Host defence & neoplasia Flashcards
1
Q
Epstein Barr Virus predisposes to what cancer(s), esp in immunodeficient patients?
A
Non-Hodgkin Lymphoma
Hodgkin Lymphoma
2
Q
Increased cancer risk in HIV/AIDS is likely due to what? Evidence?
A
immunosuppression, immunologic stimulation, oncogenic infections
Immunodeficiency (because similar to transplant pts, reduced in cART treatment)
HIV doesn’t incorporate into specific genome locations, HIV DNA/proteins not in most malignant cells
However doesn’t seem to be correlated to CD4+ count (more related to chronic antigenic stimulation, inflammation, cytokines; also more oncogenic virus infections)
3
Q
Leading cause of death of HIV pts in developed countries
A
Cancer
4
Q
AIDS-defining cancers?
A
Kaposi’s sarcoma, aggressive B-cell NH lymphoma, invasive cervical cancer
5
Q
Name 5 non-AIDS defining cancers that are common HIV-associated cancers
A
Lung Anal Oropharyngeal Hepatocellular Hodgkin's lymphoma
6
Q
What are some oncogenic viruses that may have particularly high incidence in AIDS pts
A
KSHV (HHV8), HPV, HBV = sexually-transmitted
HBV/HCV spread by needle-sharing
7
Q
Kaposi sarcoma is what type of tumor? Caused by what?
A
Malignant spindle cell tumor
Human Herpesvirus 8 (Kaposi sarcoma-associated herpesvirus, KSHV)
8
Q
Where are lesions in Kaposi sarcoma?
A
Cutaneous/oral plaques
can also involve internal organs: GI tract, lymph nodes, lungs, bones
9
Q
KSHV mainly transmitted via
A
Saliva
10
Q
What do Kaposi Sarcoma lesions look like?
A
Changes over time
Papular –> plaques/nodules that can coalesce or ulcerate
Light brown/pink –> darker violet; do not blanch
Most commonly lesions on trunk, extremities, face; oral lesions on hard palate
11
Q
HHV 1 = HHV 2 = HHV 3 = HHV 4 = HHV 5 = HHV 8 =
A
HSV1 HSV2 Varicella-zoster virus Epstein-Barr virus Human cytomegalovirus Kaposi's sarcoma-associated herpesvirus
12
Q
HSV-1 & -2 both cause oral, ocular, and genital infection, but which more common for which
A
1 –> oral/eye
2 –> genital
13
Q
Herpes keratitis
A
Corneal infection (HSV-1)
14
Q
First HSV-1 oral infection is usually ____ whereas recurrences are usually ____
A
Herpetic gingivostomatitis (oral mucosa/gingiva) Herpes labialis
15
Q
Neonatal HSV is usually which? Results?
A
HSV-2 (transmitted via vaginal secretions)
Mucocutaneous vesicles/CNA involvement –> major morbidity/mortality
16
Q
What severe conditions can herpes lead to in HIV patients?
A
Esophagitis, colitis, perianal ulcers
Pneumonia
Encephalitis, meningitis
17
Q
How is herpes zoster distinct from HSV on clinical exam?
A
Herpes zoster rarely recurs
More severe pain
larger lesions groups, distribution along dermatome, usually not crossing the midline
18
Q
Culture/PCR/antigen detection tests should be done for HSV infections in which populations?
A
Neonates
Immunocompromised
Pregnant
CNS/severe disease
19
Q
Clusters of vesicles/ulcers on an erythematous base on genitals is most likely
A
HSV (probably -2)
20
Q
What is the mechanism of action of acyclovir? Why is it generally considered to be a “clean” drug?
A
Chain termination (no 3' OH), dGTP analogue Prodrug is inactive, only activated in virally infected cells (viral kinase)
21
Q
Name 3 oral medicals that can be used for HSV, VSV, EBV
A
Acyclovir (oral or IV)
Famciclovir (prodrug of penciclovir, more bioavailable than acyclovir orally)
Valacyclovir (prodrug of acyclovir, more bioavailable orally)
22
Q
Treatment for keratoconjunctivitis caused by HSV?
A
Trifluridine (+optho consult)
23
Q
Treatment for keratoconjunctivitis caused by HSV?
A
Trifluridine (+optho consult)
24
Q
Treatment for neonates, immunosuppressed pts, or CNS spread of HSV?
A
IV acyclovir
25
Chicken pox is caused by what?
Varicella-zoster virus (HHV-3)
26
When is varicella contagious? Route of transmission?
From 48 hours before lesions appear until final lesions crusted
Extremely contagious via mucosal spread (droplet/airborne) + direct contact
27
Can vaccinated children develop varicella?
Yes, "breakthrough" varicella
28
Prodrome of varicella starts how long after exposure? New lesions continue to appear for how long?
1-3 weeks
| New lesions for ~5 days, most crusted by 6th day
29
In what populations might oral treatment be necessary for varicella? IV?
Oral (valacyclovir, famciclovir, acyclovir): 12+ yo, eczema, chronic lung disease, pregnancy (TORCH!)
IV: immunocompromised children & adults, severe infection in pregnant women
30
What should a high-risk individual exposed to varicella receive?
VariZIG (postexposure prophylaxis) ASAP!
31
How is varicella prevented?
LAVV (live attenuated varicella vaccine)
- contraindicated if acutely ill, immunocompromised, pregnancy
- high-dose version to prevent Herpes zoster, although recombinant vaccine preferred for that noe
32
What is herpes zoster? (pathophys)
| AKA shingles
Reactivation of VSV from posterior dorsal root ganglion --> inflames sensory root ganglia, skin of associated dermatome
(sometimes posterior/ant grey matter horns, meninges, dorsal/ventral roots)
33
What is the first sign of herpes zoster? How long does it take the rash to appear?
Dysesthesis/stabbing pain usually along dermatome
Followed in 2-3 days by rash (crops of vesicles on erythematous base), unilateral, not crossing midline, lesions form for 3-5 days
34
Recurrence of herpes zoster is rare, but ___ is more common
Postherpetic neuralgia (can last indefinitely and be debilitating)
35
Treatment of postherpetic neuralgia
Pregabalin (Lyrica), gabapentin, TCAs, topical lidocaine/capsaicin, botox
36
Oral antivirals for herpes zoster should be started when?
(Acyclovir, famciclovir, valacyclovir)
Most effective when started during prodrome, less effective if started >72 hrs after lesions appear (sooner = better!)
*IV in severely immunocompromised pts
37
In what populations is the recombinant zoster vaccine recommended?
Immunocompetent adults 50+ (regardless of whether they've had the virus or not)
Immunocompromised adults considered on case-by-case basis (CANNOT have LAZV)
38
Which 2 shingles vaccines are available in Canada? Which is recommended for whom?
Zostavax II = Live Attenuated Zoster Vaccine, LAZV, 1 dose
Shingrix = Recombinant Zoster Vaccine, RZV, 2 doses
RZV recommended for ages 50+ even if you received LZV before!! LZV in immunoCOMPETENT people only if RZV not available
39
Epstein Barr Virus infects what cells?
B lymphocytes (remains for life w/ intermittent asymptomatic shedding, >90% of adults seropositive)
40
Incubation of infectious mononucleosis
1-2 months
41
Triad of symptoms in mono?
Fever + pharyngitis + adenopathy
| +fatigue which is worst in first 2-3 wks but can last months
42
___ occurs in 50% of patients with mono
| ___ in 95% of pts
Splenomegaly in 50%
| Temporarily elevated liver enzymes
43
2 differentials considered in pt presenting with EBV-like symptoms
R/o HIV
| Test for strep, though presence of strep DOES NOT EXCLUDE MONO
44
What is seen on CBC of pt with EBV?
High numbers of morphologically atypical WBCs (heterogenous, diff than leukemia)
45
Serologic testing for EBV
Monospot: heterophilic ABs (*FNs possible if tested too early)
Specific EBV Abs (IgM for primary infection, some IgGs persist for lyfe)
46
Pts with mono should avoid ___ for at least a month. Why?
Heavy lifting/contact sports
| Splenomegaly (risk of rupture)
47
What meds can be used for EBV?
Antivirals not recommended
| steroids only for complications
48
What oncologic emergency is most common after chemo is started for hematological malignancy?
Tumor lysis syndrome
49
TLS pathophys
Rapid destruction of tumor cells --> release of intracellular components (K, PO4^3-, uric acid) --> AKI, renal failure
50
Summarize the electrolyte imbalances in TLS?
PUKE Calcium
Phosphate, Uric acid (nucleotides), K are Elevated
Calcium decreased (binds phosphate)
51
Consequences of electrolyte imbalances in TLS?
PO4 --> low Ca --> crystals obstruct renal tubules (AKI); hypocalcemia --> tetany, muscle cramps, seizures
Hyperkalemia --> arrhythmia, nausea/vomiting, diarrhea, seizures, sudden cardiac death
Nucleic acids --> hyperuricemia --> urate nephropathy (crystals in kidney stroma) --> AKI
52
Management of TLS
Fluid therapy (K-free!)
RRT may be required
Uric acid reduction (allopurinol prophylaxis, prevents synth; rasburicase breaks down for treatment or high-risk prophylaxis)
Oral phosphate binders, may require some Ca, glucose/insulin for hyperkalemia
53
Oncologic emergency most common in acute leukemia (AML > ALL)
Leukostasis: blasts increase blood viscosity --> microvascular obstruction --> tissue hypoxemia/infarction (--> end-organ damage; resp, ophtho, neuro, etc)
54
Treatment of leukostasis
Inductive chemo, leukapheresis, hydroxyurea
55
Back pain in a cancer patient is ___ until proven otherwise
| Usually caused by?
SC compression!
| Metastasis to bone (e.g. prostate, breast, lung cancers)
56
Urgent diagnostics for possible SC compression in cancer patient
Urgent MRI w/ contrast
57
Treatment of SC compression?
Palliative (symptom management)
Steroids even if don't have MRI (treat edema encroaching upon SC)
Surgery + radiotherapy (unless not surgical candidate)
58
Some things that may make someone with SC compression not a surgical candidate and just XRT instead?
Multiple lesions spaced out
Life expectancy <3 months
ECOC 3-4 (poor performance status)
Extensive extraaxial metastases
59
___ in SC compression means surgery is advisable if possible
Spinal instability (caused by 2/3 of the anterior, middle, and posterior spinal columns compromised)
60
Brain mets come from what primary cancers? Are they more common than primary brain cancers?
10x more common than primary (better periph treatments making it more common)
30% lung/breast cancer, 70% melanoma
61
Median survival of SC compression oncology pt
3 mo
62
Prognosis of brain metastasis
1-2 mo w/out treatment
| 1.5 years w/ treatment
63
Default treatment for brain mets
Dexamethasone for symptomatic relief
| ```
Stereotactic Radiosurgery
if very large mass or causing mass effect then do Sx
```
64
WBRT vs SRS
Whole brain radiotherapy = standard dose
| Stereotactic radiosurgery = higher dose, smaller area; may work even in radiation-resistant tumors
65
Treatment of bone metastasis
NSAIDS, steroids, narcotics
Bisphophonates
Local XRT (reduces cell counts though because usually met is in axial skeleton where most BM is)
Brachytherapy
Kyphoplasty to restore height after fractures
66
Oncologic emergency most commonly caused by non small cell lung cancer?
SVCO
67
Presentation of pt w/ SVCO?
DYSPNEA (airway compression = main emergency!)
Swelling of face/arms
R chest mass
68
Diagnosis of SVCO?
CXR & CT will show mass
| Tissue biopsy to confirm to stage tumor
69
Treatment of SVCO?
Often palliative, occasionally not
Chemo, XRT
Stent = most rapid palliation
Steroids for symptoms
70
Diagnostic criteria for febrile neutropenia
Neutrophils <1.5 x 10^9 (esp if <0.5)
| Fever >38 (2x, 1 hr apart) or >38.3 x1
71
FN infections are typically __ or ___
Bacteria or fingi
| Esp Gram + bacteria (indwelling catheters/PICC lines)
72
How do you decide if a pt w/ febrile neutropenia should be managed inpatient or outpatient?
Inpatient IV ABs unless
- low risk (no medical comorbidities, clinically stable, anticipated neutropenia <7 days)
- pt easy to contact and close to hospital w/ transportation
- able to tolerate oral meds
73
Antibiotics for FN:
Inpatient IV: any of pip/taz, carbapenem, ceftazidime, cefepime; + vanco if skin/soft tissue infection, catheter-associated, pneumonia, hemodynamic instability, MRSA...
Outpatient oral: ciprofloxacin + amoxicillin-clavuanate
74
What do you do if FN persists after 4-7 days of treatment?
Add broad-spectrum fungal coverage
75
In all cases of fever + neutropenia consider ____ and ____ immediately
Sepsis (full workup)
| Treat w/ antibiotics immediately even if non-infectious cause postulated
76
2 strategies to PREVENT febrile neutropenia during chemo?
1) Antibiotic prophylaxis (hematological malignancies)
| 2) Recombinant granulocyte-colony stimulating factor (rG-CSF) - no mortality benefit
77
Symptoms of hypercalcemia of malignancy
Stones (nephrolithiasis)
Bones (fractures/pain)
Groans (abdominal gramps, nausea, ileus, constipation)
Thrones (polyuria/dehydration)
Psychiatric overtones (lethargy, depression, psychosis, stupor/coma)
78
What correction has to be done when measuring Ca?
Albumin (decrease of 10 --> increase Ca by 0.2)
| *most advanced cancer pts are hypoalbuminemic
79
Treatments for hypercalcemia of malignancy?
IV normal saline +/- furosemide (forced diuresis)
Bisphosphonates (pamidronate, zoledronate)
Dialysis if severe
2nd line: glucocorticoids, calcitonin
80
Define primary, secondary, and tertiary prevention
```
Primary = before disease occurs
Secondary = early detection of disease (subclinical) = screening
Tertiary = treating established disease to reduce severity/sequelae
```
81
Cancer screening programs in Ontario (4)
Breast
Lung
Colon
Cervical
82
The vast majority of women who have an abnormal mammogram...
Do NOT have breast cancer (0.5% of total screened women have BC, but 8% screen positive)
83
Average- and high-risk Ontario Breast Screening Program guidelines?
Average: 50-74yo, mammography every 2 years
| High-risk: from 30-69 get annual mammogram + breast MRI (or U/S if MRI not appropriate)
84
What makes someone "high risk" for breast cancer
Known gene mutation (BRCA1/2, TP53, etc)
First degree relative has known mutation & pt has received genetic counselling and refuses testing
>25% lifetime risk based on family Hx (genetics clinic assessment)
Radiation therapy to chest for other cancer <30yo, 8+ years ago
85
Possible next steps after abnormal mammogram
More mammography, U/S, MRI, biopsies
86
Ontario Lung Cancer Screening includes who?
55-74 yo
| Smoked cigarettes daily for cumulative 20+ years
87
Lung cancer screening test =
low-dose CT scan
88
Cervical cancer screening guidelines
Pap every 3 years from ages 25-70 (if 3 neg in past decade at 70)
89
Women who are not sexually active by the age of initiation [should/should not] delay cervical cancer screening until sexually active.
Should!
90
Should you have a pap during pregnancy?
Yes if it's due at that time
91
Women who are immunocompromised should receive ___ screening for cervical cancer
Annual
92
ColonCancerCheck Ontario average risk definition + screening
50-74yo, no 1st degree relative w/ CC
No PMHx of pre-cancerous colorectal polyps requiring surveillance or IBD
Fecal immunochemical test (FIT) every 2 years (if abnormal, colonoscopy within 8 wks)
OR sigmoidoscopy every 10 yrs
93
ColonCancerCheck Ontario HIGH risk definition + screening
FmHx colon cancer in 1st-degree relative(s)
Colonoscopies starting 50yo or 10 years before relative's age of diagnosis
every 5 yrs of relative diagnosed before 60, otherwise every 10 yrs
94
ColonCancerCheck Ontario doesn't screen who?
People @ high risk w/ hereditary colorectal cancer syndromes (FAP, Lynch syndrome)
These people must be managed by geneticist/gastro
95
Is FIT more or less sensitive for colon cancer screening than FOBT?
FIT
96
3 lung risks caused by asbestos exposure
asbestosis, lung cancer, and mesothelioma (which can be of the pleura as well as the peritoneum)
97
Characteristics that point twd a potential hereditary cancer disorder
(4 for individual + fam characteristics)
Multiple primary tumors (same/diff/paired organs)
Young age at diagnosis (<50)
Rare histology
Sex not usually expected for that cancer
Fam characteristics:
- 1st degree relatives w/ same/related tumor or suspicious signs, family members w/ tumors belonging to known familial syndrome, rare cancers
98
HER2 is an ____ related to ___ cancer but it's NOT ____
Oncogene
Breast cancer
NOT hereditary (acquired)
99
Define HBOC syndrome
Hereditary Breast & Ovarian Cancer Syndrome
Autosomal dominant
Behind up to 10% of BECAUSE
Mutations in one of several genes, half the time it's BRCA1 or BRCA2 (tumor suppressors)
100
HBOC increases the risk of what cancers? (5)
```
Breast!!
Ovarian!!
Prostate
Fallopian tube
Pancreatic
```
101
Define Lynch syndrome
Hereditary nonpolyposis colon cancer syndrome
Familial cancer syndrome caused by autosomal dominant mutation in DNA MMR
--> adenomas --> can rapidly progress to CRC
Also predisposes to endometrial, gastric, ovarian cancer
102
Define Li-Fraumeni syndrome
autosomal dominant mutation of p53 tumor suppressor
(one abnormal copy inherited, 2nd hit --> multiple malignancies at early age; breast, osteosarcoma, leukemia/lymphoma, brain tumors, adrenocortical carcinoma)
BLAST53: Breast/Brain, Leukemia/Lymphoma, Adrenocortical carcinoma, Sarcoma, Tp53
103
Familial adenomatous polyposis (mutation, symptoms, treatment)
Autosomal dominant mutations in APC tumor suppressor gene (25% spontaneous, 75% have family Hx)
Polyposis appears in teens/20s --> const/diarrhea, blood in stool, abdo pain
100% risk of CRC by 45yo! Can get prophylactic proctocolectomy + ileoanal anastomosis
104
Why do people with FAP need upper endoscopies as well?
Increased risk of gastric/duodenal cancers
105
Highly aggressive B cell lymphoma associated with EBV
| AIDS-defining cancer
Burkitt lymphoma
106
Specific type of pneumonia which is an AIDS-defining illness, the most common opp infection in HIV patients, and the most common cause of death in AIDS.
What is unusual about treatment?
```
Pneumocystis jirovecii
(fungus but doesn't respond to antifungals, need AB treatment)
```
107
3 steps to reduce maternal-infant HIV transmission
1) ARVT in mother
2) C-section
3) Treat bebe
108
How do HIV virions leave the cell?
Budding (enveloped virus)
109
What has to bind in order for HIV to attach/penetrate host cell
HIV Env = gp41 + gp120
gp120 binds CD4 on host cell --> conformation changes --> diff part of gp120 binds coreceptor(s) (CCR5 and/or CXCR4 depending on strain)
110
HIV effects on humoral immunity
B cell hyperplasia --> lymphadenopathy
| Hyperglobulinemia for previously-encountered Ags
111
HIV-2 restricted almost completely to...
West Africa
112
What is anemia of chronic disease?
normocytic --> microcytic anemia
| Inflammatory cytokines upregulate hepcidin --> more storage, less absorption (binds/downregulates ferroportin)
113
Most sensitive/specific test for HIV in first few weeks of infection?
Plasma HIV RNA
114
Recommended diagnostic test for HIV?
Combined antigen/antibody immunoassay
| (antigen = p24 = core viral protein, detectable before Abs during "window period"
115
CD4 count = ?
| Normal = ?
WBC x %lymphocytes x %CD4
| Normal = 750 +/- 250 /ul (500-1000)
116
3 stages of HIV based on CD4 count
Stage 1 = 500+
Stage 2 = 200-499
Stage 3 <200
117
What does the CD4/CD8 ratio tell us in HIV?
Measure of immune dysfunction
| Normally >1, decreases in AIDS (CD4 destruction and/or CD8 proliferation)
118
What is IRIS?
Immune reconstitution inflammatory syndrome = clinical deterioration as CD4 rises because of IS responding to subclinical opp infections
Paradoxical: infection previously diagnosed
Masked IRIS: opportunistic infection previously unknown
119
Common med regimes for ART
3 NRTIs OR 2 NRTIs + 1 NNRTS OR 1 PI OR 1 INI
120
Name 3 NRTIs
Abacavir
Zidovudine
Lamivudine
121
Name the 4 stages of the HIV life cycle at which meds can intervene, and which meds
Attachment & penetration (CCR5-antagonists, fusion inhibitors)
Reverse transcription (NRTIs, NtRTIs, NNRTIs)
Integration (INIs)
Post-translational modifications (protease inhibitors)
122
HIV resistance to meds comes from mutations in which gene?
Pol gene (encodes RT/integrase/protease)
123
Which ART is given to pregnant HIV+ women during labour and orally to neonate after birth?
Zidovudine
124
Common PrEP med combo?
TDF/FTC = tenofovir (NtRTI) + emtricitabine (NRTIs)
125
How long to continue prep after exposure?
1 month (if exposure won't repeat again)
126
PEP should contain __ ARTs and be started within ___ hrs and continued for ___
3+
72 hrs (MAX, sooner is much better!!!)
28 days
127
TH1 cells are more involved in the ___ immune response, where TH2 cells are more involved in ____ immunity
```
TH1 = cellular; more involved in autoimmunity
TH2 = humoral; more involved in allergies
```
128
Name 4 SMALL cutaneous lesions (<0.5 cm) & their large counterparts
Macule vs Patch (flat)
Papule vs nodule (raised, solid) or plaque (superficially raised)
Vesicle/pustule (clear vs pus) vs Bulla
129
Superficial dilated BV =
telangectasia
130
Purpura are ___ lesions that ___ under presure
Red-purple
| Do not blanch
131
Adenocarcinoma forms from ___ cells
Glandular epithelial cells
132
Viruses contribute to ___ of all cancers
20%
133
The majority of primary immunodeficiencies involve defective ___ immunity. 2 examples?
Humoral immunity
Selective IgA deficiency
Common variable immunodeficiency (CVID)
134
Labs show what in CVID?
Decreased levels of all Igs and plasma cells
| Normal B/T cells on flow cytometry
135
5 categories of primary immunodeficiencies
```
Humoral
Cellular
Combined
Phagocytic
Complement
```
136
CVID usually diagnosed when? Heritability?
```
20-40yo
Usually sporadic (no FMHx)
```
137
Name 3 combined immunodeficiencies
SCID
Wiskott-Aldrich syndrome
Hyper-IgM syndrome
138
Define SCID. Prognosis if untreated?
Severe combined immunodeficiency
| Multiple mutations --> defective B&T cells --> death in 1 year if untreated
139
Genetics of Wiskott-Aldrich syndrome?
Mutation in WASp gene (X-linked recessive)
WASp is important in cytoskeleton (platelets, T cells, NK cells, phagocytes)
Small mutation --> thrombocytopenia, large --> WAS
140
Ig levels in WAS
low IgG/IgM, high IgE/IgA
141
WAS AKA?
Eczema-thrombocytopenia-immunodeficiency syndrome
| Triad = eczema + purpura + recurrent OIs
142
Hyper-IgM syndrome bloodwork?
High IgM, low IgG/IgA/IgE (class-switching defect, impaired interaction b/w B&T cells, usually CD40 ligant)
143
Consequences of complement protein primary immunodeficiency? (2 pathways)
Defective opsonization/phagocytosis/lysis --> recurrent infection
Reduced clearance of Ag-Ab complexes --> autoimmunity, SLE, glomerulonephritis
144
Immune deficiency that presents <6mo old is likely to be a ___ defect
T-cell (maternal Abs until 6-9 mo)
145
T-cell IDs: Cervical lymph nodes/adenoids/tonsillar tissues ____ despite recurrent infections
Small or absent
146
Aplastic anemia =
Pancytopenia due to BM deficiency
147
Screening for SCID
* SCID screening is performed using the same blood samples that are collected for routine newborn screening.
* NSO uses a DNA test (real-time polymerase chain reaction) to measure T-cell receptor excision circles (TRECs), which are small pieces of DNA made during the maturation of the T-cells of the immune system. Newborns with SCID lack or have low TRECs.
148
Which Igs cross placenta? Breast milk?
IgG crosses placenta
| IgA secreted into breast milk
149
Define adjuvant & neo-adjuvant chemo
Neo --> shrinks tumors to optimize surg/XRT
| Adjuvant --> after surg/XRT
150
Scales used to describe pt functioning when choosing chemo (or when describing outcomes in trial)
Karnofsky for adults
| Lansky for children
151
What category of chemo drugs causes single-strand breaks and/or crosslinking of DNA
Incld mitrogen mustards, nitrosoureas, alkyl sulfonates,
Cyclophosphamide
Alkylating agents
152
Chemo category of drugs that imitate building blocks of DNA. 2 examples?
Anti-metabolites:
Methotrexate
6-mercaptopurine (purine anlogue)
153
Plant alkloid chemos, including vinca alkaloids and taxanes work how? examples?
Disrupt microtubules (mitotic spindle, cytoskeleton, etc)
Vinca alkaloids: vincristine, vinblastine (prevent MT assembly)
Taxanes: Paclitaxel (taxol) prevents MT disassembly
154
What ABs can be used for chemo? What do they do?
Intercalating DNA or oxidation/forming free rads
Anthracyclines (e.g. doxorubicin)
Actinomycin
Bleomycin
155
What class of chemo interferes w/ enzymes maintaining DNA topology
Topoisomerase I & II inhibitors
156
4 examples of targeted chemo therapies
Anti-angiogenesis (Bevacizumab targets VEGF)
Tyrosine kinase inhibitors (Imatinib - bcr-abl)
Receptor mediated apoptosis (Rituximab, CD20)
Immune therapy (pembrolizumab, PD-L1)
157
Drugs ending in -ib are...
Small molecule inhibitors
158
Max tolerated chemo dose usually defined by
BM suppression (RBCs/anemia, WBCs/infections, platelets/bleeding)
159
BM counts start falling ____ after chemo, hit nadir around ____
3-5 days, nadir around 7-10 days
160
Chemo can cause nausea/vomiting and ___
| N/V happens when? ___ when?
Mucositis worst 5-7 days after chemo
| Nausea acute within 24 hours, delayed >1 week slater
161
radioactive isotopes put near/inside tumor =
brachytherapy
162
Carcinoma before and after permeating the basement membrane?
Carcinoma in situ
| Invasive carcinoma
163
Most carcinomas metastasize via...
Lymphatic spread
164
Define organ tropism in the context of cancer
Tendency for certain cancers to spread to particular organs
| target organ usually the first capillary bed encountered by disseminated cells
165
name 3 common sites for cancer metastasis
Liver, Bone, Brain
166
what 3 cancers metastasize to the liver?
Colon, Stomach, Pancreas
| Cancers Spread Progressively to the liver
167
Specific grading systems for breast/prostate cancer
Nottingham/Gleason
168
AJCC grading system for nonhematological malignancies: define lowest and highest
```
G1 = low-grade = well-differentiated
G4 = high-grade = undifferentiated/anaplastic
```
169
Is tumor staging or grading better for prognostic value?
Staging is a better indicator!! (higher stage is worse than higher grade)
170
in TNM staging, each letter has ____ prognostic value. ___ & ___ are the most important for prognosis
Independent
| N&M most important
171
Staging:
T =
N =
M =
```
T = extent of primary tumor (Tis = in situ, 1-4 where 4 = infiltration of neighbouring organs)
N = regional lymph node involvement (N0-3)
M = distant metastases (0-1, x = unknown)
```
172
What are the 3 non small cell lung cancers? Which is most common in women/nonsmokers? Which is central?
Lung adenocarcinoma, lung squamous cell carcinoma, large cell carcinoma
Squamous = "sentral"
adenocarcinoma most common in women/nonsmokers; better prognosis
173
Lung cancer most commonly metastasizes where?
```
BLAB
Bone
Liver
Adrenals
Brain
```
174
Steps after incidentally finding solidary pulmonary nodule on CXR?
1. Compare with previous imaging if available (if stable 2-3yrs, no f/u reqd)
2. Chest CT, assess malignancy risk
3. High risk --> surgical excision; intermediate --> PET or biopsy, serial CT scans, or reassurance depending on size
175
Is upper or lower/middle lobe location of a pulmonary nodule higher cancer risk?
Upper lobe = higher risk
176
AJCC staging
0 =
I-III =
IV =
```
0 = carcinoma in situ
I-III = spread to nearby tissues
IV = distant metastasis
```
177
Lynch syndrome involves mutation of a protein involved in ____.
AKA _____
Predisposes to ____
DNA repair
Hereditary non-polyposis colorectal cancer (HNPCC)
Colorectal cancer
(There is also an increased risk of developing other types of cancers, such as endometrial (uterine), stomach, breast, ovarian, small bowel (intestinal), pancreatic, prostate, urinary tract, liver, kidney, and bile duct cancers.)
178
Prostate cancer is most commonly a _____ expressing ____ in the ____ zone
Adenocarcinoma
Expressing PSA
Peripheral zone (posterior lobe)
179
The ___ zone is the main area felt against the rectum on DRE
Peripheral
180
Common metastasis sites for prostate cancer
Lung
Liver
Bone
181
Utility of DRE for screening for prostate cancer
NOT effective
Low sensitivity even in symptomatic pts
High specificity if irregular/nodular & painless
182
How would BPH feel on prostate exam?
Homogenous, rubbery, nontender
183
How would prostatitis feel on prostate exam?
Painful/swollen
184
___ of abnormal PSAs are actually due to cancer
25%
| Can be high due to BPH, UTI, prostatitis, trauma, manipulation of prostate gland
185
APC (gene) stands for what? Mutated in what disease?
Adenomatous polyposis coli gene
| mutated in FAP
186
Name 3 genes that when mutated can lead to polyps/colorectal cancer
APC
p-53
K-RAS (oncogene)
187
Colon cancer patterns in ascending vs descending colon
Ascending: grows BEYOND mucosa (no obstruction)
Descending: lumen narrowing (napkin-ring constriction)
188
Apple-core sign is seen where?
Descending colon cancer
| Barium enema x-ray
189
AB prophylaxis for post-op infections
start before incision (within 1 hour, 2 hrs for vancomycin/fluoroquinones), continue postoperatively for <24 hrs (48 for cardiothoracic surgery)
190
__ is used most often for surgical prophylaxis in patients with no history of beta-lactam allergy, no history of MRSA infection, and no surgical sites in which the most probable organisms that are not covered by cefazolin alone (e.g., appendectomy, colorectal).
If MRSA risk, ___ may be used
Cefazolin (1st-gen cephalosporin)
Vancomycin
191
Define sepsis & septic shock according to the 3rd international consensus definition
Sepsis = dysregulated response to infection --> tissue/organ damage + organ dysfunction
Septic shock = above + need vasopressors for MAP >65 & persistent lactic acidosis despite fluid resuscitation
192
4 SIRS criteria for systemic inflammatory response syndrome? How many do you need?
2 + suspected infection
| Temp (>38 or <36), HR >90, RR >20, WBC high/low or high bands
193
What is the SOFA score?
Sequential Organ Failure Assessment score
| Calculate after 24 hrs in ICU then every 48 hrs to predict MORTALITY (not diagnostic)
194
Most common etiology of sepsis
Pneumonia
195
Hour 1 bundle for sepsis/septic shock
1) Blood cultures
2) Serum lactate
3) IV crystalloids (30 mg/kg)
4) Vasopressors
5) Broad-spectrum ABs (as soon as cultures drawn)
196
What vasopressors are used in shock?
1st line = norepinephrine
2nd = +vasopressin OR +continuous IV epinephrine
3rd = and/or dopamine, dobutamine
+corticosteroids if refractory or adrenal insufficiency
197
Common empiric AB regime for sepsis in pt w/ unknown risk factors
Vancomycin
+ one of the following:
- broad-spectrum carbapenem
- extended-range penicillin/B-lactamase inhibitor (Pip/taz, ticarcillin/clavulanate)
- 3rd or 4th gen cephalosporine (cefepime, ceftriaxone, etc.)
