neu is a gene that encodes for the receptor tyrosine-protein kinase erbB-2.
182
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
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VEGF roles
Causative factor in blood vessel permeability and development VEGFRs are predominantly found on endothelial cells and bone marrow derived cells
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PI3K/AKT/mTOR pathway
PI3K-AKT-mTOR pathway promotes cell growth/survival and inhibits apoptosis and autophagy 1. PI3K (phosphatidylinositol-3-kinase) is activated by Growth factor receptor or RAS 2. Activated PI3K generates PIP3 (phosphatidylinositol-3-4-5-triphosphate) 3. PIP3 activates PDK (phosphoinositide-dependent-kinase) 3.5. [PTEN inhibits PIP3]. 4. PDK phosphorylates AKT. 5. 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
185
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
186
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
187
Estrogen isoforms created by
Alternative splicing vs. Alternate promoter usage ## Footnote 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
188
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
189
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
190
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
191
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
192
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
193
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
194
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
195
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
196
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
197
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
198
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
199
Breast cancer screening for BRCA
annual MRI 25-29yo; 30-75yo annual mammo + breast MRI/ (NCCN 2/24) 
200
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
201
Least recommended colon ca screening for lynch/HNPCC **TEST QUESTION **
Sigmoidoscopy aka flex sig (majority right sided tumors prior to splenic flexure)
202
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
203
BRCA1 cancer risks
breast (>60% absolute risk), male breast cancer (0.2%–1.2%) ovary (39%–58%), pancreas (≤5%), prostate (7%–26%), Uterine serous
204
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....
205
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. ## Footnote 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
206
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
207
Best med for anticipatory chemo-induced nausea A 5HT3 antagonist B benzo C steroid D NK1R antagonist
benzo
208
Best criteria to diagnose HNPCC A MSI B Amsterdam C MLH1 methylation D MMR gene alterations **TEST QUESTION **
MMR gene alterations
209
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 ## Footnote Age 10-15y for APC mutation (Famililal adenomatous polyposis) Age 18 for STK11 (PJS)
210
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"
211
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. ## Footnote 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.
212
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. ## Footnote JD: would add - "Anti-angiogenesis agent"
213
3 ways that oncogenes are activated, which is not? A mutation in promoter region regulating inactivation B amplification C hypermethylation D chromosome rearrangement
hypermethylation
214
BRCA1 chromosome location (Duplicate)
17q21 (Same chromosome as TP53)
215
TP53 chromosome location
17p13 (Same chromosome as BRCA1)
216
BRCA2 chromosome location (Duplicate)
13q12 (Same chromosome as RB)
217
PTEN chromosome location
10q23
218
Rb gene location
13q14 (Same chromosome as BRCA2)
219
What are the three BRCA1/2 founders mutations?
BRCA1 185delAG BRCA1 5382insC BRCA2 6174delT
220
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)
221
most common mutation location p53
Exons 5-8
222
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.
223
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
224
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 ## Footnote Reminder Rucaparb elevated Cr due to MATE1/2 inhibition
225
purine bases
adenine & guanine (pure As Gold)
226
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 🥧
227
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
228
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.”
229
VUS in BARD1 gene found age 40 What to do? A Routine mammogram B MRI C tamoxifen D risk reduction surgery
Routine mammogram ## Footnote BRIP=normal breast screening, RRSO "RIP=ovary, like IP chemo" BARD=MRI/mammo, no ovary "BAD BREAST"
230
Endo cancer with medullary thyroid and hamartomas, what is genetic mutation ** TEST QUESTION**
Cowden's syndrome; PTEN mutation
231
Cardiac SE with taxol ** TEST QUESTION**
asymptomatic bradycardia
232
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.
233
most common G3-4 tox with olaparib (Duplicate)
anemia (21%) | next closest=neutropenia at 6%
234
Growth factor associated with endometrial cancer ** TEST QUESTION **
Insulin Like Growth Factor -1 (IGF1)
235
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
236
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.
237
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
238
Most lethal impact of radiation
DOUBLE STRANDED BREAKS other options: single stranded break, 2 other choices
239
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 ## Footnote Predisposing risk factors: previous abdominal surgery, PID, thin body habitus, HTN, and DM
240
Most common organ with toxicity in HDR (or any pelvic radiation)
Rectum HDR terminal ileum WPRT
241
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. ## Footnote LDR where radioactive source (Cs) positioned inside for a few days vs HDR (Ir) temporary placement of radioactive source; more precise
242
Just completed radiation, perforated sigmoid and feculent
choices: Loop ileostomy end ileostomy rectosigmoidectomy with end stoma (this one??)
243
How to reduce small bowel complications with radiation?
Answer: tx with full bladder wrong choices: prone position decubitus position
244
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) ## Footnote Increased OS and dx control with chemoRT. Also get more morbidity but worth it (AW)
245
Dose of brachy after hyst for endometrial cancer is dosed to where
0.5cm deep and 0.5cm wide; 5mm! ## Footnote NCCN: 7 Gy x 3 fractions prescribed at a depth of 0.5 cm from the vaginal surface is a regimen used by many
246
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
247
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 ## Footnote 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
248
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
249
Advantage of HRD over LDR?
Answer: less exposure to staff to radiation for prolonged periods of time Other wrong answers: less treatments, less toxicity
250
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
251
What's the half life of Cesium?
30 years ## Footnote seize the day in your 30s
252
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
253
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
254
Superior border EBRT
answer: L4-5 interspace wrong: L4 vertebral body, L5 vertebral body ## Footnote 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.
255
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
256
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
257
At what energies do certain radiotherapy principles dominate?
1. Photo electric effect 10-25 kEV 2. Compton scattering 25kEV - 25mEV 3. Pair production (does not start until 1.02 MeV, dominant >30 mEV)
258
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)"
259
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
260
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)
261
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)
262
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 ## Footnote 12mEV dose = 4 cm depth...4cmx3=12
263
How to decrease acute effects of radiation
Decrease total dose and treatment time --> affects mucosal cells
264
How to decrease chronic effects of radiation
Decrease DOSE PER FRACTION --> affects endothelial cells
265
What does the shoulder of the cell survival curve represent?
Sublethal damage that is repaired
266
What is the minimum amt of energy to cause ionization?
35 eV
267
Max dose small bowel?
45 Gy (that's why dose for cervix is that.. And required to sterilize occult dz for adjv radiation)
268
Max dose for bladder and rectum and lower 1/3 vagina?
75 Gy
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Name the mm/cm 1.Vaginal cancer - intracavitary alone 2.Add interstitial threshold 3.Add EBRT threshold
1. <5 mm 2. > 5mm 3. > 2 cm
270
Radiation proctitis? Name treatment
All 4 are answers Steroid suppositories Low residue diet Anti-motility drugs Hydration
271
Chronic radiation enteritis treatment?
can try cholestryamine (JS) UTD diet, hydration, antidiarrheals, bile acid sequestrants, abx for bacterial overgrowth)
272
What radiation particle is decay of radioactive isotope
Gamma rays originate within the nucleus, emitted from radioisotope
273
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
274
Alpha particle
Two protons and two neutrons (i.e. He nucleus)
275
Beta particle
high speed electrons | B- = electron B+ = positron
276
What is Gompertzian tumor growth?
Doubling time increases as the tumor size increases y axis: tumor size log scale x axis: time
277
What shifts the cell survival curve to the left?
Left = less radiation needed Oxygen and higher energy radiation ## Footnote (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
278
What shifts the cell survival curve to the left?
"Left = less radiation needed Oxygen and higher energy radiation"
279
What is max fetal dose of radiation during pregnancy?
10 Gy
280
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.
281
First order cell kill kinetics?
Constant FRACTION of cells killed with each treatment
282
When is LET best used?
necrotic tumor
283
IMRT differs from 4-field radiation in all ways except:
Delivers same dose *repeated question
284
Most common site affected in whole pelvic XRT?
answer: ileum wrong options: rectum, bladder, ureter
285
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))
286
Cobalt decay produces what radiation?
This emits high intensity gamma rays
287
Cobalt 60 half life?
5.26 year half life
288
Iridium 192 half life?
74 days
289
Cesium 137 half life
30 years! *This is asked multiple times
290
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
291
How are LET and OER related?
INVERSELY; Higher LET (linear energy transfer) is associated with lower OER (oxygen enhancement ratio)
292
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.
293
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
294
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
295
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
296
How to protect vulva SKIN during radiation?
answer: frog leg all the way baby wrong choices: antifungal, estrogen cream, dilite H2O2, cold something
297
Brachytherapy side effect that doesn't occur with EBRT?
vaginal atrophy
298
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)
299
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
300
What has the highest linear energy transfer (LET)?
alpha particle
301
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)"
302
Blind Loop Syndrome complication
small bowel bacterial overgrowth
303
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
304
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.
305
What cancer type has the least acute radiation effects?
answer: vagina wrong choices: ovary, bladder, small intestine
306
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
307
Treatment of cystitis during xrt
Oxybutinin (anti-cholinergic, antagonizes M1, M2, M3 receptors of Ach receptor) Oxybutinin aka Ditropan
308
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)
309
Most common TPN risk?
hyperGLYCEMIA
310
Most common reason for hyperkalemia postop? **TEST QUESTION **
renal dysfunction
311
Most calories from TPN come from…
answer: Glucose (40-80%) choices: fat (15-60%), protein
312
Earliest lab value to measure in nutrition progress?
answer: pre albumin other options: albumin
313
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.
314
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.
315
How much ileum resection will result in B12 deficiency?
60 cm
316
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.
317
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
318
Most common ELECTROLYTE abnormality with TPN?
Hypophosphatemia *add 15 to 30 mEq | UTD: 20-40mmol/d Angela's: 10-15 mEq to each 1L
319
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 ## Footnote Technically all are correct. Other source asked question of what def associated with alopecia and dry skin= zinc
320
Where is zinc absorbed?
small intestine
321
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
322
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).
323
Where is copper absorbed?
Stomach and Small Intestines
324
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.
325
What is associated with copper deficiency?
all of these: anemia, neutropenia, muscle weakness, ataxia, depigmentation, neurologic abnormalities NOT: bloody diarrhea
326
Which is worse - micropapillary or microinvasion in borderline tumors?
micropapillary *Micropapillary is associated with higher recurrence rate, microinvasions and invasive implants.
327
What is pathognomic for endodermal sinus tumors?
Schiller duval bodies
328
Essential fatty acids?
Omega 6 (linoleic acid) and Omega 3 (alpha-linoleic acid)
329
What is the half life of pre-albumin?
3 days
330
What is the half life of albumin?
20 days or 3 weeks
331
Calorie requirement based on weight for TPN?
30 kcal/kg/day
332
What affects HDR?
applicator, distance and source (all 3) Source Dwell time May be most important
333
How to reduce PPE sx
Cold packs, emoillents, B6, dose reduction, vitamin E
334
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
335
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.
336
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)
337
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
338
Temporary clamp on ureter, what to do
Stent
339
Rectosigmoid - distal stenosis after radiation, mgmt A Progressive dilation B loop colostomy C LAR with Hartman's pouch
A Progressive dilation
340
Pancreatic leak seen postoperatively, how to manage
Percutaneous drain
341
Old lady died after unvaccinated and splenectomy done, likely cause?
Strep pneumo
342
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)
343
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
344
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
345
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
346
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%.
347
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)
348
Patient with history of Left hemicolectomy and needs diversion. What procedure to do?
Ileostomy on notes. MLH not verified
349
Least thermal injury A pure coag B blend cut & coag C pure cut D spray
pure unblend cut
350
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
351
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"
352
Bowel injury during L/S no bowel prep, 1 cm, what do you do
Primary repair (answer if < = 1 cm)
353
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
354
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
355
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 ## Footnote ? 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
356
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. ## Footnote Sustained intra-abdominal pressure >20 mmHg (with or without APP <60 mmHg) associated with new organ dysfunction
357
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. ## Footnote proper positioning, improving abdominal wall compliance (eg, pain control, sedation, paralysis, mechanical ventilation), and reducing intra-abdominal volume
358
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
359
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
360
What nerve injury is associated with numbness over the thigh after a pelvic LND?
genfem
361
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
362
Tensile strength at 10% for PDS
56 days / 8w
363
Tensile strength at 10% for polyglycolic acid (vicryl)
28 days / 4w
364
Tensile strength at 10% for chromic catgut
14 days / 2w ## Footnote also seen 21-28 days listed (excel detroit sheet says 28d, Justin says 14d)
365
Tensile strength at 10% for catgut
5 days / 1w
366
What is max total local lido dose (mg) w/o epi? With epi?
300 mg WITHOUT epi 500 mg WITH epi
367
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
368
Tx for lidocaine tox Duplicate
Usually supportive - use benzos for seizures Dialysis is not useful
369
EKG changes with HYPERmag
prolongation of the PR interval increase in QRS duration increase in QT interval. ## Footnote Complete heart block and cardiac arrest may occur at a plasma magnesium concentration above 15
370
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
371
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
372
What is associated with increasing opiate dose
Tolerance associated with increasing dose (THIS ONE) Other option included dependence, 2 other choices
373
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)
374
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%? ## Footnote 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.
375
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)
376
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
377
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)
378
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 ## Footnote 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)
379
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)
380
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)
381
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.
382
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/
383
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
384
Most likely means to transmit cdiff
Not washing hands b/t patients
385
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) ## Footnote Detroit excel lists Pneumothorax (Gemini supports) (AW)
386
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
387
Mechanism of action for bisphosphonates
Inhibit osteoclastic bone resorption (primary) -- also reduce decreased osteoclast progenitor development and recruitment by promoting osteoclast apoptosis
388
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
389
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)
390
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.
391
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.
392
Euvolemic Hyponatremia with high urine sodium (>40)
High urine Na >40, high urine osmolality >300 = SIADH
393
Euvolemic Hyponatremia with low urine sodium (<25)
Low urine Na <25, low urine osm <100 = primary polydipsia, malnutrition, potomania, or surreptitious diuretic use
394
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)
395
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. ## Footnote 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)
396
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.
397
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
398
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. ## Footnote 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.
399
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)
400
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
401
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
402
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
403
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
404
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].
405
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
406
What element is required in RBC production?
Copper
407
What is a normal ventilator tidal volume setting based on weight?
6-8 cc/kg (more than 10cc/kg associated with lung injury)
408
What is a normal A-a gradient?
5-10 mmHg
409
What does PCWP approximate?
LA pressure
410
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
411
Which diuretics may lead to HYPERKALEMIA Duplicate
Potassium-sparing diuretics such as spironolactone, amiloride, and triamterene
412
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
413
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
414
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
415
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
416
How long can you store RBC
42 days (6 weeks) due to current Anticoagulant-preservative (A-P) solutions
417
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)
418
Which component of the clotting cascade does PTT measure?
Intrinsic "PTT=play table tennis, Inside" ## Footnote Intrinsic
419
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)
420
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%). ## Footnote AS: UTD says Coag neg staph 16.4%, S. aureus 13.2%, Enterococcus 15.2%, Candida 13.3% as most common
421
Tx of SVT
Adenosine
422
What does labeling index do?
Measures proliferation and cells that have COMPLETED S phase ## Footnote Example: Ki-67 proliferative index
423
What lab or vital sign abnormality is First and most sensitive to blood loss?
Pulse/tachycardia
424
What to give if patient has low fibrinogen?
Cryoprecipitate
425
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
426
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
427
What is a southern blot?
Measures DNA ## Footnote "DNA is bigger/heavier, things are bigger in the south"
428
What is a northern blot?
Measures RNA
429
What is malignant hyperthermia?
Justines answer: reaction to anesthesia, tx with dantrolene, develop rhabdo. RYR1 mutation
430
Which are vitamin K dependent coag factors?
II, VII, IX, X (2+7=9 and 10)
431
What to do if suspect air embolism after Swan Ganz?
Answer: Left lateral and t-burg Wrong answer: try to aspirate
432
Describe nec fasc
Gray margins, irregular borders, erythema, pain out of proportion, crepitus, fever ## Footnote AS: lymphangitis often = for erysipelas (group A strep)
433
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%
434
What abx for high risk endocarditis undergoing dental procedure?
Ampicillin
435
Ideal time to stop smoking before surgery?
4 weeks | at least 4-6wk
436
Which does not cause an increased A-a gradient?
hypoventilation wrong answers: shunting, V/Q mismatch
437
Which is least likely to affect A-a gradient?
Hypoventilation wrong answers: ARDS, PNA, PE, pulmonary edema *Repeated question
438
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.
439
OR is closer to RR if prevalence is high or low?
Low
440
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.
441
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.
442
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/
443
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.
444
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.
445
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
446
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
447
What is the relationship between standard deviation and variance?
Standard deviation = square root of variance ## Footnote SD = "how far datapoint is from measured mean". Variance = "how variable datapoints are from each other"
448
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
449
Doing multiple t-tests results in more of what type of error?
Type I (false positive aka erroneously rejecting null hypothesis)
450
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.
451
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.
452
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).
453
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
454
ERAS style intraop fluid management most likely to cause what detrimental effect?
Cause AKI https://www.sciencedirect.com/science/article/abs/pii/S009082582100651X
455
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
456
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.
457
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 ## Footnote ICU- cystatin C (if neither option, uninfluenced)
458
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.
459
What is timing of HIT
Occurs 5-10 days after heparin exposure, or within 24hrs if antibodies already present
460
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
461
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.
462
Renal Dose reduction of lovenox
CrCl >=30: No dose adjustment necessary CrCl <30mL/min: 30mg daily prophylaxis, 1mg/kg once daily for therapeutic
463
Standard dose of lovenox
Ppx: 40mg daily Treatment: 1 mg/kg every 12 hours (preferred) or 1.5 mg/kg once every 24 hours.
464
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
465
what opiate causes prolonged QT and torsades
methadone
466
70 yo with DM, HTN, AFIB sp TLH/BSO what anti coag post op
lovenox
467
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)
468
Medicine class most associated with delirium in elderly post-operative patients?
Benzos Others: cimetidine, corticosteroids, diphenhydramine, belladonna, promethazine, warfarin, narcotics, benzodiazepines, and antiparkinsonian drugs
469
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)
470
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
471
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
472
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
473
ABG for PE
Respiratory alkalosis (tachypnic), decreased CO2 and PaO2; elevated A-a gradient
474
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"
475
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
476
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).
477
Best predictor of weaning off vent
Rapid shallow breathing index (RR/TV); Successful weaning predicted if RSBI <105 Weaning failure predicted if >=105
478
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
479
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.
480
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 ## Footnote JD: yeah, octreotide only for >3L and developes tachy. Bad. The rest are all neccessary.
481
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))
482
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)
483
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 ## Footnote JD: I cannot confirm the above, and think likely thrombocytopenia https://emcrit.org/ibcc/dic/
484
Is dialysis useful for lidocaine overdose
No Not dialyzable
485
How often should splenectomy patients get vaccinated?
Every 5 years ## Footnote JD: MenB every 2-3 yrs (new as of 2019 ACIP reccomendation) PPSV23 and MenACWY every 5 years
486
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 ## Footnote 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
487
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 ## Footnote JD: unable to verify this as well
488
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 ## Footnote 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.
489
What bowel diversion is best to do following a left hemicolectomy?
Ileostomy
490
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%) ## Footnote 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+.
491
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)