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Cardiac Surgery: Answers
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during the first 6 months following transplantation.
Biopsies are performed initially every 7 to
10 days in the early
postoperative period and eventually reduced to 3- to 6-month
intervals
after the first year. Suspicion of rejection warrants additional
biopsies.
Corticosteroids are the mainstay for antirejection therapy. The
treatment of choice for any
rejection episode occurring during the
first 1 to 3 postoperative months or for an episode
considered to
be severe is a short course (3 days) of intravenous methylprednisolone (1000
mg/d). Practically all other episodes are treated initially with increased
doses of oral
prednisone (100 mg/d) followed by a reduction to baseline
over several weeks. Although not
yet universally accepted,
many centers have tapered the doses of these corticosteroids
successfully with reversal rates of rejection similar to traditional
dosing.
Repeat endomyocardial biopsy should be performed 7 to 10 days
after the discontinuation
of antirejection therapy to assess adequacy
of treatment. If the biopsy does not show
significant improvement,
a second trial of pulse-steroid therapy is recommended; if rejection
has advanced (or if the patient becomes haemodynamically unstable),
rescue therapy is
indicated.
References
Taylor DO, Edwards LB, Boucek MM, et al. Registry of the International Society for Heart
and Lung Transplantation: Twenty-second official adult heart transplant report—2005. J
Heart Lung Transplant 2005;24:945-55.
Horwitz PA, Tsai EJ, Putt ME, et al. Detection of cardiac allograft rejection and response to
immunosuppressive therapy with peripheral blood gene expression. Circulation
2004;110:3815-3821.
Sharples LD, Caine N, Mullins P, et al. Risk factor analysis for the major hazards following
heart transplantation: Rejection, infection, and coronary occlusive disease.
Transplantation 1991;52:244-52.
2.59 Answer: C
Cardiac allograft vasculopathy (CAV) is a unique, rapidly progressive form of
atherosclerosis
in transplant recipients. It is characterized in its early
stages by intimal
proliferation and in its later stages by luminal
stenosis of epicardial branches, occlusion of
smaller arteries,
and myocardial infarction. Long-term survival of cardiac
transplant recipients
is limited primarily by the development
of CAV. It is the leading cause of death after the first
year posttransplantation.
Angiographically evident CAV is reported in approximately
40 to
50% of patients by 5 years after transplantation. Although
CAV resembles atherosclerosis,
there are some important differences.
The lesions
in CAV are diffuse, involving both distal
and proximal portions of
the coronary tree and intimal
proliferation is concentric rather than
eccentric. Calcification is uncommon, and the elastic
lamina remains intact.
The detailed pathogenesis of CAV is unknown. However, it is strongly evident that
immunologic mechanisms that are regulated by nonimmunologic risk
factors are the major
causes of this phenomenon. The immunologic mechanisms
include acute rejection and anti-
HLA antibodies. Additional implicated risk factors relating to the transplant itself
or the
recipient include donor age, hypertension, hyperlipidemia,
and preexisting diabetes. The side
effects often linked
with immunosuppression with calcineurin inhibitors or corticosteroids,
e.g., CMV infection, nephrotoxicity, and new-onset diabetes,
after transplantation also play
important roles.
Shahzad G. Raja
200
It is generally agreed that the initiating event of CAV is
subclinical endothelial cell injury
in the coronary artery of
the allograft. This results in a cascade of immunologic processes
involving cytokines, inflammatory mediators, complement activation,
and leukocyte adhesion
molecules. These changes produce inflammation
and, ultimately, thrombosis, smooth muscle
cell proliferation,
and vessel constriction. The initial endothelial injury may
be triggered by
ischemia-reperfusion damage or the host-versus-graft immune
response.
CAV may begin within several weeks posttransplantation and progress surreptitiously at
an accelerated rate to complete obliteration of the coronary
lumen with allograft failure
secondary to ischemia. The clinical diagnosis
of CAV is challenging and complicated by
allograft denervation resulting
in silent myocardial ischemia. Ventricular arrhythmias,
congestive
heart failure, and sudden death are frequently the initial presentation
of significant
CAV. An annual coronary angiogram usually
is performed for CAV surveillance.
Intravascular ultrasound
(IVUS) is better equipped to furnish important quantitative
information
regarding vessel wall morphology and the degree of intimal thickening.
Angiography and IVUS are invasive tests with increased risks
for patients. On the other
hand, noninvasive tests (e.g., thallium scintigraphy and
dobutamine stress echocardiography),
are neither sensitive nor specific enough to be a reliable screen for CAV.
Other possible
diagnostic modalities include pulse-wave tissue Doppler
imaging, electron beam computed
tomography (CT), fast CT scanning,
and MRI. These diagnostic modalities may replace
invasive procedures in
the future.
Currently, the only definitive treatment for advanced CAV is
retransplantation. However,
retransplantation has risks for the patient and poses
problems associated with shortage of
donor organs. Procedures such
as stenting and angioplasty are inherently less effective than
in
nontransplant patients and result in a higher need for repeated
procedures owing to
the diffuse
and distal nature of the disease. Prophylactic management therefore is of prime
importance.
Pre-transplantation, the focus should be on
preventing endothelial injury at brain death,
reducing cold
ischemia time, and improving myocardial preservation during
storage and
transportation. Postransplantation care concentrates
on empirical risk factor modification
(e.g., dietary and pharmacologic
reduction of serum cholesterol, cessation of smoking,
hypertension
control, etc.). There is evidence from several studies that patients treated with a
calcium channel blocker, angiotensin-converting enzyme
and statins demonstrate a decrease
in
CAV.
Newer immunosuppressive drugs, specifically the proliferation
signal inhibitors (e.g.,
everolimus and sirolimus), may be effective in reducing the incidence and severity of CAV
and slowing disease
progression.
References
Avery RK. Cardiac-allograft vasculopathy. New Engl J Med 2003;349:829-30.
Valantine H. Cardiac allograft vasculopathy after heart transplantation: Risk factors and
management. J Heart Lung Transplant 2004;23:S187-93.
2.60 Answer: D
Retransplantation is responsible for fewer than 3% of the cardiac
transplants currently
performed. Primary indications for retransplantation
are early graft failure, allograft coronary
artery disease,
and refractory acute rejection. The operative technique and
immunosuppressive
regimen are similar to those used for
the initial transplantation. Despite reduced mortality in
Cardiac Surgery: Answers
201
the
cyclosporine era, actuarial survival remains srikingly reduced.
Analysis of the ISHLT
registry for retransplantations performed
between 1987 and 1998 reveals survival to be 65%,
59%, and 55%
for 1, 2, and 3 years, respectively. Intertransplant interval
of 6 months or less
was associated with a dismal 1-year survival
of 50% in this analysis. Conversely, 1-year
survival after retransplantation approached that of primary transplantation when the interval
between
primary and retransplantation was more than 2 years.
Similarly, in the 2005 registry
report, when the subset of recipients
in the more recent era between 1996 and 2003 was
analyzed, patients
undergoing retransplantation at 12 months or more after initial
transplantation have 1-year survival rates of approximately
82% (similar to the contemporary
cohort of primary transplants
at 83%). Amongst these recipients advanced donor age was also
a predictor of increased mortality. These data suggest that despite association of significant
morbidity
and mortality with cardiac retransplantation, careful selection of patients, especially
those
who are younger and with longer intertransplant intervals, may result in
favorable
outcome. Nonetheless, the
discrepancy between the demand and supply for donor hearts
makes cardiac
retransplantation an ethical issue.
References
Taylor DO, Edwards LB, Boucek MM, et al. Registry of the International Society for Heart
and Lung Transplantation: Twenty-second official adult heart transplant report—2005. J
Heart Lung Transplant 2005;24:945-55.
Radovancevic B, McGiffin DC, Kobashigawa JA, et al. Retransplantation in 7290 primary
transplant patients: A 10-year multi-institutional study. J Heart Lung Transplant
2003;22:862-68.
Steinman TI, Becker BN, Frost AE, et al. Guidelines for the referral and management of
patients eligible for solid organ transplantation. Transplantation 2001;71:1189-204.
2.61 Answer: C
The REMATCH trial randomly assigned 129 patients with end-stage heart failure who
were ineligible for cardiac transplantation to receive a left ventricular assist device (68
patients) or optimal medical management (61). All patients had symptoms of New York Heart
Association class IV heart failure. Kaplan-Meier survival analysis showed a reduction of 48
percent in the risk of death from any cause in the group that received left ventricular assist
devices as compared with the medical-therapy group (relative risk, 0.52; 95 percent
confidence interval, 0.34 to 0.78; P=0.001). The rates of survival at one year were 52 percent
in the device group and 25 percent in the medical-therapy group (P=0.002), and the rates at
two years were 23 percent and 8 percent (P=0.09), respectively. The frequency of serious
adverse events in the device group was 2.35 (95 percent confidence interval, 1.86 to 2.95)
times that in the medical-therapy group, with a predominance of infection, bleeding, and
malfunction of the device. The quality of life was significantly improved at one year in the
device group. The use of a left ventricular assist device in patients with advanced heart failure
resulted in a clinically meaningful survival benefit and an improved quality of life. The trial
demonstrated that a left ventricular assist device is an acceptable alternative therapy in
selected patients who are not candidates for cardiac transplantation.
Shahzad G. Raja
202
References
Rose EA, Gelijns AC, Moskowitz AJ,et al; Randomized Evaluation of Mechanical Assistance
for the Treatment of Congestive Heart Failure (REMATCH) Study Group.Long-term use
of a left ventricular assist device for end-stage heart failure. N Engl J Med.
2001;345:1435-43.
2.62 Answer: D
SYNTAX is an 85-centre randomized clinical trial (n= 1800). Prospectively screened,
consecutive left main stem (LM) and/or triple vessel disease (3VD) patients were randomized
if amenable to equivalent revascularization using either technique; if not, they were entered
into a registry. Patients in the randomized cohort will continue to be followed for 5 years. At
3 years, major adverse cardiac and cerebrovascular events [MACCE: death, stroke,
myocardial infarction (MI), and repeat revascularization; CABG 20.2% vs. PCI 28.0%, P<
0.001], repeat revascularization (10.7 vs. 19.7%, P< 0.001), and MI (3.6 vs. 7.1%, P= 0.002)
were elevated in the PCI arm. Rates of the composite safety endpoint (death/stroke/MI 12.0
vs. 14.1%, P= 0.21) and stroke alone (3.4 vs. 2.0%, P= 0.07) were not significantly different
between treatment groups. Major adverse cardiac and cerebrovascular event rates were not
significantly different between arms in the LM subgroup (22.3 vs. 26.8%, P= 0.20) but were
higher with PCI in the 3VD subgroup (18.8 vs. 28.8%, P< 0.001).
References
Kappetein AP, Feldman TE, Mack MJ, et al. Comparison of coronary bypass surgery with
drug-eluting stenting for the treatment of left main and/or three-vessel disease: 3-year
follow-up of the SYNTAX trial. Eur Heart J. 2011;32:2125-34.
2.63 Answer: C
The ROOBY trial was a controlled, single-blind, randomized trial conducted from
February 2002 through May 2008 at 18 VA medical centers. Patients who were scheduled for
urgent or elective CABG-only procedures were screened for enrollment. Exclusion criteria
were any clinically significant valve disease (i.e., moderate, moderate-to-severe, or severe
valve disease), a status requiring immediate surgery, small target vessels (<1.1 mm in internal
diameter) or diffuse coronary disease, clinical reservations of the surgical team regarding
patients with risk-factor profiles that predisposed them to an extremely high risk of an adverse
event, or the inability or unwillingness of the patient to provide consent. While in the
preoperative holding area, patients underwent randomization with the use of an automated
central telephone system in a blocked randomization scheme. Assignments of the patients
were balanced for each attending surgeon.
The primary short-term end point was a composite of death or major complications
(reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure requiring
dialysis) occurring within 30 days after surgery or before discharge, whichever was later. The
primary long-term composite end point was death from any cause within 1 year, nonfatal
myocardial infarction between 30 days and 1 year, or repeat revascularization between 30
days and 1 year. Composite end points were selected for feasibility and fiscal reasons.
Secondary end points included the completeness of revascularization (determined by the
number of grafts performed as compared with the number planned), graft patency at 1 year,
Cardiac Surgery: Answers
203
and scores on a battery of neuropsychological tests (derived from previously published tests),
which were performed preoperatively and 1 year postoperatively.
Overall, 2203 patients were randomly assigned to either on-pump surgery (1099 patients)
or off-pump surgery (1104 patients). Baseline demographic and clinical characteristics were
similar in the two groups and consistent with those of the overall VA CABG population.
There was no significant difference between off-pump and on-pump CABG in the rate of the
30-day composite outcome (7.0% and 5.6%, respectively; P=0.19). The rate of the 1-year
composite outcome was higher for off-pump than for on-pump CABG (9.9% vs. 7.4%,
P=0.04). The proportion of patients with fewer grafts completed than originally planned was
higher with off-pump CABG than with on-pump CABG (17.8% vs. 11.1%, P<0.001).
Follow-up angiograms in 1371 patients who underwent 4093 grafts revealed that the overall
rate of graft patency was lower in the off-pump group than in the on-pump group (82.6% vs.
87.8%, P<0.01). There were no treatment-based differences in neuropsychological outcomes
or short-term use of major resources.
References
Shroyer AL, Grover FL, et al; Veterans Affairs Randomized On/Off Bypass (ROOBY) Study
Group. On-pump versus off-pump coronary-artery bypass surgery. N Engl J Med.
2009;361:1827-37.
2.64 Answer: E
Aortic dissection is the most commonly diagnosed lethal condition
of the aorta.
Dissection occurs nearly three times more frequently
than rupture of an abdominal aortic
aneurysm in the United States.
There is an estimated worldwide prevalence of 0.5 to 2.95 per
100,000 per year. The prevalence ranges from 0.2 to 0.8 per
100,000 per year in the U.S. This
results in roughly 2000 new
cases per year. These figures are, however, only an estimate.
In
one autopsy series, the antemortem diagnosis was made in
only 15% of patients, suggesting
that many immediately fatal
events go undiagnosed. Clinically, type A dissections occur
with
an overall greater frequency.
Once a dissection plane exists in the media, the aortic wall floating
within the lumen is
termed the dissection flap and is composed
of the aortic intima and partial-thickness media.
The primary
tear is usually greater than 50% of the circumference of the
aorta, but the full
circumference is rarely involved. The primary
tear in type A dissection is usually located on
the right anterior
aspect of the ascending aorta. This tear follows a somewhat predictable
course, spiraling around the arch and into the descending thoracic
and abdominal aorta on the
left and posteriorly. The dissection
may propagate in a retrograde manner for a variable
distance
as well to involve the coronary ostia. This occurs in roughly
11% of all dissections.
Nearly 80% of
deaths from acute dissection are the result of myocardial ischemia and rupture
into
the pericardium. Often the distal false lumen communicates
with the true lumen through
one or more fenestrations within
the dissection flap. The false lumen may also end blindly in
as many as 4 to 12% of patients, in which case blood in the
false lumen frequently becomes
clotted. The false lumen may
also penetrate the adventitia causing rupture and death.
Irrespective of whether the true and false lumens communicate, perfusion
of aortic side
branches may be compromised by the dissection,
resulting in end-organ ischemia. If these
acute
complications are avoided, the weakened outer aortic wall, composed
of partial media
Shahzad G. Raja
204
and the adventitia, may dilate over time resulting
in aneurysm formation. Regardless
of type,
this evolving dilatation is the reason
for operation in the majority of chronic dissections.
References
Reece TB, Green GR, Kron IL. Aortic dissection. Cohn LH, ed. Cardiac Surgery in the Adult.
New York: McGraw-Hill, 2008:1195-1222.
Erbel R, Alfonso F, Boileau C, et al. Diagnosis and management of aortic dissection. Eur
Heart J. 2001;22:1642-1681.
2.65 Answer: C
The CORONARY trial enrolled 4752 patients at 79 centers in 19 countries. The patients
were randomly assigned to undergo CABG either off-pump or on-pump. The first coprimary
outcome was a composite of death, nonfatal stroke, nonfatal myocardial infarction, or new
renal failure requiring dialysis at 30 days after randomization.
There was no significant difference in the rate of the primary composite outcome
between off-pump and on-pump CABG (9.8% vs. 10.3%; hazard ratio for the off-pump
group, 0.95; 95% confidence interval [CI], 0.79 to 1.14; P=0.59) or in any of its individual
components. The use of off-pump CABG, as compared with on-pump CABG, significantly
reduced the rates of blood-product transfusion (50.7% vs. 63.3%; relative risk, 0.80; 95% CI,
0.75 to 0.85; P<0.001), reoperation for perioperative bleeding (1.4% vs. 2.4%; relative risk,
0.61; 95% CI, 0.40 to 0.93; P=0.02), acute kidney injury (28.0% vs. 32.1%; relative risk,
0.87; 95% CI, 0.80 to 0.96; P=0.01), and respiratory complications (5.9% vs. 7.5%; relative
risk, 0.79; 95% CI, 0.63 to 0.98; P=0.03) but increased the rate of early repeat
revascularizations (0.7% vs. 0.2%; hazard ratio, 4.01; 95% CI, 1.34 to 12.0; P=0.01).
References
Lamy A, Devereaux PJ, et al.; CORONARY Investigators. Off-pump or on-pump coronary-
artery bypass grafting at 30 days. N Engl J Med. 2012;366:1489-97.
Chapter III
Thoracic Surgery
3.1 Answer: B
In order to understand and interpret findings from screening trials, one must be familiar
with concepts of incidence and prevalence. In order for screening for a disease such as cancer
to lead to significant public health benefits, the target disease should have high incidence and
prevalence rates in the screened population. Incidence refers to the number of target disease
cases that develop during a defined period of time, and is expressed as cases per year per
100,000 individuals in the population. Prevalence is the number of individuals with the target
disease that exist in a defined population at a given point in time, and is commonly expressed
as target disease cases per 100,000 individuals in the population.
Second, an effective screening test should detect disease at an early stage, while the
individual is asymptomatic thereby ensuring that cure may be possible with treatment. In
other words, the test must lead to a decreased mortality rate. The test itself should be safe,
inexpensive, and possess sufficient sensitivity (able to identify individuals with disease), and
specificity (able to identify individuals without disease). In order to decrease the mortality
rate, an effective treatment must be available to those diagnosed following a positive screen.
Effective screening tests, in association with effective treatment then, have the ability to
effect a change in the natural history of the disease in a positive manner.
Third, the benefits of screening must outweigh the risks. For example, the incidence of
false positives and false negatives must be evaluated against potential benefits. False positives
can result in unnecessary surgeries, treatments, anxiety, and public health costs. False
negatives, on the other hand, can lead to undetected disease which progresses beyond the
benefits of available interventions.
Fourth, survival and mortality are two inter-related but often misunderstood concepts that
are important in understanding the relative effectiveness of lung cancer screening techniques.
Survival rates reflect the number of individuals alive at a given time relative to their
diagnosis. Finally, mortality is the number of disease-specific deaths relative to the total
number of individuals screened. The goal of lung cancer screening is to bring down mortality,
thus an effect on mortality is vital to the validation of potential screening methods.
Shahzad G. Raja
206
References
Smith JJ, Berg CD. Lung cancer screening: promise and pitfalls. Semin Oncol Nurs.
2008;24:9-15.
3.2 Answer: A
In the 1970s, the National Cancer Institute (NCI) sponsored three randomized clinical
trials to evaluate the effectiveness of chest x-ray and sputum cytology for lung cancer
screening: the Mayo Lung Project, the Johns Hopkins Lung Project, and the Memorial Sloan-
Kettering Lung Project. The primary endpoint of all three studies was mortality.
Approximately 10,000 male smokers and former smokers were enrolled at each site. The
Johns Hopkins and Memorial Sloan-Kettering studies randomized individuals to receive
annual chest x-ray (control) or annual chest x-ray plus sputum cytology every four months
(intervention). Results showed no differences in the number of cancers detected in the two
groups and no mortality benefit.
The Mayo Lung Project randomized individuals to an intervention (screened) group to
receive chest x-ray and sputum cytology every four months for six years, or to a control group
which received guidance to have chest x-ray and sputum cytology annually for six screens.
There were 206 lung cancer cases in the intervention group, and 160 cases in the control
group. The 5-year survival rate for lung cancer was 40% in the screened group and 15% in the
control population. However, there was no difference in lung cancer mortality between the
groups. Marcus et al. re-evaluated this study in extended follow-up in 2000. Again, no
difference in mortality was identified between the two groups.
A fourth study conducted in Czechoslovakia randomized 6346 high risk male participants
to an intervention arm consisting of chest x-ray and sputum cytology every six months, or to a
control group receiving a prevalence screening x-ray and sputum cytology followed by
another screen three years later. Both groups received annual chest x-ray for an additional
three year period. Results showed a significant increase in the number of cancers detected in
the intervention group, including more instances of early stage disease. However, as in the
previously cited studies, no difference in mortality was found between the two groups. In
2000, Kubik et al. published a 15-year follow-up to the study. The follow-up concurs there is
no evidence that lung cancer screening by chest x-ray decreases mortality.
More recently, beginning in 1992, the Prostate, Lung, Colorectal, and Ovarian (PLCO)
Trial was initiated to further evaluate chest x-ray as a screening test for lung cancer. PLCO,
sponsored by NCI, is a large, multi-center, randomized clinical trial involving 154,942 male
and female participants between the ages of 55 and 74. The control group consists of 77,477
individuals who received no screening. In the intervention group, which consists of 77,465
individuals, smokers and former smokers received single-view, posterior-anterior chest x-ray
followed by three annual screens, and non-smokers received prevalence screening followed
by two annual screens. Of the 5991 individuals with a baseline positive screen, 126 were
diagnosed with cancer within 12 months of the initial screen. Higher rates of cancer were
detected in current and former smokers who had smoked within the previous 15 years. Of the
cancers detected, 44% of the cancers were stage I. Whether this early detection results in
lower mortality rates has yet to be determined.
Thoracic Surgery: Answers
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References
Fontana RS, Sanderson DR, Woolner LB, et al. Lung cancer screening: the Mayo program. J
Occup Med. 1986;28:746-750.
Frost JK, Ball WC Jr, Levin ML, et al. Early lung cancer detection: results of the initial
(prevalence) radiologic and cytologic screening in the Johns Hopkins study. Am Rev
Respir Dis. 1984;130:549-54.
Melamed MR, Flehinger BJ, Zaman MB, et al. Screening for early lung cancer. Results of the
Memorial Sloan-Kettering study in New York. Chest. 1984;86:44-53.
Sanderson D. Lung Cancer Screening: The Mayo Study. Chest. 1986;89 Supplement (4):324.
Marcus PM, Bergstralh EJ, Fagerstrom RM, et al. Lung cancer mortality in the Mayo Lung
Project: impact of extended follow-up. J Natl Cancer Inst. 2000;92:1308-1316.
Kubik A, Polak J. Lung cancer detection. Results of a randomized prospective study in
Czechoslovakia. Cancer. 1986;57:2427-2437.
Kubik AK, Parkin DM, Zatloukal P. Czech Study on Lung Cancer Screening: post-trial
follow-up of lung cancer deaths up to year 15 since enrollment. Cancer. 2000;89(11
Suppl):2363-2368..
Gohagan JK, Prorok PC, Hayes RB, Kramer BS. The Prostate, Lung, Colorectal and Ovarian
(PLCO) Cancer Screening Trial of the National Cancer Institute: history, organization,
and status. Control Clin Trials. 2000;21(6 Suppl):251S-272S.
3.3 Answer: C
There are inherent limitations of
18
F-FDG PET that can produce false-negative and false-
positive findings. False-positive
findings are most commonly related to uptake of
18
F-FDG
in
infectious or inflammatory tissue.
18
F-FDG has been
reported to concentrate in various
inflammatory processes.
Infection imaging with
18
F-FDG PET depends on the fact that
granulocytes
and mononuclear cells utilise glucose as an energy source during
and only
during their metabolic burst, which takes place
when activated by local triggers. It is therefore
not surprising
that
18
F-FDG accumulates in many types of inflammatory tissue.
For example,
18
F-FDG uptake can be seen in tissue after radiation
therapy. Inflammatory changes after
radiation therapy can be
prolonged and a potential source of false-positive findings
if the
history, timing, and volume of tissue irradiated are
not considered at the time of interpretation.
18
F-FDG uptake
can vary widely in normal tissue, and regions of discrete uptake
in areas such
as the ureters, bowel, lymphatic tissue, thymus,
brown fat, and muscle—so called normal
variants—can
be incorrectly interpreted as abnormal or can confound the correct
interpretation of the findings. Mildly to moderately increased
18
F-FDG uptake can also be
seen in a variety of benign processes,
many of which include inflammatory or hyperplastic
conditions
(e.g., villous adenomas, thyroid adenomas, Graves disease, adrenal
adenoma,
Paget's disease, and fibrous dysplasia), and familiarity
with the behavior of these and other
conditions is important
in minimising false-positive results.
Limitations of
18
F-FDG PET for cancer imaging include its limited
reconstructed spatial
resolution of 4–10 mm in available
commercial systems. Negative scan findings cannot rule
out the
presence of a small tumor or microscopic tissue involvement,
and precise anatomic
localization of the signal can be difficult
in certain anatomic regions (e.g., the head and neck).
Tumors
with a low metabolic rate (e.g., bronchoalveolar carcinoma and
mucinous
adenocarcinoma) may show minimal uptake of
18
F-FDG,
and certain tumors are known to
have poor avidity for
18
F-FDG
(prostate carcinoma and hepatocellular cancer).
18
F-FDG PET
Shahzad G. Raja
208
is also generally considered to not be effective in the assessment
of possible cerebral
metastases from known primary neoplasms.
High levels of
18
F-FDG are normally present in
the cerebral
cortex and significantly limit the utility of
18
F-FDG PET in
this application. For
this reason, most clinical examinations
are of the patient's torso and include the area from the
base
of the brain to the mid thigh.
References
Shreve PD, Anzai Y, Wahl RL. Pitfalls in oncologic diagnosis with FDG PET imaging:
physiologic and benign variants. Radiographics. 1999;19:61–77.
Bakheet SM, Saleem M, Powe J, Al-Amro A, Larsson SG, Mahassin Z. F-18
fluorodeoxyglucose chest uptake in lung inflammation and infection. Clin Nucl Med.
2000;25:273–278.
Alavi A, Reivich M. Guest editorial: the conception of FDG-PET imaging. Semin Nucl Med.
2002;32:2–5.
3.4 Answer: E
Currently there is moderate-quality evidence from three systematic reviews that
18
F-FDG
PET is beneficial, mostly by avoiding futile surgeries in low-risk
patients and enabling
curative surgeries in high-risk patients.
In low-risk patients, the negative predictive value
(NPV) of
18
F-FDG PET is extremely high;
therefore, negative
18
F-FDG PET findings can be
followed up
with observation only. However, in high-risk patients, even
negative findings
should be followed by histopathologic investigation. Generally, the predictive values of PET
depend on the prior
probability of lung cancer in the population of interest. Positive predictive
value (PPV)
will be higher in high-risk patients, whereas NPV will be higher
in low-risk
patients. Thus, PET will be most useful in patients
at an intermediate risk of lung cancer.
According to the systematic review by Birim et al., comparing PET and CT in detecting
mediastinal
metastases of non-small cell lung cancer (NSCLC), PET has an overall sensitivity
of 83% (95% CI, 77%–87%)
and an overall specificity of 92% (95% CI, 89%–95%). On
the
other hand, for detection of mediastinal lymph node metastases,
CT has an overall sensitivity
of 59% (95% CI, 50%–67%)
and an overall specificity of 78% (95% CI, 70%–84%). No
statistically significant heterogeneity in sensitivity or specificity
was detected between the 2
methods. For detection of mediastinal
lymph nodes, the PET ROC was 0.90 (95% CI, 0.86–
0.95)
and the CT ROC was 70% (95% CI, 0.65–0.75) (P < 0.0001).
18
F-FDG PET should be
used as an add-on tool for assessing lung cancer and should
not
replace the conventional work-up for the diagnosis and staging
of lung cancer. Direct
evidence from randomized
trials further shows that adding
18
F-FDG PET to the conventional
work-up can decrease futile surgeries and has a positive impact
on the management of lung
cancer patients.
References
Fletcher JW, et al. Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med.
2008;49:480-508.
Health Technology Assessment of Positron Emission Tomography (PET) in Oncology: A
Systematic Review. Institute for Clinical Evaluative Sciences. April 2004. Available at:
http://www.ices.on.ca/webpage.cfm?site_id=1&org_id=31&morg_id=0&gsec_id=0&ite
m_id=2080.