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The Official Newspaper of the AGA Institute
gambling
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Daech
drug paraphernalia
explosion
gun
human trafficking
ISIL
ISIS
Islamic caliphate
Islamic state
mixed martial arts
MMA
molestation
national rifle association
NRA
nsfw
pedophile
pedophilia
poker
porn
pornography
psychedelic drug
recreational drug
sex slave rings
slot machine
terrorism
terrorist
Texas hold 'em
UFC
substance abuse
abuseed
abuseer
abusees
abuseing
abusely
abuses
aeolus
aeolused
aeoluser
aeoluses
aeolusing
aeolusly
aeoluss
ahole
aholeed
aholeer
aholees
aholeing
aholely
aholes
alcohol
alcoholed
alcoholer
alcoholes
alcoholing
alcoholly
alcohols
allman
allmaned
allmaner
allmanes
allmaning
allmanly
allmans
alted
altes
alting
altly
alts
analed
analer
anales
analing
anally
analprobe
analprobeed
analprobeer
analprobees
analprobeing
analprobely
analprobes
anals
anilingus
anilingused
anilinguser
anilinguses
anilingusing
anilingusly
anilinguss
anus
anused
anuser
anuses
anusing
anusly
anuss
areola
areolaed
areolaer
areolaes
areolaing
areolaly
areolas
areole
areoleed
areoleer
areolees
areoleing
areolely
areoles
arian
arianed
arianer
arianes
arianing
arianly
arians
aryan
aryaned
aryaner
aryanes
aryaning
aryanly
aryans
asiaed
asiaer
asiaes
asiaing
asialy
asias
ass
ass hole
ass lick
ass licked
ass licker
ass lickes
ass licking
ass lickly
ass licks
assbang
assbanged
assbangeded
assbangeder
assbangedes
assbangeding
assbangedly
assbangeds
assbanger
assbanges
assbanging
assbangly
assbangs
assbangsed
assbangser
assbangses
assbangsing
assbangsly
assbangss
assed
asser
asses
assesed
asseser
asseses
assesing
assesly
assess
assfuck
assfucked
assfucker
assfuckered
assfuckerer
assfuckeres
assfuckering
assfuckerly
assfuckers
assfuckes
assfucking
assfuckly
assfucks
asshat
asshated
asshater
asshates
asshating
asshatly
asshats
assholeed
assholeer
assholees
assholeing
assholely
assholes
assholesed
assholeser
assholeses
assholesing
assholesly
assholess
assing
assly
assmaster
assmastered
assmasterer
assmasteres
assmastering
assmasterly
assmasters
assmunch
assmunched
assmuncher
assmunches
assmunching
assmunchly
assmunchs
asss
asswipe
asswipeed
asswipeer
asswipees
asswipeing
asswipely
asswipes
asswipesed
asswipeser
asswipeses
asswipesing
asswipesly
asswipess
azz
azzed
azzer
azzes
azzing
azzly
azzs
babeed
babeer
babees
babeing
babely
babes
babesed
babeser
babeses
babesing
babesly
babess
ballsac
ballsaced
ballsacer
ballsaces
ballsacing
ballsack
ballsacked
ballsacker
ballsackes
ballsacking
ballsackly
ballsacks
ballsacly
ballsacs
ballsed
ballser
ballses
ballsing
ballsly
ballss
barf
barfed
barfer
barfes
barfing
barfly
barfs
bastard
bastarded
bastarder
bastardes
bastarding
bastardly
bastards
bastardsed
bastardser
bastardses
bastardsing
bastardsly
bastardss
bawdy
bawdyed
bawdyer
bawdyes
bawdying
bawdyly
bawdys
beaner
beanered
beanerer
beaneres
beanering
beanerly
beaners
beardedclam
beardedclamed
beardedclamer
beardedclames
beardedclaming
beardedclamly
beardedclams
beastiality
beastialityed
beastialityer
beastialityes
beastialitying
beastialityly
beastialitys
beatch
beatched
beatcher
beatches
beatching
beatchly
beatchs
beater
beatered
beaterer
beateres
beatering
beaterly
beaters
beered
beerer
beeres
beering
beerly
beeyotch
beeyotched
beeyotcher
beeyotches
beeyotching
beeyotchly
beeyotchs
beotch
beotched
beotcher
beotches
beotching
beotchly
beotchs
biatch
biatched
biatcher
biatches
biatching
biatchly
biatchs
big tits
big titsed
big titser
big titses
big titsing
big titsly
big titss
bigtits
bigtitsed
bigtitser
bigtitses
bigtitsing
bigtitsly
bigtitss
bimbo
bimboed
bimboer
bimboes
bimboing
bimboly
bimbos
bisexualed
bisexualer
bisexuales
bisexualing
bisexually
bisexuals
bitch
bitched
bitcheded
bitcheder
bitchedes
bitcheding
bitchedly
bitcheds
bitcher
bitches
bitchesed
bitcheser
bitcheses
bitchesing
bitchesly
bitchess
bitching
bitchly
bitchs
bitchy
bitchyed
bitchyer
bitchyes
bitchying
bitchyly
bitchys
bleached
bleacher
bleaches
bleaching
bleachly
bleachs
blow job
blow jobed
blow jober
blow jobes
blow jobing
blow jobly
blow jobs
blowed
blower
blowes
blowing
blowjob
blowjobed
blowjober
blowjobes
blowjobing
blowjobly
blowjobs
blowjobsed
blowjobser
blowjobses
blowjobsing
blowjobsly
blowjobss
blowly
blows
boink
boinked
boinker
boinkes
boinking
boinkly
boinks
bollock
bollocked
bollocker
bollockes
bollocking
bollockly
bollocks
bollocksed
bollockser
bollockses
bollocksing
bollocksly
bollockss
bollok
bolloked
bolloker
bollokes
bolloking
bollokly
bolloks
boner
bonered
bonerer
boneres
bonering
bonerly
boners
bonersed
bonerser
bonerses
bonersing
bonersly
bonerss
bong
bonged
bonger
bonges
bonging
bongly
bongs
boob
boobed
boober
boobes
boobies
boobiesed
boobieser
boobieses
boobiesing
boobiesly
boobiess
boobing
boobly
boobs
boobsed
boobser
boobses
boobsing
boobsly
boobss
booby
boobyed
boobyer
boobyes
boobying
boobyly
boobys
booger
boogered
boogerer
boogeres
boogering
boogerly
boogers
bookie
bookieed
bookieer
bookiees
bookieing
bookiely
bookies
bootee
booteeed
booteeer
booteees
booteeing
booteely
bootees
bootie
bootieed
bootieer
bootiees
bootieing
bootiely
booties
booty
bootyed
bootyer
bootyes
bootying
bootyly
bootys
boozeed
boozeer
boozees
boozeing
boozely
boozer
boozered
boozerer
boozeres
boozering
boozerly
boozers
boozes
boozy
boozyed
boozyer
boozyes
boozying
boozyly
boozys
bosomed
bosomer
bosomes
bosoming
bosomly
bosoms
bosomy
bosomyed
bosomyer
bosomyes
bosomying
bosomyly
bosomys
bugger
buggered
buggerer
buggeres
buggering
buggerly
buggers
bukkake
bukkakeed
bukkakeer
bukkakees
bukkakeing
bukkakely
bukkakes
bull shit
bull shited
bull shiter
bull shites
bull shiting
bull shitly
bull shits
bullshit
bullshited
bullshiter
bullshites
bullshiting
bullshitly
bullshits
bullshitsed
bullshitser
bullshitses
bullshitsing
bullshitsly
bullshitss
bullshitted
bullshitteded
bullshitteder
bullshittedes
bullshitteding
bullshittedly
bullshitteds
bullturds
bullturdsed
bullturdser
bullturdses
bullturdsing
bullturdsly
bullturdss
bung
bunged
bunger
bunges
bunging
bungly
bungs
busty
bustyed
bustyer
bustyes
bustying
bustyly
bustys
butt
butt fuck
butt fucked
butt fucker
butt fuckes
butt fucking
butt fuckly
butt fucks
butted
buttes
buttfuck
buttfucked
buttfucker
buttfuckered
buttfuckerer
buttfuckeres
buttfuckering
buttfuckerly
buttfuckers
buttfuckes
buttfucking
buttfuckly
buttfucks
butting
buttly
buttplug
buttpluged
buttpluger
buttpluges
buttpluging
buttplugly
buttplugs
butts
caca
cacaed
cacaer
cacaes
cacaing
cacaly
cacas
cahone
cahoneed
cahoneer
cahonees
cahoneing
cahonely
cahones
cameltoe
cameltoeed
cameltoeer
cameltoees
cameltoeing
cameltoely
cameltoes
carpetmuncher
carpetmunchered
carpetmuncherer
carpetmuncheres
carpetmunchering
carpetmuncherly
carpetmunchers
cawk
cawked
cawker
cawkes
cawking
cawkly
cawks
chinc
chinced
chincer
chinces
chincing
chincly
chincs
chincsed
chincser
chincses
chincsing
chincsly
chincss
chink
chinked
chinker
chinkes
chinking
chinkly
chinks
chode
chodeed
chodeer
chodees
chodeing
chodely
chodes
chodesed
chodeser
chodeses
chodesing
chodesly
chodess
clit
clited
cliter
clites
cliting
clitly
clitoris
clitorised
clitoriser
clitorises
clitorising
clitorisly
clitoriss
clitorus
clitorused
clitoruser
clitoruses
clitorusing
clitorusly
clitoruss
clits
clitsed
clitser
clitses
clitsing
clitsly
clitss
clitty
clittyed
clittyer
clittyes
clittying
clittyly
clittys
cocain
cocaine
cocained
cocaineed
cocaineer
cocainees
cocaineing
cocainely
cocainer
cocaines
cocaining
cocainly
cocains
cock
cock sucker
cock suckered
cock suckerer
cock suckeres
cock suckering
cock suckerly
cock suckers
cockblock
cockblocked
cockblocker
cockblockes
cockblocking
cockblockly
cockblocks
cocked
cocker
cockes
cockholster
cockholstered
cockholsterer
cockholsteres
cockholstering
cockholsterly
cockholsters
cocking
cockknocker
cockknockered
cockknockerer
cockknockeres
cockknockering
cockknockerly
cockknockers
cockly
cocks
cocksed
cockser
cockses
cocksing
cocksly
cocksmoker
cocksmokered
cocksmokerer
cocksmokeres
cocksmokering
cocksmokerly
cocksmokers
cockss
cocksucker
cocksuckered
cocksuckerer
cocksuckeres
cocksuckering
cocksuckerly
cocksuckers
coital
coitaled
coitaler
coitales
coitaling
coitally
coitals
commie
commieed
commieer
commiees
commieing
commiely
commies
condomed
condomer
condomes
condoming
condomly
condoms
coon
cooned
cooner
coones
cooning
coonly
coons
coonsed
coonser
coonses
coonsing
coonsly
coonss
corksucker
corksuckered
corksuckerer
corksuckeres
corksuckering
corksuckerly
corksuckers
cracked
crackwhore
crackwhoreed
crackwhoreer
crackwhorees
crackwhoreing
crackwhorely
crackwhores
crap
craped
craper
crapes
craping
craply
crappy
crappyed
crappyer
crappyes
crappying
crappyly
crappys
cum
cumed
cumer
cumes
cuming
cumly
cummin
cummined
cumminer
cummines
cumming
cumminged
cumminger
cumminges
cumminging
cummingly
cummings
cummining
cumminly
cummins
cums
cumshot
cumshoted
cumshoter
cumshotes
cumshoting
cumshotly
cumshots
cumshotsed
cumshotser
cumshotses
cumshotsing
cumshotsly
cumshotss
cumslut
cumsluted
cumsluter
cumslutes
cumsluting
cumslutly
cumsluts
cumstain
cumstained
cumstainer
cumstaines
cumstaining
cumstainly
cumstains
cunilingus
cunilingused
cunilinguser
cunilinguses
cunilingusing
cunilingusly
cunilinguss
cunnilingus
cunnilingused
cunnilinguser
cunnilinguses
cunnilingusing
cunnilingusly
cunnilinguss
cunny
cunnyed
cunnyer
cunnyes
cunnying
cunnyly
cunnys
cunt
cunted
cunter
cuntes
cuntface
cuntfaceed
cuntfaceer
cuntfacees
cuntfaceing
cuntfacely
cuntfaces
cunthunter
cunthuntered
cunthunterer
cunthunteres
cunthuntering
cunthunterly
cunthunters
cunting
cuntlick
cuntlicked
cuntlicker
cuntlickered
cuntlickerer
cuntlickeres
cuntlickering
cuntlickerly
cuntlickers
cuntlickes
cuntlicking
cuntlickly
cuntlicks
cuntly
cunts
cuntsed
cuntser
cuntses
cuntsing
cuntsly
cuntss
dago
dagoed
dagoer
dagoes
dagoing
dagoly
dagos
dagosed
dagoser
dagoses
dagosing
dagosly
dagoss
dammit
dammited
dammiter
dammites
dammiting
dammitly
dammits
damn
damned
damneded
damneder
damnedes
damneding
damnedly
damneds
damner
damnes
damning
damnit
damnited
damniter
damnites
damniting
damnitly
damnits
damnly
damns
dick
dickbag
dickbaged
dickbager
dickbages
dickbaging
dickbagly
dickbags
dickdipper
dickdippered
dickdipperer
dickdipperes
dickdippering
dickdipperly
dickdippers
dicked
dicker
dickes
dickface
dickfaceed
dickfaceer
dickfacees
dickfaceing
dickfacely
dickfaces
dickflipper
dickflippered
dickflipperer
dickflipperes
dickflippering
dickflipperly
dickflippers
dickhead
dickheaded
dickheader
dickheades
dickheading
dickheadly
dickheads
dickheadsed
dickheadser
dickheadses
dickheadsing
dickheadsly
dickheadss
dicking
dickish
dickished
dickisher
dickishes
dickishing
dickishly
dickishs
dickly
dickripper
dickrippered
dickripperer
dickripperes
dickrippering
dickripperly
dickrippers
dicks
dicksipper
dicksippered
dicksipperer
dicksipperes
dicksippering
dicksipperly
dicksippers
dickweed
dickweeded
dickweeder
dickweedes
dickweeding
dickweedly
dickweeds
dickwhipper
dickwhippered
dickwhipperer
dickwhipperes
dickwhippering
dickwhipperly
dickwhippers
dickzipper
dickzippered
dickzipperer
dickzipperes
dickzippering
dickzipperly
dickzippers
diddle
diddleed
diddleer
diddlees
diddleing
diddlely
diddles
dike
dikeed
dikeer
dikees
dikeing
dikely
dikes
dildo
dildoed
dildoer
dildoes
dildoing
dildoly
dildos
dildosed
dildoser
dildoses
dildosing
dildosly
dildoss
diligaf
diligafed
diligafer
diligafes
diligafing
diligafly
diligafs
dillweed
dillweeded
dillweeder
dillweedes
dillweeding
dillweedly
dillweeds
dimwit
dimwited
dimwiter
dimwites
dimwiting
dimwitly
dimwits
dingle
dingleed
dingleer
dinglees
dingleing
dinglely
dingles
dipship
dipshiped
dipshiper
dipshipes
dipshiping
dipshiply
dipships
dizzyed
dizzyer
dizzyes
dizzying
dizzyly
dizzys
doggiestyleed
doggiestyleer
doggiestylees
doggiestyleing
doggiestylely
doggiestyles
doggystyleed
doggystyleer
doggystylees
doggystyleing
doggystylely
doggystyles
dong
donged
donger
donges
donging
dongly
dongs
doofus
doofused
doofuser
doofuses
doofusing
doofusly
doofuss
doosh
dooshed
doosher
dooshes
dooshing
dooshly
dooshs
dopeyed
dopeyer
dopeyes
dopeying
dopeyly
dopeys
douchebag
douchebaged
douchebager
douchebages
douchebaging
douchebagly
douchebags
douchebagsed
douchebagser
douchebagses
douchebagsing
douchebagsly
douchebagss
doucheed
doucheer
douchees
doucheing
douchely
douches
douchey
doucheyed
doucheyer
doucheyes
doucheying
doucheyly
doucheys
drunk
drunked
drunker
drunkes
drunking
drunkly
drunks
dumass
dumassed
dumasser
dumasses
dumassing
dumassly
dumasss
dumbass
dumbassed
dumbasser
dumbasses
dumbassesed
dumbasseser
dumbasseses
dumbassesing
dumbassesly
dumbassess
dumbassing
dumbassly
dumbasss
dummy
dummyed
dummyer
dummyes
dummying
dummyly
dummys
dyke
dykeed
dykeer
dykees
dykeing
dykely
dykes
dykesed
dykeser
dykeses
dykesing
dykesly
dykess
erotic
eroticed
eroticer
erotices
eroticing
eroticly
erotics
extacy
extacyed
extacyer
extacyes
extacying
extacyly
extacys
extasy
extasyed
extasyer
extasyes
extasying
extasyly
extasys
fack
facked
facker
fackes
facking
fackly
facks
fag
faged
fager
fages
fagg
fagged
faggeded
faggeder
faggedes
faggeding
faggedly
faggeds
fagger
fagges
fagging
faggit
faggited
faggiter
faggites
faggiting
faggitly
faggits
faggly
faggot
faggoted
faggoter
faggotes
faggoting
faggotly
faggots
faggs
faging
fagly
fagot
fagoted
fagoter
fagotes
fagoting
fagotly
fagots
fags
fagsed
fagser
fagses
fagsing
fagsly
fagss
faig
faiged
faiger
faiges
faiging
faigly
faigs
faigt
faigted
faigter
faigtes
faigting
faigtly
faigts
fannybandit
fannybandited
fannybanditer
fannybandites
fannybanditing
fannybanditly
fannybandits
farted
farter
fartes
farting
fartknocker
fartknockered
fartknockerer
fartknockeres
fartknockering
fartknockerly
fartknockers
fartly
farts
felch
felched
felcher
felchered
felcherer
felcheres
felchering
felcherly
felchers
felches
felching
felchinged
felchinger
felchinges
felchinging
felchingly
felchings
felchly
felchs
fellate
fellateed
fellateer
fellatees
fellateing
fellately
fellates
fellatio
fellatioed
fellatioer
fellatioes
fellatioing
fellatioly
fellatios
feltch
feltched
feltcher
feltchered
feltcherer
feltcheres
feltchering
feltcherly
feltchers
feltches
feltching
feltchly
feltchs
feom
feomed
feomer
feomes
feoming
feomly
feoms
fisted
fisteded
fisteder
fistedes
fisteding
fistedly
fisteds
fisting
fistinged
fistinger
fistinges
fistinging
fistingly
fistings
fisty
fistyed
fistyer
fistyes
fistying
fistyly
fistys
floozy
floozyed
floozyer
floozyes
floozying
floozyly
floozys
foad
foaded
foader
foades
foading
foadly
foads
fondleed
fondleer
fondlees
fondleing
fondlely
fondles
foobar
foobared
foobarer
foobares
foobaring
foobarly
foobars
freex
freexed
freexer
freexes
freexing
freexly
freexs
frigg
frigga
friggaed
friggaer
friggaes
friggaing
friggaly
friggas
frigged
frigger
frigges
frigging
friggly
friggs
fubar
fubared
fubarer
fubares
fubaring
fubarly
fubars
fuck
fuckass
fuckassed
fuckasser
fuckasses
fuckassing
fuckassly
fuckasss
fucked
fuckeded
fuckeder
fuckedes
fuckeding
fuckedly
fuckeds
fucker
fuckered
fuckerer
fuckeres
fuckering
fuckerly
fuckers
fuckes
fuckface
fuckfaceed
fuckfaceer
fuckfacees
fuckfaceing
fuckfacely
fuckfaces
fuckin
fuckined
fuckiner
fuckines
fucking
fuckinged
fuckinger
fuckinges
fuckinging
fuckingly
fuckings
fuckining
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Three Sisters Embrace ‘Collaborative Spirit’ of GI Science
They all share the same genes—and job title.
Each has her own lab, working in different specialties. But if one sister needs the others, it’s reassuring to know they’re not far away.
“We have very different points of view. I’m interested in microbes. Amy’s really interested in myosin mediated trafficking and Kristen’s interested in viruses and purinergic signaling. It’s awesome that we can all work in the same field but have very different questions. And there’s so many questions that we can tackle,” said Mindy Engevik, the oldest of the trio.
If Mindy’s students need help with staining, she sends them to Amy’s lab. If they need help with calcium signaling and live cell imaging, she’ll send them to Kristen’s lab. “We interchange our expertise a lot,” said Mindy.
It’s nice to have a sister down the hall at work who can advise you on RNA sequencing analysis or immunofluorescence imaging, noted Amy Engevik. “You can ask them: ‘Can you just walk my student through this for a minute?’ Or, could they help with organoid cultures you don’t have time for right now?”
Kristen, who joined her older sisters at MUSC in 2024, observed that “having a little bit of the variety with our backgrounds and training really helps bring out the collaborative spirit of science.”
In an interview, the Engevik sisters spoke more about their familial network, their shared love of gastroenterology (GI) science, and how they’ve parlayed their expertise into other critical areas of research.
Growing up, did you ever think that you would choose similar career paths? How did you all become interested in GI research?
Mindy Engevik: As kids we were all interested in nature and the world around us. We all liked being outside. Amy and I were obsessed with rocks and classifying plants and rocks. We all had a general interest in science. But I personally didn’t think that all three of us would go into the same thing and that we’d be working together as adults.
Amy Engevik: Once we got into high school and college, we all became very close and we all majored in biology. That set the stage for our interest in science and our love of science. Then, we all kind of fell in love with the GI tract and chose postdocs that were GI focused. Since Mindy and I graduated a year apart, ultimately our goal was to form a lab and work together.
Kristen Engevik: I was interested in science when my sisters were both at college studying for biology and talking about the things they were learning in microbiology and physiology. But I don’t think until I joined the PhD program that I was ever like: ‘Oh yeah, we’re all going to be in science and it’s all going to be one big giant collaborative multi-lab collaboration.’
What do each of you love about the field of gastroenterology?
Mindy Engevik: At our heart, we’re all people that love problem solving. A fun fact about us is on Thursdays once a month, we do a puzzle competition here in Charleston. We’re really into it. But I think we genuinely like the problem-solving nature of the GI tract, and there’s so many diverse questions that you can answer.
Amy Engevik: I love that the scientific community in the GI community is so wonderful. They are very kind, helpful people. Some other fields are more competitive and more cutthroat. I feel like I have such a great network of people to reach out to if I have problems or questions. And I think other fields don’t have such a wonderful welcoming community that is very inclusive and dynamic.
Kristen Engevik: The nice thing with studying the GI tract is all things essentially lead to the gut. You can collaborate with other scientists and go into the gut-brain axis, or there’s the cardiovascular-gut axis and all these different places that you can also go, or different diseases that don’t necessarily seem to originate at the gut but have a lot of effects on the gut. There’s a lot of variation that we can do within GI.
Each of you has focused on a different area of digestive disease. Can each of you briefly discuss your areas of study and any findings or discoveries you’d like to highlight?
Mindy Engevik: My research focuses on microbial-host interactions. We’re really interested in how microbes colonize the gastrointestinal tract, how they interact with mucus – which I think is an important aspect of the gut that sometimes is overlooked – and how their metabolites really impact host health. One thing that I’m particularly proud of is we’ve really been starting to understand the neurotransmitters that bacteria generate and how they influence specific cells within the gut. It’s an exciting time to be doing both microbiology and gut physiology.
Amy Engevik: I study the host side of things; the gastric or the GI epithelium, and how a specific molecular motor contributes to trafficking in the GI tract. Recently, I’ve been going back to some of my PhD work in the stomach. In a high fat diet model, we’re finding that there are early metaplastic changes in the stomach. I think the stomach is very often overlooked within the GI tract. And I think it really sets the stage for the lower GI tract for the microbiome that colonizes the colon and the small intestine. I think that changes in the stomach really should come to the forefront of GI. Those changes have profound impacts on things like colorectal cancer and inflammatory bowel disease.
Kristen Engevik: I’m also more on the epithelial side with Amy. My new lab’s work is going to be focusing on understanding cell communications, specifically through extracellular purines, which is known as purinergic signaling, and understanding what the effects are during both homeostasis and disease, since it hasn’t been studied within the gut itself. From my work in postdoctoral training, we found that this communication is important for a lot of aspects, specifically during viral infection. But I have some preliminary data that shows it may also have an important role during disease, like colitis. My lab is interested in understanding what this epithelial communication is and are there ways to increase or decrease the signaling depending on the disease.
You’re all skilled in analyzing bioinformatics data. How do you apply this skill in your GI research?
Mindy Engevik: We all got our PhDs in systems biology and physiology, so we were forced to take computational analysis classes. I remember at the time thinking, ‘Oh, I’m probably not going to use a bunch of this.’ And then it really captured our attention. We realized how valuable it was and how much information you could glean.
We do a lot of work using publicly available data sets. I think there’s a wealth of information out there now with single cell sequencing data and bulk RNA sequencing data of different sites in the GI tract. It’s been a very valuable time to data mine and look especially at inflammatory bowel disease and colorectal cancer. We’ve been really focused on all our favorite genes of interest. I’ve been looking at a lot of the mucins and IBD (inflammatory bowel disease) and cancer. Amy’s been looking at Myosin-Vb and other myosin and binding partners like Rabs, and Kristen has been looking at purinergic signaling receptors.
All three of you recently worked together to identify a possible genetic driver of uterine corpus endometrial cancer, the fourth deadliest cancer in women. Where are you in the research process right now?
Mindy Engevik: Our mom was diagnosed with cancer, so we took quite a bit of time off to go to California to help her with her chemotherapy, surgery, and radiation. While we were there, we decided to do some computational analyses of cancers that affect women as our way to deal with this devastating disease. We were really fascinated to find that Myosin-Vb, which is Amy’s favorite gene of interest, was highly up-regulated in tumors from uterine and corpus endometrial cancer.
This was independent of the age of the patient, the stage of the cancer, the grade of the tumors. We figured out that the promoter region of the gene was hypomethylated, so it was having a higher expression. And that led to changes in metabolism and it linked very closely with what we were seeing in the gut, what Myosin-Vb was doing. We have some uterine cancer tumor cells in the lab that we’ve been growing and we’re going to really prove that it’s Myosin-Vb that’s driving some of these metabolism phenotypes. And the nice thing is at least there is a Myosin-Vb inhibitor available.
We also have a paper under review, identifying what Myosin-Vb is doing in cancer in the colon. So we’re excited to continue both the uterine cancer part but then also the colorectal cancer part using our same processes.
Amy Engevik: We’re going to be generating a mouse model that I think will be helpful since it’s in vivo. Sometimes things in vivo behave very differently than they do in vitro, so I think it’ll be a nice coupling of in vitro data with in vivo, taking that computational base and expanding it into more mechanistic studies and more experimental approaches where we can actually develop uterine cancer in the mice and then see if we can knock out Myosin-Vb specifically in that tissue and prevent it from either happening in the first place or decrease its pathogenesis.
What challenges have you faced in your career? How do you offer each other support?
Mindy Engevik: I think for any female scientists trying to have an independent career, there are some hurdles. An article in Nature recently stated that women receive less credit than their male counterparts and another article in Science demonstrated that women who are last authors on publications are cited less. That’s something that all women must deal with everywhere. I think it’s been incredibly helpful for us since there’s three of us. I think it gives us extra visibility in the field.
Amy Engevik: There’s a lot of microaggressions and things that can hinder your career success. I think that we’ve definitely had that. And I think the academic landscape is changing a little bit now that more women are becoming principal investigators and then rising through the ranks of academia. So I think there’s a lot of hope for the future women, but I think it’s still quite challenging.
Kristen Engevik: Things do seem to be getting better as there are more women as faculty members in certain departments. Science is getting better as things progress. However, there are still a lot of difficulties in trying to get credit for what you do, and getting the promotions.
Mindy Engevik: We have a built-in sisterhood, if you will. So I’m always going to champion Amy or Kristen. If there’s an award that I can nominate them for, I’m always going to do it. If there’s something that I think they should apply for that maybe they hadn’t seen, I’m going to make sure I put it on the radar. I think that’s just incredibly helpful, having people that have your best interest in mind.
Every project we have is basically a big collaboration. We have a lot of papers from our postdocs where we are coauthors. Now, as principal investigators, we have a lot of papers together. And I think in the future you’ll be seeing a lot of coauthored publications from our group as well.
Lightning Round
Texting or talking?
KE: Talking
Favorite city in US besides the one you live in?
AE: Boston
Favorite breakfast?
ME: Biscuits and grits
Place you most want to travel?
KE: Antarctica
Favorite junk food?
AE: French fries
Favorite season?
ME: Fall
Favorite ice cream flavor?
KE: Black raspberry chip
Number of cups of coffee you drink per day?
AE: None, I like Diet Coke
Last movie you watched?
ME: Inside Out 2
If you weren’t a gastroenterologist, what would you be?
KE: National Park ranger
Best Halloween costume you ever wore?
AE: Princess Leia
Favorite type of music?
ME: ABBA
Favorite movie genre?
KE: Romantic comedies
Cat person or dog person?
AE: Neither, I like rabbits
Favorite sport?
ME: Surfing
What song do you have to sing along with when you hear it?
KE: Mama Mia
Introvert or extrovert?
AE: Introvert
Favorite holiday?
ME: Halloween
They all share the same genes—and job title.
Each has her own lab, working in different specialties. But if one sister needs the others, it’s reassuring to know they’re not far away.
“We have very different points of view. I’m interested in microbes. Amy’s really interested in myosin mediated trafficking and Kristen’s interested in viruses and purinergic signaling. It’s awesome that we can all work in the same field but have very different questions. And there’s so many questions that we can tackle,” said Mindy Engevik, the oldest of the trio.
If Mindy’s students need help with staining, she sends them to Amy’s lab. If they need help with calcium signaling and live cell imaging, she’ll send them to Kristen’s lab. “We interchange our expertise a lot,” said Mindy.
It’s nice to have a sister down the hall at work who can advise you on RNA sequencing analysis or immunofluorescence imaging, noted Amy Engevik. “You can ask them: ‘Can you just walk my student through this for a minute?’ Or, could they help with organoid cultures you don’t have time for right now?”
Kristen, who joined her older sisters at MUSC in 2024, observed that “having a little bit of the variety with our backgrounds and training really helps bring out the collaborative spirit of science.”
In an interview, the Engevik sisters spoke more about their familial network, their shared love of gastroenterology (GI) science, and how they’ve parlayed their expertise into other critical areas of research.
Growing up, did you ever think that you would choose similar career paths? How did you all become interested in GI research?
Mindy Engevik: As kids we were all interested in nature and the world around us. We all liked being outside. Amy and I were obsessed with rocks and classifying plants and rocks. We all had a general interest in science. But I personally didn’t think that all three of us would go into the same thing and that we’d be working together as adults.
Amy Engevik: Once we got into high school and college, we all became very close and we all majored in biology. That set the stage for our interest in science and our love of science. Then, we all kind of fell in love with the GI tract and chose postdocs that were GI focused. Since Mindy and I graduated a year apart, ultimately our goal was to form a lab and work together.
Kristen Engevik: I was interested in science when my sisters were both at college studying for biology and talking about the things they were learning in microbiology and physiology. But I don’t think until I joined the PhD program that I was ever like: ‘Oh yeah, we’re all going to be in science and it’s all going to be one big giant collaborative multi-lab collaboration.’
What do each of you love about the field of gastroenterology?
Mindy Engevik: At our heart, we’re all people that love problem solving. A fun fact about us is on Thursdays once a month, we do a puzzle competition here in Charleston. We’re really into it. But I think we genuinely like the problem-solving nature of the GI tract, and there’s so many diverse questions that you can answer.
Amy Engevik: I love that the scientific community in the GI community is so wonderful. They are very kind, helpful people. Some other fields are more competitive and more cutthroat. I feel like I have such a great network of people to reach out to if I have problems or questions. And I think other fields don’t have such a wonderful welcoming community that is very inclusive and dynamic.
Kristen Engevik: The nice thing with studying the GI tract is all things essentially lead to the gut. You can collaborate with other scientists and go into the gut-brain axis, or there’s the cardiovascular-gut axis and all these different places that you can also go, or different diseases that don’t necessarily seem to originate at the gut but have a lot of effects on the gut. There’s a lot of variation that we can do within GI.
Each of you has focused on a different area of digestive disease. Can each of you briefly discuss your areas of study and any findings or discoveries you’d like to highlight?
Mindy Engevik: My research focuses on microbial-host interactions. We’re really interested in how microbes colonize the gastrointestinal tract, how they interact with mucus – which I think is an important aspect of the gut that sometimes is overlooked – and how their metabolites really impact host health. One thing that I’m particularly proud of is we’ve really been starting to understand the neurotransmitters that bacteria generate and how they influence specific cells within the gut. It’s an exciting time to be doing both microbiology and gut physiology.
Amy Engevik: I study the host side of things; the gastric or the GI epithelium, and how a specific molecular motor contributes to trafficking in the GI tract. Recently, I’ve been going back to some of my PhD work in the stomach. In a high fat diet model, we’re finding that there are early metaplastic changes in the stomach. I think the stomach is very often overlooked within the GI tract. And I think it really sets the stage for the lower GI tract for the microbiome that colonizes the colon and the small intestine. I think that changes in the stomach really should come to the forefront of GI. Those changes have profound impacts on things like colorectal cancer and inflammatory bowel disease.
Kristen Engevik: I’m also more on the epithelial side with Amy. My new lab’s work is going to be focusing on understanding cell communications, specifically through extracellular purines, which is known as purinergic signaling, and understanding what the effects are during both homeostasis and disease, since it hasn’t been studied within the gut itself. From my work in postdoctoral training, we found that this communication is important for a lot of aspects, specifically during viral infection. But I have some preliminary data that shows it may also have an important role during disease, like colitis. My lab is interested in understanding what this epithelial communication is and are there ways to increase or decrease the signaling depending on the disease.
You’re all skilled in analyzing bioinformatics data. How do you apply this skill in your GI research?
Mindy Engevik: We all got our PhDs in systems biology and physiology, so we were forced to take computational analysis classes. I remember at the time thinking, ‘Oh, I’m probably not going to use a bunch of this.’ And then it really captured our attention. We realized how valuable it was and how much information you could glean.
We do a lot of work using publicly available data sets. I think there’s a wealth of information out there now with single cell sequencing data and bulk RNA sequencing data of different sites in the GI tract. It’s been a very valuable time to data mine and look especially at inflammatory bowel disease and colorectal cancer. We’ve been really focused on all our favorite genes of interest. I’ve been looking at a lot of the mucins and IBD (inflammatory bowel disease) and cancer. Amy’s been looking at Myosin-Vb and other myosin and binding partners like Rabs, and Kristen has been looking at purinergic signaling receptors.
All three of you recently worked together to identify a possible genetic driver of uterine corpus endometrial cancer, the fourth deadliest cancer in women. Where are you in the research process right now?
Mindy Engevik: Our mom was diagnosed with cancer, so we took quite a bit of time off to go to California to help her with her chemotherapy, surgery, and radiation. While we were there, we decided to do some computational analyses of cancers that affect women as our way to deal with this devastating disease. We were really fascinated to find that Myosin-Vb, which is Amy’s favorite gene of interest, was highly up-regulated in tumors from uterine and corpus endometrial cancer.
This was independent of the age of the patient, the stage of the cancer, the grade of the tumors. We figured out that the promoter region of the gene was hypomethylated, so it was having a higher expression. And that led to changes in metabolism and it linked very closely with what we were seeing in the gut, what Myosin-Vb was doing. We have some uterine cancer tumor cells in the lab that we’ve been growing and we’re going to really prove that it’s Myosin-Vb that’s driving some of these metabolism phenotypes. And the nice thing is at least there is a Myosin-Vb inhibitor available.
We also have a paper under review, identifying what Myosin-Vb is doing in cancer in the colon. So we’re excited to continue both the uterine cancer part but then also the colorectal cancer part using our same processes.
Amy Engevik: We’re going to be generating a mouse model that I think will be helpful since it’s in vivo. Sometimes things in vivo behave very differently than they do in vitro, so I think it’ll be a nice coupling of in vitro data with in vivo, taking that computational base and expanding it into more mechanistic studies and more experimental approaches where we can actually develop uterine cancer in the mice and then see if we can knock out Myosin-Vb specifically in that tissue and prevent it from either happening in the first place or decrease its pathogenesis.
What challenges have you faced in your career? How do you offer each other support?
Mindy Engevik: I think for any female scientists trying to have an independent career, there are some hurdles. An article in Nature recently stated that women receive less credit than their male counterparts and another article in Science demonstrated that women who are last authors on publications are cited less. That’s something that all women must deal with everywhere. I think it’s been incredibly helpful for us since there’s three of us. I think it gives us extra visibility in the field.
Amy Engevik: There’s a lot of microaggressions and things that can hinder your career success. I think that we’ve definitely had that. And I think the academic landscape is changing a little bit now that more women are becoming principal investigators and then rising through the ranks of academia. So I think there’s a lot of hope for the future women, but I think it’s still quite challenging.
Kristen Engevik: Things do seem to be getting better as there are more women as faculty members in certain departments. Science is getting better as things progress. However, there are still a lot of difficulties in trying to get credit for what you do, and getting the promotions.
Mindy Engevik: We have a built-in sisterhood, if you will. So I’m always going to champion Amy or Kristen. If there’s an award that I can nominate them for, I’m always going to do it. If there’s something that I think they should apply for that maybe they hadn’t seen, I’m going to make sure I put it on the radar. I think that’s just incredibly helpful, having people that have your best interest in mind.
Every project we have is basically a big collaboration. We have a lot of papers from our postdocs where we are coauthors. Now, as principal investigators, we have a lot of papers together. And I think in the future you’ll be seeing a lot of coauthored publications from our group as well.
Lightning Round
Texting or talking?
KE: Talking
Favorite city in US besides the one you live in?
AE: Boston
Favorite breakfast?
ME: Biscuits and grits
Place you most want to travel?
KE: Antarctica
Favorite junk food?
AE: French fries
Favorite season?
ME: Fall
Favorite ice cream flavor?
KE: Black raspberry chip
Number of cups of coffee you drink per day?
AE: None, I like Diet Coke
Last movie you watched?
ME: Inside Out 2
If you weren’t a gastroenterologist, what would you be?
KE: National Park ranger
Best Halloween costume you ever wore?
AE: Princess Leia
Favorite type of music?
ME: ABBA
Favorite movie genre?
KE: Romantic comedies
Cat person or dog person?
AE: Neither, I like rabbits
Favorite sport?
ME: Surfing
What song do you have to sing along with when you hear it?
KE: Mama Mia
Introvert or extrovert?
AE: Introvert
Favorite holiday?
ME: Halloween
They all share the same genes—and job title.
Each has her own lab, working in different specialties. But if one sister needs the others, it’s reassuring to know they’re not far away.
“We have very different points of view. I’m interested in microbes. Amy’s really interested in myosin mediated trafficking and Kristen’s interested in viruses and purinergic signaling. It’s awesome that we can all work in the same field but have very different questions. And there’s so many questions that we can tackle,” said Mindy Engevik, the oldest of the trio.
If Mindy’s students need help with staining, she sends them to Amy’s lab. If they need help with calcium signaling and live cell imaging, she’ll send them to Kristen’s lab. “We interchange our expertise a lot,” said Mindy.
It’s nice to have a sister down the hall at work who can advise you on RNA sequencing analysis or immunofluorescence imaging, noted Amy Engevik. “You can ask them: ‘Can you just walk my student through this for a minute?’ Or, could they help with organoid cultures you don’t have time for right now?”
Kristen, who joined her older sisters at MUSC in 2024, observed that “having a little bit of the variety with our backgrounds and training really helps bring out the collaborative spirit of science.”
In an interview, the Engevik sisters spoke more about their familial network, their shared love of gastroenterology (GI) science, and how they’ve parlayed their expertise into other critical areas of research.
Growing up, did you ever think that you would choose similar career paths? How did you all become interested in GI research?
Mindy Engevik: As kids we were all interested in nature and the world around us. We all liked being outside. Amy and I were obsessed with rocks and classifying plants and rocks. We all had a general interest in science. But I personally didn’t think that all three of us would go into the same thing and that we’d be working together as adults.
Amy Engevik: Once we got into high school and college, we all became very close and we all majored in biology. That set the stage for our interest in science and our love of science. Then, we all kind of fell in love with the GI tract and chose postdocs that were GI focused. Since Mindy and I graduated a year apart, ultimately our goal was to form a lab and work together.
Kristen Engevik: I was interested in science when my sisters were both at college studying for biology and talking about the things they were learning in microbiology and physiology. But I don’t think until I joined the PhD program that I was ever like: ‘Oh yeah, we’re all going to be in science and it’s all going to be one big giant collaborative multi-lab collaboration.’
What do each of you love about the field of gastroenterology?
Mindy Engevik: At our heart, we’re all people that love problem solving. A fun fact about us is on Thursdays once a month, we do a puzzle competition here in Charleston. We’re really into it. But I think we genuinely like the problem-solving nature of the GI tract, and there’s so many diverse questions that you can answer.
Amy Engevik: I love that the scientific community in the GI community is so wonderful. They are very kind, helpful people. Some other fields are more competitive and more cutthroat. I feel like I have such a great network of people to reach out to if I have problems or questions. And I think other fields don’t have such a wonderful welcoming community that is very inclusive and dynamic.
Kristen Engevik: The nice thing with studying the GI tract is all things essentially lead to the gut. You can collaborate with other scientists and go into the gut-brain axis, or there’s the cardiovascular-gut axis and all these different places that you can also go, or different diseases that don’t necessarily seem to originate at the gut but have a lot of effects on the gut. There’s a lot of variation that we can do within GI.
Each of you has focused on a different area of digestive disease. Can each of you briefly discuss your areas of study and any findings or discoveries you’d like to highlight?
Mindy Engevik: My research focuses on microbial-host interactions. We’re really interested in how microbes colonize the gastrointestinal tract, how they interact with mucus – which I think is an important aspect of the gut that sometimes is overlooked – and how their metabolites really impact host health. One thing that I’m particularly proud of is we’ve really been starting to understand the neurotransmitters that bacteria generate and how they influence specific cells within the gut. It’s an exciting time to be doing both microbiology and gut physiology.
Amy Engevik: I study the host side of things; the gastric or the GI epithelium, and how a specific molecular motor contributes to trafficking in the GI tract. Recently, I’ve been going back to some of my PhD work in the stomach. In a high fat diet model, we’re finding that there are early metaplastic changes in the stomach. I think the stomach is very often overlooked within the GI tract. And I think it really sets the stage for the lower GI tract for the microbiome that colonizes the colon and the small intestine. I think that changes in the stomach really should come to the forefront of GI. Those changes have profound impacts on things like colorectal cancer and inflammatory bowel disease.
Kristen Engevik: I’m also more on the epithelial side with Amy. My new lab’s work is going to be focusing on understanding cell communications, specifically through extracellular purines, which is known as purinergic signaling, and understanding what the effects are during both homeostasis and disease, since it hasn’t been studied within the gut itself. From my work in postdoctoral training, we found that this communication is important for a lot of aspects, specifically during viral infection. But I have some preliminary data that shows it may also have an important role during disease, like colitis. My lab is interested in understanding what this epithelial communication is and are there ways to increase or decrease the signaling depending on the disease.
You’re all skilled in analyzing bioinformatics data. How do you apply this skill in your GI research?
Mindy Engevik: We all got our PhDs in systems biology and physiology, so we were forced to take computational analysis classes. I remember at the time thinking, ‘Oh, I’m probably not going to use a bunch of this.’ And then it really captured our attention. We realized how valuable it was and how much information you could glean.
We do a lot of work using publicly available data sets. I think there’s a wealth of information out there now with single cell sequencing data and bulk RNA sequencing data of different sites in the GI tract. It’s been a very valuable time to data mine and look especially at inflammatory bowel disease and colorectal cancer. We’ve been really focused on all our favorite genes of interest. I’ve been looking at a lot of the mucins and IBD (inflammatory bowel disease) and cancer. Amy’s been looking at Myosin-Vb and other myosin and binding partners like Rabs, and Kristen has been looking at purinergic signaling receptors.
All three of you recently worked together to identify a possible genetic driver of uterine corpus endometrial cancer, the fourth deadliest cancer in women. Where are you in the research process right now?
Mindy Engevik: Our mom was diagnosed with cancer, so we took quite a bit of time off to go to California to help her with her chemotherapy, surgery, and radiation. While we were there, we decided to do some computational analyses of cancers that affect women as our way to deal with this devastating disease. We were really fascinated to find that Myosin-Vb, which is Amy’s favorite gene of interest, was highly up-regulated in tumors from uterine and corpus endometrial cancer.
This was independent of the age of the patient, the stage of the cancer, the grade of the tumors. We figured out that the promoter region of the gene was hypomethylated, so it was having a higher expression. And that led to changes in metabolism and it linked very closely with what we were seeing in the gut, what Myosin-Vb was doing. We have some uterine cancer tumor cells in the lab that we’ve been growing and we’re going to really prove that it’s Myosin-Vb that’s driving some of these metabolism phenotypes. And the nice thing is at least there is a Myosin-Vb inhibitor available.
We also have a paper under review, identifying what Myosin-Vb is doing in cancer in the colon. So we’re excited to continue both the uterine cancer part but then also the colorectal cancer part using our same processes.
Amy Engevik: We’re going to be generating a mouse model that I think will be helpful since it’s in vivo. Sometimes things in vivo behave very differently than they do in vitro, so I think it’ll be a nice coupling of in vitro data with in vivo, taking that computational base and expanding it into more mechanistic studies and more experimental approaches where we can actually develop uterine cancer in the mice and then see if we can knock out Myosin-Vb specifically in that tissue and prevent it from either happening in the first place or decrease its pathogenesis.
What challenges have you faced in your career? How do you offer each other support?
Mindy Engevik: I think for any female scientists trying to have an independent career, there are some hurdles. An article in Nature recently stated that women receive less credit than their male counterparts and another article in Science demonstrated that women who are last authors on publications are cited less. That’s something that all women must deal with everywhere. I think it’s been incredibly helpful for us since there’s three of us. I think it gives us extra visibility in the field.
Amy Engevik: There’s a lot of microaggressions and things that can hinder your career success. I think that we’ve definitely had that. And I think the academic landscape is changing a little bit now that more women are becoming principal investigators and then rising through the ranks of academia. So I think there’s a lot of hope for the future women, but I think it’s still quite challenging.
Kristen Engevik: Things do seem to be getting better as there are more women as faculty members in certain departments. Science is getting better as things progress. However, there are still a lot of difficulties in trying to get credit for what you do, and getting the promotions.
Mindy Engevik: We have a built-in sisterhood, if you will. So I’m always going to champion Amy or Kristen. If there’s an award that I can nominate them for, I’m always going to do it. If there’s something that I think they should apply for that maybe they hadn’t seen, I’m going to make sure I put it on the radar. I think that’s just incredibly helpful, having people that have your best interest in mind.
Every project we have is basically a big collaboration. We have a lot of papers from our postdocs where we are coauthors. Now, as principal investigators, we have a lot of papers together. And I think in the future you’ll be seeing a lot of coauthored publications from our group as well.
Lightning Round
Texting or talking?
KE: Talking
Favorite city in US besides the one you live in?
AE: Boston
Favorite breakfast?
ME: Biscuits and grits
Place you most want to travel?
KE: Antarctica
Favorite junk food?
AE: French fries
Favorite season?
ME: Fall
Favorite ice cream flavor?
KE: Black raspberry chip
Number of cups of coffee you drink per day?
AE: None, I like Diet Coke
Last movie you watched?
ME: Inside Out 2
If you weren’t a gastroenterologist, what would you be?
KE: National Park ranger
Best Halloween costume you ever wore?
AE: Princess Leia
Favorite type of music?
ME: ABBA
Favorite movie genre?
KE: Romantic comedies
Cat person or dog person?
AE: Neither, I like rabbits
Favorite sport?
ME: Surfing
What song do you have to sing along with when you hear it?
KE: Mama Mia
Introvert or extrovert?
AE: Introvert
Favorite holiday?
ME: Halloween
Searching for the Optimal CRC Surveillance Test
About a third of the US population are eligible for colorectal cancer screening but aren’t up to date on screening.
Many patients are reluctant to test for colon cancer for a variety of reasons, said Jeffrey K. Lee, MD, MPH, a research scientist at the Kaiser Permanente Northern California Division of Research and an attending gastroenterologist at Kaiser Permanente San Francisco Medical Center.
“As a gastroenterologist, I strongly believe we should emphasize the importance of colorectal cancer screening. And there’s many tests available, not just a colonoscopy, to help reduce your chances of developing colorectal cancer and even dying from colorectal cancer,” said Dr. Lee.
Many patients prefer a test that’s more convenient, that doesn’t require them to take time out of their busy schedules. “We must educate our patients that there are some noninvasive screening options that are helpful, and to be able to share with them some of the benefits, but also some of the drawbacks compared to colonoscopy and allow them to have a choice,” he advised.
He is a recipient of the AGA Research Scholar Award, and has in turn supported other researchers by contributing to the AGA Research Foundation. In 2012, Dr. Lee received a grant from the Sylvia Allison Kaplan Clinical Research Fund to fund a study on long-term colorectal cancer risk in patients with normal colonoscopy results.
The findings, published in JAMA Internal Medicine, determined that 10 years after a negative colonoscopy, Kaiser Permanente members had a 46% lower risk of being diagnosed with CRC and were 88% less likely to die from disease compared with patients who didn’t undergo screening.
“Furthermore, the reduced risk of developing colorectal cancer, even dying from it, persisted for more than 12 years after the examination compared with an unscreened population,” said Dr. Lee. “I firmly believe our study really supports the ten-year screening interval after a normal colonoscopy, as currently recommended by our guidelines.”
In an interview, he discussed his research efforts to find the best detection regimens for CRC, and the mentors who guided his career path as a GI scientist.
Q: Why did you choose GI?
During medical school I was fortunate to work in the lab of Dr. John M. Carethers at UC San Diego. He introduced me to GI and inspired me to choose GI as a career. His mentorship was invaluable because he not only solidified my interest in GI, but also inspired me to become a physician scientist, focusing on colorectal cancer prevention and control. His amazing mentorship drew me to this field.
Q: One of your clinical focus areas is hereditary gastrointestinal cancer syndromes. How did you become interested in this area of GI medicine?
My interest in hereditary GI cancer syndromes stemmed from my work as a medical student in Dr. Carethers’ lab. One of my research projects was looking at certain gene mutations among patients with hereditary GI cancer syndromes, specifically, familial hamartomatous polyposis syndrome. It was through these research projects and seeing how these genetic mutations impacted their risk of developing colorectal cancer, inspired me to care for patients with hereditary GI cancer syndromes.
Q: Have you been doing any research on the reasons why more young people are getting colon cancer?
We recently published work looking at the potential factors that may be driving the rising rates of early onset colorectal cancer. One hypothesis that’s been floating around is antibiotic exposure in early adulthood or childhood because of its effect on the microbiome. Using our large database at Kaiser Permanente Northern California, we did not find an association between oral antibiotic use during early adulthood and the risk of early-onset colorectal cancer.
You have the usual suspects like obesity and diabetes, but it’s not explaining all that risk. While familial colorectal cancer syndromes contribute to a small proportion of early-onset colorectal, these syndromes are not increasing across generations. I really do feel it’s something in the diet or how foods are processed and environmental factors that’s driving some of the risk of early onset colorectal cancer and this should be explored further.
Q: In 2018, you issued a landmark study which found an association between a 10-year follow-up after negative colonoscopy and reduced risk of disease and mortality. Has there been any updates to these findings over the last 6 years?
We recently saw a study in JAMA Oncology of a Swedish cohort that showed a negative colonoscopy result was associated with a reduced risk of developing and even dying from colorectal cancer 15 years from that examination, compared to the general population of Sweden. I think there’s some things that we need to be cautious about regarding that study. We have to think about the comparison group that they used and the lack of information regarding the indication of the colonoscopy and the quality of the examination. So, it remains uncertain whether future guidelines are going to stretch out that 10-year interval to 15 years.
Q: What other CRC studies are you working on now?
We have several studies that we are working on right now. One is called the PREVENT CRC study, which is looking at whether a polygenic risk score can improve risk stratification following adenoma removal for colorectal cancer prevention and tailoring post-polypectomy surveillance. This is a large observational cohort study that we have teamed up with the Fred Hutchinson Cancer Center, Erasmus University, and Kaiser Permanente Northwest to answer this important question that may have implications for personalized medicine.
Then there’s the COOP study, funded by the Patient-Centered Outcomes Research Institute. This is looking at the best surveillance test to use among older adults 65 years and older with a history of polyps. The trial is randomizing them to either getting a colonoscopy for surveillance or annual fecal immunochemical test (FIT) for surveillance. This is to see which test is best for detecting colorectal cancer among older adults with a history of polyps.
Q: Do you think FIT tests could eventually replace colonoscopy, given that it’s less invasive?
Although FIT and other stool-based tests are less invasive and have been shown to have high accuracy for detecting colorectal cancer, I personally do not think they are going to replace colonoscopy as the most popular screening modality in the United States. Colonoscopy remains the gold standard for detecting and removing precancerous polyps and has the highest accuracy for detecting colorectal cancer.
Q: Besides Dr. Carethers, what teacher or mentor had the greatest impact on you?
Clinically it’s been Dr. Jonathan Terdiman from UCSF, who taught me everything I know about clinical GI, and the art of colonoscopy. In addition, Douglas A. Corley, MD, PhD, the Permanente Medical Group’s chief research officer, has made the greatest impact on my research career. He’s really taught me how to rigorously design a research study to answer important clinically relevant questions, and has given me the skill set to write NIH grants. I would not be here without these mentors who are truly giants in the field of GI.
Q: When you’re not being a GI, how do you spend your free weekend afternoons? Are you still a “Cal Bears” fan at your alma mater, UC Berkeley?
I spend a lot of time taking my kids to their activities on the weekends. I just took my son to a Cal Bears Game Day, which was hosted by ESPN at Berkeley.
It was an incredible experience hearing sports analyst Pat McAfee lead all the Cal chants, seeing Nick Saban from the University of Alabama take off his red tie and replace it with a Cal Bears tie, and watching a Cal student win a hundred thousand dollars by kicking a football through the goal posts wearing checkered vans.
Lightning Round
Texting or talking?
Text
Favorite breakfast?
Taiwanese breakfast
Place you most want to travel to?
Japan
Favorite junk food?
Trader Joe’s chili lime chips
Favorite season?
Springtime, baseball season
Favorite ice cream flavor?
Mint chocolate chip
How many cups of coffee do you drink per day?
2-3
Last movie you watched?
Oppenheimer
Best place you ever went on vacation?
Hawaii
If you weren’t a gastroenterologist, what would you be?
Barber
Best Halloween costume you ever wore?
SpongeBob SquarePants
Favorite sport?
Tennis
What song do you have to sing along with when you hear it?
Any classic 80s song
Introvert or extrovert?
Introvert
About a third of the US population are eligible for colorectal cancer screening but aren’t up to date on screening.
Many patients are reluctant to test for colon cancer for a variety of reasons, said Jeffrey K. Lee, MD, MPH, a research scientist at the Kaiser Permanente Northern California Division of Research and an attending gastroenterologist at Kaiser Permanente San Francisco Medical Center.
“As a gastroenterologist, I strongly believe we should emphasize the importance of colorectal cancer screening. And there’s many tests available, not just a colonoscopy, to help reduce your chances of developing colorectal cancer and even dying from colorectal cancer,” said Dr. Lee.
Many patients prefer a test that’s more convenient, that doesn’t require them to take time out of their busy schedules. “We must educate our patients that there are some noninvasive screening options that are helpful, and to be able to share with them some of the benefits, but also some of the drawbacks compared to colonoscopy and allow them to have a choice,” he advised.
He is a recipient of the AGA Research Scholar Award, and has in turn supported other researchers by contributing to the AGA Research Foundation. In 2012, Dr. Lee received a grant from the Sylvia Allison Kaplan Clinical Research Fund to fund a study on long-term colorectal cancer risk in patients with normal colonoscopy results.
The findings, published in JAMA Internal Medicine, determined that 10 years after a negative colonoscopy, Kaiser Permanente members had a 46% lower risk of being diagnosed with CRC and were 88% less likely to die from disease compared with patients who didn’t undergo screening.
“Furthermore, the reduced risk of developing colorectal cancer, even dying from it, persisted for more than 12 years after the examination compared with an unscreened population,” said Dr. Lee. “I firmly believe our study really supports the ten-year screening interval after a normal colonoscopy, as currently recommended by our guidelines.”
In an interview, he discussed his research efforts to find the best detection regimens for CRC, and the mentors who guided his career path as a GI scientist.
Q: Why did you choose GI?
During medical school I was fortunate to work in the lab of Dr. John M. Carethers at UC San Diego. He introduced me to GI and inspired me to choose GI as a career. His mentorship was invaluable because he not only solidified my interest in GI, but also inspired me to become a physician scientist, focusing on colorectal cancer prevention and control. His amazing mentorship drew me to this field.
Q: One of your clinical focus areas is hereditary gastrointestinal cancer syndromes. How did you become interested in this area of GI medicine?
My interest in hereditary GI cancer syndromes stemmed from my work as a medical student in Dr. Carethers’ lab. One of my research projects was looking at certain gene mutations among patients with hereditary GI cancer syndromes, specifically, familial hamartomatous polyposis syndrome. It was through these research projects and seeing how these genetic mutations impacted their risk of developing colorectal cancer, inspired me to care for patients with hereditary GI cancer syndromes.
Q: Have you been doing any research on the reasons why more young people are getting colon cancer?
We recently published work looking at the potential factors that may be driving the rising rates of early onset colorectal cancer. One hypothesis that’s been floating around is antibiotic exposure in early adulthood or childhood because of its effect on the microbiome. Using our large database at Kaiser Permanente Northern California, we did not find an association between oral antibiotic use during early adulthood and the risk of early-onset colorectal cancer.
You have the usual suspects like obesity and diabetes, but it’s not explaining all that risk. While familial colorectal cancer syndromes contribute to a small proportion of early-onset colorectal, these syndromes are not increasing across generations. I really do feel it’s something in the diet or how foods are processed and environmental factors that’s driving some of the risk of early onset colorectal cancer and this should be explored further.
Q: In 2018, you issued a landmark study which found an association between a 10-year follow-up after negative colonoscopy and reduced risk of disease and mortality. Has there been any updates to these findings over the last 6 years?
We recently saw a study in JAMA Oncology of a Swedish cohort that showed a negative colonoscopy result was associated with a reduced risk of developing and even dying from colorectal cancer 15 years from that examination, compared to the general population of Sweden. I think there’s some things that we need to be cautious about regarding that study. We have to think about the comparison group that they used and the lack of information regarding the indication of the colonoscopy and the quality of the examination. So, it remains uncertain whether future guidelines are going to stretch out that 10-year interval to 15 years.
Q: What other CRC studies are you working on now?
We have several studies that we are working on right now. One is called the PREVENT CRC study, which is looking at whether a polygenic risk score can improve risk stratification following adenoma removal for colorectal cancer prevention and tailoring post-polypectomy surveillance. This is a large observational cohort study that we have teamed up with the Fred Hutchinson Cancer Center, Erasmus University, and Kaiser Permanente Northwest to answer this important question that may have implications for personalized medicine.
Then there’s the COOP study, funded by the Patient-Centered Outcomes Research Institute. This is looking at the best surveillance test to use among older adults 65 years and older with a history of polyps. The trial is randomizing them to either getting a colonoscopy for surveillance or annual fecal immunochemical test (FIT) for surveillance. This is to see which test is best for detecting colorectal cancer among older adults with a history of polyps.
Q: Do you think FIT tests could eventually replace colonoscopy, given that it’s less invasive?
Although FIT and other stool-based tests are less invasive and have been shown to have high accuracy for detecting colorectal cancer, I personally do not think they are going to replace colonoscopy as the most popular screening modality in the United States. Colonoscopy remains the gold standard for detecting and removing precancerous polyps and has the highest accuracy for detecting colorectal cancer.
Q: Besides Dr. Carethers, what teacher or mentor had the greatest impact on you?
Clinically it’s been Dr. Jonathan Terdiman from UCSF, who taught me everything I know about clinical GI, and the art of colonoscopy. In addition, Douglas A. Corley, MD, PhD, the Permanente Medical Group’s chief research officer, has made the greatest impact on my research career. He’s really taught me how to rigorously design a research study to answer important clinically relevant questions, and has given me the skill set to write NIH grants. I would not be here without these mentors who are truly giants in the field of GI.
Q: When you’re not being a GI, how do you spend your free weekend afternoons? Are you still a “Cal Bears” fan at your alma mater, UC Berkeley?
I spend a lot of time taking my kids to their activities on the weekends. I just took my son to a Cal Bears Game Day, which was hosted by ESPN at Berkeley.
It was an incredible experience hearing sports analyst Pat McAfee lead all the Cal chants, seeing Nick Saban from the University of Alabama take off his red tie and replace it with a Cal Bears tie, and watching a Cal student win a hundred thousand dollars by kicking a football through the goal posts wearing checkered vans.
Lightning Round
Texting or talking?
Text
Favorite breakfast?
Taiwanese breakfast
Place you most want to travel to?
Japan
Favorite junk food?
Trader Joe’s chili lime chips
Favorite season?
Springtime, baseball season
Favorite ice cream flavor?
Mint chocolate chip
How many cups of coffee do you drink per day?
2-3
Last movie you watched?
Oppenheimer
Best place you ever went on vacation?
Hawaii
If you weren’t a gastroenterologist, what would you be?
Barber
Best Halloween costume you ever wore?
SpongeBob SquarePants
Favorite sport?
Tennis
What song do you have to sing along with when you hear it?
Any classic 80s song
Introvert or extrovert?
Introvert
About a third of the US population are eligible for colorectal cancer screening but aren’t up to date on screening.
Many patients are reluctant to test for colon cancer for a variety of reasons, said Jeffrey K. Lee, MD, MPH, a research scientist at the Kaiser Permanente Northern California Division of Research and an attending gastroenterologist at Kaiser Permanente San Francisco Medical Center.
“As a gastroenterologist, I strongly believe we should emphasize the importance of colorectal cancer screening. And there’s many tests available, not just a colonoscopy, to help reduce your chances of developing colorectal cancer and even dying from colorectal cancer,” said Dr. Lee.
Many patients prefer a test that’s more convenient, that doesn’t require them to take time out of their busy schedules. “We must educate our patients that there are some noninvasive screening options that are helpful, and to be able to share with them some of the benefits, but also some of the drawbacks compared to colonoscopy and allow them to have a choice,” he advised.
He is a recipient of the AGA Research Scholar Award, and has in turn supported other researchers by contributing to the AGA Research Foundation. In 2012, Dr. Lee received a grant from the Sylvia Allison Kaplan Clinical Research Fund to fund a study on long-term colorectal cancer risk in patients with normal colonoscopy results.
The findings, published in JAMA Internal Medicine, determined that 10 years after a negative colonoscopy, Kaiser Permanente members had a 46% lower risk of being diagnosed with CRC and were 88% less likely to die from disease compared with patients who didn’t undergo screening.
“Furthermore, the reduced risk of developing colorectal cancer, even dying from it, persisted for more than 12 years after the examination compared with an unscreened population,” said Dr. Lee. “I firmly believe our study really supports the ten-year screening interval after a normal colonoscopy, as currently recommended by our guidelines.”
In an interview, he discussed his research efforts to find the best detection regimens for CRC, and the mentors who guided his career path as a GI scientist.
Q: Why did you choose GI?
During medical school I was fortunate to work in the lab of Dr. John M. Carethers at UC San Diego. He introduced me to GI and inspired me to choose GI as a career. His mentorship was invaluable because he not only solidified my interest in GI, but also inspired me to become a physician scientist, focusing on colorectal cancer prevention and control. His amazing mentorship drew me to this field.
Q: One of your clinical focus areas is hereditary gastrointestinal cancer syndromes. How did you become interested in this area of GI medicine?
My interest in hereditary GI cancer syndromes stemmed from my work as a medical student in Dr. Carethers’ lab. One of my research projects was looking at certain gene mutations among patients with hereditary GI cancer syndromes, specifically, familial hamartomatous polyposis syndrome. It was through these research projects and seeing how these genetic mutations impacted their risk of developing colorectal cancer, inspired me to care for patients with hereditary GI cancer syndromes.
Q: Have you been doing any research on the reasons why more young people are getting colon cancer?
We recently published work looking at the potential factors that may be driving the rising rates of early onset colorectal cancer. One hypothesis that’s been floating around is antibiotic exposure in early adulthood or childhood because of its effect on the microbiome. Using our large database at Kaiser Permanente Northern California, we did not find an association between oral antibiotic use during early adulthood and the risk of early-onset colorectal cancer.
You have the usual suspects like obesity and diabetes, but it’s not explaining all that risk. While familial colorectal cancer syndromes contribute to a small proportion of early-onset colorectal, these syndromes are not increasing across generations. I really do feel it’s something in the diet or how foods are processed and environmental factors that’s driving some of the risk of early onset colorectal cancer and this should be explored further.
Q: In 2018, you issued a landmark study which found an association between a 10-year follow-up after negative colonoscopy and reduced risk of disease and mortality. Has there been any updates to these findings over the last 6 years?
We recently saw a study in JAMA Oncology of a Swedish cohort that showed a negative colonoscopy result was associated with a reduced risk of developing and even dying from colorectal cancer 15 years from that examination, compared to the general population of Sweden. I think there’s some things that we need to be cautious about regarding that study. We have to think about the comparison group that they used and the lack of information regarding the indication of the colonoscopy and the quality of the examination. So, it remains uncertain whether future guidelines are going to stretch out that 10-year interval to 15 years.
Q: What other CRC studies are you working on now?
We have several studies that we are working on right now. One is called the PREVENT CRC study, which is looking at whether a polygenic risk score can improve risk stratification following adenoma removal for colorectal cancer prevention and tailoring post-polypectomy surveillance. This is a large observational cohort study that we have teamed up with the Fred Hutchinson Cancer Center, Erasmus University, and Kaiser Permanente Northwest to answer this important question that may have implications for personalized medicine.
Then there’s the COOP study, funded by the Patient-Centered Outcomes Research Institute. This is looking at the best surveillance test to use among older adults 65 years and older with a history of polyps. The trial is randomizing them to either getting a colonoscopy for surveillance or annual fecal immunochemical test (FIT) for surveillance. This is to see which test is best for detecting colorectal cancer among older adults with a history of polyps.
Q: Do you think FIT tests could eventually replace colonoscopy, given that it’s less invasive?
Although FIT and other stool-based tests are less invasive and have been shown to have high accuracy for detecting colorectal cancer, I personally do not think they are going to replace colonoscopy as the most popular screening modality in the United States. Colonoscopy remains the gold standard for detecting and removing precancerous polyps and has the highest accuracy for detecting colorectal cancer.
Q: Besides Dr. Carethers, what teacher or mentor had the greatest impact on you?
Clinically it’s been Dr. Jonathan Terdiman from UCSF, who taught me everything I know about clinical GI, and the art of colonoscopy. In addition, Douglas A. Corley, MD, PhD, the Permanente Medical Group’s chief research officer, has made the greatest impact on my research career. He’s really taught me how to rigorously design a research study to answer important clinically relevant questions, and has given me the skill set to write NIH grants. I would not be here without these mentors who are truly giants in the field of GI.
Q: When you’re not being a GI, how do you spend your free weekend afternoons? Are you still a “Cal Bears” fan at your alma mater, UC Berkeley?
I spend a lot of time taking my kids to their activities on the weekends. I just took my son to a Cal Bears Game Day, which was hosted by ESPN at Berkeley.
It was an incredible experience hearing sports analyst Pat McAfee lead all the Cal chants, seeing Nick Saban from the University of Alabama take off his red tie and replace it with a Cal Bears tie, and watching a Cal student win a hundred thousand dollars by kicking a football through the goal posts wearing checkered vans.
Lightning Round
Texting or talking?
Text
Favorite breakfast?
Taiwanese breakfast
Place you most want to travel to?
Japan
Favorite junk food?
Trader Joe’s chili lime chips
Favorite season?
Springtime, baseball season
Favorite ice cream flavor?
Mint chocolate chip
How many cups of coffee do you drink per day?
2-3
Last movie you watched?
Oppenheimer
Best place you ever went on vacation?
Hawaii
If you weren’t a gastroenterologist, what would you be?
Barber
Best Halloween costume you ever wore?
SpongeBob SquarePants
Favorite sport?
Tennis
What song do you have to sing along with when you hear it?
Any classic 80s song
Introvert or extrovert?
Introvert
Giving the Smallest GI Transplant Patients a New Lease On Life
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Everyday life for them is a challenge.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Everyday life for them is a challenge.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
The best part about working with kids is that “I get to laugh every day,” said Ke-You (Yoyo) Zhang, MD, clinical assistant professor for pediatrics–gastroenterology and hepatology at Stanford Medicine in California.
Everyday life for them is a challenge.
Dealing with sick children is difficult. “But I think the difference between pediatrics and adults is despite how hard things get, children are the single most resilient people you’re ever going to meet,” she said.
Kids don’t always know they’re sick and they don’t act sick, even when they are. “Every day, I literally get on the floor, I get to play, I get to run around. And truly, I have fun every single day. I get excited to go to work. And I think that’s what makes work not feel like work,” said Dr. Zhang.
In an interview, she discussed the satisfaction of following patients throughout their care continuum and her research to reduce the likelihood of transplant rejection.
She also shared an inspirational story of one young patient who spent his life tied to an IV, and how a transplant exposed him to the normal joys of life, like swimming, going to camp and getting on a plane for the first time.
Q: Why did you choose this subspecialty of pediatric GI?
I think it’s the best subspecialty because I think it combines a lot of the things that I enjoy, which is long-term continuity of care. It’s about growing up with your patients and seeing them through all the various stages of their life, often meeting patients when they’re babies. I get pictures of high school graduations and life milestones and even see some of my patients have families of their own. Becoming a part of their family is very meaningful to me. I also like complexity and acuity, and gastroenterology and hepatology provide those things.
And then lastly, it’s great to be able to exercise procedural skills and constantly learn new procedural skills.
Q: How did you become interested in the field of pediatric intestinal and liver transplantation?
I did all my training here at Stanford. We have one of the largest pediatric transplant centers and we also have a very large intestinal rehabilitation population.
Coming through residency and fellowship, I had a lot of exposure to transplant and intestinal failure, intestinal rehabilitation. I really liked the longitudinal relationship I got to form with my patients. Sometimes they’re in the neonatal ICU, where you’re meeting them in their very first days of life. You follow them through their chronic illness, through transplant and after transplant for many years. You become not just their GI, but the center of their care.
Q: What challenges are unique to this type of transplant work?
Pediatric intestinal failure and intestinal transplant represents an incredibly small subset of children. Oftentimes, they do not get the resources and recognition on a national policy level or even at the hospital level that other gastrointestinal diseases receive. What’s difficult is they are such a small subset but their complexity and their needs are probably in the highest percentile. So that’s a really challenging combination to start with. And there’s only a few centers that specialize in doing intestinal rehabilitation and intestinal transplantation for children in the country.
Developing expertise has been slow. But I think in the last decade or so, our understanding and success with intestinal rehabilitation and intestinal transplantation has really improved, especially at large centers like Stanford. We’ve had a lot of success stories and have not had any graft loss since 2014.
Q: Are these transplants hard to acquire?
Yes, especially when you’re transplanting not just the intestines but the liver as well. You’re waiting for two organs, not just one organ. And on top of that, you’re waiting for an appropriately sized donor; usually a child who’s around the same size or same age who’s passed away. Those organs would have to be a good match. Children can wait multiple years for a transplant.
Q: Is there a success story you’d like to share?
One patient I met in the neonatal ICU had congenital short bowel syndrome. He was born with hardly any intestines. He developed complications of being on long-term intravenous nutrition, which included recurrent central line infections and liver disease. He was never able to eat because he really didn’t have a digestive system that could adequately absorb anything. He had a central line in one of his large veins, so he couldn’t go swimming.
He had to have special adaptive wear to even shower or bathe and couldn’t travel. It’s these types of patients that benefit so much from transplant. Putting any kid through transplant is a massive undertaking and it certainly has risks. But he underwent a successful transplant at the age of 8—not just an intestinal transplant, but a multi-visceral transplant of the liver, intestine, and pancreas. He’s 9 years old now, and no longer needs intravenous nutrition. He ate by mouth for the very first time after transplant. He’s trying all sorts of new foods and he was able to go to a special transplant camp for children. Getting on a plane to Los Angeles, which is where our transplant camp is, was a huge deal.
He was able to swim in the lake. He’s never been able to do that. And he wants to start doing sports this fall. This was really a life-changing story for him.
Q: What advancements lie ahead for this field of work? Have you work on any notable research?
I think our understanding of transplant immunology has really progressed, especially recently. That’s what part of my research is about—using novel therapies to modulate the immune system of pediatric transplant recipients. The No. 1 complication that occurs after intestinal transplant is rejection because obviously you’re implanting somebody else’s organs into a patient.
I am involved in a clinical trial that’s looking at the use of extracellular vesicles that are isolated from hematopoietic stem cells. These vesicles contain various growth factors, anti-inflammatory proteins and tissue repair factors that we are infusing into intestinal transplant patients with the aim to repair the intestinal tissue patients are rejecting.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
My husband and I have an almost 2-year-old little girl. She keeps us busy and I spend my afternoons chasing after a crazy toddler.
Lightning Round
Texting or talking?
Huge texter
Favorite junk food?
French fries
Cat or dog person?
Dog
Favorite ice cream?
Strawberry
If you weren’t a gastroenterologist, what would you be?Florist
Best place you’ve traveled to?
Thailand
Number of cups of coffee you drink per day?
Too many
Favorite city in the US besides the one you live in?
New York City
Favorite sport?
Tennis
Optimist or pessimist?
Optimist
In a Parallel Universe, “I’d Be a Concert Pianist” Says Tennessee GI
She also relishes opportunities to think, to analyze, and solve problems for her patients.
One of her chief interests is inflammatory bowel disease (IBD). It’s reassuring to focus on a field of work “where I know exactly what’s causing the issue, and I can select a therapeutic approach (medication and lifestyle changes) that help a patient achieve remission,” said Dr. Pointer, co-owner and managing partner of Digestive and Liver Health Specialists in Hendersonville, Tenn. She’s also the medical director and a principal investigator of Quality Medical Research in Nashville, and currently serves as chair of the AGA Trainee and Early Career Committee.
Starting her own practice has been just as challenging and rewarding as going through medical school. Medical training does not prepare you for starting your own practice, Dr. Pointer said, so she and her business partner have had to learn as they go. “But I think we’ve done very well. We’ve taken the ups and downs in stride.”
In an interview, Dr. Pointer spoke more about her work in IBD and the ways in which she’s given back to the community through music and mentoring.
Q: Why did you choose GI?
I knew from a very young age that I was going to be a physician. I had always been interested in science. When I got into medical school and became exposed to the different areas, I really liked the cognitive skills where you had to think through a problem or an issue. But I also liked the procedural things as well.
During my internal medicine residency training, I felt that I had a knack for it. As I was looking at different options, I decided on gastroenterology because it combined both cognitive thinking through issues, but also taking it to the next step and intervening through procedures.
Q: During fellowship, your focus was inflammatory bowel disease. What drew your interest to this condition?
There are a lot of different areas within gastroenterology that one can subspecialize in, as we see the full gamut of gastrointestinal and hepatic disorders. But treating some conditions, like functional disorders, means taking more of a ‘trial and error’ approach, and you may not always get the patient a hundred percent better. That’s not to say that we can’t improve a patient’s quality of life, but it’s not always a guarantee.
But inflammatory bowel disease is a little bit different. Because I can point to an exact spot in the intestines that’s causing the problem, it’s very fulfilling for me as a physician to take a patient who is having 10-12 bloody bowel movements a day, to normal form stools and no abdominal pain. They’re able to gain weight and go on about their lives and about their day. So that was why I picked inflammatory bowel disease as my subspecialty.
Q: Tell me about the gastroenterology elective you developed for family medicine residents and undergraduate students. What’s the status of the program now?
I’ve always been interested in teaching and giving back to the next generations. I feel like I had great mentor opportunities and people who helped me along the way. In my previous hospital position, I was able to work with the family medicine department and create an elective through which residents and even undergraduate students could come and shadow and work with me in the clinic and see me performing procedures.
That elective ended once I left that position, at least as far as I’m aware. But in the private practice that I co-own now, we have numerous shadowing opportunities. I was able to give a lecture at Middle Tennessee State University for some students. And through that lecture, many students have reached out to me to shadow. I have allowed them to come shadow and do clinic work as a medical assistant and watch me perform procedures. I have multiple students working with me weekly.
Q: Years ago, you founded the non-profit Enchanted Fingers Piano Lessons, which gave free piano lessons to underserved youth. What was that experience like?
Piano was one of my first loves. In some parallel universe, there’s a Dr. Pointer who is a classical, concert pianist. I started taking piano lessons when I was in early middle school, and I took to it very quickly. I was able to excel. I just loved it. I enjoyed practicing and I still play.
The impetus for starting Enchanted Fingers Piano lessons was because I wanted to give back again to the community. I came from an underserved community. Oftentimes children and young adults in those communities don’t get exposed to extracurricular activities and they don’t even know what they could potentially have a passion for. And I definitely had a passion for piano. I partnered with a church organization and they allowed me to use their church to host these piano lessons, and it was a phenomenal and rewarding experience. I would definitely like to start it up again one day in the future. It was an amazing experience.
It’s actually how I met my husband. He was one of the young adult students who signed up to take lessons. We both still enjoy playing the piano together.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
I’m a creative at heart. I really enjoy sewing and I’m working on a few sewing projects. I just got a serger. It is a machine that helps you finish a seam. It can also be used to sew entire garments. That has been fun, learning how to thread that machine. When I’m not doing that or just relaxing with my family, I do enjoy curling up with a good book. Stephen King is one of my favorite authors.
Lightning Round
Texting or talking?
Talking
Favorite junk food?
Chocolate chip cookies
Cat or dog person?
Cat
Favorite vacation?
Hawaii
How many cups of coffee do you drink per day?
I don’t drink coffee
Favorite ice cream?
Butter pecan
Favorite sport?
I don’t watch sports
Optimist or pessimist?
Optimist
She also relishes opportunities to think, to analyze, and solve problems for her patients.
One of her chief interests is inflammatory bowel disease (IBD). It’s reassuring to focus on a field of work “where I know exactly what’s causing the issue, and I can select a therapeutic approach (medication and lifestyle changes) that help a patient achieve remission,” said Dr. Pointer, co-owner and managing partner of Digestive and Liver Health Specialists in Hendersonville, Tenn. She’s also the medical director and a principal investigator of Quality Medical Research in Nashville, and currently serves as chair of the AGA Trainee and Early Career Committee.
Starting her own practice has been just as challenging and rewarding as going through medical school. Medical training does not prepare you for starting your own practice, Dr. Pointer said, so she and her business partner have had to learn as they go. “But I think we’ve done very well. We’ve taken the ups and downs in stride.”
In an interview, Dr. Pointer spoke more about her work in IBD and the ways in which she’s given back to the community through music and mentoring.
Q: Why did you choose GI?
I knew from a very young age that I was going to be a physician. I had always been interested in science. When I got into medical school and became exposed to the different areas, I really liked the cognitive skills where you had to think through a problem or an issue. But I also liked the procedural things as well.
During my internal medicine residency training, I felt that I had a knack for it. As I was looking at different options, I decided on gastroenterology because it combined both cognitive thinking through issues, but also taking it to the next step and intervening through procedures.
Q: During fellowship, your focus was inflammatory bowel disease. What drew your interest to this condition?
There are a lot of different areas within gastroenterology that one can subspecialize in, as we see the full gamut of gastrointestinal and hepatic disorders. But treating some conditions, like functional disorders, means taking more of a ‘trial and error’ approach, and you may not always get the patient a hundred percent better. That’s not to say that we can’t improve a patient’s quality of life, but it’s not always a guarantee.
But inflammatory bowel disease is a little bit different. Because I can point to an exact spot in the intestines that’s causing the problem, it’s very fulfilling for me as a physician to take a patient who is having 10-12 bloody bowel movements a day, to normal form stools and no abdominal pain. They’re able to gain weight and go on about their lives and about their day. So that was why I picked inflammatory bowel disease as my subspecialty.
Q: Tell me about the gastroenterology elective you developed for family medicine residents and undergraduate students. What’s the status of the program now?
I’ve always been interested in teaching and giving back to the next generations. I feel like I had great mentor opportunities and people who helped me along the way. In my previous hospital position, I was able to work with the family medicine department and create an elective through which residents and even undergraduate students could come and shadow and work with me in the clinic and see me performing procedures.
That elective ended once I left that position, at least as far as I’m aware. But in the private practice that I co-own now, we have numerous shadowing opportunities. I was able to give a lecture at Middle Tennessee State University for some students. And through that lecture, many students have reached out to me to shadow. I have allowed them to come shadow and do clinic work as a medical assistant and watch me perform procedures. I have multiple students working with me weekly.
Q: Years ago, you founded the non-profit Enchanted Fingers Piano Lessons, which gave free piano lessons to underserved youth. What was that experience like?
Piano was one of my first loves. In some parallel universe, there’s a Dr. Pointer who is a classical, concert pianist. I started taking piano lessons when I was in early middle school, and I took to it very quickly. I was able to excel. I just loved it. I enjoyed practicing and I still play.
The impetus for starting Enchanted Fingers Piano lessons was because I wanted to give back again to the community. I came from an underserved community. Oftentimes children and young adults in those communities don’t get exposed to extracurricular activities and they don’t even know what they could potentially have a passion for. And I definitely had a passion for piano. I partnered with a church organization and they allowed me to use their church to host these piano lessons, and it was a phenomenal and rewarding experience. I would definitely like to start it up again one day in the future. It was an amazing experience.
It’s actually how I met my husband. He was one of the young adult students who signed up to take lessons. We both still enjoy playing the piano together.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
I’m a creative at heart. I really enjoy sewing and I’m working on a few sewing projects. I just got a serger. It is a machine that helps you finish a seam. It can also be used to sew entire garments. That has been fun, learning how to thread that machine. When I’m not doing that or just relaxing with my family, I do enjoy curling up with a good book. Stephen King is one of my favorite authors.
Lightning Round
Texting or talking?
Talking
Favorite junk food?
Chocolate chip cookies
Cat or dog person?
Cat
Favorite vacation?
Hawaii
How many cups of coffee do you drink per day?
I don’t drink coffee
Favorite ice cream?
Butter pecan
Favorite sport?
I don’t watch sports
Optimist or pessimist?
Optimist
She also relishes opportunities to think, to analyze, and solve problems for her patients.
One of her chief interests is inflammatory bowel disease (IBD). It’s reassuring to focus on a field of work “where I know exactly what’s causing the issue, and I can select a therapeutic approach (medication and lifestyle changes) that help a patient achieve remission,” said Dr. Pointer, co-owner and managing partner of Digestive and Liver Health Specialists in Hendersonville, Tenn. She’s also the medical director and a principal investigator of Quality Medical Research in Nashville, and currently serves as chair of the AGA Trainee and Early Career Committee.
Starting her own practice has been just as challenging and rewarding as going through medical school. Medical training does not prepare you for starting your own practice, Dr. Pointer said, so she and her business partner have had to learn as they go. “But I think we’ve done very well. We’ve taken the ups and downs in stride.”
In an interview, Dr. Pointer spoke more about her work in IBD and the ways in which she’s given back to the community through music and mentoring.
Q: Why did you choose GI?
I knew from a very young age that I was going to be a physician. I had always been interested in science. When I got into medical school and became exposed to the different areas, I really liked the cognitive skills where you had to think through a problem or an issue. But I also liked the procedural things as well.
During my internal medicine residency training, I felt that I had a knack for it. As I was looking at different options, I decided on gastroenterology because it combined both cognitive thinking through issues, but also taking it to the next step and intervening through procedures.
Q: During fellowship, your focus was inflammatory bowel disease. What drew your interest to this condition?
There are a lot of different areas within gastroenterology that one can subspecialize in, as we see the full gamut of gastrointestinal and hepatic disorders. But treating some conditions, like functional disorders, means taking more of a ‘trial and error’ approach, and you may not always get the patient a hundred percent better. That’s not to say that we can’t improve a patient’s quality of life, but it’s not always a guarantee.
But inflammatory bowel disease is a little bit different. Because I can point to an exact spot in the intestines that’s causing the problem, it’s very fulfilling for me as a physician to take a patient who is having 10-12 bloody bowel movements a day, to normal form stools and no abdominal pain. They’re able to gain weight and go on about their lives and about their day. So that was why I picked inflammatory bowel disease as my subspecialty.
Q: Tell me about the gastroenterology elective you developed for family medicine residents and undergraduate students. What’s the status of the program now?
I’ve always been interested in teaching and giving back to the next generations. I feel like I had great mentor opportunities and people who helped me along the way. In my previous hospital position, I was able to work with the family medicine department and create an elective through which residents and even undergraduate students could come and shadow and work with me in the clinic and see me performing procedures.
That elective ended once I left that position, at least as far as I’m aware. But in the private practice that I co-own now, we have numerous shadowing opportunities. I was able to give a lecture at Middle Tennessee State University for some students. And through that lecture, many students have reached out to me to shadow. I have allowed them to come shadow and do clinic work as a medical assistant and watch me perform procedures. I have multiple students working with me weekly.
Q: Years ago, you founded the non-profit Enchanted Fingers Piano Lessons, which gave free piano lessons to underserved youth. What was that experience like?
Piano was one of my first loves. In some parallel universe, there’s a Dr. Pointer who is a classical, concert pianist. I started taking piano lessons when I was in early middle school, and I took to it very quickly. I was able to excel. I just loved it. I enjoyed practicing and I still play.
The impetus for starting Enchanted Fingers Piano lessons was because I wanted to give back again to the community. I came from an underserved community. Oftentimes children and young adults in those communities don’t get exposed to extracurricular activities and they don’t even know what they could potentially have a passion for. And I definitely had a passion for piano. I partnered with a church organization and they allowed me to use their church to host these piano lessons, and it was a phenomenal and rewarding experience. I would definitely like to start it up again one day in the future. It was an amazing experience.
It’s actually how I met my husband. He was one of the young adult students who signed up to take lessons. We both still enjoy playing the piano together.
Q: When you’re not being a GI, how do you spend your free weekend afternoons?
I’m a creative at heart. I really enjoy sewing and I’m working on a few sewing projects. I just got a serger. It is a machine that helps you finish a seam. It can also be used to sew entire garments. That has been fun, learning how to thread that machine. When I’m not doing that or just relaxing with my family, I do enjoy curling up with a good book. Stephen King is one of my favorite authors.
Lightning Round
Texting or talking?
Talking
Favorite junk food?
Chocolate chip cookies
Cat or dog person?
Cat
Favorite vacation?
Hawaii
How many cups of coffee do you drink per day?
I don’t drink coffee
Favorite ice cream?
Butter pecan
Favorite sport?
I don’t watch sports
Optimist or pessimist?
Optimist
GI Endoscopists Want More Training in Moderate Sedation
PHOENIX — , and a majority would be interested in providing physician-directed propofol sedation, especially after in-person or online training, according to results from an ongoing survey presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
The dwindling supply of anesthesiology professionals in the US puts pressure on endoscopists, Dayna S. Early, MD, professor of medicine in the Gastroenterology Division at the Washington University, director of endoscopy at Barnes-Jewish Hospital, both in St. Louis, and chair of an ACG task force on anesthesia issues, told meeting attendees. However, preliminary results from the survey found that only about 4% of respondents said they used solely endoscopist-directed moderate sedation.
This could be because — as the survey also showed — GI fellows are not receiving adequate training in moderate sedation, which requires no interventions to maintain a patient airway, she reported. About 80% of program directors and 75% of senior fellows responding to the survey said they received training in moderate/conscious sedation during their fellowship.
These numbers are not impressive, said Early.
The Accreditation Council for Graduate Medical Education (ACGME) requires gastroenterology fellows to demonstrate competence in conscious sedation, along with other core skills, she explained. “What if I substituted training in mucosal biopsy or training in colonoscopy with polypectomy, which are other core requirements? I think you’d be shocked.”
The survey was small, with only 92 of 250 program directors and 33 of 655 fellows responding, but Early said the task force continues to collect responses.
Is Existing Training Enough?
Ten percent of fellows who replied to the survey did not participate in any moderate sedation procedures during training. And about a third of program directors said fellows participated in less than 100 such procedures.
“We really don’t know if that’s enough, in this era of competency-based assessment, which really values competency measures over numbers,” said Early.
Of the fellows who did receive training, 37% received hands-on training, a quarter received didactic lecture training, 11% used online modules, and 17% received a combination of the above training methods.
Just two thirds of program directors said they or their fellows were competent in moderate sedation, while close to 70% of fellows judged themselves competent.
While the majority of program directors (80%) knew that training in conscious sedation was a core ACGME requirement, only around a quarter of fellows were aware of the requirement.
Most gastroenterologists rely on anesthesiologists or certified registered nurse anesthetists (CRNAs) to deliver moderate or deep sedation, said Early, citing results from a separate survey sent to practicing clinicians.
Ongoing Shortages of CRNAs and Anesthesiologists
Shortages of anesthesiologists and CRNAs will continue to limit endoscopy procedure volume, especially in rural areas of the US, said Early.
The nation is expected to be short by 450,000 CRNAs this year and by 6300 anesthesiologists within a decade, she reported. Anesthesia providers are burned out or nearing retirement age, and there are not enough residency programs to produce new anesthesiologists at the rate needed to meet the demand, she said.
Gastroenterologists have become reliant on anesthesia providers, but adding a clinician is more expensive and “doesn’t appear to resolve and improve safety as compared with endoscopist-directed sedation for routine procedures,” said Early.
When practicing clinicians were asked if they’d be interested in providing physician-directed propofol sedation, 20% said yes, while 35% said no. But 16% said they would want to provide moderate sedation after completing in-person training, and 19% said they would after completing online training.
It may take time for gastroenterologists to get appropriate training and reduce reliance on anesthesia providers, Early said. But she said it may be increasingly possible in states allowing endoscopist-directed, nurse-administered propofol, and with medications such as remimazolam, a rapid-acting benzodiazepine that has shown similar efficacy and lower adverse event rates than propofol.
There will have to be a really deliberate step in order to take back control of endoscopic sedation from anesthesia and start performing more modest sedation, she said.
Early reported having no conflicts.
A version of this article first appeared on Medscape.com.
PHOENIX — , and a majority would be interested in providing physician-directed propofol sedation, especially after in-person or online training, according to results from an ongoing survey presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
The dwindling supply of anesthesiology professionals in the US puts pressure on endoscopists, Dayna S. Early, MD, professor of medicine in the Gastroenterology Division at the Washington University, director of endoscopy at Barnes-Jewish Hospital, both in St. Louis, and chair of an ACG task force on anesthesia issues, told meeting attendees. However, preliminary results from the survey found that only about 4% of respondents said they used solely endoscopist-directed moderate sedation.
This could be because — as the survey also showed — GI fellows are not receiving adequate training in moderate sedation, which requires no interventions to maintain a patient airway, she reported. About 80% of program directors and 75% of senior fellows responding to the survey said they received training in moderate/conscious sedation during their fellowship.
These numbers are not impressive, said Early.
The Accreditation Council for Graduate Medical Education (ACGME) requires gastroenterology fellows to demonstrate competence in conscious sedation, along with other core skills, she explained. “What if I substituted training in mucosal biopsy or training in colonoscopy with polypectomy, which are other core requirements? I think you’d be shocked.”
The survey was small, with only 92 of 250 program directors and 33 of 655 fellows responding, but Early said the task force continues to collect responses.
Is Existing Training Enough?
Ten percent of fellows who replied to the survey did not participate in any moderate sedation procedures during training. And about a third of program directors said fellows participated in less than 100 such procedures.
“We really don’t know if that’s enough, in this era of competency-based assessment, which really values competency measures over numbers,” said Early.
Of the fellows who did receive training, 37% received hands-on training, a quarter received didactic lecture training, 11% used online modules, and 17% received a combination of the above training methods.
Just two thirds of program directors said they or their fellows were competent in moderate sedation, while close to 70% of fellows judged themselves competent.
While the majority of program directors (80%) knew that training in conscious sedation was a core ACGME requirement, only around a quarter of fellows were aware of the requirement.
Most gastroenterologists rely on anesthesiologists or certified registered nurse anesthetists (CRNAs) to deliver moderate or deep sedation, said Early, citing results from a separate survey sent to practicing clinicians.
Ongoing Shortages of CRNAs and Anesthesiologists
Shortages of anesthesiologists and CRNAs will continue to limit endoscopy procedure volume, especially in rural areas of the US, said Early.
The nation is expected to be short by 450,000 CRNAs this year and by 6300 anesthesiologists within a decade, she reported. Anesthesia providers are burned out or nearing retirement age, and there are not enough residency programs to produce new anesthesiologists at the rate needed to meet the demand, she said.
Gastroenterologists have become reliant on anesthesia providers, but adding a clinician is more expensive and “doesn’t appear to resolve and improve safety as compared with endoscopist-directed sedation for routine procedures,” said Early.
When practicing clinicians were asked if they’d be interested in providing physician-directed propofol sedation, 20% said yes, while 35% said no. But 16% said they would want to provide moderate sedation after completing in-person training, and 19% said they would after completing online training.
It may take time for gastroenterologists to get appropriate training and reduce reliance on anesthesia providers, Early said. But she said it may be increasingly possible in states allowing endoscopist-directed, nurse-administered propofol, and with medications such as remimazolam, a rapid-acting benzodiazepine that has shown similar efficacy and lower adverse event rates than propofol.
There will have to be a really deliberate step in order to take back control of endoscopic sedation from anesthesia and start performing more modest sedation, she said.
Early reported having no conflicts.
A version of this article first appeared on Medscape.com.
PHOENIX — , and a majority would be interested in providing physician-directed propofol sedation, especially after in-person or online training, according to results from an ongoing survey presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
The dwindling supply of anesthesiology professionals in the US puts pressure on endoscopists, Dayna S. Early, MD, professor of medicine in the Gastroenterology Division at the Washington University, director of endoscopy at Barnes-Jewish Hospital, both in St. Louis, and chair of an ACG task force on anesthesia issues, told meeting attendees. However, preliminary results from the survey found that only about 4% of respondents said they used solely endoscopist-directed moderate sedation.
This could be because — as the survey also showed — GI fellows are not receiving adequate training in moderate sedation, which requires no interventions to maintain a patient airway, she reported. About 80% of program directors and 75% of senior fellows responding to the survey said they received training in moderate/conscious sedation during their fellowship.
These numbers are not impressive, said Early.
The Accreditation Council for Graduate Medical Education (ACGME) requires gastroenterology fellows to demonstrate competence in conscious sedation, along with other core skills, she explained. “What if I substituted training in mucosal biopsy or training in colonoscopy with polypectomy, which are other core requirements? I think you’d be shocked.”
The survey was small, with only 92 of 250 program directors and 33 of 655 fellows responding, but Early said the task force continues to collect responses.
Is Existing Training Enough?
Ten percent of fellows who replied to the survey did not participate in any moderate sedation procedures during training. And about a third of program directors said fellows participated in less than 100 such procedures.
“We really don’t know if that’s enough, in this era of competency-based assessment, which really values competency measures over numbers,” said Early.
Of the fellows who did receive training, 37% received hands-on training, a quarter received didactic lecture training, 11% used online modules, and 17% received a combination of the above training methods.
Just two thirds of program directors said they or their fellows were competent in moderate sedation, while close to 70% of fellows judged themselves competent.
While the majority of program directors (80%) knew that training in conscious sedation was a core ACGME requirement, only around a quarter of fellows were aware of the requirement.
Most gastroenterologists rely on anesthesiologists or certified registered nurse anesthetists (CRNAs) to deliver moderate or deep sedation, said Early, citing results from a separate survey sent to practicing clinicians.
Ongoing Shortages of CRNAs and Anesthesiologists
Shortages of anesthesiologists and CRNAs will continue to limit endoscopy procedure volume, especially in rural areas of the US, said Early.
The nation is expected to be short by 450,000 CRNAs this year and by 6300 anesthesiologists within a decade, she reported. Anesthesia providers are burned out or nearing retirement age, and there are not enough residency programs to produce new anesthesiologists at the rate needed to meet the demand, she said.
Gastroenterologists have become reliant on anesthesia providers, but adding a clinician is more expensive and “doesn’t appear to resolve and improve safety as compared with endoscopist-directed sedation for routine procedures,” said Early.
When practicing clinicians were asked if they’d be interested in providing physician-directed propofol sedation, 20% said yes, while 35% said no. But 16% said they would want to provide moderate sedation after completing in-person training, and 19% said they would after completing online training.
It may take time for gastroenterologists to get appropriate training and reduce reliance on anesthesia providers, Early said. But she said it may be increasingly possible in states allowing endoscopist-directed, nurse-administered propofol, and with medications such as remimazolam, a rapid-acting benzodiazepine that has shown similar efficacy and lower adverse event rates than propofol.
There will have to be a really deliberate step in order to take back control of endoscopic sedation from anesthesia and start performing more modest sedation, she said.
Early reported having no conflicts.
A version of this article first appeared on Medscape.com.
FROM ACG 2025
FDA OKs Linzess for IBS With Constipation in Kids
, making it the first approved treatment for pediatric IBS-C.
The recommended dosage in pediatric patients is 145 mcg/d oral linaclotide.
Linaclotide is already approved in the US for IBS-C in adults, as well as functional constipation in children aged 6 years or older and chronic idiopathic constipation in adults.
IBS-C is common in children and adolescents. Symptoms include infrequent bowel movements with hard stools that can be difficult or painful to pass.
There is no known underlying organic cause and there are typically multiple contributing factors, the FDA said in a statement announcing the approval.
The efficacy of linaclotide to treat IBS-C in children aged 7 years or older was supported by extrapolation of efficacy from studies in adults and a 12-week double-blind, randomized, parallel-group trial in pediatric patients aged 7-17 years who met modified Rome III criteria for child/adolescent IBS-C, the FDA noted.
The primary endpoint was the proportion of patients who achieved at least a 30% reduction in abdominal pain and an increase of at least two naturally occurring bowel movements per week from baseline for at least 6 weeks of the 12-week treatment period.
The efficacy results in children with IBS-C were consistent with results seen in adults with IBS-C, with no new safety signals.
The most common side effect with linaclotide is diarrhea. If severe diarrhea occurs, linaclotide should be discontinued and rehydration started.
Linaclotide is contraindicated in children younger than 2 years. Patients with known or suspected mechanical gastrointestinal obstruction should not take linaclotide.
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
, making it the first approved treatment for pediatric IBS-C.
The recommended dosage in pediatric patients is 145 mcg/d oral linaclotide.
Linaclotide is already approved in the US for IBS-C in adults, as well as functional constipation in children aged 6 years or older and chronic idiopathic constipation in adults.
IBS-C is common in children and adolescents. Symptoms include infrequent bowel movements with hard stools that can be difficult or painful to pass.
There is no known underlying organic cause and there are typically multiple contributing factors, the FDA said in a statement announcing the approval.
The efficacy of linaclotide to treat IBS-C in children aged 7 years or older was supported by extrapolation of efficacy from studies in adults and a 12-week double-blind, randomized, parallel-group trial in pediatric patients aged 7-17 years who met modified Rome III criteria for child/adolescent IBS-C, the FDA noted.
The primary endpoint was the proportion of patients who achieved at least a 30% reduction in abdominal pain and an increase of at least two naturally occurring bowel movements per week from baseline for at least 6 weeks of the 12-week treatment period.
The efficacy results in children with IBS-C were consistent with results seen in adults with IBS-C, with no new safety signals.
The most common side effect with linaclotide is diarrhea. If severe diarrhea occurs, linaclotide should be discontinued and rehydration started.
Linaclotide is contraindicated in children younger than 2 years. Patients with known or suspected mechanical gastrointestinal obstruction should not take linaclotide.
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
, making it the first approved treatment for pediatric IBS-C.
The recommended dosage in pediatric patients is 145 mcg/d oral linaclotide.
Linaclotide is already approved in the US for IBS-C in adults, as well as functional constipation in children aged 6 years or older and chronic idiopathic constipation in adults.
IBS-C is common in children and adolescents. Symptoms include infrequent bowel movements with hard stools that can be difficult or painful to pass.
There is no known underlying organic cause and there are typically multiple contributing factors, the FDA said in a statement announcing the approval.
The efficacy of linaclotide to treat IBS-C in children aged 7 years or older was supported by extrapolation of efficacy from studies in adults and a 12-week double-blind, randomized, parallel-group trial in pediatric patients aged 7-17 years who met modified Rome III criteria for child/adolescent IBS-C, the FDA noted.
The primary endpoint was the proportion of patients who achieved at least a 30% reduction in abdominal pain and an increase of at least two naturally occurring bowel movements per week from baseline for at least 6 weeks of the 12-week treatment period.
The efficacy results in children with IBS-C were consistent with results seen in adults with IBS-C, with no new safety signals.
The most common side effect with linaclotide is diarrhea. If severe diarrhea occurs, linaclotide should be discontinued and rehydration started.
Linaclotide is contraindicated in children younger than 2 years. Patients with known or suspected mechanical gastrointestinal obstruction should not take linaclotide.
Full prescribing information is available online.
A version of this article first appeared on Medscape.com.
Chance to Diagnose Eosinophilic Esophagitis in the ED Commonly Missed
PHOENIX — The opportunity to diagnose eosinophilic esophagitis (EoE) when patients present to the emergency department (ED) with the classic symptom of esophageal food impaction (EFI) is commonly missed, with necessary biopsies provided at strikingly low rates, despite guideline recommendations, new research showed.
“This is the first study to assess the rate of biopsies at time of esophageal food impaction in a large, real-world dataset of community practices,” the authors explained in research presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
The findings underscore that “.”
Research shows patients with EoE, a chronic and progressive type 2 inflammatory disease, have an average delay of 4 years before being diagnosed, with a delay of up to 10 years in about a third of cases. With those delays comes the likelihood of disease progression.
The latest guidelines from the ACG indicate that for diagnosis, “from a practical standpoint,” the preferred approach is to obtain at least two to four biopsies from at least two distinct esophageal areas, while targeting areas of visual inflammation.
However, prior evidence suggests that the biopsies are commonly not performed when patients present with the symptoms of EFI.
To further investigate the management of EFI during and after ED visits in a real-world setting, first author Walker D. Redd, MD, Center for Gastrointestinal Biology and Disease, UNC School of Medicine, Chapel Hill, North Carolina, and colleagues conducted a retrospective cohort study of 2566 patients in a multistate gastrointestinal practice group at 143 care centers in seven US states.
The patients were treated for esophageal food or foreign body removal between 2018 and 2024.
Among them, 1434 patients received evaluation with esophagogastroduodenoscopy (EGD), with 754 having no EGD and 378 receiving EGD for non-EFI.
The patients had a mean age of 63, with nearly 60% being older than 60 years, and 44.9% were women.
At the index EGD, only 19% had records of having esophageal biopsies. Among them, nearly half, 47%, were determined to have biopsy-confirmed EoE.
Of those who did not receive biopsies, only 7% had records of having received a follow-up EGD with an esophageal biopsy within 1 year, with 40% of those having EoE confirmed from a biopsy.
Among the remaining 93% of patients who had no record of such follow-up care within 1 year, 41% were lost to follow-up.
“We found that only about one fifth of patients had esophageal biopsies collected at the time of esophageal food impaction, which is similar to previous reports,” Redd said.
Overall, “esophageal biopsy rates at the time of esophageal food impaction remain low, and follow-up EGD with biopsy rates are also very low.”
Responding to a comment from the audience, Redd agreed that a limitation of the study was the scenario of patients from out of town being treated at an ED and then going back home, where their follow-up status may not be known.
Nevertheless, awareness of the low rates “represent an important opportunity to reduce the diagnostic delay and improve quality of care in EoE,” he said.
Commenting on the study, Danny Issa, MD, an interventional gastroenterologist at UCLA Health, agreed that the low rates of follow-up were troubling.
“Only 1 in 10 is a very low rate of follow-up endoscopy,” he told GI & Hepatology News.
“These results show we need to encourage quality improvement initiatives to make sure those patients are followed up,” he said.
Furthermore, “additional studies are needed to better understand the barriers behind the lack of follow-up, which were not addressed fully in the study.”
Co-moderator Sita S. Chokhavatia, MD, AGAF, a gastroenterologist at Valley Medical Group, in Paramus, New Jersey, added that “the point that needs to be made is that these patients need biopsies so you can diagnose and subsequently treat them.”
Redd reported having a consulting relationship with Sanofi. Issa reported having relationships with Boston Scientific and Eli Lilly. Chokhavatia had no disclosures to report.
A version of this article first appeared on Medscape.com.
PHOENIX — The opportunity to diagnose eosinophilic esophagitis (EoE) when patients present to the emergency department (ED) with the classic symptom of esophageal food impaction (EFI) is commonly missed, with necessary biopsies provided at strikingly low rates, despite guideline recommendations, new research showed.
“This is the first study to assess the rate of biopsies at time of esophageal food impaction in a large, real-world dataset of community practices,” the authors explained in research presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
The findings underscore that “.”
Research shows patients with EoE, a chronic and progressive type 2 inflammatory disease, have an average delay of 4 years before being diagnosed, with a delay of up to 10 years in about a third of cases. With those delays comes the likelihood of disease progression.
The latest guidelines from the ACG indicate that for diagnosis, “from a practical standpoint,” the preferred approach is to obtain at least two to four biopsies from at least two distinct esophageal areas, while targeting areas of visual inflammation.
However, prior evidence suggests that the biopsies are commonly not performed when patients present with the symptoms of EFI.
To further investigate the management of EFI during and after ED visits in a real-world setting, first author Walker D. Redd, MD, Center for Gastrointestinal Biology and Disease, UNC School of Medicine, Chapel Hill, North Carolina, and colleagues conducted a retrospective cohort study of 2566 patients in a multistate gastrointestinal practice group at 143 care centers in seven US states.
The patients were treated for esophageal food or foreign body removal between 2018 and 2024.
Among them, 1434 patients received evaluation with esophagogastroduodenoscopy (EGD), with 754 having no EGD and 378 receiving EGD for non-EFI.
The patients had a mean age of 63, with nearly 60% being older than 60 years, and 44.9% were women.
At the index EGD, only 19% had records of having esophageal biopsies. Among them, nearly half, 47%, were determined to have biopsy-confirmed EoE.
Of those who did not receive biopsies, only 7% had records of having received a follow-up EGD with an esophageal biopsy within 1 year, with 40% of those having EoE confirmed from a biopsy.
Among the remaining 93% of patients who had no record of such follow-up care within 1 year, 41% were lost to follow-up.
“We found that only about one fifth of patients had esophageal biopsies collected at the time of esophageal food impaction, which is similar to previous reports,” Redd said.
Overall, “esophageal biopsy rates at the time of esophageal food impaction remain low, and follow-up EGD with biopsy rates are also very low.”
Responding to a comment from the audience, Redd agreed that a limitation of the study was the scenario of patients from out of town being treated at an ED and then going back home, where their follow-up status may not be known.
Nevertheless, awareness of the low rates “represent an important opportunity to reduce the diagnostic delay and improve quality of care in EoE,” he said.
Commenting on the study, Danny Issa, MD, an interventional gastroenterologist at UCLA Health, agreed that the low rates of follow-up were troubling.
“Only 1 in 10 is a very low rate of follow-up endoscopy,” he told GI & Hepatology News.
“These results show we need to encourage quality improvement initiatives to make sure those patients are followed up,” he said.
Furthermore, “additional studies are needed to better understand the barriers behind the lack of follow-up, which were not addressed fully in the study.”
Co-moderator Sita S. Chokhavatia, MD, AGAF, a gastroenterologist at Valley Medical Group, in Paramus, New Jersey, added that “the point that needs to be made is that these patients need biopsies so you can diagnose and subsequently treat them.”
Redd reported having a consulting relationship with Sanofi. Issa reported having relationships with Boston Scientific and Eli Lilly. Chokhavatia had no disclosures to report.
A version of this article first appeared on Medscape.com.
PHOENIX — The opportunity to diagnose eosinophilic esophagitis (EoE) when patients present to the emergency department (ED) with the classic symptom of esophageal food impaction (EFI) is commonly missed, with necessary biopsies provided at strikingly low rates, despite guideline recommendations, new research showed.
“This is the first study to assess the rate of biopsies at time of esophageal food impaction in a large, real-world dataset of community practices,” the authors explained in research presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
The findings underscore that “.”
Research shows patients with EoE, a chronic and progressive type 2 inflammatory disease, have an average delay of 4 years before being diagnosed, with a delay of up to 10 years in about a third of cases. With those delays comes the likelihood of disease progression.
The latest guidelines from the ACG indicate that for diagnosis, “from a practical standpoint,” the preferred approach is to obtain at least two to four biopsies from at least two distinct esophageal areas, while targeting areas of visual inflammation.
However, prior evidence suggests that the biopsies are commonly not performed when patients present with the symptoms of EFI.
To further investigate the management of EFI during and after ED visits in a real-world setting, first author Walker D. Redd, MD, Center for Gastrointestinal Biology and Disease, UNC School of Medicine, Chapel Hill, North Carolina, and colleagues conducted a retrospective cohort study of 2566 patients in a multistate gastrointestinal practice group at 143 care centers in seven US states.
The patients were treated for esophageal food or foreign body removal between 2018 and 2024.
Among them, 1434 patients received evaluation with esophagogastroduodenoscopy (EGD), with 754 having no EGD and 378 receiving EGD for non-EFI.
The patients had a mean age of 63, with nearly 60% being older than 60 years, and 44.9% were women.
At the index EGD, only 19% had records of having esophageal biopsies. Among them, nearly half, 47%, were determined to have biopsy-confirmed EoE.
Of those who did not receive biopsies, only 7% had records of having received a follow-up EGD with an esophageal biopsy within 1 year, with 40% of those having EoE confirmed from a biopsy.
Among the remaining 93% of patients who had no record of such follow-up care within 1 year, 41% were lost to follow-up.
“We found that only about one fifth of patients had esophageal biopsies collected at the time of esophageal food impaction, which is similar to previous reports,” Redd said.
Overall, “esophageal biopsy rates at the time of esophageal food impaction remain low, and follow-up EGD with biopsy rates are also very low.”
Responding to a comment from the audience, Redd agreed that a limitation of the study was the scenario of patients from out of town being treated at an ED and then going back home, where their follow-up status may not be known.
Nevertheless, awareness of the low rates “represent an important opportunity to reduce the diagnostic delay and improve quality of care in EoE,” he said.
Commenting on the study, Danny Issa, MD, an interventional gastroenterologist at UCLA Health, agreed that the low rates of follow-up were troubling.
“Only 1 in 10 is a very low rate of follow-up endoscopy,” he told GI & Hepatology News.
“These results show we need to encourage quality improvement initiatives to make sure those patients are followed up,” he said.
Furthermore, “additional studies are needed to better understand the barriers behind the lack of follow-up, which were not addressed fully in the study.”
Co-moderator Sita S. Chokhavatia, MD, AGAF, a gastroenterologist at Valley Medical Group, in Paramus, New Jersey, added that “the point that needs to be made is that these patients need biopsies so you can diagnose and subsequently treat them.”
Redd reported having a consulting relationship with Sanofi. Issa reported having relationships with Boston Scientific and Eli Lilly. Chokhavatia had no disclosures to report.
A version of this article first appeared on Medscape.com.
FROM ACG 2025
Cholecystectomy Delay Linked to Substantially Increased Complication Risk
, regardless of the receipt of sphincterotomy or stenting, new research showed.
“These findings suggest an opportunity for systemic interventions, including prioritization algorithms and better perioperative coordination, to address preventable delays,” reported the authors in the study, presented at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
Choledocholithiasis can occur in up to 20% of symptomatic gallstone cases, and while guidelines recommend having a cholecystectomy concurrently with ERCP, data on the best timing is inconsistent and delays in gall bladder removal are consequently common.
One large study, for instance, the PONCHO trial conducted at 23 hospitals in Netherlands, showed complications to be significantly lower with same-admission vs interval cholecystectomy (4.7% vs 16.9%; P = .02).
Meanwhile, other research has suggested that delayed cholecystectomy is a preferred approach, allowing for removal when there is less inflammation.
Real world data meanwhile shows, despite the guidelines, the procedures are performed at the same time as ERCP only in about 41% of cases, first author Jessica El Halabi, MD, of the Johns Hopkins Hospital, Baltimore, said.
To further investigate outcomes associated with those delays, El Halabi and colleagues conducted a retrospective cohort study involving 507 patients admitted with choledocholithiasis at the hospital and community hospitals between 2005 and 2023 who had 12 months or more follow-up.
The patients had a mean age of 59 years and 59.4% were women.
Of the patients, 265 (52.3%) underwent early cholecystectomy, defined as surgery during the index admission, while 242 (47.7%) underwent delayed cholecystectomy, defined as postdischarge cholecystectomy or if cholecystectomy was not performed.
Overall, biliary complications occurred in as many as 23% of those who had delayed cholecystectomy compared with just 0.8% among those having the early cholecystectomy (P < .001).
Of patients who had delayed cholecystectomy and developed complications, 15.5% did so within 3 months, 6.5% by 6 months, and 1% by 12 months.
Among those who had ERCP with sphincterotomy, there were no significant differences in rates of biliary complications vs those who did not have sphincterotomy (26% vs 21%; P = .74), while stenting also did not reduce the risk (25% vs 27%; P = .81).
The leading reasons for delayed cholecystectomy included patients having a high surgical risk (27.3%), concurrent biliary pathology (19.2%), and physician preference (14%).
The findings underscore that “concurrent cholecystectomy is associated with the lowest risk of biliary complications,” El Halabi said.
“Delayed cholecystectomy is associated with an approximately 23% incidence of biliary complications with 1 year of initial admission, with the highest incidence occurring within 3 months,” she added. “Neither sphincterotomy nor stenting during ERCP mitigates this risk.”
“Early cholecystectomy during the index admission remains the most reliable strategy to reduce recurrent events.”
Findings Underscore Importance of Timing
Commenting on the study, Luis F. Lara, MD, division chief of digestive diseases at the University of Cincinnati, who co-moderated the session, agreed that evidence soundly supports early cholecystectomy.
“We also did a large study looking at this and there’s no doubt that doing it during the index admission has a tremendous effect on long-term outcomes,” Lara told GI & Hepatology News.
Lara noted that “part of it is people don’t show up again until they get sick again, so we don’t want to lose that opportunity the first time, during the index admission,” he said.
Lara’s previous studies have specifically documented how early cholecystectomy for acute biliary pancreatitis improves outcomes of hospitalization for cirrhosis and factors associated with early unplanned readmissions following same-admission cholecystectomy for acute biliary pancreatitis.
Akwi W. Asombang, MD, an interventional gastroenterologist at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, both in Boston, agreed that the findings are important.
“We know that if a cholecystectomy is not performed in the same admission as ERCP, the stones in the gallbladder remain and may migrate out into the bile duct, resulting in further complications as described in the study,” Asombang, also a session co-moderator, told GI & Hepatology News.
She noted that the practice can vary between institutions based on factors including the availability of physicians to perform the cholecystectomy.
Potential complications in delaying the procedure can range from inflammation and pancreatitis to obstruction of the bile duct, “which then can result in cholangitis and eventually sepsis or even death,” Asombang cautioned.
“So the timing of the procedure with ERCP is definitely significant,” she said.
El Halabi and Asombang had no disclosures to report. Lara reported a relationship with AbbVie.
A version of this article first appeared on Medscape.com.
, regardless of the receipt of sphincterotomy or stenting, new research showed.
“These findings suggest an opportunity for systemic interventions, including prioritization algorithms and better perioperative coordination, to address preventable delays,” reported the authors in the study, presented at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
Choledocholithiasis can occur in up to 20% of symptomatic gallstone cases, and while guidelines recommend having a cholecystectomy concurrently with ERCP, data on the best timing is inconsistent and delays in gall bladder removal are consequently common.
One large study, for instance, the PONCHO trial conducted at 23 hospitals in Netherlands, showed complications to be significantly lower with same-admission vs interval cholecystectomy (4.7% vs 16.9%; P = .02).
Meanwhile, other research has suggested that delayed cholecystectomy is a preferred approach, allowing for removal when there is less inflammation.
Real world data meanwhile shows, despite the guidelines, the procedures are performed at the same time as ERCP only in about 41% of cases, first author Jessica El Halabi, MD, of the Johns Hopkins Hospital, Baltimore, said.
To further investigate outcomes associated with those delays, El Halabi and colleagues conducted a retrospective cohort study involving 507 patients admitted with choledocholithiasis at the hospital and community hospitals between 2005 and 2023 who had 12 months or more follow-up.
The patients had a mean age of 59 years and 59.4% were women.
Of the patients, 265 (52.3%) underwent early cholecystectomy, defined as surgery during the index admission, while 242 (47.7%) underwent delayed cholecystectomy, defined as postdischarge cholecystectomy or if cholecystectomy was not performed.
Overall, biliary complications occurred in as many as 23% of those who had delayed cholecystectomy compared with just 0.8% among those having the early cholecystectomy (P < .001).
Of patients who had delayed cholecystectomy and developed complications, 15.5% did so within 3 months, 6.5% by 6 months, and 1% by 12 months.
Among those who had ERCP with sphincterotomy, there were no significant differences in rates of biliary complications vs those who did not have sphincterotomy (26% vs 21%; P = .74), while stenting also did not reduce the risk (25% vs 27%; P = .81).
The leading reasons for delayed cholecystectomy included patients having a high surgical risk (27.3%), concurrent biliary pathology (19.2%), and physician preference (14%).
The findings underscore that “concurrent cholecystectomy is associated with the lowest risk of biliary complications,” El Halabi said.
“Delayed cholecystectomy is associated with an approximately 23% incidence of biliary complications with 1 year of initial admission, with the highest incidence occurring within 3 months,” she added. “Neither sphincterotomy nor stenting during ERCP mitigates this risk.”
“Early cholecystectomy during the index admission remains the most reliable strategy to reduce recurrent events.”
Findings Underscore Importance of Timing
Commenting on the study, Luis F. Lara, MD, division chief of digestive diseases at the University of Cincinnati, who co-moderated the session, agreed that evidence soundly supports early cholecystectomy.
“We also did a large study looking at this and there’s no doubt that doing it during the index admission has a tremendous effect on long-term outcomes,” Lara told GI & Hepatology News.
Lara noted that “part of it is people don’t show up again until they get sick again, so we don’t want to lose that opportunity the first time, during the index admission,” he said.
Lara’s previous studies have specifically documented how early cholecystectomy for acute biliary pancreatitis improves outcomes of hospitalization for cirrhosis and factors associated with early unplanned readmissions following same-admission cholecystectomy for acute biliary pancreatitis.
Akwi W. Asombang, MD, an interventional gastroenterologist at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, both in Boston, agreed that the findings are important.
“We know that if a cholecystectomy is not performed in the same admission as ERCP, the stones in the gallbladder remain and may migrate out into the bile duct, resulting in further complications as described in the study,” Asombang, also a session co-moderator, told GI & Hepatology News.
She noted that the practice can vary between institutions based on factors including the availability of physicians to perform the cholecystectomy.
Potential complications in delaying the procedure can range from inflammation and pancreatitis to obstruction of the bile duct, “which then can result in cholangitis and eventually sepsis or even death,” Asombang cautioned.
“So the timing of the procedure with ERCP is definitely significant,” she said.
El Halabi and Asombang had no disclosures to report. Lara reported a relationship with AbbVie.
A version of this article first appeared on Medscape.com.
, regardless of the receipt of sphincterotomy or stenting, new research showed.
“These findings suggest an opportunity for systemic interventions, including prioritization algorithms and better perioperative coordination, to address preventable delays,” reported the authors in the study, presented at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
Choledocholithiasis can occur in up to 20% of symptomatic gallstone cases, and while guidelines recommend having a cholecystectomy concurrently with ERCP, data on the best timing is inconsistent and delays in gall bladder removal are consequently common.
One large study, for instance, the PONCHO trial conducted at 23 hospitals in Netherlands, showed complications to be significantly lower with same-admission vs interval cholecystectomy (4.7% vs 16.9%; P = .02).
Meanwhile, other research has suggested that delayed cholecystectomy is a preferred approach, allowing for removal when there is less inflammation.
Real world data meanwhile shows, despite the guidelines, the procedures are performed at the same time as ERCP only in about 41% of cases, first author Jessica El Halabi, MD, of the Johns Hopkins Hospital, Baltimore, said.
To further investigate outcomes associated with those delays, El Halabi and colleagues conducted a retrospective cohort study involving 507 patients admitted with choledocholithiasis at the hospital and community hospitals between 2005 and 2023 who had 12 months or more follow-up.
The patients had a mean age of 59 years and 59.4% were women.
Of the patients, 265 (52.3%) underwent early cholecystectomy, defined as surgery during the index admission, while 242 (47.7%) underwent delayed cholecystectomy, defined as postdischarge cholecystectomy or if cholecystectomy was not performed.
Overall, biliary complications occurred in as many as 23% of those who had delayed cholecystectomy compared with just 0.8% among those having the early cholecystectomy (P < .001).
Of patients who had delayed cholecystectomy and developed complications, 15.5% did so within 3 months, 6.5% by 6 months, and 1% by 12 months.
Among those who had ERCP with sphincterotomy, there were no significant differences in rates of biliary complications vs those who did not have sphincterotomy (26% vs 21%; P = .74), while stenting also did not reduce the risk (25% vs 27%; P = .81).
The leading reasons for delayed cholecystectomy included patients having a high surgical risk (27.3%), concurrent biliary pathology (19.2%), and physician preference (14%).
The findings underscore that “concurrent cholecystectomy is associated with the lowest risk of biliary complications,” El Halabi said.
“Delayed cholecystectomy is associated with an approximately 23% incidence of biliary complications with 1 year of initial admission, with the highest incidence occurring within 3 months,” she added. “Neither sphincterotomy nor stenting during ERCP mitigates this risk.”
“Early cholecystectomy during the index admission remains the most reliable strategy to reduce recurrent events.”
Findings Underscore Importance of Timing
Commenting on the study, Luis F. Lara, MD, division chief of digestive diseases at the University of Cincinnati, who co-moderated the session, agreed that evidence soundly supports early cholecystectomy.
“We also did a large study looking at this and there’s no doubt that doing it during the index admission has a tremendous effect on long-term outcomes,” Lara told GI & Hepatology News.
Lara noted that “part of it is people don’t show up again until they get sick again, so we don’t want to lose that opportunity the first time, during the index admission,” he said.
Lara’s previous studies have specifically documented how early cholecystectomy for acute biliary pancreatitis improves outcomes of hospitalization for cirrhosis and factors associated with early unplanned readmissions following same-admission cholecystectomy for acute biliary pancreatitis.
Akwi W. Asombang, MD, an interventional gastroenterologist at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, both in Boston, agreed that the findings are important.
“We know that if a cholecystectomy is not performed in the same admission as ERCP, the stones in the gallbladder remain and may migrate out into the bile duct, resulting in further complications as described in the study,” Asombang, also a session co-moderator, told GI & Hepatology News.
She noted that the practice can vary between institutions based on factors including the availability of physicians to perform the cholecystectomy.
Potential complications in delaying the procedure can range from inflammation and pancreatitis to obstruction of the bile duct, “which then can result in cholangitis and eventually sepsis or even death,” Asombang cautioned.
“So the timing of the procedure with ERCP is definitely significant,” she said.
El Halabi and Asombang had no disclosures to report. Lara reported a relationship with AbbVie.
A version of this article first appeared on Medscape.com.
FROM ACG 2025
Approach to Weight Management in GI Practice
Introduction
The majority of patients in the United States are now overweight or obese, and as gastroenterologists we treat a number of conditions that are caused or worsened by obesity.1 Cirrhosis related to metabolic associated fatty liver disease (MAFLD) is now a leading indication for liver transplantation in the US2 and obesity is a clear risk factor for all major malignancies of the GI tract, including esophageal, gastric cardia, pancreatic, liver, gallbladder, colon, and rectum.3 Obesity is associated with dysbiosis and impacts barrier function: increasing permeability, abnormal gut bacterial translocation, and inflammation.4 It is more common than malnutrition in our patients with inflammatory bowel disease (IBD), where it impacts response to biologic drugs, increases the technical difficulty of surgeries, such as IPAA, and is associated with worse surgical outcomes.5 Furthermore, patients with obesity may be less likely to undergo preventative cancer screenings and are at increased risk related to sedation for endoscopic procedures.6 With over 40% of Americans suffering from obesity, and increasingly effective treatments available,
Understanding the Mechanisms of Obesity
There are complex orexigenic and anorexigenic brain pathways in the hypothalamus which control global energy balance.7 Obesity results when energy intake exceeds energy expenditure. While overeating and a sedentary lifestyle are commonly blamed, there are a number of elements that contribute, including genetics, medical conditions, medications, psychosocial factors, and environmental components. For example, sleep loss contributes to weight gain by several mechanisms including increasing ghrelin and decreasing leptin levels, thereby increasing hunger and appetite, as well as by decreasing insulin sensitivity and increasing cortisol. Subjects exposed to sleep deprivation in research settings take in 550 kcal more the following day.8 Medications used commonly in GI practice including corticosteroids, antihistamines, propranolol, and amitriptyline, are obesogenic9 and cannabis can impact hypothalamic pathways to stimulate hunger.10
When patients diet or exercise to lose weight, as we have traditionally advised, there are strong hormonal changes and metabolic adaptations that occur to preserve the defended fat mass or “set point.” Loss of adipose tissue results in decreased production of leptin, a hormone that stimulates satiety pathways and inhibits orexigenic pathways, greatly increasing hunger and cravings. Increases in ghrelin production by the stomach decreases perceptions of fullness. With weight loss, energy requirements decrease, and muscles become more efficient, meaning fewer kcal are needed to maintain bodily processes.11 Eventually a plateau is reached, while motivation to diet and restraint around food wane, and hedonistic (reward) pathways are activated. These powerful factors result in the regain of lost weight within one year in the majority of patients.
Implementing Weight Management into GI Practice
Given the stigma and bias around obesity, patients often feel shame and vulnerability around the condition. It is important to have empathy in your approach, asking permission to discuss weight and using patient-first language (e.g. “patient with obesity” not “obese patient”). While BMI is predictive of health outcomes, it does not measure body fat percentage and may be misleading, such as in muscular individuals. Other measures of adiposity including waist circumference and body composition testing, such as with DEXA, may provide additional data. A BMI of 30 or above defines obesity, though newer definitions incorporate related symptoms, organ disfunction, and metabolic abnormalities into the term “clinical obesity.”12 Asian patients experience metabolic complications at a lower BMI, and therefore the definition of obese is 27.5kg/m2 in this population.
Begin by taking a weight history. Has this been a lifelong struggle or is there a particular life circumstance, such as working a third shift or recent pregnancy which precipitated weight gain? Patients should be asked about binge eating or eating late into the evening or waking at night to eat, as these disordered eating behaviors are managed with specific medications and behavioral therapies. Inquire about sleep duration and quality and refer for a sleep study if there is suspicion for obstructive sleep apnea. Other weight-related comorbidities including hyperlipidemia, type 2 diabetes mellitus (T2DM), and MAFLD should be considered and merit a more aggressive approach, as does more severe obesity (class III, BMI ≥40). Questions about marijuana and alcohol use as well as review of the medication list for obesogenic medications can provide further insight into modifiable contributing factors.
Pillars of Weight Management
The internet is awash with trendy diet recommendations, and widespread misconceptions about obesity management are even ingrained into how physicians approach the disease. It is critical to remember that this is not a consequence of bad choices or lack of self-control. Exercise alone is insufficient to result in significant weight loss.13 Furthermore, whether it is through low fat, low carb, or intermittent fasting, weight loss will occur with calorie deficit.14 Evidence-based diet and lifestyle recommendations to lay the groundwork for success should be discussed at each visit (see Table 1). The Mediterranean diet is recommended for weight loss as well as for several GI disorders (i.e., MAFLD and IBD) and is the optimal eating strategy for cardiovascular health.15 Patients should be advised to engage in 150 minutes of moderate exercise per week, such as brisk walking, and should incorporate resistance training to build muscle and maintain bone density.
Anti-obesity Medications
There are a number of medications, either FDA approved or used off label, for treatment of obesity (see Table 2).16 All are indicated for patients with a BMI of ≥ 30 kg/m2 or for those with a BMI between 27-29 kg/m2 with weight-related comorbidities and should be used in combination with diet and lifestyle interventions. None are approved or safe in pregnancy. Mechanisms of action vary by type and include decreased appetite, increased energy expenditure, improved insulin sensitivity, and interfere with absorption.
The newest and most effective anti-obesity medications (AOM), the glucagon-like peptide-1 receptor agonists (GLP-1 RA) are derived from gut hormones secreted in the distal small bowel and colon in response to a meal, which function to delay gastric emptying, increase insulin release from the pancreas, and reduce hepatic gluconeogenesis. Central nervous system effects are not yet entirely understood, but function to decrease appetite and increase satiety. Initially developed for treatment of T2DM, observed weight reduction in patients treated with GLP-1 RA led to clinical trials for treatment of obesity. Semaglutide treatment resulted in weight reduction of 16.9% of total body weight (TBW), and one third of subjects lost ≥ 20% of TBW.17 Tirzepatide combines GLP-1 RA and a gastric inhibitory polypeptide (GIP) receptor agonist, which also has an incretin effect and functions to slow gastric emptying. In the pivotal SURMOUNT trial, approximately 58% of patients achieved ≥20% loss of TBW18 with 15mg weekly dosing of tirzepatide. This class of drugs is a logical choice in patients with T2DM and obesity. Long-term treatment appears necessary, as patients typically regain two-thirds of lost weight within a year after GLP-1 RA are stopped.
Based on tumors observed in rodents, GLP-1 RA are contraindicated in patients with a personal or family history of multiple endocrine neoplasia type 2 (MEN II) or medullary thyroid cancer. These tumors have not been observed in humans treated with GLP-1 RA. They should be used with caution in patients with history of pancreatitis, gastroparesis, or diabetic retinopathy, though a recent systematic review and meta-analysis suggests showed little to no increased risk for biliary events from GLP-1 RA.19 Side effects are most commonly gastrointestinal in nature (nausea, reflux, constipation or diarrhea) and are typically most severe with initiation of the drug and with dose escalation. Side effects can be mitigated by initiating these drugs at lowest doses and gradually titrating up (every four weeks) based on effectiveness and tolerability. Antisecretory, antiemetic, and laxative medications can also be used to help manage GLP-1 RA related side effects.
There is no reason to escalate to highest doses if patients are experiencing weight loss and reduction in food cravings at lower doses. Both semaglutide and tirzepatide are administered subcutaneously every seven days. Once patients have reached goal weight, they can either continue maintenance therapy at that same dose/interval, or if motivated to do so, may gradually reduce the weekly dose in a stepwise approach to determine the minimally effective dose to maintain weight loss. There are not yet published maintenance studies to guide this process. Currently the price of GLP-1 RA and inconsistent insurance coverage make them inaccessible to many patients. The manufacturers of both semaglutide and tirzepatide offer direct to consumer pricing and home delivery.
Bariatric Surgery
In patients with higher BMI (≥35kg/m2) or those with BMI ≥30kg/m2 and obesity-related metabolic disease and the desire to avoid lifelong medications or who fail or are intolerant of AOM, bariatric options should be considered.20 Sleeve gastrectomy has become the most performed surgery for treatment of obesity. It is a restrictive procedure, removing 80% of the stomach, but a drop in circulating levels of ghrelin afterwards also leads to decreased feelings of hunger. It results in weight loss of 25-30% TBW loss. It is not a good choice for patients who suffer from severe GERD, as this typically worsens afterwards; furthermore, de novo Barrett’s has been observed in nearly 6% of patients who undergo sleeve gastrectomy.21
Roux-en-Y gastric bypass is a restrictive and malabsorptive procedure, resulting in 30-35% TBW loss. It has beneficial and immediate metabolic effects, including increased release of endogenous GLP-1, which leads to improvements in weight-related T2DM. The newer single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) starts with a sleeve gastrectomy, making a smaller tube-shaped stomach. The duodenum is divided just after the stomach and then a loop of ileum is brought up and connected to the stomach (see Figure 1). This procedure is highly effective, with patients losing 75-95% of excess body weight and is becoming a preferred option for patients with greater BMI (≥50kg/m2). It is also an option for patients who have already had a sleeve gastrectomy and are seeking further weight loss. Because there is only one anastomosis, perioperative complications, such as anastomotic leaks, are reduced. The risk of micronutrient deficiencies is present with all malabsorptive procedures, and these patients must supplement with multivitamins, iron, vitamin D, and calcium.
Endoscopic Therapies
Endoscopic bariatric and metabolic therapies (EBMTs) have been increasingly studied and utilized, and this less invasive option may be more appropriate for or attractive to many patients. Intragastric balloons, which reduce meal volume and delay gastric emptying, can be used short term only (six months) resulting in loss of about 6.9% of total body weight (TBW) greater than lifestyle modification (LM) alone, and may be considered in limited situations, such as need for pre-operative weight loss to reduce risks in very obese individuals.22
Endoscopic gastric remodeling (EGR), also known as endoscopic sleeve gastrectomy (ESG), is a purely restrictive procedure in which the stomach is cinched to resize and reshape using an endoscopic suturing device (see Figure 2).23 It is an option for patients with class 1 or 2 obesity, with data from a randomized controlled trial in this population demonstrating mean percentage of TBW loss of 13.6% at 52 weeks compared to 0.8% in those treated with LM alone.24 A recent meta-analysis of 21 observational studies, including patients with higher BMIs (32.5 to 49.9 kg/m2) showed pooled average weight loss of 17.3% TBW at 12 months with EGR.22 This procedure has potential advantages of fewer complications, quicker recovery, and much less new-onset GERD compared to laparoscopic sleeve gastrectomy. Furthermore, it may be utilized in combination with AOMs to achieve optimum weight loss and metabolic outcomes.25,26 Potential adverse events include abdominal pain, nausea and vomiting (which may be severe), as well as rare instances of intra/extra luminal bleeding or abdominal abscess requiring drainage.22
Recent joint American/European Gastrointestinal Endoscopy guidelines suggest the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity.22 Small bowel interventions including duodenal-jejunal bypass liner and duodenal mucosal resurfacing are being investigated for patients with obesity and type 2 diabetes but not yet commercially available.
Conclusion
Given the overlap of obesity with many GI disorders, it is entirely appropriate for gastroenterologists to consider it worthy of aggressive treatment, particularly in patients with MAFLD and other serious weight related comorbidities. With a compassionate and empathetic approach, and a number of highly effective medical, endoscopic, and surgical therapies now available, weight management has the potential to be extremely rewarding when implemented in GI practice.
Dr. Kelly is based in the Department of Medicine, Division of Gastroenterology, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston, Massachusetts. She serves on the clinical advisory board for OpenBiome (unpaid) and has served on an advisory board for Eli Lilly and Company.
References
1. Hales CM, et al. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS Data Brief 2020 Feb:(360):1–8.
2. Pais R, et al. NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol. 2016 Dec. doi: 10.1016/j.jhep.2016.07.033.
3. Lauby-Secretan B, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug. doi: 10.1056/NEJMsr1606602.
4. Kim A. Dysbiosis: A Review Highlighting Obesity and Inflammatory Bowel Disease. J Clin Gastroenterol. 2015 Nov-Dec. doi: 10.1097/MCG.0000000000000356.
5. Singh S, et al. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol. 2017 Feb. doi: 10.1038/nrgastro.2016.181.
6. Sundararaman L, Goudra B. Sedation for GI Endoscopy in the Morbidly Obese: Challenges and Possible Solutions. J Clin Med. 2024 Aug. doi: 10.3390/jcm13164635.
7. Bombassaro B, et al. The hypothalamus as the central regulator of energy balance and its impact on current and future obesity treatments. Arch Endocrinol Metab. 2024 Nov. doi: 10.20945/2359-4292-2024-0082.
8. Beccuti G, Pannain S. Sleep and obesity. Curr Opin Clin Nutr Metab Care. 2011 Jul. doi: 10.1097/MCO.0b013e3283479109.
9. Desalermos A, et al. Effect of Obesogenic Medications on Weight-Loss Outcomes in a Behavioral Weight-Management Program. Obesity (Silver Spring). 2019 May. doi: 10.1002/oby.22444.
10. Lord MN, Noble EE. Hypothalamic cannabinoid signaling: Consequences for eating behavior. Pharmacol Res Perspect. 2024 Oct. doi: 10.1002/prp2.1251.
11. Farhana A, Rehman A. Metabolic Consequences of Weight Reduction. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572145/.
12. Rubino F, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 2025 Mar. doi: 10.1016/S2213-8587(24)00316-4.
13. Cox CE. Role of Physical Activity for Weight Loss and Weight Maintenance. Diabetes Spectr. 2017 Aug. doi: 10.2337/ds17-0013.
14. Chaput JP, et al. Widespread misconceptions about obesity. Can Fam Physician. 2014 Nov. PMID: 25392431.
15. Muscogiuri G, et al. Mediterranean Diet and Obesity-related Disorders: What is the Evidence? Curr Obes Rep. 2022 Dec. doi: 10.1007/s13679-022-00481-1.
16. Gudzune KA, Kushner RF. Medications for Obesity: A Review. JAMA. 2024 Aug. doi: 10.1001/jama.2024.10816.
17. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Feb. doi: 10.1056/NEJMoa2032183.
18. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jun. doi: 10.1056/NEJMoa2206038.
19. Chiang CH, et al. Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.003.
20. Aderinto N, et al. Recent advances in bariatric surgery: a narrative review of weight loss procedures. Ann Med Surg (Lond). 2023 Nov. doi: 10.1097/MS9.0000000000001472.
21. Chandan S, et al. Risk of De Novo Barrett’s Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies With Long-Term Follow-Up. Clin Gastroenterol Hepatol. 2025 Jan. doi: 10.1016/j.cgh.2024.06.041.
22. Jirapinyo P, et al. American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity. Gastrointest Endosc. 2024 Jun. doi: 10.1016/j.gie.2023.12.004.
23. Nduma BN, et al. Endoscopic Gastric Sleeve: A Review of Literature. Cureus. 2023 Mar. doi: 10.7759/cureus.36353.
24. Abu Dayyeh BK, et al. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Lancet. 2022 Aug. doi: 10.1016/S0140-6736(22)01280-6.
25. Gala K, et al. Outcomes of concomitant antiobesity medication use with endoscopic sleeve gastroplasty in clinical US settings. Obes Pillars. 2024 May. doi: 10.1016/j.obpill.2024.100112.
26. Chung CS, et al. Endoscopic sleeve gastroplasty combined with anti-obesity medication for better control of weight and diabetes. Clin Endosc. 2025 May. doi: 10.5946/ce.2024.274.
Introduction
The majority of patients in the United States are now overweight or obese, and as gastroenterologists we treat a number of conditions that are caused or worsened by obesity.1 Cirrhosis related to metabolic associated fatty liver disease (MAFLD) is now a leading indication for liver transplantation in the US2 and obesity is a clear risk factor for all major malignancies of the GI tract, including esophageal, gastric cardia, pancreatic, liver, gallbladder, colon, and rectum.3 Obesity is associated with dysbiosis and impacts barrier function: increasing permeability, abnormal gut bacterial translocation, and inflammation.4 It is more common than malnutrition in our patients with inflammatory bowel disease (IBD), where it impacts response to biologic drugs, increases the technical difficulty of surgeries, such as IPAA, and is associated with worse surgical outcomes.5 Furthermore, patients with obesity may be less likely to undergo preventative cancer screenings and are at increased risk related to sedation for endoscopic procedures.6 With over 40% of Americans suffering from obesity, and increasingly effective treatments available,
Understanding the Mechanisms of Obesity
There are complex orexigenic and anorexigenic brain pathways in the hypothalamus which control global energy balance.7 Obesity results when energy intake exceeds energy expenditure. While overeating and a sedentary lifestyle are commonly blamed, there are a number of elements that contribute, including genetics, medical conditions, medications, psychosocial factors, and environmental components. For example, sleep loss contributes to weight gain by several mechanisms including increasing ghrelin and decreasing leptin levels, thereby increasing hunger and appetite, as well as by decreasing insulin sensitivity and increasing cortisol. Subjects exposed to sleep deprivation in research settings take in 550 kcal more the following day.8 Medications used commonly in GI practice including corticosteroids, antihistamines, propranolol, and amitriptyline, are obesogenic9 and cannabis can impact hypothalamic pathways to stimulate hunger.10
When patients diet or exercise to lose weight, as we have traditionally advised, there are strong hormonal changes and metabolic adaptations that occur to preserve the defended fat mass or “set point.” Loss of adipose tissue results in decreased production of leptin, a hormone that stimulates satiety pathways and inhibits orexigenic pathways, greatly increasing hunger and cravings. Increases in ghrelin production by the stomach decreases perceptions of fullness. With weight loss, energy requirements decrease, and muscles become more efficient, meaning fewer kcal are needed to maintain bodily processes.11 Eventually a plateau is reached, while motivation to diet and restraint around food wane, and hedonistic (reward) pathways are activated. These powerful factors result in the regain of lost weight within one year in the majority of patients.
Implementing Weight Management into GI Practice
Given the stigma and bias around obesity, patients often feel shame and vulnerability around the condition. It is important to have empathy in your approach, asking permission to discuss weight and using patient-first language (e.g. “patient with obesity” not “obese patient”). While BMI is predictive of health outcomes, it does not measure body fat percentage and may be misleading, such as in muscular individuals. Other measures of adiposity including waist circumference and body composition testing, such as with DEXA, may provide additional data. A BMI of 30 or above defines obesity, though newer definitions incorporate related symptoms, organ disfunction, and metabolic abnormalities into the term “clinical obesity.”12 Asian patients experience metabolic complications at a lower BMI, and therefore the definition of obese is 27.5kg/m2 in this population.
Begin by taking a weight history. Has this been a lifelong struggle or is there a particular life circumstance, such as working a third shift or recent pregnancy which precipitated weight gain? Patients should be asked about binge eating or eating late into the evening or waking at night to eat, as these disordered eating behaviors are managed with specific medications and behavioral therapies. Inquire about sleep duration and quality and refer for a sleep study if there is suspicion for obstructive sleep apnea. Other weight-related comorbidities including hyperlipidemia, type 2 diabetes mellitus (T2DM), and MAFLD should be considered and merit a more aggressive approach, as does more severe obesity (class III, BMI ≥40). Questions about marijuana and alcohol use as well as review of the medication list for obesogenic medications can provide further insight into modifiable contributing factors.
Pillars of Weight Management
The internet is awash with trendy diet recommendations, and widespread misconceptions about obesity management are even ingrained into how physicians approach the disease. It is critical to remember that this is not a consequence of bad choices or lack of self-control. Exercise alone is insufficient to result in significant weight loss.13 Furthermore, whether it is through low fat, low carb, or intermittent fasting, weight loss will occur with calorie deficit.14 Evidence-based diet and lifestyle recommendations to lay the groundwork for success should be discussed at each visit (see Table 1). The Mediterranean diet is recommended for weight loss as well as for several GI disorders (i.e., MAFLD and IBD) and is the optimal eating strategy for cardiovascular health.15 Patients should be advised to engage in 150 minutes of moderate exercise per week, such as brisk walking, and should incorporate resistance training to build muscle and maintain bone density.
Anti-obesity Medications
There are a number of medications, either FDA approved or used off label, for treatment of obesity (see Table 2).16 All are indicated for patients with a BMI of ≥ 30 kg/m2 or for those with a BMI between 27-29 kg/m2 with weight-related comorbidities and should be used in combination with diet and lifestyle interventions. None are approved or safe in pregnancy. Mechanisms of action vary by type and include decreased appetite, increased energy expenditure, improved insulin sensitivity, and interfere with absorption.
The newest and most effective anti-obesity medications (AOM), the glucagon-like peptide-1 receptor agonists (GLP-1 RA) are derived from gut hormones secreted in the distal small bowel and colon in response to a meal, which function to delay gastric emptying, increase insulin release from the pancreas, and reduce hepatic gluconeogenesis. Central nervous system effects are not yet entirely understood, but function to decrease appetite and increase satiety. Initially developed for treatment of T2DM, observed weight reduction in patients treated with GLP-1 RA led to clinical trials for treatment of obesity. Semaglutide treatment resulted in weight reduction of 16.9% of total body weight (TBW), and one third of subjects lost ≥ 20% of TBW.17 Tirzepatide combines GLP-1 RA and a gastric inhibitory polypeptide (GIP) receptor agonist, which also has an incretin effect and functions to slow gastric emptying. In the pivotal SURMOUNT trial, approximately 58% of patients achieved ≥20% loss of TBW18 with 15mg weekly dosing of tirzepatide. This class of drugs is a logical choice in patients with T2DM and obesity. Long-term treatment appears necessary, as patients typically regain two-thirds of lost weight within a year after GLP-1 RA are stopped.
Based on tumors observed in rodents, GLP-1 RA are contraindicated in patients with a personal or family history of multiple endocrine neoplasia type 2 (MEN II) or medullary thyroid cancer. These tumors have not been observed in humans treated with GLP-1 RA. They should be used with caution in patients with history of pancreatitis, gastroparesis, or diabetic retinopathy, though a recent systematic review and meta-analysis suggests showed little to no increased risk for biliary events from GLP-1 RA.19 Side effects are most commonly gastrointestinal in nature (nausea, reflux, constipation or diarrhea) and are typically most severe with initiation of the drug and with dose escalation. Side effects can be mitigated by initiating these drugs at lowest doses and gradually titrating up (every four weeks) based on effectiveness and tolerability. Antisecretory, antiemetic, and laxative medications can also be used to help manage GLP-1 RA related side effects.
There is no reason to escalate to highest doses if patients are experiencing weight loss and reduction in food cravings at lower doses. Both semaglutide and tirzepatide are administered subcutaneously every seven days. Once patients have reached goal weight, they can either continue maintenance therapy at that same dose/interval, or if motivated to do so, may gradually reduce the weekly dose in a stepwise approach to determine the minimally effective dose to maintain weight loss. There are not yet published maintenance studies to guide this process. Currently the price of GLP-1 RA and inconsistent insurance coverage make them inaccessible to many patients. The manufacturers of both semaglutide and tirzepatide offer direct to consumer pricing and home delivery.
Bariatric Surgery
In patients with higher BMI (≥35kg/m2) or those with BMI ≥30kg/m2 and obesity-related metabolic disease and the desire to avoid lifelong medications or who fail or are intolerant of AOM, bariatric options should be considered.20 Sleeve gastrectomy has become the most performed surgery for treatment of obesity. It is a restrictive procedure, removing 80% of the stomach, but a drop in circulating levels of ghrelin afterwards also leads to decreased feelings of hunger. It results in weight loss of 25-30% TBW loss. It is not a good choice for patients who suffer from severe GERD, as this typically worsens afterwards; furthermore, de novo Barrett’s has been observed in nearly 6% of patients who undergo sleeve gastrectomy.21
Roux-en-Y gastric bypass is a restrictive and malabsorptive procedure, resulting in 30-35% TBW loss. It has beneficial and immediate metabolic effects, including increased release of endogenous GLP-1, which leads to improvements in weight-related T2DM. The newer single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) starts with a sleeve gastrectomy, making a smaller tube-shaped stomach. The duodenum is divided just after the stomach and then a loop of ileum is brought up and connected to the stomach (see Figure 1). This procedure is highly effective, with patients losing 75-95% of excess body weight and is becoming a preferred option for patients with greater BMI (≥50kg/m2). It is also an option for patients who have already had a sleeve gastrectomy and are seeking further weight loss. Because there is only one anastomosis, perioperative complications, such as anastomotic leaks, are reduced. The risk of micronutrient deficiencies is present with all malabsorptive procedures, and these patients must supplement with multivitamins, iron, vitamin D, and calcium.
Endoscopic Therapies
Endoscopic bariatric and metabolic therapies (EBMTs) have been increasingly studied and utilized, and this less invasive option may be more appropriate for or attractive to many patients. Intragastric balloons, which reduce meal volume and delay gastric emptying, can be used short term only (six months) resulting in loss of about 6.9% of total body weight (TBW) greater than lifestyle modification (LM) alone, and may be considered in limited situations, such as need for pre-operative weight loss to reduce risks in very obese individuals.22
Endoscopic gastric remodeling (EGR), also known as endoscopic sleeve gastrectomy (ESG), is a purely restrictive procedure in which the stomach is cinched to resize and reshape using an endoscopic suturing device (see Figure 2).23 It is an option for patients with class 1 or 2 obesity, with data from a randomized controlled trial in this population demonstrating mean percentage of TBW loss of 13.6% at 52 weeks compared to 0.8% in those treated with LM alone.24 A recent meta-analysis of 21 observational studies, including patients with higher BMIs (32.5 to 49.9 kg/m2) showed pooled average weight loss of 17.3% TBW at 12 months with EGR.22 This procedure has potential advantages of fewer complications, quicker recovery, and much less new-onset GERD compared to laparoscopic sleeve gastrectomy. Furthermore, it may be utilized in combination with AOMs to achieve optimum weight loss and metabolic outcomes.25,26 Potential adverse events include abdominal pain, nausea and vomiting (which may be severe), as well as rare instances of intra/extra luminal bleeding or abdominal abscess requiring drainage.22
Recent joint American/European Gastrointestinal Endoscopy guidelines suggest the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity.22 Small bowel interventions including duodenal-jejunal bypass liner and duodenal mucosal resurfacing are being investigated for patients with obesity and type 2 diabetes but not yet commercially available.
Conclusion
Given the overlap of obesity with many GI disorders, it is entirely appropriate for gastroenterologists to consider it worthy of aggressive treatment, particularly in patients with MAFLD and other serious weight related comorbidities. With a compassionate and empathetic approach, and a number of highly effective medical, endoscopic, and surgical therapies now available, weight management has the potential to be extremely rewarding when implemented in GI practice.
Dr. Kelly is based in the Department of Medicine, Division of Gastroenterology, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston, Massachusetts. She serves on the clinical advisory board for OpenBiome (unpaid) and has served on an advisory board for Eli Lilly and Company.
References
1. Hales CM, et al. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS Data Brief 2020 Feb:(360):1–8.
2. Pais R, et al. NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol. 2016 Dec. doi: 10.1016/j.jhep.2016.07.033.
3. Lauby-Secretan B, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug. doi: 10.1056/NEJMsr1606602.
4. Kim A. Dysbiosis: A Review Highlighting Obesity and Inflammatory Bowel Disease. J Clin Gastroenterol. 2015 Nov-Dec. doi: 10.1097/MCG.0000000000000356.
5. Singh S, et al. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol. 2017 Feb. doi: 10.1038/nrgastro.2016.181.
6. Sundararaman L, Goudra B. Sedation for GI Endoscopy in the Morbidly Obese: Challenges and Possible Solutions. J Clin Med. 2024 Aug. doi: 10.3390/jcm13164635.
7. Bombassaro B, et al. The hypothalamus as the central regulator of energy balance and its impact on current and future obesity treatments. Arch Endocrinol Metab. 2024 Nov. doi: 10.20945/2359-4292-2024-0082.
8. Beccuti G, Pannain S. Sleep and obesity. Curr Opin Clin Nutr Metab Care. 2011 Jul. doi: 10.1097/MCO.0b013e3283479109.
9. Desalermos A, et al. Effect of Obesogenic Medications on Weight-Loss Outcomes in a Behavioral Weight-Management Program. Obesity (Silver Spring). 2019 May. doi: 10.1002/oby.22444.
10. Lord MN, Noble EE. Hypothalamic cannabinoid signaling: Consequences for eating behavior. Pharmacol Res Perspect. 2024 Oct. doi: 10.1002/prp2.1251.
11. Farhana A, Rehman A. Metabolic Consequences of Weight Reduction. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572145/.
12. Rubino F, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 2025 Mar. doi: 10.1016/S2213-8587(24)00316-4.
13. Cox CE. Role of Physical Activity for Weight Loss and Weight Maintenance. Diabetes Spectr. 2017 Aug. doi: 10.2337/ds17-0013.
14. Chaput JP, et al. Widespread misconceptions about obesity. Can Fam Physician. 2014 Nov. PMID: 25392431.
15. Muscogiuri G, et al. Mediterranean Diet and Obesity-related Disorders: What is the Evidence? Curr Obes Rep. 2022 Dec. doi: 10.1007/s13679-022-00481-1.
16. Gudzune KA, Kushner RF. Medications for Obesity: A Review. JAMA. 2024 Aug. doi: 10.1001/jama.2024.10816.
17. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Feb. doi: 10.1056/NEJMoa2032183.
18. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jun. doi: 10.1056/NEJMoa2206038.
19. Chiang CH, et al. Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.003.
20. Aderinto N, et al. Recent advances in bariatric surgery: a narrative review of weight loss procedures. Ann Med Surg (Lond). 2023 Nov. doi: 10.1097/MS9.0000000000001472.
21. Chandan S, et al. Risk of De Novo Barrett’s Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies With Long-Term Follow-Up. Clin Gastroenterol Hepatol. 2025 Jan. doi: 10.1016/j.cgh.2024.06.041.
22. Jirapinyo P, et al. American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity. Gastrointest Endosc. 2024 Jun. doi: 10.1016/j.gie.2023.12.004.
23. Nduma BN, et al. Endoscopic Gastric Sleeve: A Review of Literature. Cureus. 2023 Mar. doi: 10.7759/cureus.36353.
24. Abu Dayyeh BK, et al. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Lancet. 2022 Aug. doi: 10.1016/S0140-6736(22)01280-6.
25. Gala K, et al. Outcomes of concomitant antiobesity medication use with endoscopic sleeve gastroplasty in clinical US settings. Obes Pillars. 2024 May. doi: 10.1016/j.obpill.2024.100112.
26. Chung CS, et al. Endoscopic sleeve gastroplasty combined with anti-obesity medication for better control of weight and diabetes. Clin Endosc. 2025 May. doi: 10.5946/ce.2024.274.
Introduction
The majority of patients in the United States are now overweight or obese, and as gastroenterologists we treat a number of conditions that are caused or worsened by obesity.1 Cirrhosis related to metabolic associated fatty liver disease (MAFLD) is now a leading indication for liver transplantation in the US2 and obesity is a clear risk factor for all major malignancies of the GI tract, including esophageal, gastric cardia, pancreatic, liver, gallbladder, colon, and rectum.3 Obesity is associated with dysbiosis and impacts barrier function: increasing permeability, abnormal gut bacterial translocation, and inflammation.4 It is more common than malnutrition in our patients with inflammatory bowel disease (IBD), where it impacts response to biologic drugs, increases the technical difficulty of surgeries, such as IPAA, and is associated with worse surgical outcomes.5 Furthermore, patients with obesity may be less likely to undergo preventative cancer screenings and are at increased risk related to sedation for endoscopic procedures.6 With over 40% of Americans suffering from obesity, and increasingly effective treatments available,
Understanding the Mechanisms of Obesity
There are complex orexigenic and anorexigenic brain pathways in the hypothalamus which control global energy balance.7 Obesity results when energy intake exceeds energy expenditure. While overeating and a sedentary lifestyle are commonly blamed, there are a number of elements that contribute, including genetics, medical conditions, medications, psychosocial factors, and environmental components. For example, sleep loss contributes to weight gain by several mechanisms including increasing ghrelin and decreasing leptin levels, thereby increasing hunger and appetite, as well as by decreasing insulin sensitivity and increasing cortisol. Subjects exposed to sleep deprivation in research settings take in 550 kcal more the following day.8 Medications used commonly in GI practice including corticosteroids, antihistamines, propranolol, and amitriptyline, are obesogenic9 and cannabis can impact hypothalamic pathways to stimulate hunger.10
When patients diet or exercise to lose weight, as we have traditionally advised, there are strong hormonal changes and metabolic adaptations that occur to preserve the defended fat mass or “set point.” Loss of adipose tissue results in decreased production of leptin, a hormone that stimulates satiety pathways and inhibits orexigenic pathways, greatly increasing hunger and cravings. Increases in ghrelin production by the stomach decreases perceptions of fullness. With weight loss, energy requirements decrease, and muscles become more efficient, meaning fewer kcal are needed to maintain bodily processes.11 Eventually a plateau is reached, while motivation to diet and restraint around food wane, and hedonistic (reward) pathways are activated. These powerful factors result in the regain of lost weight within one year in the majority of patients.
Implementing Weight Management into GI Practice
Given the stigma and bias around obesity, patients often feel shame and vulnerability around the condition. It is important to have empathy in your approach, asking permission to discuss weight and using patient-first language (e.g. “patient with obesity” not “obese patient”). While BMI is predictive of health outcomes, it does not measure body fat percentage and may be misleading, such as in muscular individuals. Other measures of adiposity including waist circumference and body composition testing, such as with DEXA, may provide additional data. A BMI of 30 or above defines obesity, though newer definitions incorporate related symptoms, organ disfunction, and metabolic abnormalities into the term “clinical obesity.”12 Asian patients experience metabolic complications at a lower BMI, and therefore the definition of obese is 27.5kg/m2 in this population.
Begin by taking a weight history. Has this been a lifelong struggle or is there a particular life circumstance, such as working a third shift or recent pregnancy which precipitated weight gain? Patients should be asked about binge eating or eating late into the evening or waking at night to eat, as these disordered eating behaviors are managed with specific medications and behavioral therapies. Inquire about sleep duration and quality and refer for a sleep study if there is suspicion for obstructive sleep apnea. Other weight-related comorbidities including hyperlipidemia, type 2 diabetes mellitus (T2DM), and MAFLD should be considered and merit a more aggressive approach, as does more severe obesity (class III, BMI ≥40). Questions about marijuana and alcohol use as well as review of the medication list for obesogenic medications can provide further insight into modifiable contributing factors.
Pillars of Weight Management
The internet is awash with trendy diet recommendations, and widespread misconceptions about obesity management are even ingrained into how physicians approach the disease. It is critical to remember that this is not a consequence of bad choices or lack of self-control. Exercise alone is insufficient to result in significant weight loss.13 Furthermore, whether it is through low fat, low carb, or intermittent fasting, weight loss will occur with calorie deficit.14 Evidence-based diet and lifestyle recommendations to lay the groundwork for success should be discussed at each visit (see Table 1). The Mediterranean diet is recommended for weight loss as well as for several GI disorders (i.e., MAFLD and IBD) and is the optimal eating strategy for cardiovascular health.15 Patients should be advised to engage in 150 minutes of moderate exercise per week, such as brisk walking, and should incorporate resistance training to build muscle and maintain bone density.
Anti-obesity Medications
There are a number of medications, either FDA approved or used off label, for treatment of obesity (see Table 2).16 All are indicated for patients with a BMI of ≥ 30 kg/m2 or for those with a BMI between 27-29 kg/m2 with weight-related comorbidities and should be used in combination with diet and lifestyle interventions. None are approved or safe in pregnancy. Mechanisms of action vary by type and include decreased appetite, increased energy expenditure, improved insulin sensitivity, and interfere with absorption.
The newest and most effective anti-obesity medications (AOM), the glucagon-like peptide-1 receptor agonists (GLP-1 RA) are derived from gut hormones secreted in the distal small bowel and colon in response to a meal, which function to delay gastric emptying, increase insulin release from the pancreas, and reduce hepatic gluconeogenesis. Central nervous system effects are not yet entirely understood, but function to decrease appetite and increase satiety. Initially developed for treatment of T2DM, observed weight reduction in patients treated with GLP-1 RA led to clinical trials for treatment of obesity. Semaglutide treatment resulted in weight reduction of 16.9% of total body weight (TBW), and one third of subjects lost ≥ 20% of TBW.17 Tirzepatide combines GLP-1 RA and a gastric inhibitory polypeptide (GIP) receptor agonist, which also has an incretin effect and functions to slow gastric emptying. In the pivotal SURMOUNT trial, approximately 58% of patients achieved ≥20% loss of TBW18 with 15mg weekly dosing of tirzepatide. This class of drugs is a logical choice in patients with T2DM and obesity. Long-term treatment appears necessary, as patients typically regain two-thirds of lost weight within a year after GLP-1 RA are stopped.
Based on tumors observed in rodents, GLP-1 RA are contraindicated in patients with a personal or family history of multiple endocrine neoplasia type 2 (MEN II) or medullary thyroid cancer. These tumors have not been observed in humans treated with GLP-1 RA. They should be used with caution in patients with history of pancreatitis, gastroparesis, or diabetic retinopathy, though a recent systematic review and meta-analysis suggests showed little to no increased risk for biliary events from GLP-1 RA.19 Side effects are most commonly gastrointestinal in nature (nausea, reflux, constipation or diarrhea) and are typically most severe with initiation of the drug and with dose escalation. Side effects can be mitigated by initiating these drugs at lowest doses and gradually titrating up (every four weeks) based on effectiveness and tolerability. Antisecretory, antiemetic, and laxative medications can also be used to help manage GLP-1 RA related side effects.
There is no reason to escalate to highest doses if patients are experiencing weight loss and reduction in food cravings at lower doses. Both semaglutide and tirzepatide are administered subcutaneously every seven days. Once patients have reached goal weight, they can either continue maintenance therapy at that same dose/interval, or if motivated to do so, may gradually reduce the weekly dose in a stepwise approach to determine the minimally effective dose to maintain weight loss. There are not yet published maintenance studies to guide this process. Currently the price of GLP-1 RA and inconsistent insurance coverage make them inaccessible to many patients. The manufacturers of both semaglutide and tirzepatide offer direct to consumer pricing and home delivery.
Bariatric Surgery
In patients with higher BMI (≥35kg/m2) or those with BMI ≥30kg/m2 and obesity-related metabolic disease and the desire to avoid lifelong medications or who fail or are intolerant of AOM, bariatric options should be considered.20 Sleeve gastrectomy has become the most performed surgery for treatment of obesity. It is a restrictive procedure, removing 80% of the stomach, but a drop in circulating levels of ghrelin afterwards also leads to decreased feelings of hunger. It results in weight loss of 25-30% TBW loss. It is not a good choice for patients who suffer from severe GERD, as this typically worsens afterwards; furthermore, de novo Barrett’s has been observed in nearly 6% of patients who undergo sleeve gastrectomy.21
Roux-en-Y gastric bypass is a restrictive and malabsorptive procedure, resulting in 30-35% TBW loss. It has beneficial and immediate metabolic effects, including increased release of endogenous GLP-1, which leads to improvements in weight-related T2DM. The newer single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) starts with a sleeve gastrectomy, making a smaller tube-shaped stomach. The duodenum is divided just after the stomach and then a loop of ileum is brought up and connected to the stomach (see Figure 1). This procedure is highly effective, with patients losing 75-95% of excess body weight and is becoming a preferred option for patients with greater BMI (≥50kg/m2). It is also an option for patients who have already had a sleeve gastrectomy and are seeking further weight loss. Because there is only one anastomosis, perioperative complications, such as anastomotic leaks, are reduced. The risk of micronutrient deficiencies is present with all malabsorptive procedures, and these patients must supplement with multivitamins, iron, vitamin D, and calcium.
Endoscopic Therapies
Endoscopic bariatric and metabolic therapies (EBMTs) have been increasingly studied and utilized, and this less invasive option may be more appropriate for or attractive to many patients. Intragastric balloons, which reduce meal volume and delay gastric emptying, can be used short term only (six months) resulting in loss of about 6.9% of total body weight (TBW) greater than lifestyle modification (LM) alone, and may be considered in limited situations, such as need for pre-operative weight loss to reduce risks in very obese individuals.22
Endoscopic gastric remodeling (EGR), also known as endoscopic sleeve gastrectomy (ESG), is a purely restrictive procedure in which the stomach is cinched to resize and reshape using an endoscopic suturing device (see Figure 2).23 It is an option for patients with class 1 or 2 obesity, with data from a randomized controlled trial in this population demonstrating mean percentage of TBW loss of 13.6% at 52 weeks compared to 0.8% in those treated with LM alone.24 A recent meta-analysis of 21 observational studies, including patients with higher BMIs (32.5 to 49.9 kg/m2) showed pooled average weight loss of 17.3% TBW at 12 months with EGR.22 This procedure has potential advantages of fewer complications, quicker recovery, and much less new-onset GERD compared to laparoscopic sleeve gastrectomy. Furthermore, it may be utilized in combination with AOMs to achieve optimum weight loss and metabolic outcomes.25,26 Potential adverse events include abdominal pain, nausea and vomiting (which may be severe), as well as rare instances of intra/extra luminal bleeding or abdominal abscess requiring drainage.22
Recent joint American/European Gastrointestinal Endoscopy guidelines suggest the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity.22 Small bowel interventions including duodenal-jejunal bypass liner and duodenal mucosal resurfacing are being investigated for patients with obesity and type 2 diabetes but not yet commercially available.
Conclusion
Given the overlap of obesity with many GI disorders, it is entirely appropriate for gastroenterologists to consider it worthy of aggressive treatment, particularly in patients with MAFLD and other serious weight related comorbidities. With a compassionate and empathetic approach, and a number of highly effective medical, endoscopic, and surgical therapies now available, weight management has the potential to be extremely rewarding when implemented in GI practice.
Dr. Kelly is based in the Department of Medicine, Division of Gastroenterology, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston, Massachusetts. She serves on the clinical advisory board for OpenBiome (unpaid) and has served on an advisory board for Eli Lilly and Company.
References
1. Hales CM, et al. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS Data Brief 2020 Feb:(360):1–8.
2. Pais R, et al. NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol. 2016 Dec. doi: 10.1016/j.jhep.2016.07.033.
3. Lauby-Secretan B, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug. doi: 10.1056/NEJMsr1606602.
4. Kim A. Dysbiosis: A Review Highlighting Obesity and Inflammatory Bowel Disease. J Clin Gastroenterol. 2015 Nov-Dec. doi: 10.1097/MCG.0000000000000356.
5. Singh S, et al. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol. 2017 Feb. doi: 10.1038/nrgastro.2016.181.
6. Sundararaman L, Goudra B. Sedation for GI Endoscopy in the Morbidly Obese: Challenges and Possible Solutions. J Clin Med. 2024 Aug. doi: 10.3390/jcm13164635.
7. Bombassaro B, et al. The hypothalamus as the central regulator of energy balance and its impact on current and future obesity treatments. Arch Endocrinol Metab. 2024 Nov. doi: 10.20945/2359-4292-2024-0082.
8. Beccuti G, Pannain S. Sleep and obesity. Curr Opin Clin Nutr Metab Care. 2011 Jul. doi: 10.1097/MCO.0b013e3283479109.
9. Desalermos A, et al. Effect of Obesogenic Medications on Weight-Loss Outcomes in a Behavioral Weight-Management Program. Obesity (Silver Spring). 2019 May. doi: 10.1002/oby.22444.
10. Lord MN, Noble EE. Hypothalamic cannabinoid signaling: Consequences for eating behavior. Pharmacol Res Perspect. 2024 Oct. doi: 10.1002/prp2.1251.
11. Farhana A, Rehman A. Metabolic Consequences of Weight Reduction. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572145/.
12. Rubino F, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 2025 Mar. doi: 10.1016/S2213-8587(24)00316-4.
13. Cox CE. Role of Physical Activity for Weight Loss and Weight Maintenance. Diabetes Spectr. 2017 Aug. doi: 10.2337/ds17-0013.
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15. Muscogiuri G, et al. Mediterranean Diet and Obesity-related Disorders: What is the Evidence? Curr Obes Rep. 2022 Dec. doi: 10.1007/s13679-022-00481-1.
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17. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Feb. doi: 10.1056/NEJMoa2032183.
18. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jun. doi: 10.1056/NEJMoa2206038.
19. Chiang CH, et al. Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.003.
20. Aderinto N, et al. Recent advances in bariatric surgery: a narrative review of weight loss procedures. Ann Med Surg (Lond). 2023 Nov. doi: 10.1097/MS9.0000000000001472.
21. Chandan S, et al. Risk of De Novo Barrett’s Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies With Long-Term Follow-Up. Clin Gastroenterol Hepatol. 2025 Jan. doi: 10.1016/j.cgh.2024.06.041.
22. Jirapinyo P, et al. American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity. Gastrointest Endosc. 2024 Jun. doi: 10.1016/j.gie.2023.12.004.
23. Nduma BN, et al. Endoscopic Gastric Sleeve: A Review of Literature. Cureus. 2023 Mar. doi: 10.7759/cureus.36353.
24. Abu Dayyeh BK, et al. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Lancet. 2022 Aug. doi: 10.1016/S0140-6736(22)01280-6.
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Resmetirom Reduces Liver Stiffness in MASH Cirrhosis
PHOENIX — according to the results of a new study.
As well as showing sustained reduction in liver stiffness on vibration-controlled transient elastography (VCTE) after 2 years of treatment with resmetirom, the study suggested that up to 35% of patients could “potentially reverse their cirrhosis,” said lead author Naim Alkhouri, MD, chief medical officer and director of the steatotic liver program at Arizona Liver Health in Phoenix.
Alkhouri presented data on patients with compensated cirrhosis from a 1-year open-label extension of the already-completed MAESTRO-NAFLD-1 study at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
The FDA approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals) in 2024 for MASH and moderate-to-advanced liver fibrosis (consistent with stage F2 and F3 disease), to be used in conjunction with diet and exercise. The agency granted the once-daily, oral thyroid hormone receptor beta-selective agonist breakthrough therapy designation and priority review.
According to the American Liver Foundation, about 5% of adults in the US have MASH — one of the leading causes of liver transplantation in the country. There is currently no FDA-approved therapy for compensated cirrhosis caused by MASH, said Alkhouri. Patients with MASH cirrhosis with clinically significant portal hypertension (CSPH) experience major adverse liver outcomes.
In an analysis of 122 patients with Child Pugh A MASH cirrhosis who completed both a year in an open-label arm of MAESTRO-NAFLD-1 and a 1-year extension, 113 (93%) completed 2 years of treatment with resmetirom (80 mg). Of the 122 patients, only 114 received MRI proton density fat fraction (MRI-PDFF) testing — 93 (82%) had a baseline of > 5% indicating cirrhosis, while 21 (18%) had an MRI-PDFF of < 5%.
Patients were assessed for baseline portal hypertension (Baveno VII) with FibroScan VCTE and platelet count, which was confirmed using magnetic resonance elastography (MRE). Noninvasive biomarkers and imaging were analyzed at baseline and out to 2 years.
At baseline, 63% of patients were categorized as probable/definitive CSPH (Baveno VII). At 1 year of treatment with resmetirom, 20% of patients who were CSPH positive no longer met the criteria, and at 2 years this number had increased to 28%.
After 2 years of treatment, more than half of the patients had a sustained reduction in liver stiffness of more than 25%, as measured by VCTE; and 35% of patients with confirmed F4 at baseline (liver biopsy F4 and/or platelets < 140/MRE ≥ 5 with VCTE ≥ 15) had a conversion to F3.
Patients taking resmetirom also had significant improvements in MRI-PDFF and MRE at 2 years. Almost a third of those with a baseline MRI-PDFF > 5% improved, while 43% of those with a baseline of < 5% improved.
Although 113 patients had an adverse event — primarily gastrointestinal — the observed events were consistent with previous studies. Twenty-seven patients had a serious adverse event, but none were related to the study drug, said Alkhouri. The researchers reported that only 8% of patients discontinued the medication.
Changing the Treatment Landscape for MASH-Related Cirrhosis
When asked to comment by GI & Hepatology News, Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, said that “reversal of cirrhosis from F4 to F3 and reduction of portal hypertension are quite surprising, since cirrhosis typically progresses slowly.”
Ayesh said it was notable that the researchers had used imaging to confirm both functional and hemodynamic improvements in liver architecture not just biochemical changes. Given the results, “clinicians may reasonably consider off-label use in selected compensated patients until more outcome data become available,” he said.
A phase 3 study is underway to examine those outcomes, MAESTRO-NASH OUTCOMES, with 845 patients with MASH cirrhosis, and should be completed in 2027.
“Resmetirom could change the treatment landscape for MASH-related cirrhosis,” said Ayesh, adding, “this drug offers a chance to target the disease process itself,” while other therapies focus on preventing complications.
“For patients without access to liver transplant, a therapy that can slow or reverse disease progression could be transformative,” he told GI & Hepatology News.
Alkhouri disclosed that he is a consultant and speaker for Madrigal Pharmaceuticals. Three coauthors are Madrigal employees and own stock options in the company. Two coauthors are Madrigal consultants and advisers. Ayesh reported no conflicts.
A version of this article appeared on Medscape.com.
PHOENIX — according to the results of a new study.
As well as showing sustained reduction in liver stiffness on vibration-controlled transient elastography (VCTE) after 2 years of treatment with resmetirom, the study suggested that up to 35% of patients could “potentially reverse their cirrhosis,” said lead author Naim Alkhouri, MD, chief medical officer and director of the steatotic liver program at Arizona Liver Health in Phoenix.
Alkhouri presented data on patients with compensated cirrhosis from a 1-year open-label extension of the already-completed MAESTRO-NAFLD-1 study at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
The FDA approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals) in 2024 for MASH and moderate-to-advanced liver fibrosis (consistent with stage F2 and F3 disease), to be used in conjunction with diet and exercise. The agency granted the once-daily, oral thyroid hormone receptor beta-selective agonist breakthrough therapy designation and priority review.
According to the American Liver Foundation, about 5% of adults in the US have MASH — one of the leading causes of liver transplantation in the country. There is currently no FDA-approved therapy for compensated cirrhosis caused by MASH, said Alkhouri. Patients with MASH cirrhosis with clinically significant portal hypertension (CSPH) experience major adverse liver outcomes.
In an analysis of 122 patients with Child Pugh A MASH cirrhosis who completed both a year in an open-label arm of MAESTRO-NAFLD-1 and a 1-year extension, 113 (93%) completed 2 years of treatment with resmetirom (80 mg). Of the 122 patients, only 114 received MRI proton density fat fraction (MRI-PDFF) testing — 93 (82%) had a baseline of > 5% indicating cirrhosis, while 21 (18%) had an MRI-PDFF of < 5%.
Patients were assessed for baseline portal hypertension (Baveno VII) with FibroScan VCTE and platelet count, which was confirmed using magnetic resonance elastography (MRE). Noninvasive biomarkers and imaging were analyzed at baseline and out to 2 years.
At baseline, 63% of patients were categorized as probable/definitive CSPH (Baveno VII). At 1 year of treatment with resmetirom, 20% of patients who were CSPH positive no longer met the criteria, and at 2 years this number had increased to 28%.
After 2 years of treatment, more than half of the patients had a sustained reduction in liver stiffness of more than 25%, as measured by VCTE; and 35% of patients with confirmed F4 at baseline (liver biopsy F4 and/or platelets < 140/MRE ≥ 5 with VCTE ≥ 15) had a conversion to F3.
Patients taking resmetirom also had significant improvements in MRI-PDFF and MRE at 2 years. Almost a third of those with a baseline MRI-PDFF > 5% improved, while 43% of those with a baseline of < 5% improved.
Although 113 patients had an adverse event — primarily gastrointestinal — the observed events were consistent with previous studies. Twenty-seven patients had a serious adverse event, but none were related to the study drug, said Alkhouri. The researchers reported that only 8% of patients discontinued the medication.
Changing the Treatment Landscape for MASH-Related Cirrhosis
When asked to comment by GI & Hepatology News, Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, said that “reversal of cirrhosis from F4 to F3 and reduction of portal hypertension are quite surprising, since cirrhosis typically progresses slowly.”
Ayesh said it was notable that the researchers had used imaging to confirm both functional and hemodynamic improvements in liver architecture not just biochemical changes. Given the results, “clinicians may reasonably consider off-label use in selected compensated patients until more outcome data become available,” he said.
A phase 3 study is underway to examine those outcomes, MAESTRO-NASH OUTCOMES, with 845 patients with MASH cirrhosis, and should be completed in 2027.
“Resmetirom could change the treatment landscape for MASH-related cirrhosis,” said Ayesh, adding, “this drug offers a chance to target the disease process itself,” while other therapies focus on preventing complications.
“For patients without access to liver transplant, a therapy that can slow or reverse disease progression could be transformative,” he told GI & Hepatology News.
Alkhouri disclosed that he is a consultant and speaker for Madrigal Pharmaceuticals. Three coauthors are Madrigal employees and own stock options in the company. Two coauthors are Madrigal consultants and advisers. Ayesh reported no conflicts.
A version of this article appeared on Medscape.com.
PHOENIX — according to the results of a new study.
As well as showing sustained reduction in liver stiffness on vibration-controlled transient elastography (VCTE) after 2 years of treatment with resmetirom, the study suggested that up to 35% of patients could “potentially reverse their cirrhosis,” said lead author Naim Alkhouri, MD, chief medical officer and director of the steatotic liver program at Arizona Liver Health in Phoenix.
Alkhouri presented data on patients with compensated cirrhosis from a 1-year open-label extension of the already-completed MAESTRO-NAFLD-1 study at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
The FDA approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals) in 2024 for MASH and moderate-to-advanced liver fibrosis (consistent with stage F2 and F3 disease), to be used in conjunction with diet and exercise. The agency granted the once-daily, oral thyroid hormone receptor beta-selective agonist breakthrough therapy designation and priority review.
According to the American Liver Foundation, about 5% of adults in the US have MASH — one of the leading causes of liver transplantation in the country. There is currently no FDA-approved therapy for compensated cirrhosis caused by MASH, said Alkhouri. Patients with MASH cirrhosis with clinically significant portal hypertension (CSPH) experience major adverse liver outcomes.
In an analysis of 122 patients with Child Pugh A MASH cirrhosis who completed both a year in an open-label arm of MAESTRO-NAFLD-1 and a 1-year extension, 113 (93%) completed 2 years of treatment with resmetirom (80 mg). Of the 122 patients, only 114 received MRI proton density fat fraction (MRI-PDFF) testing — 93 (82%) had a baseline of > 5% indicating cirrhosis, while 21 (18%) had an MRI-PDFF of < 5%.
Patients were assessed for baseline portal hypertension (Baveno VII) with FibroScan VCTE and platelet count, which was confirmed using magnetic resonance elastography (MRE). Noninvasive biomarkers and imaging were analyzed at baseline and out to 2 years.
At baseline, 63% of patients were categorized as probable/definitive CSPH (Baveno VII). At 1 year of treatment with resmetirom, 20% of patients who were CSPH positive no longer met the criteria, and at 2 years this number had increased to 28%.
After 2 years of treatment, more than half of the patients had a sustained reduction in liver stiffness of more than 25%, as measured by VCTE; and 35% of patients with confirmed F4 at baseline (liver biopsy F4 and/or platelets < 140/MRE ≥ 5 with VCTE ≥ 15) had a conversion to F3.
Patients taking resmetirom also had significant improvements in MRI-PDFF and MRE at 2 years. Almost a third of those with a baseline MRI-PDFF > 5% improved, while 43% of those with a baseline of < 5% improved.
Although 113 patients had an adverse event — primarily gastrointestinal — the observed events were consistent with previous studies. Twenty-seven patients had a serious adverse event, but none were related to the study drug, said Alkhouri. The researchers reported that only 8% of patients discontinued the medication.
Changing the Treatment Landscape for MASH-Related Cirrhosis
When asked to comment by GI & Hepatology News, Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, said that “reversal of cirrhosis from F4 to F3 and reduction of portal hypertension are quite surprising, since cirrhosis typically progresses slowly.”
Ayesh said it was notable that the researchers had used imaging to confirm both functional and hemodynamic improvements in liver architecture not just biochemical changes. Given the results, “clinicians may reasonably consider off-label use in selected compensated patients until more outcome data become available,” he said.
A phase 3 study is underway to examine those outcomes, MAESTRO-NASH OUTCOMES, with 845 patients with MASH cirrhosis, and should be completed in 2027.
“Resmetirom could change the treatment landscape for MASH-related cirrhosis,” said Ayesh, adding, “this drug offers a chance to target the disease process itself,” while other therapies focus on preventing complications.
“For patients without access to liver transplant, a therapy that can slow or reverse disease progression could be transformative,” he told GI & Hepatology News.
Alkhouri disclosed that he is a consultant and speaker for Madrigal Pharmaceuticals. Three coauthors are Madrigal employees and own stock options in the company. Two coauthors are Madrigal consultants and advisers. Ayesh reported no conflicts.
A version of this article appeared on Medscape.com.
FROM ACG 2025












