High Yields 2018 Qs Flashcards
How does the PD-1/PD-L1 interaction relate to tumor growth?
TEST QUESTION
Programmed cell death protein 1 (PD-1) is a transmembrane protein expressed on T cells, B cells, and natural killer (NK) cells. It has an inhibitory effect and binds to the programmed cell death ligand 1 and 2.
PDL-1 is expressed on the surface of multiple tissue types, including many tumor cells, as well as hematopoietic cells.
PD-1 is the negative regulator of cell activation.
The tumor microenvironment up-regulates PD-1 on tumor reactive T cells, and contributes to impaired antitumor immune responses (the PD-1/PDL-1 intercation inhibits apoptosis of the tumor cell)
- PD-1 inhibitors:
Nivolumab
Pembrolizumab
Cemiplimab
Dostarlimab
Retifanlimab
Toripalimab
Tislelizumab
PDL-1 inhibitors:
Atezolizumab
Avelumab
Durvalumab
CTLA-4 inhibitors:
Ipilimumab
Tremelimumab
what are Interferons?
non specific immune modulators named for interfering with viral machinery
*INF Gamma upregulates PD-1 and PDL-1. It is also an important activator of macrophages and inducer of major histocompatibility complex class II molecule expression.
what part of the Her2 receptor is the target of intervention? (ie: Intracellular, tyrosine kinase, extracellular, transmembrane)
extracellular portion
What is the other name for protein Ca125?
The gene for CA 125 is called MUC16 or mucin16
What distinguishes PSTT from choriocarcinoma?
1.INTERMEDIATE trophoblasts
2.Human Placenta Lactogen
3. Lower betaHCG
*all of these
What distinguishes endometrial stromal nodule (ESN) from low grade endometrial stromal sarcoma (LG-ESS)?
A ESS has more mitoses
B ESS has more atypia
C presence of spiral arterioles
D absence of LVSI in ESN
Absence of LVSI is the correct answer choice
The histologic features of ESN are identical to LG-ESS but ESN has a circumscribed, noninfiltrating border without evidence of myometrial or vascular invasion. ESN is a benign neoplasm that is cured with simple hysterectomy.
B&H: Because diagnosis is based on complete circumscription and absence of lymphovascular invasion, the distinction between stromal nodule and stromal sarcoma can usually be made only at the time of hysterectomy.
Ratio of tumor markers for ovca and colon cancer?
CA125/CEA (this one, 25:1), HE4/CEA
Picture of pap serous uterine cancer histology
pap serous
other test options that are wrong: LMS, endometrioid
Architecture:
Papillary with or without appreciable fibrovascular cores; micropapillary pattern can be seen
Slit-like spaces
Gland-like spaces may be observed
Psammoma bodies may be present in up to 33% of cases
Cytoplasm usually scant but can be abundant with eosinophilia or clearing
Tumor cells can colonize existing endometrial glands
Tumor cells can appear discohesive
Nuclei are typically high grade with pleomorphism, hyperchromasia, prominent nucleoli and frequent mitotic figures (including atypical mitotic figures)
Napsin A (IHC stain)
clear cell carcinoma
- Immunophenotype: most often lacks estrogen receptors and WT-1. Do have: p53 expression, napsin-A, hypoxia-inducible factor 1 alpha (HIF-1 alpha), glypican-3, and hepatocyte nuclear factor 1-beta (HNF-1 beta).
POLE mutated (group 1)
excellent prognosis regardless of grade POLE (why? high tumor mutation burden, tumor neoantigen production, and tumor infiltrating T cells)
MSI hypermutated (group 2)
Most common methylation of MLH1; also can have mutated MLH1, MSH2, MSH6, PMS2; MLH1 + PMS2, MSH2 + MSH6 form dimers so if one degraded the other is; immunotherapy candidates if recurrent; radiation beneficial
High TMB ≥10 mutations/megabase > pembrolizumab.
dMMR/MSI-H: pembrolizumab or dorstalimab.
Tumors without dMMR or high TMB: Pembrolizumab plus lenvatinib
MSS/copy number low (group 3 - PTEN, ARID1A, PIK3CA mut, ER/PR pos)
Good prognosis; respond to hormonal therapy; PI3K/mTOR inhibitors for metastatic disease
Copy number high (group 4) of endometrial cancer molecular subgroup is most likely what histology?
serous; p53 mutated; poor prognosis; trastuz if HER2 +/ERBB2 amp
what are the most common MMR defects in Hnpcc?
MLH1/MSH2 (this one); PMS2, MSH6
MLH1 and MSH2 genes are by far the most commonly mutated in Lynch syndrome patients accounting for ~70% of the mutations identified (32% in MLH1 and 38% in MSH2)
KRAS associations?
Type 1 ovary tumors, mucinous histology ; also recurrent low grade serous carcinoma (unlike BRAF)
Integrin role in cancer?
metastases role (cell invasion and migration)
adhesion of leukocytes to endothelial cells
Mechanism of ERBB2 oncogenicity?
AMPLIFICATION of oncogene producing HER2 protein
How do kinases work?
Phosphorylation
*Tyrosine kinases are enzymes that selectively phosphorylates tyrosine residue in different substrates. Receptor tyrosine kinases are activated by ligand binding to their extracellular domain. Ligands are extracellular signal molecules (e.g. EGF, PDGF etc) that induce receptor dimerization (except Insulin receptor) and a cascade of events.
Which of the following is a tumor site not included in risk for HNPCC ?
A breast
B gastric
C pancreatic
D urethral
E brain
“breast // does include endometrial, colon, gastric, ovarian, pancreatic, urethral, brain (glioblastoma), small intestinal,
sebaceous gland adenomatous polyps, keratoacanthomas
Histopath of leiomyosarcoma?
List 3
-prominent cellular atypia
-abundant mitoses (≥10 per 10 high power fields)
-areas of coagulative necrosis
*Two of these are necessary for a diagnosis
Grade 1 endometrioid, young, normal weight - tumor most likely to express:
A MSH2
B CK7
C ER
D PR
MSH2
Germ cell tumor least likely to have elevated AFP
Dysgerminoma and choriocarcinoma both not elevated
Genetic mut associated with type I endometrial cancer
PTEN (PTEN tumor suppressor is the most important negative regulator of PI3K signaling)
How does Loss of heterozygosity occur (two mechanisms)
Deletion (most common) or methylation
*Loss of heterozygosity: refers to a type of mutation that results in the loss of one copy of a segment of DNA
*LOH occurs when a cancer cell that is originally heterozygous at a locus loses one of its two alleles at that locus, either by simple deletion of one allele (copy-loss LOH), or by deletion of one allele accompanied by duplication of the remaining allele (copy-neutral LOH). When a cancer cell undergoes LOH of an essential gene, further loss or inhibition specifically of the allele retained in the tumor should not be tolerated, whereas normal cells will be able to survive relying solely on the remaining allele
High LET has what effect on cancer cells?
Tumor necrosis, higher LET is more direct damage
*Linear energy transfer (LET) average amount of energy lost per unit track length in tissue by a type of radiation
*High LET radiation: particles with substantial mass and charge such as alpha particles or neutrons
*Low LET radiation: X-rays, gamma rays
Elevated CA19-9 and CEA
mucinous tumor
Downstream effect of VEGF receptor binding
Capillary permeability (THIS ONE), increased intratumor pressure, other options
Cowden
What is the germline mutation?
Clinical picture (non-cancer)?
Screening?
PTEN
Clinical picture: GI polyps, thyroid disease, benign breast disease, mucocutaneous lesions
Cancer risk: breast, thyroid, endometrial
Screening for breast cancer: breast self awareness from 18yo, clinical breast exam q6-12mo from age 25 (or 5-10 years before earliest family dx), annual MMG+MRI from 35yo (or 10 years before earliest family dx) per NCCN 6/2023
Screening for colon: start c/scope age 35-40 or 5-10yr before earliest family dx)
Screening for endometrial cancer: start 35yo. prompt eval of AUB. consider q1-2yr EMB per NCCN 6/2023
invasive/image screenings all start at 35
Cowden most common GYN cancer
Endometrial cancer (lifetime risk 19-28%)
Cowden most common cancer
Breast
- The lifetime risk of breast cancer for affected female patients is frequently reported at between 25 and 50 percent, although more recent reports project a cumulative risk as high as 81 to 91 percen
What causes invasion through the basement membrane?
MMP
Matrix metalloproteinases
Function of integrins?
migration and invasion
What tumor is associated with FOXL2 mutation?
Granulosa cell tumor
*FOXL2 encodes a transcription factor that is expressed as a nuclear protein and is critically important in the development of granulosa cells. Somatic mutations in FOXL2 have been identified in 97 percent of adult subtype granulosa cell tumors and only 1 of 10 juvenile subtype granulosa cell tumors
Which common medication inhibits the mTOR pathway?
Metformin
Which of the following is an oncogene: listed choices were PTEN, P53, BRCA and c-myc?
c-myc
CA 125 is also known as?
MUC 16
*Direct questions
BRAF mutation in which ovarian tumor?
low grade serous
What type of endometrial cancer is associated with p53 and her2neu?
Type II endometrial cancer
Copy number High
Kras mutation in which ovarian histology- mucinous, serous, clear cell, endometrioid?
MUCINOUS
*Direct question: also low grade serous, this was 2 different questions on the exam
First step in carcinogenesis of ovarian cancer: p53 mutation, fallopian tube stic, a few other options - which one?
p53 mutation
MC germline mutation in ovarian cancer?
BRCA 1
Mutation most common in p53?
Missense mutation
Exons 5-8
How do you protect vulva skin during radiation?
anti fungal
estrogen cream
positioning (frogleg)
cold packs
Using a diluted water/H2O2 rinse
positioning (frogleg)
Based on MCG RadOnc text consult
Diluted hydrogen peroxide water on the vulvar during EBRT to decrease - Wake RadOnc Lecture
How does HDR differ from LDR?
decreased treatment time
How does cisplatin augment radiation?
inability to repair DNA
What radiation source the longest half-life?
Radium
-cesium 137 - 30 years
-irdium 192 - 74 days (SHORTEST)
-radium 226: very long like 1600 years
-colbalt 60 - 5 years
What is the half life of cesium?
30 years
What type of radiation is produced by cobalt ?
Gamma
Cobalt (Gamma ray, from nucleus, avg Cobalt energy is ~1.25MeV)
What is most sensitive to side effects from pelvic radiation?
ileum
*2 questions on this topic
What do you call the area around the gross tumor volume that might have microscopic tumor?
clinical target volume
Inverse square law, if you go from 2 cm to 1 cm how much does dose increase?
400%
*this is on every year
The radiation inverse square law specifies that: the intensity of the radiation goes down by the square of the distance from the source. For instance if you move twice as far from the source the intensity of the radiation will decrease by a factor of 4.
Intensity = 1 / (distance ^2)
Adjuvant treatment for positive right inguinal lymph node?
bilateral radiation to nodes and pelvic field
XRT vs brachy - which symptom is shared?
FATIGUE (answer)
-wrong answers: vaginal stenosis, 2 other
Which chemo causes delayed bone marrow suppression?
TEST QUESTION
mitomycin C
Marrow suppression at 28 to 42 days with recovery 40 to 60 days after treatment
And Melphalan and chlorambucil
Which drug do you need to dose reduce for renal insufficiency?
A bev
B vinca
C taxol
D etoposide
**TEST QUESTION **
Etoposide
A BICC THE MMP require renal dosing modifications
ActD,
Bleo, ifos, cytoxan, capecitabine,
Topo, hydroxyurea, etopo,
mtx/pemetrexed, melphalan, platinum (carbo/cis, oxali)
Dose limiting toxicity of carbo?
**TEST QUESTION **
thrombocytopenia
What drug is most likely to cause constipation?
a. Paclitaxel
b. Vincristine
c. Cisplatin
d. Gemcitabine
**TEST QUESTION **
Vincristine
FYI per the SGO chemo book, vinblastine»_space;vincristine
SGO handbook says “vinblastine, rarely vincristine”
What is the mechanism of action of Capecitabine?
a. Inhibits topoisomerase I
b. Creates DNA crosslinks
c. Prodrug, converted to 5-FU in the tumor tissue
d. Prodrug, converted to 5-FU in the liver
**TEST QUESTION **
c. Prodrug, converted to 5-FU in the tumor tissue
“Capecitabine is an oral fluorouracil prodrug that is
converted in tumor tissue to the active cytotoxic agent, 5-FU.” SGO HB
What is the mechanism of action of gemcitabine?
a. Prodrug, converted to 5-FU
b. Creates ss DNA breaks
c. Stabilizes microtubules
d. Prodrug, converted to a fraudulent base pair
**TEST QUESTION **
d. Prodrug, converted to a fraudulent base pair
Also important that it requires active transport
How does liposomal doxorubicin differ in mechanism of action from doxorubicin
a. Liposomal coating creates a more basic tumor microenvironment
b. Liposomal coat causes increased receptor affinity with the tumor cells
c. Liposomal coat causes slower drug release which decreases toxicity
d. Liposomal coat causes increased hepatic metabolization
**TEST QUESTION **
c. Liposomal coat causes slower drug release which decreases toxicity
How to reduce thrombocytopenia in patient getting taxol/carbo?
**TEST QUESTION **
Dose reduce carbo
Carbo causes thrombocytopenia
Imatinib: MOA, target, drug class
** TEST QUESTION **
BCR-ABL Tyrosine Kinase Inhibitor
Bcr-Abl tyrosine kinase is the constitutive abnormal gene product of the PHL chromosome in CML.
Inhibition of this enzyme blocks proliferation and induces apoptosis in Bcr-Abl positive cell lines.
Also inhibits tyrosine kinase for platelet-derived growth factor (PDGF), stem cell factor (SCF), c-kit, and cellular events mediated by PDGF and SCF.
Also used in GIST tumors
What do tyrosine kinase receptors do?
a. Increase the membrane action potential by increasing flow through ion channels
b. Activate cell replication machinery
c. Activate DNA repair mechanisms
d. Activate/phosphorylate proteins through signal transduction cascades
**TEST QUESTION **
Activate/phosphorylate proteins through signal transduction cascades
What to do if you have patient with family h/o colon cancer, has endometrial ca at young age?
**TEST QUESTION **
Screen for Lynch with IHC testing first
What is homologous recombination repair?
** TEST QUESTION **
High fidelity, template dependent DNA repair mechanism for double stranded DNA breaks
Steps:
1. dsDNA breaks are recognized by the MRN complex and checkpoint proteins
2. 5’-3 exonuclease generates 3’ overhangs, which are coded with replication protein a
3. BRCA1/RAD51 forms a complex.
4. RAD51 assembles onto single stranded ends.
5. Homology search, strand invasion, and DNA synthesis.
6. Links between DNA strands (double holliday junctions) resolved to produce exchange between chromosomes or no exchange.
Which immune cell releases granules?
A NK cells
B B cells
C macrophages
NK cells release granzymes & perforins
NK cells secrete preformed secretory lysosomes called lytic granules (LGs) directly toward bound target cells, a process known as cell-mediated cytotoxicity
True granules released by: mast cells, basophils, neutrophils, eosinophils (granulocytes)
Effect of statins on endometrial cancer growth
statins inhibit phosphorylation of AKT and also inhibit mTORC1 preventing progression of PI3K pathway leading to multiple downstream effects (see image). Exert anti-inflammatory effects via a myriad of molecular mechanisms, reflected by decreased levels of C-reactive protein (CRP) and interleukin-6 (IL-6). Inhibit Th1 immune response
PI3K —> PIP3 —> PDK —> AKT—> mTOR
statins = HMG-CoA reductase inhibitors
What happens when you alternate Tamoxifen and Megace?
Tamoxifen increases PR expression which sensitizes to Megace
Effect of EGF binding to its receptor
After ligand binding, EGFR (ErbB-1) dimerizes with itself or with its homologs ErbB-2 (her2/neu), ErbB-3, or ErbB-4 and consequently increases its intracellular tyrosine kinase activity. This activates signaling cascades that have many effects: cell proliferation, reduced apoptosis, and angiogenesis.
RAS —> RAF —> MEK —> MAPK [—> to nucleus] —> promote transcription of genes involved in tumor growth (e.g., MYC, JUN, FOS).
-or-
PI3K —> PIP3 —> PDK —> AKT —> mTOR
effect of IGF1 on endometrial cancer
**TEST QUESTION **
IGF‐1 is known to promote cancer development by inhibiting apoptosis and stimulating cell proliferation.
(Insulin like growth factor)
Binding to IGRF1 stimulates PI3K —> PIP3 —> PDK —> AKT —> mTOR
Metformin increases your IGF1 binding globulin and inhibits IGF-1 binding, the opposite of insulin!
What tumor is associated with ARID1A mutation?
** TEST QUESTION **
Clear cell ovarian cancer > Endometrioid ovarian cancer
Endometriosis related cancers
Tumor suppressor gene: participates in DNA repair through interaction with checkpoint kinase ATR
ARID1A = AT-rich interactive domain-containing protein 1A
Kras mutation in which ovarian histology
A mucinous
B serous
C clear cell
D endometrioid
**TEST QUESTION **
Mucinous
50-70% of mucinous cases, missense MT
25-50% borderline
20-50% low grade serous
Recommended screening for BRCA variant of unknown significance?
**TEST QUESTION **
Routine screening
Per NCCN: Retrospective analyses have estimated that 82.1% to 91.2% of the time, if a VUS is reclassified, it is downgraded to benign or likely benign, while 8.7% to 17.9% are upgraded from VUS to pathogenic. Therefore, VUS should not be used to alter medical management. (AW)
Most common cancer in Cowdens?
** TEST QUESTION **
Breast
lifetime risk 25-50%
lifetime risk for endometrial cancer approx 19% to 28% (AW)
lifetime risk of thryoid cancer approx 3-38% (AW)
Reduction in breast ca risk in brca patient with BSO
** TEST QUESTION **
50%; however, this has recently been called into question on lit review
60 year old getting chemo, what vaccine would you most recommend?
a. live intranasal flu
b. shingles (zostavax)
c. MMR
d. pneumococcal
**TEST QUESTION **
Pneumonia normally after 65, but anytime if weakened immune sys.
All 50+yo need shingles.
*new shingles vaccine is dead = shingrix
*old shingles vax is live = zostavax
live vaccines should not be given during chemo.
Per NCCN: pneumococcal conjugate vaccine (PCV20) should be administered to adults newly diagnosed with cancer who are pneumococcal vaccine-naïve. meningococcal vaccination recommended for patients at increased risk for meningococcal disease = persistent complement component deficiencies, taking a complement C5 inhibitor (eg, eculizumab, ravulizumab),or anatomic or functional asplenia (AW)
Cause of chronic metabolic alkalosis:
**TEST QUESTION **
Duplicate
long-term NGT suctioning
Notes says: NG tube. two most common causes of metabolic alkalosis in general are loss of gastric acid (vomiting, NG drainage) and diuretics (specifically furosemide and thiazides)
Which opioid causes prolonged QT?
**test question **
Methadone
What is the best initial management of hyperkalemia with EKG changes?
**TEST QUESTION **
●Intravenous calcium to antagonize the membrane actions of hyperkalemia (if electrocardiogram (ECG) changes consistent with hyperkalemia are present)
EKG changes for hypokalemia
**TEST QUESTION **
Duplicate
Flattened or inverted T waves,
depression of ST segment,
prominent U waves,
prolongation of QT interval —> can lead to torsades
EKG changes for hypomagnesemia
**TEST QUESTION **
Duplicate
QT prolongation —> torsades de pointes
Long PR, QRS
Peaked T waves initially —> flatten at higher concentrations
artial/ventricular arrhythmias
EKG changes for hypercalcemia
**TEST QUESTION **
Shortening of QT interval
EKG changes for hypocalcemia
**TEST QUESTION **
Prolonged QT interval —> torsades de pointes
EKG changes for hyperkalemia
**TEST QUESTION **
Peaked T waves (1st),
flattened P waves, PR prolong (2nd),
prolonged QRS complexes —> sine wave —> ventricular fibrillation / cardiac arrest
ST depression
What electrolyte derangement is most likely for patient with refractory hypokalemia:
hypomag
Which of the following is a cause of non-anion gap Metabolic acidosis?
A pancreatic fistula
B rhabdomyolysis
C renal failure
D salicylates
TEST QUESTION
(Duplicate)
Pancreatic fistula
Loss of bicarbonate-rich pancreatic fluid via a pancreatic fistula can result in a hyperchloraemic or normal anion gap metabolic acidosis.
“USED PART”: Urinary diversion, Small bowel fistula, Extra Chloride, Diarrhea, Pancreatic fistula, Addisons/Acetazolamide, Renal tubular acidosis, Tenofivir/Topiramate
High AG metabolic acidosis
MUD PILES: Methanol, Uremia, Diabetes, Paraldehyde, Iron (and Isoniazid), Lactate, Ethylene glycol, and Salicylate.
Rhabdo —> lactic acidosis
electrolyte changes in patients with urinary conduits
**TEST QUESTION **
DUPLICATE
Hyperchloremic metabolic acidosis
can result from resorption of excreted metabolites through the intestinal mucosa of the diversion: ammonia, hydrogen and chloride are reabsorbed=chronic acid load
Best abx for MRSA:
vanco
Best management for neutropenic fever anc 850:
cefepime
Other choices: cefepime + growth factors, other abx choices
Longest ½ life of narcotic
**TEST QUESTION **
methadone
Best opioid in renal failure:
Fentanyl
Per B& H: Fentanyl or methadone best = no active metabolites
- Buprenorphine, ketamine, lidocaine remifentanil also ok=no prolonged clearance
Morphine and codeine are not recommended, because the accumulation of their metabolites may cause neurotoxic symptoms
How to correct DIC in CHF w fibrinogen <100?
**TEST QUESTION **
Cryoprecipitate, also called “cryo” (1 unit = 10 to 20 mL)
Indicated for DIC
Notes were unsure of cryo vs concentrated fibrinogen but pretty sure its cryo (AW)
Fibrinogen concentrates: prepared from pooled human plasma and are available as lyophilized powders… reconstituted in a small volume. More for prevention and congenital fibrinogen def., off label for DIC.
https://www.ncbi.nlm.nih.gov/books/NBK537184/
FFP higher volume (1 unit = 200 to 300 mL) indicated for DIC, not good for CHF
Most sensitive test for heparin induced thrombocytopenia?
anti-platelet factor 4 antibodies
*gold standard=Serotonin release assay (SRA). measures plt activation via detecing release of serotonin from test plts in presence of pt serum and heparin. Sens/spec >95%
More commonly used=ELISA: detects the presence of Ab to -platelet factor 4 (PF4)/heparin complex in patient serum. Sensitivity 91->97%, but low specificity
Reason to check an anti-Xa level in patient on Lovenox:
obesity
anti-Xa monitoring when optimal dosing less predictable:
renal insufficiency,
under/overweight (≤ 40 kg or ≥150 kg),
pregnancy
newborns/children
prolonged therapy (≥7–10 days)
advanced age
80 yo patient s/p surgery, CrCl 40, what dose of prophylactic Lovenox do you give? (no weight given):
**TEST QUESTION **
Duplicate
Standard dosing (40mg/daily)
CrCl 30 to 50 mL/minute: No dose adjustment necessary for most indications.
BMI ≥40 kg/m2:
- 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)
Which of anticoagulant needs renal dose reduction?
** TEST QUESTION **
Skinny answer: LMWH + Rivaroxaban
lovenox, nadroparin (not US): requires renal dose reduction CrCl <30
Xarelto/Rivaroxaban, Edoxaban: requires renal dose reduction CrCl<50
Dalteparin: no adjustment, avoid CrCl <30
Tinzaparin (not US drug): no adjustment, avoid CrCl <30
Fondaparanux: consider decrease in ppx dose if CrCl <50. avoid CrCl <30
Eliquis/Apixiban: no dose adjustment for VTE/PE
Warfarin: no specific adjustements, check INR more freq, start lower dose
Heparin: NO DOSE REDUCTION
Argatroban: NO DOSE REDUCTION
Aw edited the long version to match UTD
When do you stop heparin and start fonadaparinux
Transitioning from UFH continuous infusion to fondaparinux: Start fondaparinux within one hour after UFH continuous infusion has been stopped
Option for anticoagulation treatment in the setting of HIT
What are the treatment options for HIT?
** TEST QUESTION **
Duplicate
argatroban (Parenteral direct thrombin inhibitor) is probably best option
Others:
Bivalirudin (Parenteral DTI)
Danaparoid (Parenteral inhibitor of thrombin and factor Xa (indirect, heparinoid)
Fondaparinux (parental Xa inhibitor)
Apixaban, Edoxaban, Rivaroxaban (PO Xa inhibitor)
Dabigatran (ODTI)
Warfarin (CANNOT BE USED INITIALLY)
What is Heparin-induced thrombocytopenia (HIT)?
Duplicate
Life-threatening complication of exposure to heparin (UFH, LMWH). Occurs in up to 5% of pts exposed, regardless of dose, schedule, or route of administration.
plt drop >50% baseline, new onset plts <150, occurs 5-10d after exposure (could be earlier if recently exposed to heparin). resolution after stopping heparin is usually 7d
HIT results from an autoantibody directed against platelet factor 4 (PF4) in complex with heparin (referred to as a HIT antibody).
HIT antibodies activate platelets and can cause catastrophic arterial and venous thrombosis (50%, venous > arterial).
THROMBOSIS (can lead to skin necrosis, limb gangrene, organ infarction)
Mortality rate as high as 20-30%, w/ improved recognition and early intervention, mortality rates < 2% reported.
Best test to diagnose c.diff?
If choose just one, NAAT
?best is gold standard cell culture cytotox assay (aw)
two-step approach: enzyme immunoassay (EIA) test first for glutamate dehydrogenase (GDH), followed by a toxin test and/or a nucleic acid test.
Alternatively, in institutions where established clinical algorithms guide testing, a nucleic acid test alone is acceptable.
Best is combination of EIA GDH then EIA for toxins A&B or NAAT
Cdiff tests:
●NAAT: specific for toxigenic strains but do not test for active toxin protein production and are capable of detecting asymptomatic carriers of C. difficile
●Enzyme immunoassay for C. difficile GDH: GDH antigen enzyme is produced by all C. difficile isolates; cannot distinguish btw toxigenic and nontoxigenic strains… useful initial screening step in multistep approach
●Enzyme immunoassay for C. difficile toxins A and B: sensitivity of EIA for toxins A and B is on average about 75 percent, specificity ~99%).high false-negative rate since 100-1000 pg of toxin must be present for the test to be positive. used together with toxin EIA
●Cell culture cytotoxicity assay: sensitive and specific but resource intensive and time consuming. Not routine but has been used as a gold standard test for diagnosis of C. difficile
●Selective anaerobic culture: useful for epidemiologic studies but generally too slow and labor intensive for routine use
Treatment to quickly reverse Coumadin after vitamin K and FFP?
Duplicate
4-factor prothrombin complex concentrate aka Kcentra (PCC, contains Factors II, VII, IX, and X). [these are vit K dependent factors 2+7=9, 10]
A plasma product such as thawed plasma or FFP (approximately 10 mL/kg, depending on INR) can be used as an alternative if PCC is not available.
Vitamin K (intravenous)
Hold warfarin
Recheck the prothrombin time (PT)/INR at approximately 30 minutes following PCC administration, and periodically thereafter, with the frequency determined by the severity of bleeding.
Intrabdominal compartment syndrome, how to diagnose?
**TEST QUESTION **
Intravesicular pressure
(JS: bladder pressure may not be accurate w/adhesions, pelvic hematomas, pelvic fractures, abdominal packs, or neurogenic bladder. Best when patient intubated and paralyzed)
ACS = IAP of >/=20 mmHg + organ failure
Which of the following is associated with steatosis in TPN:
excess calories due to sugar
Treatment of afib postop:
A beta blocker
B fluid
C anticoagulation
** TEST QUESTION **
Beta-blocker
Most common presenting symptom of PE?
Duplicate
The most common presenting symptom is dyspnea followed by chest pain (classically pleuritic but often dull) and cough (UTD)
How to confirm ET placement:
**TEST QUESTION **
Duplicate
ETCO2 (~40mmHg)
Waveform capnography is the most reliable tool to confirm placement of an advanced airway, both for endotracheal (ET) tubes and supraglottic-airway devices. When a device is placed correctly, a waveform and end-tidal CO2 (ETCO2) reading appear within seconds after the first ventilation is delivered to the patient
Cardiovascular collapse after insertion of Veress needle, what is best treatment?
** TEST QUESTION **
Likely getting at air embolus:
- tx is Trendelenburg and left lateral decubitus position
- desufflation of the abdomen
- The Durant or Trendelenburg position is used to direct the gas bubble into the right ventricle apex and away from the pulmonary artery.
- Ventilation with 100% oxygen could be used to wash out CO2, reduce ventilation-perfusion mismatch, and improve hypoxemia.
- Hyperventilation is also used to help eliminate CO2
Second thought is massive bleeding, but seems less likely
Question about what cancer is caused by a translocation?
transitional ovarian
granulosa cell tumor
Sertoli Leydig cell tumor
Peutz-Jeghers syndrome tumors
(Duplicate Q)
STK11 mutations only account for about half of PJS cases, and a second disease locus has been proposed at chromosome segment 19q13.4 on the basis of genetic linkage analysis in one family. We identified a t(11;19)(q13;q13.4) in a PJS polyp arising from the small bowel in a female infant age 6 days.
PJS associated with Ovarian sex cord tumor with annular tubules
granulosa: FOXL2 is a point mutation).
Though translocation in a case report:
https://www.sciencedirect.com/science/article/abs/pii/016546089290231V
JS (need to confirm)- clear cell ovary (ARID1A translocation)
endometrioid ovary (PTEN, bcatenin translocation)
small cell ovary hypercalcemic type (SMARCA4 translocations)
What vasopressor is most inotropic?
**TEST QUESTION **
Dobutamine: is not a vasopressor but rather is an inotrope that causes vasodilation
Vasopressors elevate blood pressure
Inotropes enhance cardiac output
Inotropes:
- dopamine: dose dependent. Inotropic and vasopressor
- dobutamine
- Isoproterenol: primarily an inotropic and chronotropic agent rather than a vasopressor.
Vasopressors:
- epinephrine: dose dependent. Inotropic and vasopressor
- norepinephrine: both Inotropic and vasopressor
- phenylephrine: vasopressor only
- vasopressin: antidiuretic hormone, vasopressor
- Ephedrine: mostly vasopressor. For epidural hypotension
Effects of dopamine: low / medium / high doses
** TEST QUESTION **
low dose 1 to 2 mcg/kg per minute
- dopamine-1 receptors in the renal, mesenteric, cerebral, and coronary beds, resulting in selective vasodilation.
medium dose 5 to 10 mcg/kg per minute
- also stimulates beta-1 adrenergic receptors and increases cardiac output, predominantly by increasing stroke volume with variable effects on heart rate
high dose >10 mcg/kg per minute
- stimulate alpha-adrenergic receptors and produce vasoconstriction with an increased SVR
Postop patient who is old, has hx of afib, CVA and is undergoing surgery for endometrial staging… what would you anticoag with?
A Lovenox
B ASA
C Coumadin
D Plavix
Lovenox
What shock has low SVR, high CO?
Septic shock. Low SVR, splanchnic vasoconstriction, increased cardiac output, characterize the hyperdynamic phase of shock.
Low SVR - hypotension
High CO - tachycardia
Mechanism of hypotension in early septic shock?
Inc venous capacitance
Low SVR, splanchnic vasoconstriction, increased cardiac output, characterize the hyperdynamic phase of shock.
Venous capacitance is increased and results in diminished effectiveness of the circulating the blood volume.
Which of the following is most diagnostic of ARDS?
** TEST QUESTION **
Duplicate
Berlin Definition of ARDS all of the following
●Respiratory symptoms begun within one week of a known clinical insult.
●Bilateral opacities on chest imaging.
●respiratory failure must not be fully explained by cardiac failure or fluid overload.
●A moderate to severe impairment of oxygenation must be present, as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2). The severity of the hypoxemia defines the severity of the ARDS:
•Mild ARDS – The PaO2/FiO2 is >200 mmHg, but ≤300 mmHg.
•Moderate ARDS – PaO2/FiO2 >100 mmHg, but ≤200 mmHg.
•Severe ARDS – The PaO2/FiO2 is ≤100 mmHg
Notes say: b/l infiltrates vs PaO2/FIO2 ratio <200 (we all put different answers)
- b/l infiltrates is non specific
By definition, arterial blood gas (ABG) analysis shows hypoxemia, which is often initially accompanied by acute respiratory alkalosis, and an elevated alveolar-arterial oxygen gradient
Best way to not worsen ARDS with vent settings?
** TEST QUESTION**
1 most important- low tidal volume with permissive hypercapnia (limitation of tidal volume (6 ml/kg predicted body weight) ** higher tidal volumes result in barotrauma.
How to calculate SVR?
** TEST QUESTION **
Duplicate
Systemic vascular resistance (SVR) =
80 x ([MAP – CVP or RAP]/CO)
CO =SV x HR
Normal SVR is 700 to 1,500 dynes/seconds/cm-5
right atrial pressure (RAP)
central venous pressure (CVP)
mean arterial pressure (MAP)
cardiac output (CO)
These indices can be obtained from an accurately placed pulmonary artery catheter (PAC):
●Central venous pressure (CVP)
●Right-sided intracardiac pressures (right atrium, right ventricle)
●Pulmonary arterial pressure (PAP)
●Pulmonary artery occlusion pressure (PAOP; pulmonary capillary wedge pressure [PCWP]; pulmonary artery wedge pressure [PAWP])
●Cardiac output (CO)
●Mixed venous oxyhemoglobin saturation (SvO2)
What is the purpose of PEEP?
A Decrease respiratory work
B decreases FIO2 requirement by increasing PaO2
C increases FIO2 requirement by decreasing PaO2
Decreases FIO2 requirement
Mechanism for improving oxygenation
Physiologic PEEP is 4 cm H2O
Increasing PEEP is preferred for improving oxygenation opposed to increasing the FIO2 for postop pts
Addition of PEEP recruits collapsed alveoli, improves oxygenation and lung compliance
Most common type of type of neoplastic colon lesion:
A Tubular adenoma
B hyperplastic
C tubulovillous adenoma
D inflammatory
Adenomatous (tubular adenoma) About 70 percent of all polyps are adenomatous, making it the most common type of colon polyp
Adenomas are the most frequently observed neoplasms. By definition adenomas are benign lesions but there is a relationship to the development of invasive cancer (Vogelstein 1990). There are three forms of colonic adenomas: tubular, villous, and mixed.
POD#1 s/p debulk with peritonectomy patient complains of sob. What’s the most likely etiology?
A pleural effusion
B pna
C pe
Pleural effusion: possible complication of debulking diaphragmatic disease
Pneumonia: 48 to 72 hours after hospital admission
PE: 3-20d postop
Raised border wound infx with lymphangitis, spreading erythema
A Nec fasc
B gas gangrene
C strep
D staph
Duplicate
Strep pyogenes - aka erysipelas (this one),
strep > staph
Lymphangitis most often results from an acute streptococcal infection of the skin. Less often, it is caused by a staphylococcal infection. The infection causes the lymph vessels to become inflamed. Lymphangitis may be a sign that a skin infection is getting worse
Effect of intraop fluid restriction?
Decreased postoperative complications
What leads to decreased hospital stay?
POD#0 feeding > POD Ambulation (JS: cannot confirm nor deny…)
Patient who is a smoker, BMI 40, low albumin, has endometrial cancer, what is the best way to decrease her risk of SSI?
A continue abx postop
B quit smoking
C diet modifications to increase albumin
D do surgery MIS
MIS
What is the most likely reason to have leak after LAR?
a. Anastomosis >5cm from anal verge
b. Anastomosis <5cm from anal verge
c. Stapled anastomosis
d. Pelvic drain
Anastomosis <5cm from anal verge
(JS) RF for leak:
albumin <3.5, >/=1 bowel resections, <6cm from anal verge, older age, handsewn
What is the best the way to protect a LAR?
a. mechanical bowel prep
b. antibiotic prep
c. loop colostomy
d. loop ileostomy
loop ileostomy
What is the most common complication of loop colostomy?
a. Prolapse
b. Diarrhea
c. Constipation
d. High output
Prolapse
What is the best way to handle a 1cm injury to large bowel with no prep?
a. primary closure
b. primary closure with protective ileostomy
c. ostomy
d. resection/re-anastomosis
primary closure
Primary closure is best suited to small lesions (1 cm or less) that are a result of cold or sharp injury. However, thermal injury sustained via electrosurgical devices induces delayed tissue damage beyond the visible edges of the immediate defect, and surgeons should consider a resection of bowel to at least 1 cm beyond the immediately apparent injury site.
If appropriate antibiotic prophylaxis for colonic surgery has not been given prior to skin incision, it should be administered once the colotomy is identified.
Patient had previous maylard what flap should you use for exent:
gracilis (not tram/vram)
Maylard incision: deep inferior epigastric vessels are isolated, clamped, transected, and ligated.
TRAM (transverse rectus abdominus muscle) and vertical rectus abdominis myocutaneous (VRAM) flap both use deep inferior epigastric vessels as pedicles
Best plastic closure/flap for vaginal reconstruction?
A TRAM
B gracilis
C split thickness
D V-Y
**TEST QUESTION **
VRAM or TRAM best based on the below, if not option, gracillis
For full thickness defects, a variety of reconstructive options
Fasciocutaneous and myocutaneous flaps are probably the most commonly used options for reconstruction of partial and circumferential vaginal defects. These have the advantage of providing a large quantity of pliable tissue, which can be used as soft tissue filler in the pelvis, in addition to tissue for vaginal reconstruction. The neovagina also tends to retain its caliber over time, and does not stenose. However, the lack of natural lubrication often necessitates the use of supplemental lubricants during sexual intercourse. Other disadvantages include incidence of partial or complete flap necrosis. However, the incidence of this is relatively low.
Flap specific complication rates are lowest for vertical rectus abdominis myocutaneous (VRAM) flaps compared with gracilis and Singapore flaps.
Easy/serious to injury when mobilizing anterior/superior liver surface?
** TEST QUESTION **
Right Hepatic vein
What IHC stains are consistent with metastatic colon cancer to the ovary?
a. CK7+ CK20+
b. CK7- CK20+
c. CK7- CK20-
d. CK7+ CK20-
**TEST QUESTION **
CK7- CK 20+ metastatic colon cancer
Ovarian mucinous CK7+ CK20+
Endometrial CK7+ CK20-
What is the most specific serum tumor marker for colon cancer?
a. CA125
b. CA19-9
c. CK
d. CEA
CEA
Splenectomy, how long to wait after to give vaccinations?
** TEST QUESTION **
Duplicate
2 wks (2 questions one was 14 days and the other gave options of 0-10days v. 2-4weeks)
UTD:
In order to optimize the immune response to vaccination, we vaccinate patients at least 2 weeks, and ideally 10 to 12 weeks, prior to splenectomy when possible. When vaccines cannot be given at least two weeks prior to splenectomy, we vaccinate two weeks following the procedure.
Splenectomy common complications?
bleeding, thrombosis, and infections.
Notes say: thrombocytosis. This seems to be incorrect based on below
AS (Chi): acute complications hemorrhage, LLL atelectasis, splenic vein thrombosis. Most common infection: s. pneumo (3.2% prevalence)
Which has higher rate of injury laparoscopically than open?
A Bowel
B urinary tract
C vascular
Urinary tract
Notes said: we all put different things but right answer is probably bowel
Elderly lady, unexpected splenectomy what is worst bug?
A H. flu
B s. pneu
C n. meningitidis
D e. coli
** TEST QUESTION **
The single most important pathogen is S. pneumoniae. This organism accounts for approximately 40 to 60 percent of cases of severe infection and overwhelming sepsis in splenectomized patients [10,13,14]. Although the overall incidence of S. pneumoniae infections is declining because of widespread pneumococcal vaccination [29,30], patients with impaired splenic function are still at higher risk for S. pneumoniae infection and poorer outcomes when compared with patients who have normal splenic function
Why to do TPN as opposed to enteral feeds for critically ill pt in ICU?
Direct comparisons of enteral nutrition with parenteral nutrition in critically ill patients from randomized trials indicate that outcomes in patient receiving enteral or parenteral nutrition are comparable
Probably not a fair question. Notes say: Mortality vs caloric requirements
UTD: Earlier evidence suggests early parenteral nutrition may increase the risk of infection. Data since then refutes these findings, and better safety practices may account for comparable outcomes between enteral nutrition and parenteral nutrition.
Most common cause for wrong site surgery:
A high volume surgeon
B teaching hospital
C OR start time
D lack of universal protocol / time out
(Duplicate)
The answer is D.
“In response to the occurrence of these preventable errors, the Joint Commission issued two National Patient Safety Goals on January 1, 2003 to target wrong-site surgery:
Goal 1—to improve the accuracy of patient identification by using two patient identifiers and a “time-out” procedure before invasive procedures."
What is this pathology?
A uterine endometrioid carcinoma
B uterine LMS
C uterine serous carcinoma
D endometrial stromal sarcoma
uterine serous carcinoma
Architecture:
Papillary with or without appreciable fibrovascular cores; micropapillary pattern can be seen
Slit-like spaces
Gland-like spaces may be observed
Psammoma bodies may be present in up to 33% of cases
Cytoplasm usually scant but can be abundant with eosinophilia or clearing
Tumor cells can colonize existing endometrial glands
Tumor cells can appear discohesive
Nuclei are typically high grade with pleomorphism, hyperchromasia, prominent nucleoli and frequent mitotic figures (including atypical mitotic figures)
