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Vol. 30 No.

7 July 2007

What’s New in ACP Medicine


DAVID C. DALE, MD, FACP, Editor-in-Chief DANIEL D. FEDERMAN, MD, MACP, Founding Editor
WENDY LEVINSON, MD, FACP, Associate Medical Editor, What’s New in ACP Medicine

PRACTICE OF THIS MONTH’S UPDATES


MEDICINE
Understanding the Good 1 CARDIOVASCULAR MEDICINE majority of patients undergo more
than one imaging study.
News about Breast Cancer XII Diseases of the Aorta 1. Hayter RG, Rhea JT, Small A, et al: Suspected
KAREN ANTMAN, MD KIM A. EAGLE, MD, FACP
aortic dissection and other aortic disorders: multi-
detector row CT in 373 cases in the emergency set-
Boston University School of Medicine University of Michigan Health System ting. Radiology 238:841, 2006 [PMID 16452396]
rends in the risk of developing
T cancer, as determined by age-
adjusted incidence per 100,000 pop-
WILLIAM F. ARMSTRONG, MD
University of Michigan Medical School
Will This Patient Survive
Surgery?
ulation, and of dying from cancer, Blocking before Resecting efinitive repair of dissections of the
measured by overall mortality and
ppropriate preoperative evaluation D ascending aorta includes resection of
deaths per 100,000 population, are
tracked via state cancer registries.
A and management are critical in a
patient undergoing elective aortic aneurysm
the dissected aorta and insertion of an

The risk varies considerably by the


resection. In both urgent and emergent continued on page 3
section of the country. Statistics on
cases, the usual medical approach is to
incidence and mortality normally assume the patient may have preexist-
lag a few years because of reporting
delays. In early 2007, Jemal and
colleagues reported that in 2004,
ing coronary disease. Unless contra-
indicated, beta blockers should be used In This Issue
to treat such patients. Ideally, beta
the absolute number of deaths in blockers should be started days to sev- Practice of Medicine
the United States from all cancers eral weeks before surgery; the dose Understanding the Good News about
decreased for the second consecutive should be titrated to achieve a target Breast Cancer 1
year, on the basis of mortality data heart rate of 50 to 60 beats a minute.1 1 Cardiovascular Medicine
from the National Center for Health XII Diseases of the Aorta 1
1. ACC/AHA 2006 guideline update on periopera-
Statistics.1 Age-standardized cancer tive cardiovascular evaluation for noncardiac 12 Oncology
mortality in the United States fell surgery: focused update on perioperative beta- XV Chronic Lymphoid Leukemias and
blocker therapy: a report of the American College
13.5% between 1991 and 2004. of Cardiology/American Heart Association Task Plasma Cell Disorders 3
Nevertheless, for Americans Force on Practice Guidelines. J Am Coll Cardiol 10 Nephrology
younger than 85 years, cancer 47:2343, 2006 [PMID 16750714]
X Chronic Renal Failure and Dialysis 4
remains the most common cause of 14 Respiratory Medicine
death, exceeding mortality from Imaging Suspected Dissection XXI Diseases of the Mediastinum
heart disease. urrently, four diagnostic tools are
Jemal and colleagues also
reviewed incidence data through
C used to evaluate patients with sus-
pected aortic dissection: multidetector
and Hilum
7 Infectious Disease
XXXII Human Retroviral Infections
6

2003 from state cancer registries computed tomography angiography Other Than HIV Infection 7
and found that the incidence of (MDCTA),1 echocardiography, mag- 2 Dermatology
breast cancer—which had been netic resonance imaging, and aortogra- XVI Approach to the Diagnosis of
increasing by about 1% per year phy. In general, the choice of which Skin Disease 8
imaging modality to initially employ Special Alerts and Clinical Practice
since 1980—leveled off from 2001
will depend on local expertise and Guidelines 6
to 2003. The authors speculated
availability. In most hospitals, the FDA Approval Report
that this change may have stemmed
choice is either MDCTA or trans- New Treatment for Advanced Breast
Cancer 5
continued on page 2 esophageal echocardiography, and the
2 What’s New in ACP Medicine • July 2007 www.acpmedicine.com

PRACTICE OF MEDICINE
continued from page 1
Published by WebMD

from full utilization of mammogra- breast cancers, Ravdin and col-


5

phy, as well as the reduced use of leagues did not comment on histol- EDITOR-IN-CHIEF: David C. Dale, M.D., F.A.C.P.,
hormone replacement therapy Seattle
ogy subsets in their analysis of the
FOUNDING EDITOR: Daniel D. Federman, M.D.,
(HRT) in postmenopausal women.1 decreased incidence. M.A.C.P., Boston
More recently, Ravdin and col- The speed of the fall in incidence ASSOCIATE MEDICAL EDITOR, What’s New in
leagues analyzed quarterly data and ACP Medicine: Wendy Levinson, M.D., F.A.C.P.,
suggests that discontinuing HRT Toronto
reported that breast cancer inci- had a withdrawal effect on preclini- EDITORIAL BOARD:
dence had fallen by 6.7% in 2003 cal occult disease, consistent with Karen Antman, M.D., Boston; John P.
compared with 2002; this was fol- tumor shrinkage of measurable Atkinson, M.D., F.A.C.P., St. Louis; Mark
lowed by a small incremental Feldman, M.D., F.A.C.P., Dallas; Raymond
breast cancer upon withdrawal of Gibbons, M.D., Rochester, MN; R. Brian
decrease in 2004 that the investiga- Haynes, M.D., M.A.C.P., Hamilton, Ontario; Janet
hormone therapies such as tamox- B. Henrich, M.D., New Haven, CT; William L.
tors described as a leveling off. In
ifen.2 Whether the decrease repre- Henrich, M.D., F.A.C.P., San Antonio, TX;
fact, these researchers found that the Michael J. Holtzman, M.D., St. Louis; Mark G.
incidence of breast cancer peaked in sents a temporary drop or a sus- Lebwohl, M.D., New York; Wendy Levinson,

mid-2001 and then declined by tained decline in breast cancer inci- M.D., F.A.C.P., Toronto, Ontario; Lynn Loriaux,
M.D., PH.D., M.A.C.P., Portland, OR; Shaun
8.6% through 2004.2 dence depends on the extent to Ruddy, M.D., M.A.C.P., Richmond,VA; Jerry S.
which these occult tumors require Wolinsky, M.D., Houston
A decrease in mammographic
screening would also lead to a hormone stimulation for growth. DIRECTOR OF PUBLISHING:
decrease in incidence, but Ravdin Whether mortality from breast Cynthia M. Chevins

and colleagues discounted this possi- cancer will demonstrate a similar DIRECTOR, ELECTRONIC PUBLISHING:
Liz Pope
bility. Instead, they concluded that decline requires longer observation.
EDITORIAL DEPARTMENT:
the abrupt change in breast cancer The drop in incidence may not be Erin Michael Kelly, Managing Editor; Maureen
incidence was most likely a result of sustained, in which case a fall in O’Sullivan, Associate Managing Editor; Nancy
R. Terry, John Heinegg, Development Editors;
the 38% decrease in the use of HRT mortality would not be expected. David Terry, Copy Editor
between 2002 and 2003. However, Furthermore, the mortality after the ELECTRONIC PUBLISHING DEPARTMENT:
Jemal and colleagues, in a follow-up diagnosis of breast cancer is lower Janet Zinn, Electronic Projects Manager;
analysis, again concluded that satu- Betsy Klarfeld, Art and Design Editor;
in women who have taken post- Diane Joiner, Jennifer Smith, Wayne Anderson,
ration of mammography and a drop menopausal HRT than in women Associate Producers
in detection of smaller tumors con- who have not.6 Thus, the decreased ACP Medicine (ISSN 1548-9345) (USPS 482-310),
tributed to the effect, given the tim- formerly WebMD Scientific American® Medicine, is
incidence may not translate into a published monthly by WebMD Professional Publishing,
ing of the fall in incidence.3 111 Eighth Avenue, Suite 700, New York, NY 10011.
similar decrease in mortality. Copyright © 2007 by WebMD. All rights reserved. No
The sharp decline in HRT use was part of this issue may be reproduced by any mechanical,
photographic, or electronic process or in the form of a
precipitated by the announcement References phonographic recording, nor may it be stored in a
retrieval system, transmitted, or otherwise copied for
by the Women’s Health Initiative of 1. Jemal A, Siegel R, Ward E, et al: Cancer statis- public or private use without written permission of the
publisher. Periodical postage paid at New York, NY,
an increased risk of heart disease tics, 2007. CA Cancer J Clin 57:43, 2007 [PMID and at additional mailing offices. Individual subscription
and breast cancer associated with 17237035] rates–USA, its possessions, and Canada: $349 for the
first year ($324 for residents and students) and $269 for
postmenopausal estrogen and prog- 2.Ravdin PM, Cronin KA, Howlader N, et al: renewals ($249 for residents and students). Institutional
subscription rates–USA, its possessions, and Canada:
esterone use.4 When Ravdin and col- The decrease in breast-cancer incidence in 2003 $449 for the first year and $369 for renewals. Separate
in the United States. N Engl J Med 356:1670, shipping and handling apply. POSTMASTER: Send
leagues looked closely at quarterly 2007 [PMID 17442911]
address changes to ACP Medicine,WebMD Professional
Publishing, P.O. Box 1819, Danbury, CT 06813-9663.
statistics, they found that the 3. Jemal A, Ward E, Thun MJ: Recent trends in
drop had begun in 2002 and was breast cancer incidence rates by age and tumor
FOR ASSISTANCE WITH YOUR SUBSCRIPTION
Please address all inquiries to Fulfillment Department,
temporally related to the first report characteristics among U.S. women. Breast Cancer WebMD Professional Publishing, P.O. Box 1819,
Res 9:R28, 2007 [PMID 17477859] Danbury, CT 06813-9663, or call 800-545-0554 or
by the Women’s Health Initiative of 203-790-2087, fax us at 203-790-2066, or e-mail us at
4. Rossouw JE, Anderson GL, Prentice RL, et al: acpmedicine@webmd.net. For change of address, please
the increased risk associated with provide both your new and your old addresses (include
Risks and benefits of estrogen plus progestin in
HRT.2 Jemal and colleagues con- healthy postmenopausal women: principal results
your update mailing label if possible); be sure to notify us
at least six weeks before you expect to move to avoid
cluded that the drop had begun in from the Women's Health Initiative randomized interruptions in your service.

1999, and thus mammography was controlled trial. JAMA 288:321, 2002 [PMID YOUR FEEDBACK IS WELCOME
also implicated.3 12117397] • E-mail: whatsnew@webmd.net
The decreased incidence of breast 5. Chen CL, Weiss NS, Newcomb P, et al: • Write: WebMD Professional
Hormone replacement therapy in relation to Publishing
cancer after 2003, apparent only for breast cancer. JAMA 287:734, 2002 [PMID 111 Eighth Avenue, Suite 700
women 50 years of age or older, pre- 11851540] New York, NY 10011
dominantly involved estrogen recep- 6. Schuetz F, Diel IJ, Pueschel M, et al: Reduced
tor–positive breast cancers.2 Al- incidence of distant metastases and lower mortal-
though other studies have suggested ity in 1072 patients with breast cancer with a
history of hormone replacement therapy. Am J
that HRT increases the risk of lobu- Obstet Gynecol 196:342, 2007 [PMID
lar cancer compared with ductal 17403414]
www.acpmedicine.com ACP Medicine 3

THIS MONTH’S UPDATES


continued from page 1

aortic graft. In high-volume centers, (ascending aorta) dissection is most assessment of cytogenetic abnormali-
valve replacement is required in only influenced by the preexisting underly- ties by FISH has also been shown to
25% of cases.1 For most patients, the ing comorbidities, including age, prior be a predictive factor for progression-
aortic repair includes reimplantation of cardiac surgery, and atherosclerosis.1 free survival after treatment with flu-
the coronary arteries. In some patients, 1. Tsai T, Evangelista A, Nienaber CA, et al: darabine-based regimens; in such
this repair includes resection and place- Long-term survival in patients presenting with cases, the presence of 17p– or 11q–
type A acute aortic dissection: insights from the
ment of a graft to the aortic arch. Even international registry of acute aortic dissection predicts shorter progression-free sur-
in the best of centers, surgical mortali- (IRAD). Circulation 114(1 suppl):I350, 2006 vival (< 2 years).2,3
[PMID 16820599]
ty ranges from 10% to 35%, depend- 1. Shanafelt TD, Witzig TE, Fink SR, et al:
ing on comorbidity.1,2 Major contribu- Prospective evaluation of clonal evolution during
long-term follow-up of patients with untreated
tors to surgical mortality include hypo- early-stage chronic lymphocytic leukemia. J Clin
tension and shock, pulse deficits, and 12 ONCOLOGY Oncol 24:4634, 2006 [PMID 17008705]
the presence of cardiac tamponade.2 2. Byrd JC, Gribben JG, Peterson BL, et al: Select
high-risk genetic features predict earlier progres-
1. Trimarchi S, Nienaber CA, Rampoldi V, et al: XV Chronic Lymphoid Leukemias sion following chemoimmunotherapy with flu-
Contemporary results of surgery in acute type A
aortic dissection: the international registry of
and Plasma Cell Disorders darabine and rituximab in chronic lymphocytic
acute aortic dissection experience. J Thorac leukemia: justification for risk-adapted therapy. J
TAIT D. SHANAFELT, MD Clin Oncol 24:437, 2006 [PMID 16344317]
Cardiovasc Surg 129:112, 2005 [PMID
15632832] MORIE A. GERTZ, MD, FACP 3. Grever MR, Lucas DM, Dewald GW, et al:
2. Rampoldi V, Trimarchi S, Eagle KA, et al: Mayo Clinic College of Medicine Comprehensive assessment of genetic and molec-
Simple risk models to predict surgical mortality ular features predicting outcome in patients with
in acute type A aortic dissection: the internation- chronic lymphocytic leukemia: results from the
al registry of acute aortic dissection score. Ann The Future by FISH US Intergroup Phase III Trial E2997. J Clin
Thorac Surg 83:55, 2007 [PMID 17184630] Oncol 25:799, 2007[PMID 17283363]
hromosome analysis by fluorescent
Dissection Therapy Aftercare C in situ hybridization (FISH) can pre-
dict survival in chronic lymphoid leuk-
Transplantation in CLL
ighly selected individuals with chron-
A t many centers, either MDCTA or
MRI is performed on a regular basis
emia. In a retrospective analysis of a
heterogeneous population of patients,
H ic lymphocytic leukemia (CLL)
who are younger than 70 years and
after initial treatment of aortic dissec- many of whom had advance-stage dis-
have good performance status are
tion. Imaging of the aorta is repeated 3 ease and had been previously treated,
candidates for allogeneic stem cell
to 6 months after surgery to screen for Dohner and colleagues developed a
transplantation. Consensus recom-
the development of aneurysm in the hierarchical system that assigns pa-
mendations suggest considering allo-
false channel or at the margins of a tients to one of five categories with
geneic transplantation (myeloablative
surgical repair. Persistence of blood widely different median survival [see
or nonmyeloablative) for patients
flow in the residual false lumen may Table, below].1
who have experienced relapse of
indicate that a patient is likely to expe- A subsequent prospective series of
poor-risk CLL (i.e., CLL with an
rience continued expansion of the 159 untreated patients evaluated by
aggressive course and significantly
aneurysmal aorta. After the 6-month FISH shortly after diagnosis (median,
screening, patients undergo aortic reduced survival).1 Such patients are
3 months) and then prospectively fol-
imaging annually, and scrupulous defined by the following criteria:
lowed (median, 10 years) confirmed
attention is directed to antihyperten- the ability of the Dohner system to • Failure to respond to first-line ther-
sive therapy and modification of risk predict survival in newly diagnosed apy with a purine nucleoside ana-
factors. Long-term survival after suc- patients with early-stage disease.1 In logue (PNA)
cessful surgical repair of type A addition to its value for prognosis, • Relapse within 12 months after re-
ceiving a purine nucleoside ana-
Assessment of Prognosis in Chronic Lymphocytic logue (PNA)–based treatment or
within 24 months after receiving a
Leukemia Using Fluorescent In Situ PNA-based combination regimen
Hybridization • Need for therapy and presence of a
17p– abnormality on FISH testing.
Leukemic Cell Karyotype Median Survival (Years)
Such patients should be referred to a
17p– ± any other abnormalities 2–5 transplant center for evaluation. At
11– ± any other abnormalities except 17p– 7–9 the present time, there is no role for
autologous transplantation in the treat-
Trisomy 12 ± any other abnormalities ment of CLL, outside of clinical trials.
9–10
except 17p– or 11q–
1. Dreger P, Corradini P, Kimby E, et al:
Normal karyotype >9 Indications for allogeneic stem cell transplanta-
tion in chronic lymphocytic leukemia: the EBMT
13q– as the only abnormality present > 11 transplant consensus. Leukemia 21:12, 2007
[PMID 17109028]
4 What’s New in ACP Medicine • July 2007 www.acpmedicine.com

Staging Multiple Myeloma


International Staging System for
lthough the Durie-Salmon staging
A system served well for over 30 years,
it has several limitations: stage I patients
Multiple Myeloma
Stage I
are often not candidates for treatment; Serum β2 microglobulin < 3.5 mg/dl
the assessment of bone lesions used in Serum albumin ≥ 3.5 g/dl
this system is subjective; and a dispro-
Stage 2
portionate number of patients (80%)
Serum β2 microglobulin 3.5–5.5 mg/dl
are assigned to stage III. Consequently, and/or
the International Staging System for Serum albumin < 3.5 g/dl
multiple myeloma should be used for
Stage 3
all patients. This system was validated
Serum β2 microglobulin > 5.5 mg/dl
in over 10,000 patients on several con-
Note: Age is the only other factor that significantly affects outcome; older
tinents and is independent of conven- patients with myeloma have poorer outcomes than other myeloma
tional or high-dose therapy. An evalua- patients. Although cytogenetic status influences outcome, chromosome 13
tion of five different staging systems deletion and complex cytogenetic abnormalities do not increase the effects
of age, β2 microglobulin level, and albumin level on outcome.
reflected the superiority of the
International Staging System.1
The International Staging System
categorizes patients on the basis of
serum levels of β2 microglobulin and 10 NEPHROLOGY dialysis patients just as it does in
predialysis patients with chronic
albumin [see Table, right]. Serum β2
X Chronic Renal Failure and renal failure. Its control is achieved
microglobulin is shed from the surface
Dialysis by dietary phosphorus restriction,
of the myeloma cell and therefore
ERIC P. COHEN, MD, FACP
use of phosphate binders, and ongo-
provides an indirect reflection of
tumor mass. Albumin is a negative ing dialysis. Cross-sectional data
Medical College of Wisconsin
acute phase reactant, and its level is have shown a greater risk of mortali-
depressed as the interleukin-6 (IL-6) The Disappointment of Statins ty when the serum phosphorus level
level rises and IL-6 exerts growth is greater than 6.5 mg/dl in patients
he lipid-lowering statins that have a
effects on the myeloma population.
The staging system divides patients
T beneficial effect in lowering the risk
of coronary artery disease in the gener-
on long-term dialysis, a finding that
emphasizes the importance of inter-
into groups of equal size and distinct ventions to limit hyperphosphatemia.
al population may not be beneficial in
differences in median survival. Aluminum-containing phosphate
dialysis patients. A study of atorva-
1. Mihou D, Katodritou I, Zervas K: Evaluation of binders are no longer used in stan-
statin in diabetic patients on dialysis
five staging systems in 470 patients with multiple dard practice because of the danger
myeloma. Haematologica 91:1149, 2006 [PMID found that use of this statin was not
of aluminum intoxication. Evidence
16885059] associated with a reduction in the inci-
suggests that calcium-containing
dence of cardiovascular disease.1 In
Preserving Bone in Myeloma phosphate binders may exacerbate
another study, atorvastatin showed a
existing calcific atherosclerosis. A
isphosphonate therapy is now rou- similar lack of benefit in lowering
B tinely given to all patients with
myeloma bone disease. Long-term bis-
coronary artery disease endpoints in
patients with stage IV chronic kidney
recent randomized study showed a
greater risk of death over a 5-year
follow-up period among new dialysis
phosphonate use can be complicated disease who were not yet on dialysis.2
patients receiving calcium-containing
by osteonecrosis of the jaw; guidelines In addition to evidence of a lack of
phosphate binders as compared with
developed by the Mayo Clinic suggest benefit, the use of statins is associated
patients receiving sevelamer, which
that although intravenous pamidro- with an increased risk of rhabdomyo-
does not contain calcium.1
nate and intravenous zoledronic acid lysis.3 These findings suggest that
1. Block GA, Raggi P, Bellasi A, et al: Mortality
are equally effective in multiple myelo- statins should be used with caution in effect of coronary calcification and phosphate binder
ma, pamidronate appears less likely to patients who have severe renal failure. choice in incident hemodialysis patients. Kidney Int
1. Wanner C, Krane V, Marz W, et al: Atorva- 71:438, 2007 [PMID 17200680]
result in jaw osteonecrosis.1 The Mayo statin in patients with type 2 diabetes mellitus
Clinic guidelines recommend cessation undergoing dialysis. N Engl J Med 353:238, Reining in the Parathyroids
of bisphosphonate use after 2 years of 2005 [PMID 16034009]
irtually all patients on long-term
therapy for patients who have
achieved either a complete response or
2. Stegmayr BG, Brannstrom M, Bucht S, et al:
Low dose atorvastatin in severe chronic kidney
disease patients: a randomized controlled end-
V dialysis have secondary hyper-
parathyroidism. If left untreated,
a plateau phase; for patients whose point study. Scand J Urol Nephrol 39:489, 2005
the hyperparathyroidism may result
disease is active, who have not 3. Jamal SM, Eisenberg MJ, Christopoulos S:
in bone pain, fractures, or soft tis-
Rhabdomyolysis associated with hydroxymethyl-
achieved a response, or who continue glutaryl coenzyme A reductase inhibitors. Am sue calcification. Management of
to have threatening bone disease, the Heart J 147:956, 2004 [PMID 15199341] this condition includes not only the
frequency of bisphosphonate therapy treatment of hyperphosphatemia
should be reduced to every 3 months.1 A Better Way to Bind
but also the use of parenteral vita-
1. Lacy MQ, Dispenzieri A, Gertz MA, et al: Mayo Phosphate? min D preparations—mainly cal-
clinic consensus statement for the use of bisphos-
yperphosphatemia promotes sec- citriol and paricalcitol, which are
phonates in multiple myeloma. Mayo Clin Proc
81:1047, 2006 [PMID 16901028] H ondary hyperparathyroidism in given intravenously during dialysis
www.acpmedicine.com ACP Medicine 5

FDA Approval Report


The following is selected from the FDA’s list of recently capecitabine had a statistically significant improvement in
approved products. Complete, updated information on the time to tumor progression. In addition, the tumor
FDA approvals and notifications is available on the FDA response rate was higher in the group of patients receiving
Web site (http://www.fda.gov). lapatinib with capecitabine (24% versus 14%). The sur-
vival data are not yet mature.
New Treatment for Advanced Breast Cancer
The most commonly reported side effects of lapatinib
The FDA has approved lapatinib for use in combination
included diarrhea; nausea; vomiting; rash; and hand-foot
with capecitabine (Xeloda) for patients with advanced,
syndrome, which may include numbness, tingling, redness,
metastatic breast cancer that is HER2 positive. The combi-
swelling, and discomfort of hands and feet. Decreases in
nation treatment is indicated for women who have received
heart function, which can lead to shortness of breath, have
previous therapy with other cancer drugs, including an
also been reported in a small percentage of patients; these
anthracycline, a taxane, and trastuzumab (Herceptin).
decreases are generally reversible. Patients should talk to
Lapatinib is a kinase inhibitor that works through multiple their doctor about potential side effects, potential drug
pathways to deprive tumor cells of signals needed to grow. interactions, and other medical conditions, including heart
Unlike, for example, trastuzumab—a large monoclonal and liver problems.
antibody that targets the part of the HER2 protein on the
outside of the cell—lapatinib is a small molecule that enters Lapatinib is available in 250 mg tablets. An undivided dose
the cell and blocks the function of HER2 and other pro- of 1,250 mg should be taken orally once daily for 21 days
teins. Because of this difference in mechanism of action, and in combination with capecitabine on days 1 through
lapatinib works in some HER2-positive breast cancers that 14 of a 21-day cycle.
have been treated with trastuzumab and are no longer Generic Name: Lapatinib
responding. Brand Name: Tykerb
Lapatinib was approved on the basis of a randomized clini- Distributor: GlaxoSmithKline, Research Triangle Park,
cal trial in about 400 women with advanced or metastatic North Carolina
breast cancer that was HER2 positive. In the trial, half the
patients received lapatinib with capecitabine and half FDA Approves Tykerb for Advanced Breast Cancer Patients. FDA News.
received capecitabine alone. Compared with patients receiv- U.S. Food and Drug Administration, March 13, 2007
ing capecitabine alone, patients receiving lapatinib with (http://www.fda.gov/bbs/topics/NEWS/2007/NEW01580.html)

sessions. Calcitriol and paricalcitol dence of autonomous parathyroid hor- mon in ESRD patients than in the
act directly on the parathyroid mone secretion. general population.1
glands to suppress parathormone 1. Block GA, Martin KJ, de Francisco ALM, et 1. Sood P, Sinson GP, Cohen EP: Subdural hema-
synthesis and secretion. There is evi- al: Cinacalcet for secondary hyperparathyroidism tomas in chronic dialysis patients: significant and
in patients receiving hemodialysis. N Engl J Med increasing. J Am Soc Nephrol 17:320a, 2006
dence that medical management of 350:1516, 2004 [PMID 15071126]
secondary hyperparathyroidism has 2. Strippoli GF, Tong A, Palmer SC, et al:
improved over the past 10 years, Calcimimetics for secondary hyperparathy-
roidism in chronic kidney disease patients.
thus reducing the need for surgical Cochrane Database Syst Rev (4):CD006254,
treatment. 2006 [PMID 17054287]
An additional tool in the manage-
ment of secondary hyperparathy-
3. Garside R, Pitt M, Anderson R, et al: The
cost-utility of cinacalcet in addition to standard
Coming in August
care compared to standard care alone for sec-
roidism may be the orally active cal- ondary hyperparathyroidism in end-stage renal
Clinical Essentials
cimimetic agents, such as cinacalcet, disease: a UK perspective. Nephrol Dial Trans- XII Complementary and Alternative
which act directly on the calcium plant 22:1428, 2007 [PMID 17308322] Medicine
receptors of the parathyroid gland cells 4 Gastroenterology
to suppress parathormone secretion.1,2 Bleeding Complications in I Esophageal Disorders
However, these medications are expen- Dialysis Patients 10 Nephrology
sive, and a recent cost-utility analysis VII Vascular Diseases of the Kidney
of cinacalcet suggested that it was not lthough uremic bleeding is usually
cost-effective.3 Subtotal parathyroidec-
tomy may be needed for persistent
A not a problem in the well-dialyzed
patient with end-stage renal disease
12 Oncology
XIV Bladder, Renal, and Testicular
Cancer
severe hyperparathyroidism. Severe (ESRD), the use of heparin during 14 Respiratory Medicine
hyperparathyroidism is considered to each hemodialysis session can predis- XI Respiratory Failure
be present when one or more parathy- pose a patient to hemorrhagic compli- 16 Women’s Health
roid glands are enlarged to a diameter cations. For example, subdural XVIII Hirsutism and Hyperandrogenism
greater than 1 cm or when there is evi- hematomas are ten times more com-
6 What’s New in ACP Medicine • July 2007 www.acpmedicine.com

Special Alerts Clinical Practice Guidelines


Declining rates of death and heart failure Guidelines for the Management of Community-
observed in acute coronary syndromes Acquired Pneumonia in Adults
http://jama.ama-assn.org/cgi/content/abstract/297/17/1892 The Infectious Diseases Society of America and the
American Thoracic Society have developed new consensus
For more information, see Section 1, Chapter X Unstable
guidelines for the management of community-acquired
Angina and Non-ST Segment Elevation Myocardial Infarction. pneumonia (CAP) in adults; the guidelines were issued in
Once-weekly oral alendronate protects against March 2007. They are designed to improve the care of
adults with CAP and are intended primarily for use by
bone loss in men receiving androgen deprivation thera- emergency department physicians, hospitalists, and primary
py for prostate cancer care practitioners.
http://www.medscape.com/medline/abstract/17371886?cid= http://www.journals.uchicago.edu/CID/journal/issues/v44nS2/
med&src=nlbest 41620/41620.web.pdf
For more information, see Section 12, Chapter IX Prostate For more information, see Section 7, Chapter XX
Cancer. Pneumonia and Other Pulmonary Infections.

14 RESPIRATORY MEDICINE lated thymomas can be treated with


surgery alone, whereas those with
num and sternal debridement.
Although multiple techniques have
XXI Diseases of the Mediastinum invasive lesions are candidates for been described for the treatment of
and Hilum multimodality therapy. At the these infections, aggressive surgical
JOHN C. KUCHARCZUK, MD
University of Pennsylvania, a combi- debridement with muscle flap clo-
nation of systems is used; patients sure is associated with the best
University of Pennsylvania School of
are classified on the basis of histol- overall clinical outcomes.
Medicine
ogy, using the WHO system, and 1. Toumpoulis IK, Anagnostopoulos CE, DeRose
JJ, et al: The impact of deep sternal wound infec-
Classifying Thymomas clinical findings at the time of tion on long-term survival after coronary artery
hymomas were traditionally classi- surgery, using the Masaoka system. bypass grafting. Chest 127:464, 2005 [PMID

T fied on the basis of cellular histol-


ogy. Traditional classification
1. Detterbeck FC: Clinical value of the WHO
classification system of thymoma. Ann Thorac
15705983]

Surg 81:2328, 2006 [PMID 16731193]


schemes divide thymomas into three
groups: (1) predominantly lympho-
cytic thymomas, (2) predominantly Anterior Mediastinal
Infections
This Month’s CME
epithelial thymomas, and (3) mixed
thymomas. Although simple, these cute infections of the anterior Chapters
classification systems have little clini-
cal significance. More recently, the
A mediastinal compartment are
unusual, but they do occur. Ap-
ACP Medicine offers CME in
World Health Organization (WHO) convenient online and print for-
proximately 1% to 3% of median mats. As many as 120 AMA PRA
adopted a more elaborate histologic
sternotomies for cardiac surgery are Category 1 credits can be earned
classification system. Although the at any time during the year. The
complicated by sternal wound infec-
WHO system appears to be predic- following chapters are available
tive of outcome, it is not widely tion.1 Risk factors for sternal wound
for CME credit this month:
used.1 From a clinical perspective, infections include diabetes, use of
the most commonly used thymoma bilateral internal mammary arteries, 1 Cardiovascular Medicine
classification system is the Masaoka and reoperation. Patients with ster- XII Diseases of the Aorta
classification; this classification takes nal wound infections present with 7 Infectious Disease
into consideration the clinical obser- pain, drainage, and, often, a palpa- XXXII Human Retroviral Infections
vation that thymomas are either ble mass at the sternal incision. Most Other Than HIV Infection
completely encapsulated or grossly of these infections have deep exten- 10 Nephrology
invasive of adjacent structures. Large sions into the anterior mediastinum X Chronic Renal Failure and Dialysis
series of thymomas have consistently and concomitant sternal osteomy- 12 Oncology
demonstrated that approximately elitis. A CT scan of the chest should XV Chronic Lymphoid Leukemias and
70% of thymomas are completely be obtained to determine the extent Plasma Cell Disorders
encapsulated, whereas 30% are inva- of mediastinal soilage. Recommend- 14 Respiratory Medicine
sive. This distinction is clinically rele- ed treatment involves drainage of a XXI Diseases of the Mediastinum
vant because patients with encapsu- wide area of the anterior mediasti- and Hilum
www.acpmedicine.com ACP Medicine 7

Clinical Manifestations of HTLV-1 and HTLV-2 Infections


Manifestation HTLV-1 HTLV-2

Chronic ATL Large granular cell leukemia (CD8+)


Malignancies Smoldering ATL CD8+ cutaneous lymphoma
T cell non-Hodgkin lymphoma T cell variant hairy cell leukemia

TSP/HAM TSP/HAM
Neurologic manifestations
Peripheral neuropathy

Polymyositis Hashimoto thyroiditis


Arthritis
Autoimmune disorders Uveitis
Thyroiditis
Pneumonitis

Opportunistic infections in ATL patients* Bacterial pneumonia


Infectious diseases Infective dermatitis in children Tuberculosis
Strongyloides stercoralis infections Urinary tract infections
ATL—adult T cell leukemia/lymphoma TSP/HAM—tropical spastic paraparesis or HTLV-1–associated myelopathy
*Opportunistic infections may include cytomegalovirus pneumonitis, Pneumocystis jiroveci pneumonia, disseminated herpes zoster, aspergillosis, cryptococcosis, disseminated
Mycobacterium avium infection, and miliary tuberculosis.

Treating Esophageal infections. Latent infection is character- tions have been frequently reported in
ized by intermittent episodes of acute geographic regions of high HTLV-1
Leiomyoma or subclinical disease; between seroprevalence, such as Brazil and the
consensus in the literature recom-
A mends that esophageal leiomy-
oma be surgically removed in symp-
episodes, no virus is detectable. In
chronic infection, the virus is usually
demonstrable but symptoms of disease
Caribbean. Clinical evaluations of co-
infected patients have found a frequent
association with neurologic complica-
tomatic patients; however, best treat- are absent. Persistent infection is char- tions, including HTLV-associated mye-
ment of asymptomatic patients with acterized by a long incubation period lopathy and peripheral neuropathy.
lesions smaller than 3 cm is not with slowly increasing amounts of Coinfected patients are also more like-
established. Surgery has traditionally virus, eventually leading to sympto- ly to have hematologic complications
been the treatment of choice; many matic disease. Clinical disease develops such as thrombocytopenia, as well as
experts advocate the resection of in only 5% to 10% of persons infected respiratory, urinary tract, and hepatitis
asymptomatic tumors on the basis of with human lymphotropic virus type 1 C virus infections.1 Although highly
the following considerations: (1) a (HTLV-1) or HTLV-2. active antiretroviral therapy (HAART)
benign tumor may undergo malig- HTLV-1 causes adult T cell has significantly decreased AIDS-asso-
nant transformation; (2) a patient leukemia/lymphoma (ATL), T cell non- ciated mortality, the potential benefit
who is asymptomatic may develop Hodgkin lymphoma, and an unusual of HAART in suppressing HTLV-1/2
symptoms; (3) a definitive diagnosis neurodegenerative syndrome designat- viral replication in HIV-infected indi-
can be established on the basis of ed tropical spastic paraparesis or
viduals is unclear. In fact, anecdotal
histology; and (4) malignancy can be HTLV-1–associated myelopathy
reports suggest that HAART may
excluded only by tumor resection.1 (TSP/HAM). In ATL, the latent period
actually increase HTLV-1/2 viral load.2
between infection and the emergence
1. Lee LS, Singhal S, Brinster CJ, et al: Current A 2004 cohort study documented
management of esophageal leiomyoma. J Am of disease lasts 20 to 30 years or more.
the clinical outcomes and survival
Coll Surg 198:136, 2004 [PMID 14698321] TSP/HAM has a median latency peri-
od of approximately 3 years, but the probabilities in patients coinfected
latency period can be as long as 20 to with HIV-1 and HTLV-1 or HTLV-
30 years. Clinical manifestations of 2.1 In this study, HTLV coinfection
7 INFECTIOUS DISEASE HTLV infection include malignancies, was unexpectedly shown to result in
XXXII Human Retroviral neurologic disorders, autoimmune dis- improved survival and delayed pro-
orders, and increased susceptibility to gression to AIDS. However, an
Infections Other Than HIV
certain other infectious diseases [see increased frequency of HTLV-associ-
Infection
Table, above]. ated complications was clearly evi-
MARK A. BEILKE, MD dent, including TSP/HAM and
CHRISTY BARRIOS, PHD Retroviruses as Coinfections peripheral neuropathy.
Medical College of Wisconsin TLV-1 and HTLV-2 are frequent 1. Beilke MA, Theall KP, O’Brien M, et al: Clinical out-

How Retroviral Infection H copathogens in HIV-1–infected indi-


viduals, especially in large metropoli-
comes and disease progression among patients coinfect-
ed with HIV and human T lymphotropic virus types 1
and 2. Clin Infect Dis 39:256, 2004 [PMID 15307036]
Presents tan areas where injection drug use is a 2. Turci M, Pilotti E, Ronzi P, et al: Coinfection with
HIV-1 and HTLV-II in intravenous drug users is asso-
ike other viruses, retroviruses may common mode of transmission. Fur-
L cause latent, chronic, or persistent thermore, HIV-1 and HTLV-1 coinfec-
ciated with delayed progression to AIDS. J Acquir Im-
mune Defic Syndr 41:100, 2006 [PMID 16340481]
8 What’s New in ACP Medicine • July 2007 www.acpmedicine.com

by using various antiretroviral com-


pounds have been disappointing. Corti-
Online Atlases of Dermatology costeroids and immunosuppressive
DermIS.net agents such as azathioprine may ame-
A cooperation between the Department of Clinical Social Medi- liorate disease progression but are
cine, University of Heidelberg, and the Department of Derma- unsuitable for long-term use because of
tology, University of Erlangen
their adverse effects. Immunotherapy
http://www.dermis.net/index_e.html
with IFN-α has produced minimal to
DermAtlas
moderate results, depending on the
http://www.dermatlas.med.jhmi.edu/derm
degree of inflammation and tissue
Interactive Dermatology Atlas destruction.1
www.dermatlas.net
1. Saito M, Nakagawa M, Kaseda S, et al: Decreased
University of North Carolina School of Medicine Dermatology human T lymphotropic virus type I (HTLV-I) provirus
Slide Atlas load and alteration in T cell phenotype after interferon-
www.med.unc.edu/derm/atlas/welcome.htm alpha therapy for HTLV-I–associated myelopathy/
tropical spastic paraparesis. J Infect Dis 189:29, 2004
Dermatologic Image Database [PMID 14702150]
Department of Dermatology, University of Iowa College of
Medicine
http://tray.dermatology.uiowa.edu/ImageBase.html
Loyola University Dermatology Medical Education Website 2 DERMATOLOGY
www.meddean.luc.edu/Lume/MedEd/medicine/dermatology/
melton/atlas.html XVI Approach to the Diagnosis of
Skin Disease
ROBERT T. BRODELL, MD
STEPHEN E. HELMS, MD
Treating Adult T Cell trial in the United States employs oral
zidovudine in combination with high Northeastern Ohio Universities
Leukemia doses of interferon alfa (IFN-α), admin- College of Medicine and Case Western
ll patients diagnosed with adult T istered daily. Arsenic trioxide may Reserve University School of Medicine
A cell leukemia (ATL) should be
referred to a tertiary care center with
induce cell cycle arrest and apoptosis
of ATL cells in vitro; it is under consid-
Visual Aids to Diagnosis
t is important to begin the assess-
expertise in the treatment of HTLV-
1–associated malignancies. Conven-
tional chemotherapy for lymphoid
eration as an adjuvant chemotherapeu-
tic agent in combination with IFN-α. I ment of a skin condition with a
broad differential diagnosis, noting
There are several reports from Japan
malignancies is ineffective against of successful allogeneic stem cell trans- the presentation as characteristic of
aggressive forms of ATL; therefore, plantation after cytoreductive chemo- one of the categories of skin disease:
treatment of ATL has become the sub- therapy. Other trials have attempted papulosquamous, blistering, nonscal-
ject of several clinical studies. immunotherapy using humanized ing erythematous, pigmentation, or
Combination chemotherapy specifi- monoclonal antibodies directed against tumor. Using physical findings,
cally designed for ATL has consider- IL-2R and other receptors expressed patient history, and diagnostic test-
ably elevated the treatment response on ATL cells. ing, the differential diagnosis is grad-
rate in ATL patients, but it has not suf- ually narrowed until a diagnosis is
ficiently extended the median survival Treating Retroviral determined. A review of illustrations
time seen with standard cytotoxic regi- of specific primary and secondary
mens (e.g., cyclophosphamide, doxoru- Autoimmune Disease skin lesions in various dermatology
bicin, vincristine, and prednisone), fforts to treat TSP/HAM and HTLV- atlases [see Table, above] may also
which is less than 2 years. One current E 1–associated autoimmune diseases aid in arriving at a diagnosis.