Exam 2 Flashcards
(248 cards)
1
Q
Species of plasmodium causing malaria in humans. Where are each endemic?
A
- P. falciparum: world-wide (majority of cases in US)
- P. vivax: less common in sub-Saharan Africa (majority of cases in US)
- P. malariae: world-wide
- P. ovale: Africa, Asia, Pacific Islands
- P. knowlesi: Malaysia, parts of SE Asia (recently identified)
- Most US cases acquired were Falciparum (from Africa), others were Vivax (from Asia)
2
Q
Lifecycle of Malaria
A
- Anopheles mosquito carrier (maturation in salivary glands)
- Injected into human
- Hepatic stage: maturation into merozoite in hepatocyte, latent in hepatocyte as hypnozoite (for vivax and ovale)
- Blood stage: merozoites burst out from hepatocytes and infect RBCs – proliferate – burst RBCs
3
Q
Which malarial infections are found in dormant form in liver?
A
- Vivax and ovale as hypnozoite
4
Q
Clinical presentation of malaria
A
- Malarial paroxysm associated with synchronous release of merozoites and lysis from RBCs. Symptoms = flu-like: fever, chills, HA and myalgia.
- 3 parts: cold stage (rigors, cold dry skin, tachy, nausea, vomiting) 15-60 mins; hot stage (HA, palpitations, confusion, delirium) 2-6 hrs; sweat stage (perspiration, exhaustion, sleep) 8-12 hrs
5
Q
Duration of malarial paroxysm between species
A
- Knowlesi (quotidian): q 1 day
- Vivax, falciparum*, ovale (tertian): q 2 days
- Malariae (quartan): q 3 days
- Hot stage prolonged (less time to recover between paroxysms), this is malignant tertian. Ovale and vivax are benign tertian.
6
Q
Most severe and common form of malaria
A
- Falciparum
- Known as malignant tertian malaria
7
Q
Compare and contrast tertian (malignant, benign), quotidian and quartan malaria. What species of protozoan causes each, symptoms, complications?
A
- ) Malignant Tertian: falciparum
- Symptoms: flu-like, jaundice, paroxysms ~ 2 days, splenomegaly
- Complications: cerebral malaria (coma/seizures after fever), anemia, hypoglycemia (decreased intake, depletion of glycogen, parasite eats glucose, inhibition of gluconeogenesis via TNF-alpha and IL-1), lactic acidosis, renal failure, also pneumonia, etc. - ) Benign Tertian: vivax and ovale
- Symptoms: dormant = asymptomatic, flu-like paroxysms ~ 2 days, splenomegaly
- Complications: splenic rupture, anemia - ) Quartan: malariae
- Symptoms: flu-like paroxysms ~ 3 days (persistent low level parasitemia), splenomegaly
- Complications: anemia - ) Quotidian: knowlesi
- Symptoms: daily fever, flu-like (higher parasitemia), splenomegaly
- Complications: anemia
8
Q
Most common complication of malaria. Why? Does the severity of this complication depend on the species involved in the malarial infection?
A
- Anemia
- 3 mechanism: hemolysis, suppression by cytokines (TNF-alpha, IL-1), destruction of RBCs by spleen (coated by antigens)
- Falciparum, knowlesi infect mature and young erythrocytes (more severe anemia, worst = falciparum d/t type of RBCs and high parasitemia). Vivax and ovale infect only reticulocytes. Malariae prefers older RBCs.
9
Q
Gold standard for malaria diagnosis
A
- Blood smear
10
Q
How to detect the various species of plasmodium on blood smear?
A
- Falciparum: rings, purple banana (pathognomonic); normal size RBC
- Vivax: large pale RBCs (oval), Schuffner dots
- Ovale: large pale RBCs (oval), Schuffner dots
- Malariae: band form (pathognomonic), normal size RBC
11
Q
Which plasmodium species causes the highest parasitemia in malaria?
A
- Falciparum
12
Q
Which disorders provide resistance (or some degree of) to malaria?
A
- SCA
- Thal
- G6P DH deficiency
- SE Asian ovalocytosis
- Absence of Duffy blood group antigens
13
Q
What is the “American Malaria”?
A
- Babesiosis
14
Q
Babesiosis. Transmission, locations where cases most common, symptoms, diagnosis, treatment?
A
- Transmission: reservoir = rodents/cattle; carrier = tick
- Locations: MA, NY and RI, others
- Sx: flu-like, hemolytic anemia, many are asymptomatic. Risk group = elderly, asplenic, immunosuppressed
- Dx: hx of tick bite, blood smear shows Maltese Cross (pathognomonic)
- Tx = quinine and clindamycin
15
Q
Difference between clinical and radical cure of malaria
A
- Clinical: feeling better, parasites no longer detected in blood
- *Radical: feel better and no parasites in body including liver
- *We care about this d/t dormant forms (ovale and vivax)
16
Q
How do you treat malarial infections?
A
- Intra-erythrocytic form
- Chloroquine: much resistance world-wide, only used West of Panama Canal incl. MX, Haiti, DR. Neuropsych side effects.
- Quinine (and quinidine): poor therapeutic to toxic ratio, side effect = cinchonism (tinnitus, hearing loss, nausea, vomiting, visual changes), hypoglycemia
- Malarone (combo drug of atovaquone and proguanil) - newer - Blood form
- Mefloquine: used in areas of chloroquine resistance
- Artemisinins: newer - Hepatic / hypnozoite form (vivax and ovale)
- Primaquine - Prophylaxis: mefloquine; doxycycline (+ other tetracyclines) *photosensitivity dermatitis/teeth staining in kids – contraindicated in kids and pregnant
17
Q
Which drug do you use to tx malaria west of the Panama Canal incl. Mexico, Haiti and DR?
A
- Chloroquine. Only kills intra-erythrocytic forms.
18
Q
34 yo female has recently has returned back from a year-long contract working for the UN in Gabon. Upon returning to the US, she started experiencing fevers, nausea, vomiting, chills, headaches and drowsiness. You are a first year resident on the case and you immediately begin to suspect malaria. You question the patient about how often these symptoms occur. She says every 2 days roughly. PMHx is significant for T2 DM, but patient reports well-managed BGL since her diagnosis 5 years ago. In fact, she says that she has been on a whole 30 diet for the past 6 months and has not required her metformin since. She reports normal BGL for the past 3 months. Blood work comes back and shows BGL of 50. In addition, peripheral blood smear shows RBCs with ring-like forms within. You determine what the diagnosis is and write a rx for drug X. You decide to admit the patient d/t her poor presentation and note to follow up with her the next morning. While at home, you get a 911 page stating the patient is non-responsive. You immediately return to the hospital? You work on reviving the patient and order stat blood work and a POC BGL test. BGL is 30.
a. What is the diagnosis?
b. What species is she infected with?
c. Why is she hypoglycemic after her initial blood work?
d. Why did she fall into a coma?
e. Was any of this your problem? If so, why?
A
a. Patient has malaria.
b. Infected with P. falciparum
c. Hypoglycemia is a complication of the infection. Falciparum is voracious consumer of glucose.
d. She fell into a coma d/t hypoglycemia. Patient was prescribed quinine, which has side effect of hypoglycemia as it induces release of insulin. This compounded her already severe hypoglycemia.
e. You failed pharm 101 and didn’t look at the side effects of this drug.
19
Q
Drug used to tx dormant form of malaria
A
- Primaquine. Only activity against hypnozoite form (vivax and ovale). Administer after clinically curing. Side effect: hemolysis in those with G6P DH deficiency. Need to screen in these patients.
20
Q
What meds are given to tx malarial infections (incl. prophylactically)?
A
- Area w/o chloroquine resistance: give chloroquine for prophylaxis. For tx: give chloroquine.
- Area w/chloroquine resistance: give mefloquine, Malarone and doxycycline for prophylaxis. For tx: mefloquine, Malarone, quinine all recommended. Together? Also Artemisinin recently FDA approved.
- Area where vivax and ovale are endemic give primaquine (check G6PD status) for prophylaxis and treatment. Unsure if you give other meds above first. Seems like you would first give “standard” meds and then follow up with primaquine.
- Note: patients should improve clinically within 48-72 hrs of meds. Parasitemia should be reduced by 75%.
21
Q
Classification of antibody
A
- Source of sensitization (natural or immune)
- Antibody class (IgG, IgM etc.)
- Allo (non-self) vs. Auto (self)
- Optimal temp
22
Q
What are the CHO antigens on RBCs? Which antibodies do these tend to stimulate?
A
- H, A and B
- Others
- Stimulate IgM
23
Q
What are the protein antigens on RBCs?
A
- Rh
- Others
- Stimulate IgG
24
Q
Compare and contrast hemolytic transfusion reactions. Describe where each takes place, symptoms/signs and antibody that mediates each.
A
- Intravascular
- Severe/immediate
- Takes place in blood. MAC lyses RBC, free Hgb in circulation.
- Signs/symptoms: renal dysfunction, DIC, shock, death
- Mediated by IgM antibodies
- Extravascular
- Delayed
- Takes place in RE system (inflammatory and cytokine storm follow)
- Signs/symptoms: jaundice
- Mediated by IgG antibodies
25
Antibody involved in HDFN
- IgG, which crosses placenta. NOT IgM!
26
What antigen system is the most important in blood transfusions?
- ABO leads to severe transfusion reaction
| - Rh as well
27
ABO mismatch causes what type of hemolytic transfusion?
- Intravascular. Severe (as little as 150 mL can be fatal) d/t complement.
28
Rh mismatch causes what type of hemolytic transfusion?
- Extravascular.
29
Antigen necessary to express either A or B antigens?
- H antigen. If present, depending on genes, the A and B sugar residues are added to it.
- If absent = Bombay phenotype
30
What antigen is present in O blood type?
- Only H antigen. O is not an antigen, just indicates absence of A and B.
31
T/F. ABO system refers to dominance of genes.
- False, co-dominant.
32
When do the ABO antigens develop in fetus?
- ~ 6th week of life. ~50% of adult level present at birth. Adult level reached by 3 years.
33
Group O blood type forms what antibodies? Group AB?
- Group O: forms antiA and antib
| - Group AB: forms neither
34
Most common ABO system blood type? Least common?
- Most common: O, second common: A
| - Least common: AB
35
Rh factor antigen. How are these inherited? What is the haplotype common in Caucasians? Blacks? Rh neg haplotype?
- D = main antigen. Absence of D = d.
- Others = C, c, E and e
- Inherited as closely-linked genes as haplotype.
- Caucasians: DCe (R1)
- Blacks: Dce (Ro)
- Rh neg: dce (r)
36
Which antibodies: antiA/B or antiRh causes HDFN?
- Both.
- Mild with antiA/B
- Severe with antiRh
37
Which mothers are at risk for developing HDFN? How do you treat?
- Rh neg mother
- Give RhoGAM, which is an anti-D. It is passive immunity to D antigen that causes removal of D positive RBCs before mother’s immune system forms antibody. Give one dose at 28 weeks, another after delivery.
38
Blood typing method
- Use anti-A, B and D antibodies to look at the RBCs (front-type)
- Use A and B cells with patient plasma to look for antibodies (back-type)
39
Compare and contrast the direct antiglobulin vs the indirect antiglobulin tests
1. Direct antiglobulin test (DAT): looking for in vivo antibody sensitization?
- Detects antibodies/complement complexed to pt’s RBCs
2. Indirect antiglobulin test (IAT): looking for in vitro antibody sensitization?
- Detects antibodies in pt’s serum that target antigens on RBCs
40
3 components of compatibility testing
- Blood type (ABO and Rh (D))
- Antibody screen
- Crossmatch (donor RBCs and patient plasma)
41
What is the universal donor type for RBCs?
- Type O. This blood does not have A or B antigen.
42
What is the universal donor type for plasma?
- Type AB. These individuals do not make anti-A or B antibodies.
43
If Rh negative blood is needed for a transfusion, but isn’t available, who can be transfused in an emergency?
- Patient’s without anti-D
- Males first
- Women of childbearing age last
44
Where do blood components come from?
- Whole blood (most common method)
| - Apheresis: Removing certain components from the blood
45
What are the various pRBC forms/components used for?
- RBCs (pRBCs): anemia (increase Hb), replace blood after acute bleed
- Leukoreduced pRBCs: fever, HLA alloimmunization, platelet refractoriness (pts may make antibodies to transfused platelets)?, prevent CMV infection (carried in WBCs) esp in immunocompromised
- Irradiated pRBCs: transfusion-associated graft-vs-host dz (prevent T-cell division) esp in immunocompromised
- Washed pRBCs: patients with recurrent or severe allergic rxn associated with RBC transfusion, patients with IgA deficiency (will form abs to IgA = anaphylaxis)
- Volume reduced: patients with circulatory overload (CHF, renal failure)
46
pRBCs show changes when stored. How are clinical outcomes impacted when older units are used?
- No differences in clinical outcomes per RCTs.
47
Which transfusion strategies are preferable: liberal or restrictive?
- Restrictive, meaning start transfusion at lower Hb threshold results in better patient outcomes.
48
Threshold for RBC transfusion in adults with:
a. ) Symptomatic patient
b. ) Hospitalized patient
c. ) Ambulatory outpatient
a. 10 g/dL
b. range from 7-8 to 10 g/dL
c. 7-8 g/dL for oncology pt or as needed for symptoms
49
Name the clinical indication(s) for red cell transfusion
- anemia (increase Hb), replace blood after acute bleed
50
What are leukoreduced pRBCs? Indication for use?
- Removal of leukocytes from pRBCs. Only RBCs, plasma proteins left.
- Used to prevent: fever, HLA alloimmunization, platelet refractoriness (pts may make antibodies to transfused platelets)?, CMV infection (carried in WBCs)
51
What are irradiated pRBCs? Indication for use?
- Exposed to x-rays
| - Used to prevent transfusion-associated graft-vs-host dz (prevent T-cell division) esp in immunocompromised
52
What are washed pRBCs? Indication for use?
- Removing of residual plasma and prevent complications d/t plasma proteins.
- Used for: patients with recurrent or severe allergic rxn associated with RBC transfusion, patients with IgA deficiency (will form abs to IgA = anaphylaxis)
53
What is volume reduced pRBCs? Indication for use?
- Removes preservative solution that RBCs are stored in
| - Used for: patients with circulatory overload (CHF, renal failure)
54
Two indications for transfusing FFP
1. Coagulation factor replacement: warfarin-associated bleeding, vit K deficiency bleeding, liver dz, DIC
2. Massive transfusions
3. ADAMTS 13 replacement: TTP
55
Transfusion threshold for:
a. active bleed (non-DIC/CNS)
b. DIC/CNS bleed
c. Neurosurgery
d. Eye surgery
e. Other major surgery
f. Central line placement
g. Prevention of spontaneous bleeding
a. active bleed (non-DIC/CNS):
56
What is alloimmunization that occurs between ~ 30-40 of recipients who receive platelet transfusion? How can it be prevented?
- This is referred to as platelet refractoriness. Pts who have received platelets, may rarely, make antibodies to them. D/t anti-HLA and anti-HPA. Note: there is also non-alloimmune platelet refractoriness d/t splenomegaly, sepsis and DIC.
- Implication: in future platelet transfusions, platelets may be quickly destroyed
- Prevented: find compatible platelets (random platelet units, crossmatch, find platelets with antigen that antibodies aren’t directed toward).
57
Two methods of platelet product preparation commonly used
??
58
Therapeutic constituents of cryoprecipitate and name a clinical indication for its use.
- Cryoprecip = precipitate that forms when FFP is thawed at 1-6 deg C
- Contains: factor VIII, fibrinogen, vWF and factor XIII
a. ) Factor VIII: hemophilia A
b. ) Fibrinogen: bleeding patients
c. ) vWF: von Willebrand dz
d. ) Factor XIII: factor XIII deficiency
59
Name at least one common indication for each of the following blood derivatives:
a. Factor VIII
b. Prothrombin complex concentrates
c. Albumin
d. IVIG
a. Factor VIII: hemophilia A to control and prevent bleeding events and in periop mgmt.
b. PT complex: this is a complex of vit K-dependent factors (1972) used in patients with hemophilia in the following situations – hemorrhage, periop bleeding management, routine prophylaxis of bleeding events
c. Albumin: hypoalbuminemia (d/t chronic malnutrition, low total protein, protein-losing enteropathy, liver failure, nephrotic syndrome), volume replacement
d. IVIG: primary humoral deficiencies (SCID, agammaglobulinemia to prevent bacterial infections), immune thrombocytopenia (ITP), chronic inflammatory demyelinating polyneurophaty (CIDP), post-exposure prophy (hep A, measles, rubella, varicella)
60
List the main coagulation abnormalities that occur after massive transfusion and outline the appropriate treatment for each.
1. Dilution of coagulation factors: increase in PT and PTT
- FFP given
2. Fibrinogen levels drop
- Cryoprecip (contains factor VIII, fibrinogen, vWF and factor XIII) given
61
What is directed donation? Is it more risky?
- Donation of a blood component for a specific patient
- Yes, more risky for both patient and donor. Why? Donor more likely to be untruthful when being screened b/c they want to help someone. Donor could pass out. Recipient could get infection/sepsis.
62
Three reasons why blood component therapy is preferable to whole blood therapy
- Whole blood rarely used in US. Advantage = all components in normal ratios, best for trauma.
- Blood component therapy is better for specific needs: anemia (RBCs), DIC (plasma), thrombocytopenia (platelets), low fibrinogen (cryoprecip)
- He didn’t specifically answer this question, but: infection, cost, reactions probably.
63
Identify the most effective method known to prevent the majority of acute hemolytic transfusion reactions
- Stop the transfusion
64
Types of transfusion reactions
- Fever, allergic, TACO (transfusion-associated circulatory overload), TRALI (transfusion-related acute lung injury), acute hemolytic, delayed hemolytic, post-transfusion purpura, TA-GVDH, transfusion-transmitted bacterial infection (TTBI)
65
Most common transfusion reactions
- TACO (transfusion-associated circulatory overload) and fever – about 1 in 100
66
Febrile transfusion reaction. Pathophys, clinical presentation, treatment, prevention
- Pathophys: Cytokine release (from donor leukocytes)
- Presentation: temp >= 1 C above 37 C, chills, rigors, no other etiology, up to 4 hrs post-transfusion
- Tx: stop the transfusion, antipyretic, meperidine for rigors
- Prevention: leukoreduced pRBCs, pre-medicate with acetaminophen
67
Allergic transfusion reaction. Pathophys, clinical presentation, treatment, prevention
- Pathophys: hypersensitivity to allergens (primarily aeroallergins) almost always from platelet or plasma transfusion where allergens are found
- Presentation: uticaria, within 4 hours, seldom angioedema
- Tx: stop the transfusion, diphenhydramine (pretreatment DOES NOT WORK), if severe give steroid, if worse still call a code and administer epi
- Prevention: washed RBCs, plasma reduced platelets, not washed platelets (they can activate)
68
Pathophysiology of anaphylaxis following transfusion
- Antibodies in recipient to something in component. Commonly IgA-deficient patient with antibody to IgA in component. Also to haptoglobin, penicillin and C4 of complement.
69
TACO (transfusion-associated circulatory overload). Pathophys, clinical presentation, treatment, prevention
- Pathophys: volume overload
- Presentation: INCREASE IN BP AND HR OFTEN, also gallop, JVD, elevated central venous pressure, acute pulmonary edema (dyspnea, orthopnea), new ST and T wave changes, elevated trop and BNP, within 1-2 hours, increased likelihood in those already volume overloaded
- Tx: stop the transfusion, seat pt, o2, diuretics, therapeutic phlebotomy
- Prevention: administer component more slowly, monitor I/Os, volume reduced?
70
TRALI (transfusion-related acute lung injury). Pathophys, clinical presentation, treatment, prevention
- Pathophys: two hit mechanism usually with administration of plasma or platelet transfusion
a. Neutrophil sequestration and priming – neutrophils accumulate, respond to otherwise weak signal damaging lung endothelium
b. Received component contains factor (anti-HNA/HLA, bioactive lipids) = neutrophil release of chemicals that further damage pulmonary endothelium = pulmonary edema
- Presentation: fevers, chills, dyspnea, hypoxemia (
71
How to distinguish TACO from TRALI?
- TACO Presentation: INCREASE IN BP AND HR OFTEN, also gallop, JVD, elevated central venous pressure, acute pulmonary edema (dyspnea, orthopnea), new ST and T wave changes, elevated trop and BNP, within 1-2 hours, increased likelihood in those already volume overloaded
- TRALI Presentation: FEVERS, CHILLS, dyspnea, hypoxemia (
72
Acute hemolytic transfusion reaction. Pathophys, clinical presentation, treatment, prevention
- Pathophys: antibodies in patient to antigens on transfused RBCs = INTRAVASCULAR destruction, most severe against ABO antigens
- Presentation: fever, chills, rigors if mild. Severe = pain in abdomen, chest, flank, back, hypotension, dyspnea, shock, DIC. First sign in unconscious patient = red/dark urine. Severity related to amount of component transfused.
- Tx: stop the transfusion, continuous IV saline infusion, tx hypotension, maintain renal blood flow with diuretics (consult nephron), symptomatic treatment
- Prevention: minimize clerical errors
73
Delayed hemolytic transfusion reaction. Pathophys, clinical presentation, treatment, prevention
- Pathophys: low titer of antibody and recent transfusion causes an increase = gradual destruction of RBCs; classic antibody is against RBC antigen called KIDD (ANTI-KIDD)
- Presentation: fever, anemia, jaundice, leukocytosis days to weeks after transfusion, may be no signs and symptoms; hemolysis is EXTRAVASCULAR
- Tx: monitor, supportive care, correct anemia (transfuse RBCs without antigen that antibody is directed against)
- Prevention: obtain prior transfusion records to identify known antibodies, give appropriate antigen-neg RBCs
74
Post-transfusion purpura. Pathophys, clinical presentation, treatment, prevention
- Pathophys: anti-platelet antibodies in patient’s system developed upon previous exposure to foreign platelet antigens (pregnancy, transfusion) – more in females (26:1), transfused platelets destroyed along with own platelet’s – unknown why?
- Presentation: profound thrombocytopenia, purpura, bleeding (can be intracranial), avg is 9 days post-transfusion
- Tx: high dose IVIG (dilutes antibodies responsible for rxn)
- Prevention: use platelets that do not have antigen that antibody is directed against
75
TA-GVDH (transfusion-associated graft-vs-host disease). Pathophys, at-risk group, clinical presentation, treatment, prevention
- Pathophys: donor component has different HLA-type from recipient, viable T-cells in component see patient’s HLA as foreign and initiate attack, not issue for healthy but is seen in immunocompromised
- Presentation: maculopapular rash (trunk and progress to extremities), may develop bullae, fever, enterocolitis with diarrhea, elevated LFTs, pancytopenia d/t marrow dysplasia – occurs 3 to 30 days post-transfusion. 90% OF CASES FATAL.
- Tx: not tx proven substantial
- Prevention: irradiate blood components (must request this specifically)
76
Transfusion-transmitted bacterial infection (TTBI). Pathophys, clinical presentation, treatment, prevention
- Pathophys: usually d/t platelets. Why? Growth of bacteria at room temp where platelets stored.
- Presentation: fever > 39 C or an increase > 2 C following transfusion, rigors, tachy >=40, SBP inc/dec 30; following transfusion up to 5 hours (avg 30 mins). Severity depends on type of bacteria, inoculum, patient’s immune status. May go into shock, renal failure DIC. Note: must ID both the component and the patient and match bacterium.
- Tx: stop transfusion, resuscitate patient, collect samples from arm opposite transfusion, beging empiric abx, alert blood bank and micro.
- Prevention: defer donors with ID, careful donor arm disinfection, discard first few mLs during collection, culture platelets, pathogen-reduction technology
77
Which transfusion reactions present with a fever?
- Febrile
- TRALI
- Acute hemolytic
- Delayed hemolytic (+/-)
- TA-GVHD
- TTBI
78
Name the blood component most likely to cause bacterial sepsis and explain why it occurs?
- Platelets. Platelets stored at room temp.
79
Name the three major clinical situations in which Rh immune globulin should be given to prevent HDN
- Mother Rh- and father is known to be Rh+
- Mother is Rh- and father’s Rh status is unknown
- Infant is known to be Rh+
* NOT when mother has already formed an anti-D
- Other: threatened abortion, spontaneous abortion, fetal death in 2nd/3rd trimester, ectopic, multiple fetal losses, invasive procedures (amnio, CVS), blunt trauma to abdomen
80
Leukemia vs lymphoma vs myeloma
- Leukemia: cancer starting in blood-forming tissue such as bone marrow and abnormal cells enter blood
- Lymphoma/myeloma: cancers that begin in cells of the immune system, present as masses in lymph nodes or other soft tissues.
* Note: lymphomas can present with peripheral blood involvement and leukemias can present with tissue masses and no peripheral blood involvement.
81
Compare and contrast acute vs chronic leukemia in terms of prognosis
- Acute: generally lethal within weeks w/o treatment. These include AML (acute myeloblastic leukemia) and ALL (acute lymphoblastic leukemia/lymphoma)
- Chronic: generally may survive many years w/o treatment
82
Categories of hematological malignancies. Differentiate between them.
- Lymphoid: tumors involving B cells, T cells, NK cells or their precursors. This includes leukemias, lymphomas and plasma cell disorders.
- Myeloid: tumors involving granulocytes, RBCs, platelets or their precursors. This includes myelodysplastic syndromes, chronic myeloproliferative disorders and leukemias.
- 5 general categories: myelodysplastic syndromes, chronic myeloproliferative disorders, leukemias, lymphomas and plasma cell disorders
83
Two types of acute leukemias.
- Acute myeloblastic leukemia (AML): most common acute leukemia in adults. Auer rod is seen on smear or BM biopsy. AML-M3 from flow cytometry.
- Acute lymphoblastic leukemia/lymphoma (ALL): aggressive, most common in children. Includes:
a. B-ALL – vast majority of cases
b. T-ALL – few of cases
- Both with pancytopenia.
84
Define myeloproliferative diseases. What diseases are included in this category? Briefly state the genetic and clinical differences amongst them.
- Defined: bone marrow makes too many of the cell lines causing bleeding problems, anemia, infection, fatigue, other. Certain of these become AML.
- Diseases
a. Polycythemia vera: JAK2 mutation, high level of functional RBCs
b. Primary myelofibrosis: JAK2 or MPL mutations, fibrosis and atypical megakaryocytes
c. Essential thrombocythemia: JAK2 or MPL mutations, overproduction of megakaryocytes
d. Chronic myelogenous leukemia: BCR-ABL fusion (translocation bw 9 and 22) = constitutive activity, overgrowth of granulocytic and megakaryocytic precursors. Can progress to acute leukemia.
e. Chronic neutrophilic leukemia
f. Chronic eosinophilic leukemia
85
Define myelodysplastic syndrome
- Type of CA in which bone marrow doesn’t make enough healthy blood cells (any line). Can convert to AML.
86
What disorders can convert to AML?
- Myelodysplastic syndromes
| - Some of the myeloproliferative diseases
87
Describe the major divisions in classification of lymphomas. Compare and contrast listing unique features of each
1. Lymphomas
a. Hodgkin lymphoma: Reed-Sternberg cells, arise in one LN and spread predictably, high cure rate typically
b. Non-Hodgkin lymphoma: indolent to aggressive forms w/implicated oncogenes
i. Follicular lymphoma: BCL-2 (indolent)
ii. Extranodular marginal zone lymphoma: NFkB (very indolent)
iii. Diffuse large B-cell lymphoma: BCL-6/2 (aggressive). CD marker is CD20.
iv. Burkitt lymphoma: c-MYC (very aggressive) – EBV associated
2. Chronic lymphocytic leukemia: smudge cells, not associated with translocations/predictable mutations, diagnosis median = ~70 years old
88
What differentiates Non-Hodgkin’s from Hodgkin’s lymphoma?
- Hodgkin’s lymphoma has the presence of Reed-Sternberg cells, which are large cells with two or more nuclei or nuclear lobes each containing a large eosinophilic nucleolus.
89
Smudge cells are found in what cancer?
- Chronic lymphocytic leukemia. These are fragile cells that often break during routine slide preparations.
90
Is Burkitt’s lymphoma Non-Hodgkin or Hodgkin?
- Non-Hodgkin. C-MYC oncogene is implicated in this cancer. Associated with EBV infection.
91
What is the most aggressive form of Non-Hodgkin’s lymphoma? Most indolent?
- Most aggressive = Burkitt’s, preceded by diffuse large B-cell lymphoma
- Most indolent = follicular lymphoma, followed by extranodular marginal zone lymphoma
92
List the plasma cell disorders. What are the key clinical features and lab values that allows for differentiation of these?
1. Multiple myeloma (note: lymphoid origin, not myeloid)
- Clinical: lytic bone lesions (50 – 60 yo onset)
- Lab: full / partial monoclonal Igs detected in serum/urine (M protein), rouleaux formation on blood smear
2. Plasmacytoma
- Clinical: solitary mass, risk for progression to multiple myeloma
- Lab: low or no monoclonal Igs in serum
3. Primary amyloidosis
- Clinical: organ problems d/t amyloid fibril deposits
- Lab: monoclonal light chain secretion in bone marrow, IgGk in serum
4. Monoclonal gammopathy of uncertain significance (MGUS)
- Clinical: ? no evidence for malignancy of plasma cells, risk of progression to multiple myeloma
- Lab: monoclonal Ig in serum or urine
5. POEMS syndrome
- Clinical: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Protein, Skin changes
- Lab: monoclonal protein detected?
6. Waldenstroms macroglobulinemia (aka lymphoplasmacytic lymphoma)
- Clinical: ? hyperviscosity syndrome associated
- Lab: IgM secreting
93
Rouleaux formation indicates what type of cancer
- Multiple myeloma w/ full or partial immunoglobulins in serum/urine (M proteins)
94
Plasma cell disorders that have the risk of developing into multiple myeloma
- Plasmacytoma, MGUS (monoclonal gammopathy of uncertain significance)
95
How are leukemias diagnosed?
- Usually with peripheral blood smear and/or bone marrow biopsy
96
How are lymphomas diagnosed?
- Usually with a LN biopsy
97
How are plasma cell neoplasms diagnosed?
- Usually with a bone marrow biopsy
98
Diagnostic techniques for hematological malignancies
- Morphology
- Immunophenotyping
- Histochemistry
- Cytogenetics/molecular genetics
99
Auer rod on smear/biopsy indicates what?
- Acute myelogenous leukemia
100
What CD marker is found for diffuse large B-cell lymphoma upon biopsy?
- CD-20, B-cell specific.
101
Karyotyping indicates translocation between chromosome 9 and 22. What cancer are you thinking?
- CML (chronic myelogenous leukemia) with BCR-ABL fusion. Known as Philadelphia translocation.
102
IgGk in serum indicates
- Amyloidosis, a plasma cell disorder
103
During what phase of clinical trials is a Kaplan-Meier plot done?
- Phase III, which compares the new tx and gold standard. This plot looks at survival time between the two treatments.
104
What is induction therapy? Consolidation therapy? Maintenance therapy?
- Induction: Initial tx for cancer. Goal to induce remission by reducing number of cancer cells to undetectable level.
- Consolidation: Tx given following induction therapy. Goal to eliminate any undetectable cancer cells.
- Maintenance: Tx given after patient achieved remission. Goal to maintain remission and reduce risk of relapse.
105
What is adjuvant/adjunctive therapy?
- Cancer therapy given in addition to primary therapy
106
What is palliative therapy?
- Therapy to lesson symptoms and improve quality of life in patients without curing disease.
107
What is salvage therapy?
- Tx given after other therapies have failed.
108
Total WBC count in newborn
- Highest in this period: rise in mean value at 12 hours of age, rapid fall until end of first week.
- Values between 9K and 30K are often accepted as normal. Decline steadily throughout childhood until age 12 where it is adult value. Adult upper limit = 11-12K.
109
Neutrophil count in newborn. Bands?
- Neutrophils account for approximately 50-60% of leukocytes at birth. After infancy, numbers increase slowly throughout childhood to mean adult value of 59%.
- Absolute bands is highest in first two days of life and decreases rapidly to adult norms.
110
Lymphocyte count in newborn.
- Account for ~30% of the white cells in newborn. Increases rapidly within the first month to remain near avg of 60% until 2 years of age. Then decreases to reach adult norms after 12 years of ago (~35%).
111
Calculate the I:T ratio. What is the meaning of this?
- Immature:total
- (% of bands+metamyelocytes+myelocytes) / (% of neutrophils + numerator)
- 0 – 0.15 = low suspicion for sepsis
- 0.15 – 0.20 = intermediate
- > 0.20 = high suspicion
112
How do Hgb/Hct in newborn compare to older children and adults?
- Much higher. Cord blood Hgb = 14-22
113
Why do capillary samples tend to have higher Hct than venous?
- Capillary samples involve some squeezing of the sample area causing an increased proportion of cells compared to the fluid volume.
114
Define polycythemia. Causes, List the symptoms, treatment plan for a newborn.
- Increase in RBC mass. Defined in neonatal periods as VENOUS HCT of > 65%. After neonatal period, defined as two SDs above mean. Concern = hyperviscosity leading to decreased blood flow.
- Causes: placental insufficiency (d/t PE, maternal chronic HTN, etc), endocrine abnormalities, genetic disorders, placental-fetal transfusion, twin-twin transfusion syndrome
- Symptoms: non-specific, ruddy complexion, irritability, jitteriness, tremors, feeding difficulties, lethargy, apnea, cyanosis, resp distress, seizures
- Treatment: exchange transfusion = current standard (draw blood off and replace with saline). If asymptomatic: observe and hydrate.
115
Red cell life span in newborns vs adults
- 80 in newborns, 120 in adults
116
Define physiologic anemia of infancy and when it occurs.
- Shortly following birth, erythropoiesis ceases virtually d/t o2 rich environment and excess of RBCs.
- Life span of fetal RBCs only about 80 days.
- Combination of decrease in erythropoiesis and life span of fetal RBCs, Hgb falls over next 10-12 weeks. Can reach 9 g/dL in term and 6 in preterm. Low is usually at 6-8 weeks. Following this period, it climbs to reach adult norms by age 2.
117
Calculate a normal MCV in children.
- Child 6 months: upper limit = 84 fL + (0.6 x age in years)
118
Platelet values in newborn
- Same level as adults: 150K – 450K
119
Three causes of thrombocytopenia in the neonate.
1. Alloimmune thrombocytopenia: transfer of maternal antibody, coats platelets and destroys them. SSx: petechia, bruising, intracranial bleeding. Tx with transfusion of mother’s platelets.
2. Maternal ITP: mother has ITP, her antibodies (usually IgG) form against her own platelets, can cross placenta causing destruction of neonates platelets. Tx: if mother known to have ITP, she can be treated during pregnancy with IVIG or steroids.
3. Bacterial or viral infection: products adhere to platelet or decreased platelet production from infected bone marrow.
120
Define anemia
- Reduction in # or RBCs, quantity of Hb, volume of RBCs = decreased o2 carrying potential
121
A Hgb of 11.5 is normal at what age?
A. Birth
B. 6 months
C. 13 years
- B
122
What history is consistent with iron deficiency anemia in children?
- Pallor, excessive sleepiness, tiredness, irritability, inappropriate behaviors, SOB, decreased exercise tolerance, palpitations, syncope, orthopnea
123
What diet history question(s) are important in assessment of anemia in children?
- Milk intake, also folate/b12
124
What family history question(s) are important in assessment of anemia in children?
- Family origin, racial background, cholecystectomy at young age, splenectomy
125
What drug exposures can cause anemias?
- Chemo, chloramphenicol, NSAIDS, antiepileptics.
126
What PMHx predisposes children to anemia?
- JIA: juvenile idiopathic arthritis, SLE, renal disorders, malignancy, immunodeficiency
127
What social history question(s) are important in assessment of anemia in children?
- Age of house (built before 1960), do parents work in a lead-related occupation, is daycare at a house built prior to 1960.
128
What is the anemia screening recommendation for children?
- Age 9-12, at kindergarten entrance and for adolescents
129
Lab values in iron deficiency anemia
- Hgb/Hct low
| - Microcytic (low MCV): children
130
What lab data is required to make a diagnosis of anemia?
- CBC and peripheral blood smear using venous samples (preferred to capillary samples)
- MCV is the most useful
131
What is the most useful RBC index to diagnose anemia?
- MCV
132
MCHC > 35 g/dL is characteristic of what? What about a low MCHC?
- Spherocytosis
| - Low # = iron deficiency anemia
133
How is HCT calculated?
- HCT is ~ 3 times the HGB
134
Anemia combined with increased WBCs/low platelets is a sign of?
- Hemolytic uremic syndrome
135
Anemia combined with normal WBC/low platelets is a sign of?
- ITP
136
Adequate reticulocyte count to anemia
- >2-3%
-
137
Classify childhood anemias by size of the RBC
- Microcytic: IDA, lead toxicity, thalassemia
| - Macrocytic: B12, folate deficiency
138
Normocytic anemia with decreased reticulocytes indicates what diagnosis in child?
- Diamond Blackfan anemia (congenital pure red dysplasia)
- Transient erythroblastopenia of childhood
- Parvovirus
139
Normocytic anemia with increased reticulocytes indicates what diagnosis in child?
- Blood loss
- If positive coombs: ABO incompatibility, Rh incompatibility
- If neg coombs: Non-immune, membrane defect, hemoglobinopathy, G6PD, pyruvate kinase defect
140
Check out case study L20
Check out case study L20
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Prevention of iron deficiency anemia in children
- Breast feed for > 6 months. If solely breastfed, Fe supplementation after 4 months
- Iron fortified formula/cereals
- Avoid cow’s milk in group
142
What is transient erythroblastopenia of childhood? Age group? Labs? Treatment?
- Decreased production of RBCs in the bone marrow, moderate to severe anemia. Unknown etiology, follows viral illness sometimes.
- Age group: > 1 year
- Lab: MCV normal, retic count decreased in most cases. If caught in recovery phase, can be normal or even elevated.
- Treatment: supportive only, transfuse if CV instability, self-limited with universal spontaneous recovery within one year usually
143
What is diamond blackfan anemia (aka congenital pure red cell dysplasia)? Treatment?
- Moderate to severe anemia with multiple physical findings: snub nose, hypertelorism, flattening of thenar eminences, triphalangeal or abnormal thumbs, short stature.
- Sporadic inheritance pattern, can be AR or AD. Defect in ribosomal protein synthesis and lack of progenitor cells in dz.
- Tx: prednisone, transfusion (be careful for overload of iron), bone marrow transplant may be curative
144
Treatment plan for a child with iron deficiency anemia
- 6 mg / kg / day or oral elemental iron until Hgb normal for age and then continue for an additional two months to replete iron stores.
145
Symptoms of iron overload? Acute overdose? Tx?
- Liver damage, congestive cardiomyopathy, endocrine dysfunction, hyperpigmentation
- Acute overdose = abdominal discomfort, nausea, vomiting, lethargy, hemorrhage, coma
- Tx: chelation therapy (deferoxamine)
146
Types of crises with sickle cell anemia. Treatment?
1. Vaso-occlusive: sickled-cells block small vessels causing bone and tissue infarctions, splenic sequestration, priapism and stroke. This is painful. Often precipitated by infection, acidosis, dehydration or hypoxia.
- Tx = supportive, transfusion, hydroxyurea (to increase Hgb F), bone marrow transplantation on occasion.
2. Aplastic: acute drop in Hct/Hgb accompanied by a fall in retics. Often seen in childhood, > 90% d/t parvovirus B19. Occasionally d/t exhaustion of hematinics (eg. folinic acid).
- Tx: transfusion, folic acid
3. Hemolytic/splenic sequestration: characterized by increased hemolysis resulting a cute drop in Hct/Hgb. Accompanied by increase in retics associated often with pos Coombs test. Splenic sequestration crisis = rapid increase in spleen with pooling of blood volume.
- Tx: ?
147
What infections are sickle cell children predisposed to?
- Infection with encapsulated organisms (S. pneumoniae, H. influenza, N. meningitidis)
- Bone infarctions predispose to osteomyelitis by Staph aureus, but also by Salmonella
148
Do L21 case studies
Do L21 case studies
149
What cancers are/are not surgical disease?
- Leukemia and lymphoma are not treated primarily with surgery (though port is placed for chemo)
- Many pancreatic cancers aren’t amenable to surgery but it is a surgical disease (pancreatectomies)
- Small cell lung cancer is not surgical
150
What makes someone a good surgical candidate? (Patient issues)
- Patients must be able to tolerate surgery, benefit from it.
- No co-morbidities (cardiac issues, allergic rxns to anesthesia)
- Younger age (don’t do surgery if pt will die of old age/other dz before cancer)
151
What are factors that make disease non-curable?
- Distant and widespread metastasis (ex: breast cancer to lung mets; lung cancer to groin lymph node, whereas breast cancer to lymph node is okay and lung cancer to chest lymph node can be treated)
152
What is the negative margin?
- No cancer cells around margin where tumor is cut, indicating all tumor cells have been excised
- Variation on negative margin depends on area of body (ex: GI negative margin is 5 cm)
153
What is a formal resection?
- This refers to resections done specifically for cancer treatments, which tend to be more inclusive and invasive that resections for nonmalignant disorders
- “oncologic accepted resection”
- Non-malignant operations remove the infection and fix the problem in the least invasive manner; cancer operations need as much potential cancerous tissue to measure stage of disease
154
52yoF presents with LUQ pain and fullness, palpable mass in LUQ, and lymphadenopathy of lymph nodes under ear, jaw, neck, axilla and groin. Which lymph node should you take?
- Take the one that is easiest to get – most accessible, least invasive, lowest risk of complication
- Ex: groin or axilla
155
What is the best method to obtain a LN by surgical resection?
- Breast: mammogram and needle biopsy
- Colon: colonoscopy and take out polyps
- Lung: needle biopsy if peripheral, bronchoscopy if proximal and near vessel
- Lymphoma cannot be done by needle biopsy bc need architecture of tissue
156
Special handling requirements for tissue when doing resection?
- Depends on the sample: sometime need live cells for flow cytometry, otherwise need tissue in formalin but placing all tissue in formalin will prevent accurate dx
157
What is your best resource for surgical oncology?
- NCCN.org
| - National comprehensive cancer network with guidelines for cancer tx by site of cancer
158
When is surgery used to diagnose?
- Lymphomas
| - Metastatic lesions
159
What is the role of surgery as primary treatment?
- Completely resectable
- Staged
- Patient can tolerate (ie, lung) – if removing lung will worsen pts breathing, then sx better be curative for the cancer
160
What is the sentinel lymph node?
- This is where most breast cancers go if they metastasize
| - Can biopsy this LN to test for mets – if negative, about 96-98% chance pt doesn’t have breast cancer elsewhere
161
What is the role of surgery as secondary treatment?
- Used with advanced staging, often to shrink tumor with chemo/RT prior to excision (examples: Esophageal, rectal, lung, breast)
162
What is neoadjuvant therapy?
- When chemotherapy and/or radiation are used prior to surgery to “downstage” (shrink) a tumor
163
What is the role of surgery in palliative measures?
- Alleviate symptoms/improve quality of life in pts with non-curable diseases (prevent complications from tumor)
- Colon (Bleeding, obstruction, perforation can all occur if tumor is not removed)
- Neuroendocrine tumors (remove to prevent secretion of hormones – take out some even if can’t get negative margins)
- Pain/ulceration (ie, breast)
164
What is the role of surgery in prevention?
- Hereditary cancer syndromes: BRCA, Lynch syndrome, Gardner syndrome, MEN (multiple endocrine neoplasia)
- Aggressive screening; early intervention
165
What are oncologic emergencies?
- SVC syndrome: lung tumor or metastatic dz compresses superior vena cava, blocking drainage from head to heart
- Perforated viscus (worst is perforated esophageal cancer)
166
78yoF presents post abnormal mammogram. 1.67 cm invasive ductal carcinoma of outer upper breast. What is the most appropriate way to get biopsy? How would you treat? What do you need to ask before you decide tx plan?
- Needle biopsy to dx – called stereotactic biopsy (when using imaging)
- Treat with surgery if pt is able
- Need to ask about pmhx to confirm surgical candidate
167
78yoF presents post abnormal mammogram. 1.67 cm invasive ductal carcinoma of outer upper breast. Also has hx of CAD, on Plavix for stents, says she can’t have surgery. What do you do?
- Get an echo to check cardiac, refer to cardiologist
| - If cleared, do surgery – stop Plavix to prevent excessive bleeding
168
Understand the range of therapeutic and palliative procedures performed by the interventional radiologist.
- Therapeutic procedures (7): radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization, transarterial radioembolization, transarterial drug eluting bead embolization, chemical ablation (ethanol, acetic acid)
- Palliative procedures (2): management of malignant pleural and peritoneal fluid (tunneled drainage catheters), enteral access for feeding and bowel decompression.
169
Understand the basic principles of thermal ablation.
Understand the basic principles of thermal ablation.
170
What is the most common type of renal cell carcinoma?
- Clear cell variant (85%)
| - The rest are papillary type.
171
What is the gold standard therapeutic option for renal cell carcinoma?
- Laparoscopic partial nephrectomy
172
Understand the basic principle of cryoablation. Give advantages and disadvantages compared to thermal ablation.
- Deliver cold to the tumor resulting in formation of intracellular ice, osmotic coagulative necrosis and cell death
- Advantage: ability to monitor the ablation zone during the procedure
- Disadvantage: cryoshock
173
What is cryoshock?
- A systemic inflammatory response leading to hypotension, respiratory compromise, DIC and multiorgan failure
- Rare, seen post-cryoablation
174
Describe freezing, thawing, and delayed steps post-cryoablation.
- Freezing: cell shrinkage and dehydration. Extracellular ice, decrease in free extracellular water, increase in extracellular osmolarity, intracellular ice with pore formation and H2O escape.
- Thawing: cell swelling and burst. Melted extracellular ice, increase in free extracellular water, decrease in extracellular osmolarity while intracellular ice growths, water retention. Also see edema with endothelial damage.
- Delayed: apoptosis. Endothelial damage has become ischemia, cell undergoes apoptosis, macrophages/neutrophils present, cytokines released.
175
At what temperature does cell death occur when cooled?
-
176
Describe the incidence and discovery of renal cell carcinomas.
- 2% all adult cancers, most discovered incidentally during imaging for other reasons (most asymptomatic)
- 83-88% clear cell variant
- 54k new cases in 2008, 13k deaths
177
Describe stage 1A Renal Cell Carcinoma.
- Tumor
178
Treatment of choice for stage 1A renal cell carcinoma? Prognosis?
- Treatment of choice = laparoscopic partial nephrectomy, 97-98% 5 yr cancer free survival
- Poor operative candidates, CT or US guided cryoablation, 94-95% 3 yr cancer free survival rate
179
General advantages of cryoablation?
- Outpatient procedure
- No general anesthesia
- Preserve renal function
- Fewer complications
- Can be repeated for residual tumor
180
What are some complications from cryoablation?
- Hemorrhage, pleural effusion, PTX, urine leak
181
What is ECOG and why do we care in oncology?
- Eastern Cooperative Oncology Group; status refers to how well patient does in daily life
- We do not treat above ECOG 2 – no benefit in other patients
- Rating 1: some limitations in daily life/physical activity
- Rating 2: sleeping 50% day
- Rating 3: in bed half the day
- Rating of 4: bed ridden
- 5: dead
182
What is the incidence of hepatocellular carcinomas?
- 626k cases/year, 598k deaths/year
- US incidence = 3.4/100k but has doubled since 1980
- Worldwide incidence = 15.7/100k men and 5.8/100k women
- Very common in SE Asia due to HBV
- Very fatal (note incidence and mortality rates are similar)
183
What are risk factors of hepatocellular carcinomas?
- Conditions which result in cirrhosis: HBV (#1 worldwide) and HCV (#1 US), NAFLD and NASH, alcoholic liver dz, Aflatoxin exposure (common sub-Saharan Africa), genetically acquired dz (Wilson’s, a-1-antitypsin deficiency, hemachromatosis)
184
Incidence, prevalence and virology of HBV.
- 380 million infected worldwide
- 50-55% HCC due to HBV
- Most prevalent in developing Asian countries
- DNA virus incorporates into host genome, can develop HCC without cirrhosis
- Higher HBV DNA level = increased risk
185
Incidence, prevalence and virology of HCV.
- 170 million infected worldwide
- 25-30% HCC due to HCV
- 60% HCC in USA due to HCV
- Annual rate of HCV induced HCV = 1-4%
186
Connection between ALD, HCC & HBV/HCV?
- 15-45% HCC in US from ALD
- Synergistic with HCV and HBV
- Do not need cirrhotic liver to develop HCC
- 19% with non-cirrhotic alcoholic liver dz will develop HCC
187
Prevalence & comorbidities of NAFLD and connection to HCC?
- 20-30% adults in Western countries, associated with DM, obesity, metabolic syndrome
- 10-30% HCC related to NAFLD related cirrhosis
- HCC mortality 5x higher in men with BMI>35; doubled in DM
188
Prognosis and tx options for hepatocellular carcinoma?
- 5yr survival with no treatment =
189
What are curative and non-curative HCC treatments?
- Curative: transplant, surgical resection, percutaneous ablation
- Non-curative (palliative): transarterial therapies (chemoembolization, radioembolization with drug eluting beads), systemic chemotherapy
190
Ideal therapy for HCC?
- Liver transplant
191
Mainstay of therapy for HCC? Why?
- Local regional therapy due to small percentage of surg candidates and lack of effective systemic chemo
- Includes radiofrequency and microwave ablation and transarterial therapy
192
Transarterial therapy options for HCC?
- Chemoembolization, radioembolization, drug eluting bead embolization
193
Survival rate and criteria of liver transplant therapy for HCC?
- Removes tumor and cirrhotic liver, 70-80% 5 yr survival rate
- Milan criteria: 1 lesion,
194
Survival rate and criteria of surgical resection for HCC?
- Feasible only in non-cirrhotic livers or Childs class A livers
- 50-60% 5 year survival
- Outcomes better for single tumors
195
Describe transarterial chemoembolization.
- Delivers of highly concentrated chemotherapy (10-40x systemic) in lipid medium (oily chemo) combined with arterial particulate embolization
- Result = tissue hypoxia ad death
- TAKES ADVANTAGE OF DUAL BLOOD SUPPLY to liver with tumor supply exclusively from hepatic artery
196
Transarterial chemoembolization survival rate?
- Average survival = 24 months
197
When is TACE indicated?
- Patients who are not candidates for transplantation, resection or local ablation (tumors >3cm)
198
Describe normal hepatic blood supply and hepatic tumor blood supply. Why important?
- NORMAL PORTAL VEIN 75-80% and hepatic artery 20-25%
- Hepatic tumors almost EXCLUSIVELY HEPATIC ARTERIAL BLOOD – thus allows embolization WITHOUT COMPROMISING OVERALL BLOOD SUPPLE
199
Describe drug-eluting bead embolization.
- 300-700 micron beads loaded with chemo drug are delivered directly into hepatic tumor through arterial system
200
How does drug-eluting bead embolization compare to TACE?
- Long term benefit similar to TACE
- Improved systemic dose profile
- ? toxicity profile compared with conventional TACE
201
What drug is most widely used in drug-eluting bead embolization in HCC? Colorectal?
- Doxorubicin for hepatic tumor
| - Irinotecan used for colorectal mets
202
Describe radiofrequency/microwave ablation.
- Radiofrequency: directed alternating current delivered to tumor to create ionic agitation, frictional heat and cell death
- Microwave: electromagnetic radiation delivered to cause agitation of water molecules in surrounding tissue, producing friction and heat → cell death
203
Requirements of radiofrequency/microwave ablation and survival rate?
-
204
Describe radioembolization.
- Outpatient treatment for unresectable liver tumors
- Yttrium 90-BB emitting microspheres (high dose radiation) impart local radiation effect
- Average distance 2.5 mm
205
How is radioembolization contained to tumor?
- Microspheres preferentially lodge within neo-vessels of tumor, minimizing radiation exposure to liver
206
Survival rate of radioembolization?
- 23 months in early stage disease (early data, medium survival)
207
How is radioembolization used?
- Approved tx of HCC and metastatic colorectal cancer unresponsive to conventional chemotherapy
- Ongoing studies as tx for other metastatic cancers
208
What is radioembolization advantage over TACE in HCC pt?
- If portal vein invasion limits TACE
209
What is postembolization syndrome?
- N/V/F, Abd pain, anorexia, FATIGUE
- Occurs in 90% pts following embolization (TACE), thought to be secondary to tissue ischemia & inflammatory response
- Self-limited, managed supportively, lasts up to 10-14 days, USUALY DOES NOT REQUIRE HOSPITALIZATION
210
What is post-radioembolization syndrome?
- 20-55% pts
- Less severe than with TACE
- Does not require hospitalization
- Mild pain
- Fatigue predominates
211
Describe malignant pleural effusion.
- Occurs in up to 15% pts with advanced malignancy
- POOR PROGNOSIS – median life expectancy 4 months
- Lung, breast, ovarian - most common cancers
212
Management of malignant pleural and peritoneal fluid collections?
- Periodic thora/paracentesis
- Chest tube with chemical pleurodesis (adhesion of 2 pleura to eliminate pleural space) – requires hospitalization (pts with limited life expectancy don’t want this)
- Tunneled pleural/peritoneal catheter placement for home fluid drainage
213
What are tunneled pleural/peritoneal catheters and when are they used?
- Tunneled, semi-permanent catheters placed in pleural or peritoneal cavity
- Allow pt to self-drain at home
- Outpatient procedure, local anesthesia, can be used immediately
214
Advantages and complications of tunneled pleural/peritoneal catheters?
- Advantages: outpatient procedure, self-drain, home, complete or partial reduction of sx in 90-100% pts
- Complications: empyema (2.8%), other infection (2%), PTX needing chest tube (5.9), cellulitis (3.4), catheter obstruction/malfunction (12.8), catheter removed due to complications (8.5)
215
72yoM, hx colon cancer, DM2, renal failure, CHF and NAFLD. Surveillance CT scan showed 2 cm right hepatic nodule. Biopsy = well differentiated HCC. What do we do?
- Procedure of choice = radiofrequency/microwave ablation for tumor
216
74yoF, hx metastatic colon cancer to liver, progression despite second line systemic chemo. What do we do?
- Radioembolization
217
Define definitive, adjuvant, neoadjuvant and palliative radiation treatments.
- Definitive: RT is main modality
- Adjuvant: RT after sx
- Neoadjuvant: RT before definitive tx
- Palliative: treating intact tumor (definitive tx for quality of life reasons)
218
What are the top 3 most fatal cancers for each gender?
- Women: lung/bronchus, breast, colon/rectum
| - Men: lung/bronchus, prostate, colon/rectum
219
What are the top 3 most common cancers for men and women?
- Women: breast, lunch/bronchus, colon/rectum
| - Men: prostate, lung/bronchus, colon/rectum
220
What are 4 basic patterns of cancer spreading?
- Local growth: tumor itself enlarges
- Local extension: tumor invades adjacent organs
- Lymph node metastases: breast to axilla
- Hematogenous metastases: prostate to bone, small cell to brain
221
Which stage of cancer does each pattern of spread affect?
- Local growth: size of primary tumor determines T stage
- Local extension: upstages tumor T3-4
- LN mets: affects N stage
- Hematogenous mets: affects M stage
222
Treatment options for cancer?
- Surgery
- Medical therapy (chemo, hormone – tamoxifen/lupron, biologic – Avastin/tarceva, vaccine - provenge)
- Radiation therapy (RT)
- Other, such as cryotherapy
223
In which cancers does radiation therapy replace surgery?
- Anal cancer: ChemoRT (avoid colostomy)
- Limited-stage small cell lung cancer: ChemoRT
- Esophageal: ChemoRT without surgery
- Stage IIIB (+mediastinal nodes) NSCLC: ChemoRT or Chemo then RT
224
When is RT used as an adjuvant treatment?
- Breast cancer: lumpectomy followed by RT same survival as mastectomy
- Skin cancer: surgery with + margins followed by RT
- Prostate cancer: surgery with + margins and other high risk features followed by RT
- Uterine/endometrial cancer: hysterectomy of high grade/stage followed by RT
225
What’s the difference between radiosensitive and radioresponsive?
- Radiosensitive: tumor “melts” with RT
| - Radioresponsive: tumor “melts quickly”
226
How is radiation therapy generated?
- Radioactive source: teletherapy and brachytherapy
| - Linear accelerator
227
Difference between teletherapy and brachytherapy?
- Teletherapy = external beam; brachytherapy = radiation seeds that emit a halo of radiation
228
Explain the different use of electrons vs. protons. Which is preferred in pediatrics?
- Electrons are for superficial lesions such as skin cancers (definite range); single field
- Protons are preferred for pediatrics due to the advantage of not having an exit dose (extra radiation)
- Protons are skin sparing and will treat deep lesions due to gradual falloff of absorbed dose; can combine fields
229
How does RT work?
- DNA of well-oxygenated tumor cells is the main target for biological effect of radiation
- Most important lesion induced by RT = DOUBLE STRANDED DNA BREAK
230
Where in the cell cycle is the effect of RT in tumors that are radiosensitive and radioresistant?
- Radiosensitive: M/G2 (knock-out, kills tumor)
| - Radioresistant: S
231
Explain the biological rationale for RT using the therapeutic ratio.
- TCP > NTCP
- Tumor control probability must be much higher than normal tissue complication probability or else radiation therapy is useless (uncontrolled, harmful)
232
What is the importance of the cell survival curve?
- Shows the NON-linear relationship between dose and tumor cell death
- Higher radiation dose kills more cells (smaller surviving fraction)
233
How does cell oxygenation affect RT sensitivity? Importance in killing tumors?
- Hypoxic cells are more radioresistant: oxygen enhances radiation’s ability to cause double-stranded DNA breaks
- RT relies on reoxygenation
- Central portions of many tumors are hypoxic (radioresistant) so need repeat RT as each one kills outer oxygenated cells until hypoxic center is re-oxygenated
234
What are fractionation schedules?
- These are based on amount of radiation (measured in cGy) and # treatments per day
- Standard = 180-200 cGy dose 1x daily (Palliative is a little higher at 300)
- Hyperfractionation = 120-150 cGy dose 2x daily, used to kill rapidly dividing cancers (hardly used anymore)
- Hypofractionation = 800-2200 cGy for only 1-3 fractions, used for stereotactic RT or brachytherapy (more commonly used)
235
Difference between curative and palliative RT?
- Curative is used for definitive/neoadjuvant/adjuvant therapies
- Palliative is used to improve symptoms, such as brain mets causing neuro sx or bone mets causing pain
236
What is 2D plan with RT?
- Opposed lateral beams for whole brain RT
| - Not used anymore
237
What is 3DCRT?
- Computer based tx planning – designs tx field so angle of treatment treats the tumor and avoids normal structures
- Most commonly used now
- Limits damage to nonmalignant structures
238
What is IMRT?
- Just like 3DCRT but more sophisticated because there’s no spilling of radiation to unwanted tissues
- Different portions of treatment field get different doses (compared to pointillism)
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What is SRS/SBRT?
- Stereotactic radiosurgery or stereotactic body radiation therapy
- Used to have to screw metal frame into skull to stabilize head and then 3 laser beam at x, y and z axes are turned on
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What is the purpose of immobilization devices?
- Daily reproducibility and intrafraction control of patient motion
- Used during simulation prior to actual treatment in addition to tx
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What is GTV?
- Gross demonstrable extent of tumor
| - Possible if tumor is visible, palpable or demonstrable through imaging
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What is CTV?
- Margin of GTV to account for tissue with disease spread
| - CTV assumes there are no tumor cells outside this volume
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What is ITV?
- CTV + internal margin for physiological movements and variations in size, shape and position of the CTV during therapy (ex: lung cancer moves with respiration)
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What is PTV?
- CTV or if applicable ITV + setup margin for patient movement and setup uncertainties
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What is OAR?
- Organ at risk/critical structure
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What is the purpose of beam modifiers and what is the standard of care today?
- Purpose is to change the shape of the beam to conform to target and block critical organs
- Standard is to use multileaf collimator (MLC) over Cerrobend block
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What is IGRT?
- Image guided radiation therapy: a way to verify with greater precision the tumors’ position to allow for more accurate treatment
- Indicated for tumors that move (prostate) and tumors abutting critical structures (head and neck CA)
- Use CT-like imaging and implanted markers to see where tumor is right before tx
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Describe the 2 types of IGRT.
- Stereoscopic: great for bone mets; match on markers implanted in soft tissue or match on bone to treat soft tissue
- Cone beam: used for soft tissue; uses low dose CT to compare soft tissue anatomy
