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The American Journal of GASTROENTEROLOGY VOLUME 106 | SEPTEMBER 2011 www.amjgastro.com
1724 Letters to the Editor
its overall impact on patient care may ulti-
mately be limited by cost. HRME imag-
ing provides real-time “ optical biopsies ”
with many of the same diagnostically
relevant features established for confocal
endomicro scopy, yet costs signi cantly less
than probe- and endoscope-based confo-
cal platforms. Low-cost endomicroscopy
may prove to be a more widely accessible
adjunct to standard endoscopy for manag-
ing conditions, including Barrett ’ s metapla-
sia and screening colonoscopy, by assisting
the endoscopist in selecting sites for biopsy
and / or guiding treatment.
CONFLICT OF INTEREST
Guarantor of the article: Sharmila
Anandasabapathy, MD.
Speci c author contributions: Designed
and assembled HRME instrumentation,
dra ed the manuscript, and approved the
nal dra : Mark C. Pierce; operated HRME
instrumentation and approved the nal
dra : Peter M. Vila; evaluated histopathol-
ogy and HRME image data and approved
the nal dra : Alexandros D. Polydorides;
designed the study, interpreted image data,
and approved the nal dra : Rebecca
Richards-Kortum; designed the study,
performed endoscopic image collection,
interpreted image data, and approved the
nal dra : Sharmila Anandasabapathy.
Financial support: is work was funded
by the National Institutes of Health, Grants
R01 EB007594, and R01 CA140257.
Potential competing interests: Rebecca
Richards-Kortum holds patents related to
endomicrosopy devices. e remaining
authors declare no con ict of interest.
REFERENCES
1 . Kiesslich R , Gossner L , Goetz M et al. In vivo
histology of Barrett’s esophagus and associated
neoplasia by confocal laser endomicroscopy .
Clin Gastroenterol Hepatol 2006 ; 4 : 979 – 87 .
2 . Kiesslich R , Goetz M , Vieth M et al. T e c h n o l o g y
insight: confocal laser endoscopy for in vivo
diagnosis of colorectal cancer . Nat Clin Pract
Oncol 2007 ; 4 : 480 – 90 .
3 . Goetz M , Kiesslich R . Advances of endomicro-
scopy for gastrointestinal physiology and dis-
eases . Am J Physiol Gastrointest Liver Physiol
2010 ; 298 : G797 – 806 .
4 . D u n b a r K B , O k o l o P , M o n t g o m e r y E et al.
Confocal laser endomicroscopy in Barrett’s
esophagus and endoscopically inapparent
Barrett’s neoplasia: a prospective, randomized,
double-blinded, controlled, crossover trial .
Gastrointest Endosc 2009 ; 70 : 645 – 54 .
5 . Wallace MB , Sharma P , Lightdale C et al. P r e -
liminary accuracy and interobserver agreement
for the detection of intraepithelial neoplasia in
Barrett’s esophagus with probe-based confocal
laser endomicroscopy . Gastrointest Endosc
2010 ; 72 : 19 – 24 .
6 . M u l d o o n T J , A n a n d a s a b a p a t h y S , M a r u D et al.
High-resolution imaging in Barrett’s esopha-
gus: a novel, low-cost endoscopic microscope .
Gastrointest Endosc 2008 ; 68 : 737 – 44 .
7 . P i e r c e M C , Yu D , R i c h a r d s - K o r t u m R . H i g h -
resolution ber-optic microendoscopy for
in situ cellular imaging . J Vis Exp 2011 ; 47;
http://www.jove.com/index/Details.stp?ID=2306 .
8 . M u l d o o n T J , e k k e k N , R o b l y e r D et al. E v a l u -
ation of quantitative image analysis criteria for
the high-resolution microendo scopic detection
of neoplasia in Barrett’s esophagus . J Biomed
Opt 2010 ; 15 : 026027 .
9 . B i s s c h o p s R , B e r g m a n J . P r o b e - b a s e d c o n f o c a l
laser endomicroscopy: scienti c toy or clinical
tool? Endoscopy 2010 ; 42 : 487 – 9 .
1 Rice University, Department of Bioengineering ,
Houston , Texas , USA ;
2 Mount Sinai School of
Medicine, Division of Gastroenterology , New York ,
New York , USA ;
3 Mount Sinai School of Medicine,
Department of Pathology , New York , New York ,
USA . Correspondence: Sharmila Anandasabapathy,
MD , Division of Gastroenterology, Mount Sinai
School of Medicine , 1 Gustave L. Levy Place,
New York , New York 10029 , USA .
E-mail: sharmila.anandasabapathy@mountsinai.org
Dysplastic Barrett ’ s
Esophagus in Cirrhosis:
A Treatment Dilemma
S.C. Ra opoulos , MBBS, FRACP 1 ,
M . E hymiou , MBBS, PhD, FRACP 1 ,
G . M a y , M D 1 a n d N . M a r c o n , M D 1
is letter underwent external review.
doi:10.1038/ajg.2011.174
To the Editor: A 58-year-old man with
non-alcoholic steatohepatitis-related Childs
A cirrhosis presented with bleeding eso-
phageal varices requiring band ligation. At
the time of esophagogastroduodenoscopy
(EGD), a 5 cm segment of Barrett ’ s esopha-
gus (BE) was identi ed with a focal area of
nodularity and distorted mucosal pattern
on narrow band imaging. e patient was
referred to our service for reassessment and
consideration of endoscopic therapy.
His other past medical history was
remarkable for diabetes, obesity, hyperten-
sion, and dyslipidemia.
On review at our center, repeat blood
work revealed an elevated international
normalized ratio of 1.3 and thrombocyto-
penia with platelets of 98,000 / l. At repeat
EGD he was found to have grade 1 esopha-
geal varices. e gastroesophageal junction
was at 41 cm with circumferential Barrett ’ s
mucosa to 38 cm, where a 3 mm nodule was
identi ed. e Barrett ’ s mucosa extended
for a further 2 cm in a non-circumferential
distribution (C3M5) to 41 cm ( Figure 1 ).
Endoscopic ultrasound con rmed mul-
tiple esophageal varices without any media-
stinal lymphadenopathy ( Figure 2 ). Using
a standard gastroscope and the Cook 6-
shooter band ligation device, the nodule
together with visible varices within the Bar-
rett ’ s segment were ligated with a total of ve
bands deployed. e tip of the nodule was
biopsied prior to withdrawal of the gastro-
scope. Histology revealed intestinal meta-
plasia with high-grade dysplasia (HGD).
He continued to have follow-up EGD
with band ligation of visible Barrett ’ s mucosa
at 2- to 4-month intervals with a total of
four procedures performed ( Figure 3 ). At
each endoscopy, following band ligation,
the tips of pseudopolyps were biopsied with
histo logy con rming multifocal HGD. He
was maintained on pantoprazole 40 mg o.d.
Figure 1 . White light endoscopy revealing a nodular area in a short segment of Barrett ’ s mucosa.
© 2011 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
Letters to the Editor 1725
during the course of treatment. At his most
recent follow-up, 95 % of Barrett ’ s mucosa
had been eradicated with seven small residual
islands remaining. Nine bands were deployed
with no residual Barrett ’ s remaining.
HGD associated with BE is a surrogate
marker for synchronous adenocarcinoma
in 40 % ( 1 ) of patients and also confers a
risk of 6.6 % per annum of cancer develop-
ment ( 2 ).
Ivor-Lewis esophagectomy has been the
standard of care for the management of HGD
in at mucosa or HGD in a focal lesion. How-
ever, mortality ranges from 2 to 10 % and
long-term morbidity is high at 30 – 40 % ( 3 ).
Although cirrhosis is not strictly a contrain-
dication to eso phageactomy, post-operative
complications exceed 80 % and outcomes are
worse than in the non-cirrhotic patient ( 4 ).
Endoscopic mucosal resection has
become one of the preferred modalities
of therapy in patients with short segment
BE and the sole preferred modality for the
excision and staging of nodular or ulcerated
Figure 2 . Endoscopic ultrasound showing multiple esophageal varices within the esophageal mucosa
(arrow).
Figure 3 . Endoscopic views at baseline ( a ), 4 months ( b ), 6 months ( c ), and 8 months ( d ).
areas within BE prior to other ablative
techniques ( 5 ). e technique involves the
sequential creation and snare diathermy of
pseudopolyps until the abnormal mucosa
has been eradicated. In the setting of
underlying esophageal varices, band liga-
tion followed by resection is not a suit-
able therapy due to the high potential of
bleeding. Band ligation without resection,
on the other hand, remains the treatment
of choice for management of esophageal
varices and has been shown to be both
e ective and safe ( 6,7 ).
Owing to the risk of bleeding with
EMR, patients with esophageal varices
and dysplastic BE have limited treatment
options. is is particularly relevant if
such patients are being considered for liver
transplantation due to rapid progression of
premalignant and malig nant lesions in the
setting of immuno suppression ( 8 ).
To our knowledge, this is the rst report
in the literature of successful eradication
of BE through band ligation in the context
of cirrhosis and underlying esophageal
varices. e technique described pro-
vides a safe treatment option to a subset
of patients that have high risk pro le for
surgery and are unsuitable for most other
available therapies. e main drawback
of the ligation technique without resec-
tion is the lack of a complete histological
specimen.
ACKNOWLEDGMENTS
is work has in part been supported by a
UWA Medical Research Fellowship and the
Faculty of Medicine, Dentistry and Health
Sciences in Perth, Western Australia.
CONFLICT OF INTEREST
e authors declare no con ict of interest.
REFERENCES
1 . Collard JM . High-grade dysplasia in Barrett’s
esophagus. e case for esophagectomy .
Chest Surg Clin N Am 2002 ; 12 : 77 – 92 .
2 . R a s t o g i A , P u l i S , E l - S e r a g H B et al. Incidence
of esophageal adenocarcinoma in patients
with Barrett ′ s esophagus and high-grade
dysplasia: a meta-analysis . Gastrointest Endosc
2008 ; 67 : 394 – 8 .
3 . S w a n s o n S J , B a t i r e l H F , B u e n o R et al.
Transthoracic esophagectomy with
radical mediastinal and abdominal lymph node
dissection and cervical esophagogastrostomy
for esophageal carcinoma . Ann orac Surg
2001 ; 72 : 1918 – 24 ; discussion 24 – 5 .
The American Journal of GASTROENTEROLOGY VOLUME 106 | SEPTEMBER 2011 www.amjgastro.com
1726 Letters to the Editor
4 . T a c h i b a n a M , K o t o h T , K i n u g a s a S et al.
Esophageal cancer with cirrhosis of the liver:
results of esophagectomy in 18 consecutive
patients . Ann Surg Oncol 2000 ; 7 : 758 – 63 .
5 . P o u w R E , W i r t h s K , E i s e n d r a t h P et al. E cacy
of radiofrequency ablation combined with en-
doscopic resection for barrett ′ s esophagus with
early neoplasia . Clin Gastroenterol Hepatol
2010 ; 8 : 23 – 9 .
6 . Grace ND . Diagnosis and treatment of
gastrointestinal bleeding secondary to
portal hypertension. American College of
Gastro enterology Practice Parameters
Committee . Am J Gastroenterol 1997 ; 92 :
1081 – 91 .
7 . Qureshi W , Adler DG , Davila R et al. A S G E
Guideline: the role of endoscopy in the
management of variceal hemorrhage, updated
July 2005 . Gastrointest Endosc 2005 ; 62 :
651 – 5 .
8 . Trotter JF , Brazer SR . Rapid progression to
high-grade dysplasia in Barrett ′ s esophagus
a er liver transplantation . Liver Transpl Surg
1999 ; 5 : 332 – 3 .
1 Center for Therapeutic Endoscopy and
Endoscopic Oncology, St Michael ’ s Hospital,
University of Toronto , Toronto , Ontario ,
Canada . Correspondence: S.C. Raftopoulos,
MBBS, FRACP , Center for Therapeutic Endoscopy
and Endoscopic Oncology, St Michael ’ s Hospital,
University of Toronto , Toronto , Ontario M5B 1W8,
Canada . E-mail: raft@iprimus.com.au
Lactulose: How Many
Ways Can One Drug Be
Prescribed ?
Benjamin Lukens , PharmD 1 , D a v i d M .
Nierman , MD 2 a n d o m a s D . S c h i a n o , M D 3
is letter underwent external review .
doi:10.1038/ajg.2011.182
To the Editor: Lactulose is an osmotic
laxative prescribed for the treatment of
hepatic encephalopathy (HE) and con-
stipation. Although generally considered
safe and innocuous, lactulose may be
associated with several adverse events,
including abdominal discomfort, abdom-
inal distention, increased intestinal gas
production, and atulence ( 1,2 ). Diarrhea
may also occur and may lead to more
serious adverse events, including dehy-
dration, hypokalemia, hypernatremia,
and other electrolyte disturbances. Dehy-
dration may worsen the mental status of
patients with HE ( 3 ). Hypernatremia has
been associated with dehydration and lac-
tulose use in patients with HE ( 4 – 6 ) and
may lead to acute kidney injury, which
may precipitate hepatorenal syndrome.
Overall, lactulose should be considered a
drug with potential morbidity associated
with its use ( 7 ).
To safely use lactulose, proper dosage
and administration protocols should be
followed. e indicated doses of lactulose
for constipation and HE are summarized
in Table 1 . Furthermore, patients should
be monitored for electrolyte abnormali-
ties and evidence of dehydration ( 6 ), and
appropriate dose adjustments should be
made so that patients with HE have only
2 – 3 semiformed stools daily ( 1,4 ).
To exemplify the importance of proper
lactulose dosing and monitoring, we
report here the case of a 59-year-old
male admitted for liver transplant evalu-
ation. Upon admission, lactulose 30 ml
every 4 h with titration to 3 – 4 bowel
movements daily was ordered. On day
2, the order was changed to 30 ml every
2 h without titration. Later that day, the
order was amended to include titration
to 3 – 5 bowel movements / day. However,
the dose was not titrated, the patient
had dozens of bowel movements begin-
ning the night of day 3 and continuing
through the morning of day 4, and the
patient became hypernatremic. Lactulose
therapy was suspended on day 8, but the
hypernatremia persisted until day 12. e
patient was transferred to the intensive
care unit for neurologic monitoring and
hypernatremia correction.
Review of this case suggested that lactu-
lose was not being prescribed and used uni-
formly for this patient and prompted a review
of lactulose prescribing practices at the ter-
tiary medical institution where this patient
was treated. To this end, orders for lactulose
entered into Mount Sinai ’ s Datamart data-
base from 1 January to 31 December 2009
were reviewed. Lactulose dose, frequency,
and quantity were analyzed.
e review of lactulose ordering at
Mount Sinai, an institution with long-
standing experience in using lactulose in
patients with liver disease, revealed that
lactulose orders were highly variable in
type and frequency. In 2009, there were
5,107 lactulose orders. In most cases, lac-
tulose was prescribed for constipation.
Of the 5,107 orders, 1,385 were as needed
(p.r.n.) orders, 2,743 were standing orders,
and 979 were single dose orders. Of the
2,743 standing orders, 1,513 were listed as
“ standing ” orders, 595 were listed as “ rst
dose now ” orders, 633 were listed as “ stat ”
orders, and 2 were listed as “ single ” dose
orders. ere were 28 di erent types of
p.r.n. orders ( n = 1,385), 43 di erent types
of standing orders ( n = 1,513), and 18 dif-
ferent types of single dose orders ( n = 981).
e majority of p.r.n. orders (1,349 / 1,385;
97.4 % ), standing orders (1,409 / 1,513;
93.1 % ), and single dose orders (937 / 981;
95.5 % ) were for 30 ml. e frequency and
timing of lactulose orders were variable.
Lactulose was ordered to be adminis-
tered as o en as every 1 – 2 h and as infre-
quently as every Monday, Wednesday,
and Friday. However, most p.r.n. orders
(763 / 1,385; 55.1 % ) were for daily dosing,
and most standing orders were for once-
daily (459 / 1,513; 30.3 % ) or twice-daily
(404 / 1,513; 26.7 % ) dosing. Notably, there
were at least eight di erent types of daily
dosing orders. Of the single dose orders,
most (888 / 981; 90.5 % ) were indeed written
for 1 dose; however, several (93 / 981; 9.5 % )
included a frequency order.
is very sobering review showed that
lactulose prescribing is not uniform in
the hospital and is likely just as variable
Table 1 . Indications and dosages for lactulose in adults ( 1 )
Condition Dose
Constipation 15 – 30 ml (10 – 20 g) lactulose daily. May be increased to 60 ml / day if necessary
HE 30 – 45 ml (20 – 30 g) lactulose 3 – 4 times per day. Adjusted daily to produce 2 or 3
soft stools per day
a
HE, hepatic encephalopathy.
a Hourly doses of 30 – 45 ml may be used to induce rapid laxation for the initial treatment of HE.
After laxation, the dose of lactulose should be reduced to the recommended daily dose.
