S18e - 1 10 2014

Essentials in
Gastroenterology
and Hepatology
Stephan Vavricka Reviewed by:

Martin Wilhelmi Gert van Assche
Axel Dignass
Eugeni Domènech
Fernando Gomollón García
Peter Irving
Torsten Kucharzik
James Lindsay
Gerassimos Mantzaris
Gerhard Rogler
C. Janneke van der Woude
The information contained in this brochure is intended exclusively for
physicians and pharmacists. The contents reflect current developments
in medical science. For information on indications and dosage schemes
of the drugs please refer to the current SPCs (summary of product
characteristics). Product presentations, compositions, indications and
safety information as referenced herein may differ from those in your
country. For further information, please contact Dr. Falk Pharma GmbH,
Freiburg (Germany) or your local Falk partner.
Publisher
FALK FOUNDATION e.V.

Leinenweberstr. 5
79108 Freiburg
Germany
www.falkfoundation.org
2014
All rights reserved.
Authors
PD Dr. S. Vavricka
Dr. M. Wilhelmi
Zürich
Current contributors
Dr. med. Nora Schaub
Dr. med. Christophe Petrig
Dr. med. Beat Helblig
Dr. med. Daniel Heinrich
Prof. Franc Hetzer
Dr. med. Markus Grandel
Dr. med. et. phil. nat. David Semela
PD Dr. med. Stephan Wildi
Dr. med. Christoph Gubler
Dr. med. Christine Manser
PD Dr. med. Heiko Frühauf
Dr. med. Nico Wiegand
Prof. Dr. Alex Straumann
Former contributors
Dr. med. Patrick Aepli
Dr. med. Emanuel Burri
Dr. med. Mathias Dolder
Dr. med. Michael Manz
Dr. med. Ingo Mecklenburg
Prof. Dr. med. Dr. phil. Gerhard Rogler
PD Dr. med. Alain Schoepfer
PD Dr. med. Radu Tutuian
3
Contents
Foreword 8
Endoscopy in general
Gastrointestinal Endoscopy 10
Interventional Endoscopy 17
Interventions for treating persistent
and intractable hiccups in adults 20
Esophagus
Reflux 22
Barrett esophagus 23
Gastrooesophageal Reflux Disease (GERD) 24
Eosinophilic Esophagitis 26
Eosinophilic Esophagitis and Gastroenteritis 32
Motility of the esophagus 34
Achalasia in HRM/EPT 41
Achalasia 42
Varices 46
Linton – Tube 49
Corrosive injury 51
Stomach
Dyspepsia 54
Metaplasia 55
Gastritis 56
Gastric Ulcers 63
Upper Gl bleeding 64
Functional Gl disorders 68
Intestine
Operation Techniques 70
4
Acute Diarrhea 74
Chronic Diarrhea 78
Functional Gl disorders 88
Functional Gl disorders: Constipation 96
Terminal ileitis differential diagnosis 104
IBD Therapy 106
Fistula 136
Clostridium difficile therapy 138
Celiac disease 139
Mid Gl Bleeding 143
Lower Gl Bleeding 144
Polyps 145
CRC 150
HNPCC 152
High risk colorectal cancer conditions 154
Ogilvie syndrome 160
Diverticulitis 162
Malabsorption 164
Lactose intolerance 180
Small intestine bacterial overgrowth 183
Proctology hemorrhoids 184
Proctology fissures 190
Proctology Incontinence score 192
Proctology: Fecal incontinence 193
Proctology: Condylomata acuminata
(Swiss recommendation) 195
Hepatology
Liver segments 196
Hepatopathy 200
Ascites-SBP-HRS 205
5
Contents
CHILD PUGH score 209

HCC Hepatocellular carcinoma 210
Portal vein thrombosis (PVT) 212
TIPS 214
Aethylic hepatitis 216
MELD Score 217
Alcoholic hepatitis 218
Acute Liver Failure 220
Hemochromatosis 221
Wilson Disease 223
Hepatitis B 224
Hepatitis C 227
Autoimmune hepatitis 232
Liver and pregnancy 240
Liver nodule 246
Non-Alcoholic Steatohepatitis 248
Acute Porphyria 251
Epidemiology PSC and PBC 252
Symptoms, findings and treatment options
PBC and PSC 254
Biliary Diseases
Gallbladder polyps 256
Choledocholithiasis 258
Choledochal cyst 259
Pancreas
Pancreas cyst 260
Acute pancreatitis 265
Increase of Amylase and Lipase 268
Chronic pancreatitis 270
6
Oncology
Tumor staging 274
Esophageal Cancer 277
Early Gastric Cancer 284
Gastric Cancer 285
Colon Cancer 286
Rectum Cancer 287
Anal Cancer 288
Pancreatic Cancer 290
Cholangiocarcinoma Diagnosis 292
Cholangiocarcinoma 293
Gallbladder Cancer 294
Neuroendocrine Cancer 295
Gastro-intestinal-Stroma Tumor (GIST) 296
Intestinal Lymphoma 298
7
Gastrointestinal Endoscopy
Checklist for home discharge after digestive endoscopy:
Stable vital signs for at least 1 hour

Alert and oriented to time, place, and person (infants and patients
whose mental status was initially abnormal should have returned to
their baseline status)
No excessive pain, bleeding, or nausea
Ability to dress and walk with assistance
Discharged home with a responsible adult who will remain with the
patient overnight to report any post-procedure complications
Written and verbal instructions outlining diet, activity, medications,
follow-up appointments, and a phone number to be called in case
of emergency
A contact person and circumstances that warrant seeking the
assistance of a health care professional clearly outlined
Tolerating oral fluids not mandatory, unless specified by physician
(i.e. patient is diabetic, frail, and/or elderly; not able to tolerate an
extended period of NPO status)
[Dumonceau JM et al.: Endoscopy 2010 42(11): 960–974]
Quality Indicators for Screening Colonoscopy:

1. Adenoma detection rate > 15% in females and > 25% in male
patients (NEJM)
2. Adequate bowel cleansing: at least 90% of screening examinations
should be rated as having “adequate” or better (ESGE)
3. Minimum experience for screening colonoscopists: minimum lifetime
experience of 1000 examinations and a minimum annual number of
150 screening colonoscopies (UK NHS Bowel Cancer Screening, GIE)
4. Minimum standard of 90% cecal intubation rate and minimal
withdrawal time of 6 minutes in at least 90% of purely diagnostic
examinations (ESGE)
5. At least 90% of resected polyps are retrieved for histological
analysis (ESGE)
[Kaminski MF et al., N Engl J Med 2010;362:1795-803. Corley DA et al., N Engl J Med
2014;370:1298-306. Rembacken B et al., Endoscopy 2012; 44: 957–968 (ESGE
position statement) Lee SH et al., Gastrointest Endosc. 2008 Apr;67(4):683-9]
10
Risks of complications:
Event Frequency
EGD Bleeding 0% in diagnostic EGD
< 0.1% after taking biopsies
Perforation 0.1–1% after dilatation
of benign strictures
1 – 5% after dilatation
of malignant strictures
1 – 3% after pneumatic dilatation
of achalasia
Colono- Bleeding 0.2% in total
scopy 0.3 – 10% after intervention
Perforation 0.1% in diagnostic colonoscopy
0.1 – 0.3% in therapeutic colonoscopy
Morbidity 0.2% in diagnostic colonoscopy
0.1 – 0.3% in therapeutic colonoscopy
Mortality 0 – 0.006% in total
ERCP Pancreatitis 1.3 – 6.7% post-ERCP
Mortality 0.5% (mainly due to pancreatitis)
Bleeding after sphincterotomy 1.3% (mostly mild)
PEG Leakage up to 78%
Peristomal infection up to 32%
Early mortality 8–28% mortality within 30 days
of PEG insertion
Post-PEG pneumoperitoneum 30%, but usually w/o clinical relevance
Aspiration 0.3–1%
Bleeding 0–2.5%
Buried bumper syndrome 0.3–2.4%
Peritonitis 0.5–1.3%
Accidental removal 1.6–4.4%
of the catheter
Colo-gastrocutaneus fistula 0.3–6.7%
or other fistulous tracts
Trans- or intrahepatic PEG placement
Gastric volvulus
Tumor seeding and gastric outlet obstruction
Cardiopulmonary Complications
Cardio-pulmonary complications account for about 50 % of the
potentially serious morbidity and approximately 50 % of all the
procedure-related deaths associated with GI Endoscopy.
Aspiration with possible subsequent pneumonia, myocardial ischaemia,
TIA or stroke are well-known complications of GI endoscopy.
These complications may occur up to 30 days after the procedure.
[Schrag SP et al., J Gastrointestin Liver Dis 2007; 16 (4): 407-418]

11
Attention should be paid to these possible risk factors:

rEVSBUJPOPGBOEESVHEPTBHF TFEBUJWFBHFOUT FUD
EVSJOHUIF
examination
rPMEFSBHF jGSBJMUZv
rTJHOJàDBOUDPNPSCJEJUJFT DBSEJBD QVMNPOBSZ OFVSPMPHJDBM FUD
rNPSCJEMZPCFTFQBUJFOUT
rTMFFQBQOPFBTZOESPNFPSQBUJFOUTXJUIDISPOJDSFTQJSBUPSZGBJMVSF
rNJTNBOBHFNFOUPGJOEJDBUFEESVHT FHTUPQBTQJSJO
Cardiopulmonary complications may occur in 0.9% of colonoscopic

procedures and in up to 0.6% of upper GI tract endoscopies (ASGE).
[Green J et al., BSG guideline 2006; accessed 21.05.14 -> http://www.bsg.org.
uk/clinical-guidelines/endoscopy/guidelines-on-complications-of-gastrointestinal-
endoscopy.html]
[Ben-Menachem T et al., Gastrointest Endosc. 2012 Oct;76(4):707-18.
(ASGE guideline)]
[Fisher DA et al., Gastrointest Endosc. 2011; 74(4):745-52. (ASGE guideline)]
[Gangi S et al., Gastrointest Endosc. 2004 Nov;60(5):679-85.]
[Macrae FA et al., Gut 1983; 24, 376-383.]
[Blomberg J et al., Scand J Gastroenterol. 2012; 47: 737–742.
Lynch C, Fang J. Pract Gastroenterol 2004; 28: 66–76]
Absolute and relative contraindications of PEG:

sPHARYNGEALORESOPHAGEALOBSTRUCTION
sACTIVECOAGULOPATHY
sANYOTHERGENERALCONTRAINDICATIONTOENDOSCOPY
rMBDLPGUSBOTJMMVNJOBUJPO
rHBTUSJDWBSJDFT
rQSFTFODFPGBTDJUFT
rNPSCJEPCFTJUZ
rQSJPSHBTUSPJOUFTUJOBMTVSHFSZ
rDISPOJDBNCVMBUPSZQFSJUPOFBMEJBMZTJT
rOFPQMBTUJD JOàMUSBUJWF PSJOáBNNBUPSZEJTFBTFPGUIFBCEPNJOBMXBMM
[Schrag SP et al., J Gastrointestin Liver Dis 2007; 16 (4): 407-418]
12
Chromoendoscopy for screening

of dysplasia in the colon
Indigo NaCl 0.9 % Final Dilution
carmine 0.4 %
Small 1 Ampulla 20 ml of 0.1 % 20 ml of 0.1 %
amounts (each 5 ml = 20 mg)
Larger 2 Ampullas 50 ml of 0.1% 50 ml of 0.1 %

amounts (each 5 ml = 20 mg) for Aliance-Pump for Aliance-Pump
60 to 100 ml solution are needed for the whole colon
Chromoendoscopy procedure
r Adds about 11 minutes to the duration of the procedure
r After the cecum has been reached, to reduce spasm:
iv butyl-scopolamine 20 mg
r "EFRVBUFBJSJOTVGáBUJPOJTOFDFTTBSZ
r A dye-spray catheter is inserted down the instrumentation channel,
and the tip protruded 2 to 3 cm
r Firmly squeezing the syringe, a fine mist of dye is then painted onto
the mucosa by withdrawing the colonoscope in a spiral fashion
r Spraying should be done in a segmental fashion (every 20–30 cm)
r Excess dye is suctioned, and the colonoscope reinserted proximally
r Wait a few seconds for indigo carmine to settle into the mucosal
contours
r Once that segment has been examined, the next segment is
sprayed, and so on
[Kiesslich R, Neurath M.; Gastroenterol Clin North Am. 2012 Jun;41(2):291-302]
13
Management of antiplatelet agents during endoscopy:
Bleeding Intervention: Continue Continue Continue

Risk: aspirin clopidogrel Antico-
or prasugrel agulation*
Low EGD, colonoscopy and Yes Yes Yes
enteroscopy ± biopsies
EUS without FNA Yes Yes Yes
Colonic polypectomy Yes No No**
< 1 cm
Dilation of digestive Yes No No**
stenoses
Digestive stenting Yes No Yes
ERCP without Yes Yes Yes
sphincterotomy
Argon plasma Yes No No**
coagulation
High EMR, ESD, No No No
or ampullary resection
EUS FNA of cystic No No No
lesions
Colonic polypectomy Yes No No
> 1 cm
ERCP with sphinctero- No No No
tomy or large-balloon
papillary dilation
Percutaneous endo- Yes Unknown No
scopic gastrostomy
Esophageal variceal Yes No No
band ligation
[Boustiere C et al.: Endoscopy 2011 and www.sggssg.ch]

* Coumarin, unfractionated heparin (UFH), low-molecular-weight heparin
(LMWH), Dabigatran, Rivaroxaban
** with our without bridging depending on the thrombotic risk
[Baron TH et al. N Engl. J Med 2013; 368: 2113–24]
14
Risk stratification for GI endoscopy under antiplatelet agents:
Endoscopy Endoscopy
with low with high
bleeding risk: bleeding risk:
Low thrombotic risk: Maintain r Stop ASA 5 days
r Coronary DES antiplatelet only for EUS-FNA of
> 12 months agent therapy cysts, EMR and
previously ESD, ampullary
r Bare metal coronary resection and endo-
stents inserted scopic sphincteroto-
> 6 weeks previously my with large-bal-
without associated loon papillary dilation
risk factors r In patients taking
r Stroke without thienopyridine alone,
cardiac failure > 6 it is recommended to
weeks previously substitute with aspirin
High thrombotic risk: Maintain dual r Delay endoscopy and/
r Coronary drug antiplatelet or consult cardiologist
eluting stent ≤ 12 agent therapy to discuss temporary
months previously cessation of thienopy-
r Bare metal coronary ridine:
stent ≤ 6 weeks pre- clopidogrel, 5 days
viously or > 6 weeks prasugrel, 7 days
with risk factors r ASA should be
r stroke ≤ 6 weeks maintained in all
previously cases
[Boustiere C et al.: Endoscopy 2011 43(5): 445–461]
15
Anticoagulation
Anticoagulant Risk of Stop before Start after
bleeding procedure procedure
(no inter-
vention)
UFH 4–6 h 12 h
LMWH Prophylactic dosing: 12 h 12 h
Therapeutic dosing: 24 h
Low thrombotic risk: Coumarin
- 3–5 days and 12 h
- when INR<1.8 5000 5000 IE
IE LMWH Start on LMWH
Coumarin 1.3 % / year s.c. till 12 h the same till INR>1.8
High thrombotic risk: evening 12 h bridging
- Bridging therapy with with therapy with
UFH/LMWH UFH for
(see above) 24–48 h
Rivaroxaban 2 % / year Low risk intervention*:
[anti-Xa] -1–2 days*
Dabigatran 1.8 % / year High risk intervention*: 24 h–72 h**

[anti IIa] - 2–3 days
Apixaban 0.8 % / year CAVE creatinine

[anti-Xa] clearance
< 50ml/min: 3–5 days
Ticagrelor 5 days
Prasugrel 7—10 days 24 h–72 h**
Clopidogrel
7—10 days
ASA / NSAR 0.4 % / year 7—10 days 48 h
* assuming normal renal function

** depending on bleeding risk of the procedure
NB: bridging therapy with high thrombotic risk can be considered but there should
be no overlap between heparin and NOACs (major increase in hemorrhagic risk)
[Source: Blood 2012; 120 (15): 2954-62, Gastrointestinal Endosc. 2013 ; 78 (2)
:227-39, European Journal of Internal Medicine 2014; 25: 213–20 and
www.sggssg.ch]
16
Interventional Endoscopy
OTSC® (Over The Scope Clip) ovesco
Indications
r QFSGPSBUJPO ràTUVMB
r BOBTUPNPUJDMFBL r CMFFEJOH
r OBSSPXJOHUIFBOBTUPNPTJTBGUFSHBTUSJDCZQBTTTVSHFSZ
Product
r TJ[FT mmNN
maximal outer diameter of the endoscope-tip
fitting the cap
r EFQUITPGDBQ NNCFUUFSPWFSWJFX
6 mm: grasping more tissue
r TIBQFTPG UZQFBBUSBVNBUJD
teeth: type t: traumatic
type gc: gastric closure (long and sharp)
®
Version of OTSC : type a type t type gc
Endoscopie size 8.5 – 11 mm 10.5 – 12 mm 11.5 – 14 mm
Depth of cap 3 mm
6 mm
r BQQMJDBUJPOBJET 054$"ODIPS DN

OTSC Anchor OTSC Anchor 220tt (220 cm) for thin tissue
OTSC Twin Grasper in 165 cm and 220 cm
r XPSLJOHDIBOOFM0OMZ054$4ZTUFNNJOJNBMNN
OTSC Twin Grasper OTSC System in combination with an application
aid: minimal 3.2 mm
optimal: > 3.2 mm
Pitfalls / Tips
r UIFTJ[FPGUIFDMJQJTEFQFOEFOUPOUIFTJ[FPGUIFFOEPTDPQF BOE
not of the lesion
r 054$4ZTUFNTJ[FJTNPTUMZUPPCJHUPQBTTUIFVQQFS
esophageal sphincter
r SFUSJFWJOHUIF054$4ZTUFNXJUIMPBEFEDMJQCBDLUISPVHIUIF
mouth gard: risk of accidental release on the tongue – therefore
good sedation, cutting plier nearby
r JGQPTTJCMFDPOUSPMUIFSFMFBTFPGUIFDMJQXJUIáVPSPTDPQZ
r 054$5XJO(SBTQFSEPOPUPQFOCPUITJEFTTJNVMUBOFPVTMZ
r 054$5XJO(SBTQFSQVMMCBDLJOUPUIFDBQ VOEFSáVPSPTDPQJD
control, to be sure that it is not getting fixed in the clip.
If it is not possible: only suction!
r QFSGPSBUJPOBMXBZTXJUI$02
r QFSGPSBUJPOJOUIFFTPQIBHVTFWFOUVBMMZJODPNCJOBUJPOXJUI
a covered stent
17
SEMS (Self Expanding Metal Stents)
Plastic stents are not used anymore.

Stents for bile and pancreatic ducts are not discussed.
Indications
r QFSGPSBUJPO àTUVMB BOBTUPNPUJDMFBL
r NBMJHOBOUTUSJDUVSF
r FTUBCMJTIFEFTPQIBHVT HBTUSJDPVUMFU
r DPOUSPWFSTJBMDPMPO
r FYQFSJNFOUBMTNBMMJOUFTUJOF
r DPOUSPWFSTJBMCFOJHOTUSJDUVSFT
r GVUVSFQBODSFBUJDQTFVEPDZTUT
Products / Methods
r VODPWFSFE
r GVMMZDPWFSFE
r QBSUJBMMZDPWFSFE
r FH6MUSBáFYCPUIFOETVODPWFSFE
Hanaro: below the ends uncovered
r SFTPSCBCMF
r MFOHUI EJBNFUFS SBEJPQBRVFNBSLFST TIPSUFOJOH
r UVMJQT FHNBOVGBDUVSFEUPEJNFOTJPO
r 554 5ISPVHI5IF4DPQF
NN
r QSPYJNBMSFMFBTFPSEJTUBMSFMFBTF
r PWFSHVJEFXJSF FH"NQMBU[TVQFSTUJGG
r DPOUSPMFESFMFBTFTJEFCZTJEFFOEPTDPQZ áVPSPTDPQZ
Duration
r VODPWFSFEEFàOJUJWF
r GVMMZDPWFSFENPOUIT
r QBSUJBMMZDPWFSFEDIBOHFFWFSZmXFFLT
r SFTPSCBCMF DBWFHSBOVMBUJPOUJTTVF11* TUFSPJET
18
SEMS (Self Expanding Metal Stents)
Pitfalls / Tips
r QFSGPSBUJPOFTPQIBHVTQBSUJBMMZDPWFSFE QSPYJNBMSFMFBTF
side by side endoscopy, large diameter if no stricture, duodenal
feeding tube
r FTPQIBHVTTUFOUUPPOFBSUPUIFVQQFSTQIJODUFS➔ painful
r UPPMBSHFEJBNFUFSTUFOUJTOPUFYQBOEJOHQSPQFSMZ
r TIPSUFOJOHTUFOUJTTMJQQJOHPWFSUIFMFTJPO
r UPPMPOHFYBNJOBUJPOJOUIFDPMPO BMTPXJUI$0
BJSUSBQQJOH
and risk of perforation
r "NQMBU[TVQFSTUJGGHVJEFXJSFJOUIFEJMBUFEDPMPOSJTLPGQFSGPSBUJPO
r DPMPOBOHVMBUJPO DIFNPUIFSBQZ➔ higher risk of perforation
HemosprayTM
Indications
r 6QQFSOPOWBSJDFBM(*CMFFEJOH BQQSPWFE

for variceal bleeding not yet approved
r -PXFS(*CMFFEJOH DVSSFOUMZTUJMMiPGGMBCFMVTFu
r 4VJUBCMFGPSNPOPUIFSBQZPSTBMWBHFUIFSBQZ
Product
r )FNPTQSBZTM by Cook Medical, Winston-Salem, North Carolina, USA
r )FNPTUBUJDJOPSHBOJDBHFOU
r *ODPOUBDUXJUINPJTUVSF )FNPTQSBZCFDPNFTDPIFTJWFBOE
adhesive, creating a mechanical barrier and effecting hemostasis.
r 5FDIOJRVFPGBQQMJDBUJPO
r "QQMZJOTIPSUCVSTUTGSPNUIFDBOJTUFS XJUIDBSCPOEJPYJEF
propulsion, through a 10-Fr catheter (Cook Medical) to the active
bleeding site until hemostasis is noted
r One burst on average contains 1 to 5 g of powder (Apply max. 20 g)
r 1MBDFUIFEJTUBMFOEPGUIFDBUIFUFSUPDNBXBZGSPNUIF
bleeding to prevent sticking of the catheter in moisture.
Pitfalls/Tips
r $POEJUJPOTJEFBMUPQSFGFS)FNPTQSBZBTàSTUMJOFUIFSBQZPWFS
standard hemostatic methods:
r P[JOHCMFFEJOHGSPNBNBMJHOBOUUVNPS
r CMFFEJOHJOWPMWJOHMBSHFSBSFBTPGNVDPTBUIBUXFSFOPUFBTJMZ
amenable to targeted standard therapies, such as portal hyper-
tensive gastropathy or gastric antral vascular ectasia.
r $"7&%POPUQMBDFUIFDBUIFUFSJONPJTUVSF
[Sulz MC, Frei R, Meyenberger C, et al. Routine use of Hemospray for gastrointestinal
bleeding: prospective two-center experience in Switzerland. Endoscopy 2014; Apr
25. [Epub ahead of print] PMID: 24770964] [Smith LA, Stanley AJ, Bergman JJ et
al. Hemospray application in nonvariceal upper gastrointestinal bleeding: Results of the
survey to evaluate the application of Hemospray in the luminal tract. J Clin Gastroenterol
2013: PMID: 24326829. Epub 2013 Dec 10]
19
Interventions for treating persistent and
intractable hiccups in adults
Definition:
ACUTE:
&UJPMPHZ r 4VEEFOHBTUSJDEJTUFOTJPO
r -BSHFNFBMT FBUFOGBTU
r $PME IPUPSDBSCPOBUFECFWFSBHFT
r &YDFTTJWFBMDPIPMDPOTVNQUJPO
r &OEPTDPQZ
r NFOUBMQSFTTVSF
CHRONIC:
relatively uncommon.
Æ serious detriment to patient’s quality of life
Persistent hiccups:
Hiccups lasting >48 hours
intractable hiccups:
Hiccups lasting for >1 month
&UJPMPHZ r %JTPSEFSTPGUIFDFOUSBMOFSWPVTTZTUFN
(neoplastic, infectious, ischemic)
r -FTJPOTPGUIFWBHBMPSUIFQISFOJDOFSWF
r NFUBCPMJDUPYJD BMDPIPM VSFNJB EJBCFUFT
hyponatremia, hypocalcemia)
r ESVHT CBSCJUVSBUFT EFYBNFUIBTPOF EJB[FQBN
r QPTUTVSHFSZ
r QTZDIPHFOJD
Treatment
NON-PHARMACOLOGICAL INTERVENTIONS:
r #SFBUIJOHNBOFVWFST 7BMTBMWBNBOFVWFS CSFBUIIPMET

hyperventilation, cough)
r /BTBMBOEQIBSZOHFBMTUJNVMBUJPO
- Compression on the root of the nose or upper lip
- Inhalation of ammonia, ether
- Gargling with water
- Fast drinking of iced water or vinegar
- Teaspoon of sugar, citron soaked lump sugar
- Sneeze
20
Interventions for treating persistent and
intractable hiccups in adults
- Stimulation of soft palate, Uvula

- Vagal stimuilation: compression of the bulb, carotis massage
- Gastric emptying
- Phrenic slow down (epigastric massage)
- Hypnosis
- Acupuncture
PHARMACOLOGICAL INTERVENTIONS:
Active Dosage
component
Tizanidine 2–4 mg up to 24
(max 36 mg)/d
Chlorpromazine 3 x 25–50 mg p.o.
or 25 mg i.v.
Metoclopramide 3 x 10 mg p.o. or i.v.
Baclofen 3 x 5–20 mg p.o.

Lidocaine 1–2 mg/kg i.v.
Nimodipine 3 x 30 mg p.o.
Haloperidol 3 x 1–4 mg p.o.
Valproat Increase to 20 mg/kg
Gabapentine 3 x 300 mg
Carbamazepine 3 x 100–300 mg p.o.
Amitriptyline 25–50 mg p.o.
200 mg i.v.
Phenytoin 100–300 mg/d p.o.
Nifedipine 4 x 10–20 mg p.o.
«However, there is insufficient evidence to guide the treatment of persistent or in-
tractable hiccups with either pharmacological or non-pharmacological interventions.»
[Ref.: Moretto EN et al., Cochrane Database Syst Rev 2013; 1:CD008768]
21
Esophagus
4GƃWZ
Reflux esophagitis: Los Angeles

Armstrong et al. Gastroenterology 1996;111:85-92
Grade A Grade B Grade C Grade D

Erosion(s) Erosions Erosions Erosions
n 5 mm > 5 mm Multiple Multiple
One mucosal One mucosal mucosal folds mucosal folds
fold fold n 75% > 75%
circumference circumference
Reflux esophagitis: Savary-Miller

M. Savary, G. Miller 1978
Grade I Grade II Grade III Grade IV Grade V

one or more DPOáVFOU lesion covers esophageal Barrett
OPODPOáVFOU erosive and the complete ulcer, Barrett´s esophagus
lesions with edematous esophageal epithelium,
erythema and lesions not circumference strictures and
edema covering the other chronic
complete mucosal
esophageal lesions
circumference
22
4GƃWZ
Reflux esophagitis: MUSE

Armstrong et al. Hepatogastroenterol 1992;39:3-13
Stage Metaplasia Ulcer Stricture Erosions

0 absent absent absent absent
1 (mild) fingers ± islands 1 ulcer ≥ 9 mm 1 fold
2 (severe) circumferential > 1 ulcer < 9 mm > 1 fold
Hiatus hernia: yes no
Example: M2 U0 S2 E1
Barrett esophagus
Updated Guidelines 2008 for the Diagnosis,
Surveillance and Therapy of Barrett’s Esophagus
Dysplasia Grade and Surveillance Interval
Dysplasia Documentation Follow-Up
None Two EGDs with biopsy Endoscopy every
within 1 year 3 years
Low Grade r)JHIFTUHSBEFPOSFQFBU 1 year interval until
EGD* with biopsies no dysplasia x 2
within 6 months
r&YQFSUQBUIPMPHJTU ER*
confirmation Continued 3 month
High Grade r.VDPTBMJSSFHVMBSJUZ surveillance or inter-
r3FQFBU&(%XJUI vention based on
biopsies to rule out EAC results and patient
*EGD – esophagogastroduodenoscopy; ER – endoscopic resection; EAC –
esophageal adenocarcinoma.
8
Distance (cm) from GEJ
Diagrammatic represen-
6 tation of endoscopic
Maximal extent of Barrett's esophagus
4 metaplasia: M = 5.0 cm showing an area classified
as C2M5. C: extent of
circumferential metaplasia;
2 Circumferential extent of M: maximal extent of the
metaplasia: C = 2.0 cm
metaplasia (C plus a distal
0 True position of GEJ: «tongue» of 3 cm); GEJ:
Origin = 0.0 cm gastroesophageal junction.
[Sharma P. Gastroenterology 2006;131:1392–1399]

23
Esophagus
)CUVTQGUQRJCIGCN4GƃWZ&KUGCUG
)'4&
Definitions
GERD A presumptive diagnosis of GERD

can be established in the setting of
typical symptoms of heartburn and
regurgitation.
Erosive reflux disease Erosive oesophagitis at endoscopy-
Non-erosive reflux No mucosal break at endoscopy and
disease (NERD) abnormal oesophageal acid exposure
at 24-h oesophageal pH monitoring.
Acid hypersensitive No mucosal break at endoscopy, nor-
oesophagus mal oesophageal acid exposure and
positive symptom-reflux association
analysis (SI>50%, SAP>95%) at 24-h
oesophageal pH monitoring.
Functional heartburn Heartburn refractory to PPIs without
any mucosal break at endoscopy,
normal oesophageal acid exposure
and negative symptom-reflux asso-
ciation analysis (SI<50%, SAP<95%)
at 24-h oesophageal pH monitoring.
SI= Symptom Index

/VNCFSPGSFáVYSFMBUFETZNQUPNFQJTPEFTUPUBMOVNCFSPGTZNQUPN
episodes ×100
SAP=Symptom Association Probability

Statistical parameter that expresses the likelihood that the patient’s
TZNQUPNTBSFSFMBUFEUPSFáVY
Reflux symptoms refractory to PPI

r %FàOJUJPOPG11*SFGSBDUPSZSFáVYOPSFTQPOTFPGSFáVYTZNQUPNT
(heartburn, regurgitation) to a stable double dose of a PPI during a
treatment period of at least 12 weeks.
r "QQSPYJNBUFMZPGQBUJFOUTXJUITVTQFDUFE(&3%BSFSFTJTUBOU
or partial responders to PPIs.
r .BOZPGUIFTFQBUJFOUTEPOPUIBWF(&3% CVUTVGGFSGSPN
functional heartburn or dyspepsia.
24
)CUVTQGUQRJCIGCN4GƃWZ&KUGCUG
)'4&
Algorithm for management of patients

with refractory reflux symptoms
Failure of PPIs twice daily

(for 3 months)
GERD GERD
never demonstrated previously demonstrated
Oesophagitis
Gastroscopy
24h-pH-impedance
testing on PPI
24h-pH-impedance
testing off PPI
Functional Hyper- NERD Positive Negative

heartburn sensitive Symptom- Symptom-
Oeso- Associa- Asso-
phagus tion-Ana- ciation-
lysis Analysis
(SI, SAP) (SI, SAP)
Pain - TLOSR inhibitors Pain

Modulators (Baclofen) Modulators
(SSRIs, SSRIs - Surgery (SSRIs,
Tricyclics) Tricyclics)
[Modified from:
Diagnosis and management of patients with reflux symptoms refractory to proton
pump inhibitors – Sifrim and Zerbib – Gut – 2012 61: 1340–54]
25
Esophagus
Eosinophilic Esophagitis
Definition:
r $ISPOJDFTPQIBHFBMFPTJOPQIJMQSFEPNJOBOUJOáBNNBUJPOXJUI
symptoms of esophageal dysfunction (mostly dysphagia and/or
thoracic pain)
[Liacouras C, et al. J Allergy Clin Immunol 2011 128(1): 3–20]
Important facts to remember:

r $VNVMBUJWFQSFWBMFODF
Male : female = 3:1
Allergies to aero-allergens and/or food allergens in 60–90%
of the EoE population
Diagnosis:
r FPTJOPQIJMTIJHIQPXFSàFME NBHOJàDBUJPOY
BGUFS
an 8-week trial with proton pump inhibitors in standard dose
(eg. Pantoprazole 40mg/day). Important: patient must still be under
PPI when diagnostic endoscopy is performed. Take 4 biopsies from
distal esophagus, 4 from proximal esophagus and additional
biopsies from lesions such as white exudates.
Differential diagnosis of esophageal eosinophilia:
1. EoE: persistance of symptoms and eosinophils despite
PPI treatment
2. GERD: normalization of symptoms and eosinophil counts
under PPI treatment
3. PPI-responsive esophageal eosinophilia (PPI-REE): initial clinical,
endoscopic and histologic aspect similar to EoE, but improvement
of symptoms and reduction of eosinophil counts under PPI-therapy.
Notably, there exists not yet a definition for "clinical" and/or
«histologic» response.
4. Other differential diagnoses: Crohn's disease, celiac disease,
achalasia, tissue-invasive parasites (eg. anisakis => sushi), etc.
[Liacouras C, et al. J Allergy Clin Immunol 2011]
26
Treatment:
r 11*YNHEJOQBUJFOUTXJUIPWFSMBQUP(&3%
r *OEJWJEVBMFMJNJOBUJPOEJFUJODIJMESFOXJUIQSPWFOGPPEBMMFSHZPS
6-food elimination diet (excluding cow milk protein, soy, wheat,
egg, peanut, and seafood)
[Kagalwalla AF et al.: Clin Gastroenterol Hepatol 2006]
r 4XBMMPXFEUPQJDBMTUFSPJETBTst line therapy:

- Fluticasone (spray 250 μg) or
- Budesonide (spray 250 μg):
swallow 4 spray doses b.i.d. for 12 weeks
r 4ZTUFNJDTUFSPJET FH1SFEOJTPOFNHLH
GPSBGFXXFFLTPOMZ
in refractory patients
Therapy regimen:
r *OEVDUJPOUSFBUNFOUFHCVEFTPOJEFNHGPSXFFLT
r .BJOUFOBODFUSFBUNFOUFHCVEFTPOJEFNH
Complications:
r 6OUSFBUFEFPTJOPQIJMQSFEPNJOBOUJOáBNNBUJPOMFBETUP
esophageal strictures with the risk of bolus impactions with the
inherent risk of esophageal perforation, either retching-induced
(Boerhaave syndrome) or procedure-induced (especially if
endoscopic desimpaction is performed by rigid esophagoscopy)
[Schoepfer AM, et al. Gastroenterology 2013]
r QFSGPSNFTPQIBHFBMEJMBUJPOJOTZNQUPNBUJD&P&QBUJFOUTOPU
responding to steroids and /or diets with presence of esophageal
strictures
27
Esophagus
EoE Treatment Algorithm 2013
Swallowed topical steroid (syrup or powder)

Fluticasone or budesonide;
2 mg /day, 2–3 wks
Responder Non-Responder
Swallowed topical steroid 1FSTJTUFOUJOáBNNBUJPO

Low-dose maintenance-
treatment for 1 year, reassess
symptoms, endoscopy and
histology in one year Systemic steroids
(if clinical remission) e.g. Prednisone 50 mg/day
Wean steroids
Determine maintenance Responder
regimen (options):
r OPBOUJFPTJOPQIJMUIFSBQZ
dilation if needed
r *NNVOPNPEVMBUPST
(Aza/6-MP)
r *ODMVEFJOUPTUVEZ
(eg. Anti-IL13)
[Straumann A. et al. NATURE Review 2012]
28
Diet
or
Elemental, Empirical 6-FED
Stricture Dilation
Include into study

Non-Responder (eg. CRTH2-Blocker, anti-IL13)
29
Esophagus
White exudates, edema Pinpoint-shaped white exudates

(loss of vascular pattern) and (corresponding histologically
longitudinal furrows to eosinophilic microabscesses)
Linear furrows (railroad track), Concentric rings (trachealization)

trachealization and some white JOBOPOJOáBNFEFTPQIBHVT
exudates
Prescription for a budesonide syrup for the pharmacist:

r NJYNHCVEFTPOJEFQPXEFS
FHGSPN.JáPOJEFNHDBQTVMFT
JOUPNM4VDSBMPTF
r DSFBUFTZSVQCPUUMFPGNM
30
Application technique for Eosinophilic Esophagitis
1. Force the red cover apart
2. With a screwdriver, crack the orange container open

(along the side line)
3. Take out the blister with the

60 portions of drug
4. Pull blister open and position powder

onto the tongue
[Courtesy of Prof. A. Straumann]
31
Esophagus
Eosinophilic Esophagitis and Gastroenteritis
Eosinophilic gastroenteritis (EGE)
Epidemiology:
rare, poorly defined clinical condition, in adults often chronic
relapsing, males > females affected
Gastrointestinal symptoms (non-specific):
r NVDPTBMJOWPMWFNFOUWPNJUJOH EJBSSIFB BCEPNJOBMQBJO
weight loss, failure to thrive, occult or frank bleeding
r NVTDVMBSMBZFSTJOWPMWFNFOUTJHOTBOETZNQUPNT
of obstruction
r TFSPTBMMBZFSJOWPMWFNFOUQSFTFOUBUJPOXJUIBT[JUFT
Diagnosis:
r FYDMVTJPOPGPUIFSDBVTFTGPSJOUFTUJOBMFPTJOPQIJMJB
(parasitic infection, inflammatory bowel disease, connective
tissue diseases, vasculitis, drugs, lymphoproliferative
malignancies, hypereosinophilic syndrome)
r NBZQSFTFOUXJUIQFSJQIFSBMCMPPEFPTJOPQIJMJB

iron deficiency anemia, protein loosing enteropathy
r FWBMVBUJPOPGCJPQTZPSSFTFDUJPOTQFDJNFOTBGUFS
endoscopy or laparoscopic intervention (dense eosinophilic
infiltration of one or more segments of the gastrointestinal
tract, can affect all layers of the intestinal wall)
Treatment (based on case reports and small case series):

r TFSPTBMUZQFTZTUFNJDDPSUJDPTUFSPJET
r GPSPUIFSGPSNTPQUJNBMUSFBUNFOUJTOPUEFGJOFE CVUJODMVEFT
corticosteroids, proton pump inhibitors, mast cell stabilizers,
antihistamines, leukotriene antagonists, octreotide, surgical
resection of strictured segments
32
Eosinophilic Esophagitis and Gastroenteritis
Classification of Eosinophilic Gastrointestinal

disorders (EGID)
Primary (EGID) Secondary gut eosinophilia
Eosinophilic Esophagitis Reflux esophagitis
Eosinophilic Gastroenteritis Infections:
r &PTJOPQIJMJD(BTUSJUJT protozoal and other pathogens
r &PTJOPQIJMJD&OUFSJUJT Drugs:
r &PTJOPQIJMJD$PMJUJT NSAIDs, clozapine, rifampicin,
Food Hypersensitivity/Allergy enalapril, carbamazepine,
r *H&NFEJBUFE tacrolimus
r /PO*H&NFEJBUFE Systemic diseases:
Food protein induced r )ZQFSFPTJOPQIJMJDTZOESPNF
proctocolitis of infancy r $POOFDUJWFUJTTVFEJTFBTF
vasculitis
r -ZNQIPQSPMJGFSBUJWF
disorders
r (SBGUWFSTVTIPTUEJTFBTF
r *OGMBNNBUPSZCPXFMEJTFBTF
r $FMJBDEJTFBTF
33
Esophagus
Motility of the esophagus
Conventional manometry – per swallow analysis
15 cm
10 cm
5 cm
LES (HPZ)
Lower esophageal sphincter (LES)

r LES resting pressure (LESP): average (mid-respiratory or
end-expiratory) pressure in the lower esophageal sphincter
over a period of 5 –10 seconds
r LES residual pressure (LESRP): nadir pressure in the
LES during deglutitive relaxation (i.e. after a swallow)
34
Conventional manometry – per swallow analysis
Esophageal body
r Contraction amplitude and duration in the distal and
proximal esophagus
r Distal esophageal amplitude (DEA): average contraction
amplitude in the distal esophagus measured 5 cm apart
(i.e. 5 and 10 cm above the LES high-pressure zone or
3 and 8 cm above the proximal border of the LES)
r Distal esophageal duration (DED): average contraction
duration in the distal esophagus measured 5 cm apart
(i.e. 5 and 10 cm above the LES high-pressure zone or
3 and 8 cm above the proximal border of the LES)
r Contraction onset velocity: speed of propagation of the
onset of esophageal contraction in the distal esophagus
measured 5 cm apart (i.e. between 10 to 5 cm above the
LES high-pressure zone or 8 to 3 cm above the proximal
border of the LES)
r Contraction peak velocity: speed of propagation of the
contraction peak in the distal esophagus measured 5 cm
apart (i.e. between 10 to 5 cm above the LES high-pressure
zone or 8 to 3 cm above the proximal border of the LES)
Upper esophageal sphincter (UES)

r UES resting pressure (UESP): average pressure in the upper
esophageal sphincter over a period of 2 – 5 seconds
r UES residual pressure (UESRP): nadir pressure in the UES
during deglutitive relaxation (i.e. during a swallow)
r Pharyngo-UES coordination: Time elapsed between begin-
ning of UES relaxation and onset of pharyngeal contraction
35
Esophagus
Normal values

r LES resting pressure (LESP) 10-45 mmHg:
- Hypertensive LES if LESP > 45 mmHg
- Hypotensive LES if LESP < 10 mmHg
r LES residual pressure (LESRP) < 8 mmHg:
- Poorly relaxing LES if LESRP > 8 mmHg
Esophageal body
r Contraction amplitude 30 – 180 mmHg:
- Ineffective contraction if amplitude at 5 or 10 cm above
LES < 30 mmHg
r Distal esophageal amplitude (DEA) 30 –180 mmHg:
- hypercontractile esophageal body DEA > 180 mmHg;
nutcracker esophagus if DEA > 180 mmHg
- clinically more robust diagnosis if average DEA > 220 mmHg
r Distal esophageal duration (DED) 3-6 sec:
- hypercontractile esophageal body DED> 6 sec; nutcracker
esophagus if DED > 6 sec
r Contraction onset velocity <8 cm/sec:
- Simultaneous contraction if onset velocity > 8 cm/sec or
retrograde (i.e. contraction in distal esophagus before onset
in the midesophagus – negative onset velocity)
Upper esophageal sphincter (UES)

r UES resting pressure (UESP) 30-180 mmHg:
- Hypertensive UES if UESP > 180 mmHg
- Hypotensive UES if UESP < 30 mmHg
r UES residual pressure (UESRP) < 8 mmHg:
- Poorly relaxing UES if UESRP > 8 mmHg)
r Pharyngo-UES coordination -300 to -500 msec:
- Pharyngo-UES dyscoordination if delay shorter
than -300 msec or onset of pharyngeal contraction
before the begin of UES relaxation
36
High resolution manometry – per swallow analysis
20 cm
15 cm
10 cm
5 cm
LES (HPZ)

r Integrated relaxation pressure over 4 seconds (IRP 4-sec):
Sum of lowest average LES pressures over a 4-second
period (not continuous) in the LES during deglutition
Esophageal body
r Distal contractile integral (DCI): Integration of contraction
amplitude, distance and time of the area below the transition
zone and above the proximal border of the LES after
deglutition
r Contraction front velocity: speed of propagation of the
onset of esophageal contraction below the transition zone to
the distal esophageal deceleration point
r Distal latency period (DL): time between beginning of UES
relaxation and distal esophageal deceleration point
r Proximal contractile integral (PCI): Integration of contraction
amplitude, distance and time of the area above the transition
zone and below the distal border of the UES after deglutition
37
Esophagus
Normal values

r IRP 4-sec < 15 mmHg
- EGJ outflow obstruction if IRP >15 mmHg
Esophageal body
r Peristaltic integrity: no breaks larger than 3 cm in the
30 mmHg isobaric contour or no breaks larger than 2 cm
in the 20 mmHg isobaric contour
- Breaks > 3 cm in 30 mmHg isobaric or > 2 cm in 20 mmHg
isobaric contour: hypotensive contraction
- No 30 mmHg isobaric contour in the distal esophagus:
absent peristalsis
- Simultaneous increase in esophageal pressure from the
LES to UES > 30 mmHg: pan-esophageal pressurization
r Distal contractile integral (DCI) < 5,000 mmHg*s*cm
- hypercontractile peristalsis if DCI > 5,000 mmHg*s*cm
- jackhammer esophagus if DCI > 8,000 mmHg*s*cm
Grading system for evaluating clinical

symptoms of achalasia
Score Weight loss Dysphagia Retrosternal pain Regurgitation
0 None None None None
1 < 5 kg Occasional Occasional Occasional
2 8–10 kg Daily Daily Daily
3 > 10 kg Each meal Each meal Each meal
[Eckardt VF, Aignherr C, Bernhard G. Predictors of outcome in patients with achalasia

treated by pneumatic dilation. Gastroenterology 1992;103(6):1732-1738]
38
Chicago classification motility abnormalities
Individual swallows
Integrity of contraction
Intact contraction 20 mmHg isobaric contour without large
or small break
Weak contraction a) Large break in the 20 mmHg isobaric
contour (> 5cm in length)
b) Small break in the 20 mmHg isobaric
contour (2 – 5 cm in length)
Failed peristalsis Minimal (< 3 cm) integrity of the 20 mmHg
isobaric contour distal to the proximal
pressure through (P)
Contraction pattern
(for intact or weak peristalsis with small breaks)
Premature contraction DL < 4.5 s
Hypercontractile DCI > 8,000 mmHg*-S-cm
Rapid contraction CFV > 9 cm s-1
Normal contraction Not achieving any of the above
diagnostic criteria
Intrabolus pressure pattern (30 mmHg isobaric contour)
Panesophageal
pressurization Uniform pressurization extending from
the UES to the EGI
Compartmentalized eso-
phageal pressurization Pressurization extending from the
contractile front to a sphincter
EGJ Pressurization Pressurization restricted to zone between
the LES and CD in conjunction with
hiatus hernia
Normal pressurization No bolus pressurization > 30 mmHg
Interpretation
of study Diagnosis Diagnostic Criteria
Achalasia
Type I achalasia Classic achalasia: mean IRP > upper limit
of normal, 100% failed peristalsis
Type II achalasia Achalasia with esophageal compression:
mean IRP > upper limit of normal, no
normal peristalsis, panesophageal
pressurization with ≥ 20% of swallows
39
Esophagus
Chicago classification motility abnormalities
Type III achalasia Mean IRP > upper limit of normal, no

normal peristalsis, preserved fragments
of distal peristalsis or premature (spastic)
contractions with ≥ 20% of swallows
&(+PVUáPXPCTUSVDUJPO .FBO*31VQQFSMJNJUPGOPSNBM TPNF
instances of intact peristalsis or weak
peristalsis with small peristaltic breaks
such that the criteria for achalasia are
not met (Patterns not observed in
normal individuals)
Motility Disorders Normal mean IRP, ≥ 20% premature
Distal esophageal spasm contractions
Hypercontractile At least one swallow DCI > 8000 mmHg*
esophagus s*cm with single peaked or multipeaked
(Jackhammer esophagus) contraction
Absent peristalsis Normal mean IRP, 100% of swallows
with failed peristalsis
Peristaltic abnormalities (Defined by exceeding statistical limits
of normal)
Weak peristalsis with Mean IRP < 15 mmHg and > 20% swal-
large peristaltic lows with large breaks in the 20 mmHg
defects isobaric contour (> 5cm in length)
Weak peristalsis with Mean IRP < 15 mmHg and > 30% swal-
small peristaltic lows with small breaks in the 20 mmHg
defects isobaric contour (2-5cm in length)
Frequent failed > 30%, but < 100% of swallows with
peristalsis failed peristalsis
Rapid contractions with Rapid contraction with ≥ 20% of
normal latency swallows, DL > 4.5 s
Hypertensive peristalsis Mean DCI > 5,000 mmHg*s*cm, but not
meeting criteria for hypercontractile
(Nutcracker esophagus) esophagus
Normal Not achieving any of the above
diagnostic criteria
[Bredenoord AJ, Fox M, Kahrilas PJ, Pandolfino JE, Schwizer W, Smout AJ;
International High Resolution Manometry Working Group. Chicago classification
criteria of esophageal motility disorders defined in high resolution esophageal pressu-
re topography. Neurogastroenterol Motil. 2012]
40
Esophagus
Achalasia in HRM/EPT*
* = High resolution manometry /

esophageal pressure topography
Type I Type II Type III
Length along the esophagus (cm)
1
5 150
400
10 125
100 300
15
75
20 50 200
30 mmHg
25 25 100
0 30 mmHg
30 -10
0
35
0 1 2 3 4 5 6 7 8 9 10 11 0 1 2 3 4 5 6 7 8 9 10 11 0 3 6 9 12 15 18 21
Time (seconds) Time (seconds) Time (seconds)
r 'BJMVSFPG r 'BJMVSFPG
LES-Relaxation LES-Relaxation
r "QFSJTUBMTJT r "QFSJTUBMTJT
r /PQSFTTVSJ[BUJPO r 1BOFTPQIBHFBM
in distal esophagus pressurization
<30 mmHg >30 mmHg
in >8/10 swallows in ≥2/10 swallows
s 2ESPONSETO s 2ESPONSETO
therapy: therapy:
Æ Æ
Surgical myotomy Surgical myotomy
(4/6), (13/13),
Pneumatic dilation Botulinum toxin
(3/8) (6/7)
Botulinum toxin Pneumatic dilation
(0/2) (19/26)
[Pandolfino, Gastroenterology 2008;135:1526-33]
41
Esophagus
Achalasia
Achalasia – Diagnosis and treatment

Definition:
Radiographic and Manometric Features of Achalasia
Timed barium swallow
&TTFOUJBMGFBUVSFT rjCJSETCFBLvBQQFBSBODFPGUIF-&4XJUI
incomplete opening
r-PTTPGQSJNBSZQFSJTUBMTJT
r%FMBZFEFTPQIBHFBMFNQUZJOH
Algorithm Achalasia
Low surgical risk

<40 years >40 years
Laparoscopic Failure Graded pneumatic

myotomy dilatation
Success
Repeat
Failure as needed
Refer to esophageal
Center of excellence
Pneumatic Repeat
Esophagectomy
dilation myotomy
[Richter JE, Boeckxstaens GE. Gut 2011]
42
4VQQPSUJWFGFBUVSFT r%JMBUFEPSTJHNPJEMJLFFTPQIBHVT
r&QJQISFOJDEJWFSUJDVMB
Manometry
&TTFOUJBMGFBUVSFT r"QFSJTUBMTJTJOEJTUBMPGUIFFTPQIBHVT
r"COPSNBM-&4SFMBYBUJPO
4VQQPSUJWFGFBUVSFT r)ZQFSUFOTJWF-&4QSFTTVSF
r-PXBNQMJUVEFFTPQIBHFBMDPOUSBDUJPOT
High surgical risk
Refer to esophageal
Center of excellence
Graded pneumatic Failure Botulinum

dilation toxin
Success
Repeat Failure
as needed
Calcium Channel
Blocker/ Nitrates
43
Esophagus
Achalasia
Pneumatic dilatation for achalasia

Preparation
r $POàSNFEEJBHOPTJTPGBDIBMBTJB FOEPTDPQZ CBSJVNFTPQIBHP
gram and esophageal manometry)
r *OGPSNFEDPOTFOUFGàDBDZ NBZSFRVJSFTFTTJPOT
perforation risk 2 – 3%; alternative laparoscopic myotomy (not
superior to dilatation, perioperative risks, risk of GERD symptoms
in up to 20% of patients), Botox injection of LES (recurrence rate
50% after median of 6 months)
r 4UBSU11*UIFSBQZBUMFBTUXFFLQSJPSUPQOFVNBUJDEJMBUBUJPO
r %BZCFGPSFQSPDFEVSFPOMZMJRVJEEJFUOQPBUMFBTUIPVSTQSJPS
to procedure
Procedure (balloon 30 – 35 – 40 mm, 10 PSI, at least 60 seconds)

r 4FEBUJPO QSFGFSBCMZXJUIQSPQPGPM
r *OUVCBUFFTPQIBHVTJOSJHIUMBUFSBMEFDVCJUVTUPNJOJNJ[FSJTL
of aspiration of esophageal content
r $MFBSJOHáVJETBOETPMJETPVUPGUIFFTPQIBHVTJGFTPQIBHVT
cannot be cleared consider reschedule intervention
r 1PTJUJPOHVJEFXJSFJOUIFTUPNBDIBOUSVN
r 5VSOQBUJFOUPOIJTIFSCBDL
r -PDBUFHBTUSPFTPQIBHFBMUSBOTJUJPO ;MJOF
FOEPTDPQJDBMMZBOE
radiographically
r *OTFSUEJMBUBUJPOCBMMPPO SFDPNNFOEBUJPOUPTUBSUXJUINN
balloon)
r 1PTJUJPODFOUFSPGCBMMPPOBUUIFMFWFMPGUIF&(KVODUJPO
r $POàSNXBJTUJOUIFNJEEMFPGUIFCBMMPPO DBVUJPOQSPQVMTJWF
esophageal forces tend to drag the balloon into the stomach)
r *OáBUFUIFCBMMPPOVOUJMXBJTUEJTBQQFBSTCVUOPUNPSFUIBO14*
r .BJOUBJOCBMMPPOJOáBUJPOGPSBUMFBTUTFDPOET
44
Achalasia
r %FáBUFCBMMPPOBOESFNPWF JONPTUDBTFTUIFSFXJMMCFCMPPE
on the balloon)
r &OEPTDPQJDDPOUSPMTPUIBUUIFSFJTOPUSBOTNVSBMQFSGPSBUJPO
r *ODBTFPGFTPQIBHFBMDBSEJBQFSGPSBUJPOQMBDFOBTPHBTUSBM
and 1 naso-esophageal tube, prescribe sufficient analgesia, perform
CT-thorax-abdomen, inform the surgeons of complication. Baseline
hemogram (Lc-count), CRP. Arrange for parenteral nutrition and
in-hospital observation (hospitalization 10 – 14 days), the first
24 – 48 hours ideally intermediate care (IMC) level.
Post-dilatation procedure
r $MJOJDBMPCTFSWBUJPOGPSIPVST USJBMXJUIXBUFSTXBMMPX
r 5SFBUDIFTUQBJO NVTDVMBSUFBSXJUIBDFUBNJOPQIFO NFGFOBNJDBDJE
or pethidine/fentanyl); pain should subside over the next 2 – 3 hours
r *ODBTFPGBQFSGPSBUJPOBGUFSQOFVNBUJDEJMBUBUJPODPOTJEFSDPWFSFE
esophageal prothesis and antibiotics
r $POUSBTUFTPQIBHPHSBNUPDPOàSNUIBUUIFSFJTOPMFBLBHF
(passage through EG-junction most likely delayed due to edema
and muscle spasm)
r 1BUJFOUTUBCMFXJUIPVUFWJEFODFPGMFBLDBOCFEJTDIBSHFEUIF
same day
r 0OMZMJRVJETGPSMVODIBOEEJOOFS/PSNBMEJFUTUBSUJOHOFYUNPSOJOH
r $POUJOVF11*EBJMZGPSXFFLT
r $MJOJDBMSFFWBMVBUJPOBGUFSXFFLT*GTZNQUPNTQFSTJTU DPOTJEFS
repeating pneumatic dilatation with 35 mm and if required, a third
time with a 40 mm balloon.
r 1BUJFOUTXJUIQFSTJTUFOUTZNQUPNTBGUFSEJMBUBUJPOT VQUP
40 mm) should be regarded as failures to pneumatic dilatation and
referred for laparoscopic myotomy.
45
Esophagus
Varices
Algorithm gastroesophageal varices
Acute variceal bleeding
r7PMVNFSFTUJUVUJPO
rJWDFGUSJBYPOFHE
r5BSHFUICMFWFMmHEM
r7BTPBDUJWFESVHT PDUSFPUJEF TPNBUPTUBUJO UFSMJQSFTTJO
(Octreotide 100 μg iv bolus followed by 50 μg/h i.v. 72 h)

r11*
r%JTDVTT''1 QMBUFMFUT
rMBDUVMPTF
EGD (within 12 hrs)
Fundic varices?
EGD = esophagogastroduodenoscopy
EVL = endoscopic variceal ligation
FFP = fresh frozen plasma
PPI = proton pump inhibitor Repeat every
1 – 2 weeks until
yes no obliteration
Hystoacryl therapy EVL
Bleeding Bleeding Bleeding

controlled not controlled controlled
Initiate secondary Consider TIPS, Initiate secondary

prophylaxis balloon tampona- prophylaxis
(non-selective de, selfexpandable (non- selective
beta-blockers) metal stent beta-blockers)
[According to Garcia et al. Hepatology 2007]
46
Varices
Gastric varices
Bleeding risk: 25% in 2 years
Gastro Esophageal Varices (GOV)
GOV1 GOV2
BR: 55%
GOV1: extension of esophageal varices along

the lesser curvature
(- management as for esophageal varices)
GOV2: extend along the fundus and are usually

convoluted and longer
Isolated Gastric Varices (IGV)

(absence of esophageal varices)
IGV1 IGV2
BR: 78% BR: 10%
BR = Bleeding risk in 2 years
IGV1: isolated in the fundus and are usually

convoluted and complex
(- exclude splenic vein thrombosis)
IGV2: located in the body, antrum, or around the pylorus

47
Esophagus
Varices
Esophageal varices – size classification and screening

Size classification
Small varices < 5 mm
Large varices > 5 mm
+ presence or absence of red signs
(i.e. red wale marks, red spots)
_
e «Red spots». f «Red wale marking».
Algorithm Varices
Cirrhosis
EGD Decompensation
Varices?
yes no
Episode of Repeat EGD
CMFFEJOH every 2 – 3 yrs
no yes
Non-selective
beta-blocker and/
or EVL (large
varices or con- EVL EGD yearly
traindication for
beta-blocker)
EGD = esophagogastroduodenoscopy
EVL = endoscopic variceal ligation

48
Linton – Tube
Using a 100 mL syringe, slowly push air into the stomach

balloon (300 mL) and seal the feeder with a clamp
r 1VMMUIFUVCFCBDLBTGBSBTQPTTJCMFVOUJMBáFYJCMFSFTJTUBODFJT
noticeable (cardia approx. at 40 cm). Thereafter, slowly push
200 – 300 mL air into the stomach balloon again.
r 1MBDFBPOFTJEFEDVUGPBNSVCCFSQJFDFJOGSPOUPGUIFOPTUSJM BOE
fix the tube under tension with a 500 g – 1 kg weight at the end of
the bed.
r "TBHFOFSBMSVMF UIFTUPNBDIJTXBTIFEDMFBSFWFSZNJOVUFT
with water in order to control the bleeding and aspirate the blood.
r *OPSEFSUPBWPJEIFQBUJDFODFQIBMPQBUIZ %VQIBMBDJTTVGàDJFOUMZ
administered.
r 5IFFTPQIBHVTBOETUPNBDIMVNFOBSFESBJOFE
49
Esophagus
Linton – Tube
Sengstaken – Blakemore tube

Indication: uncontrolled variceal bleeding
after failed band ligation (+/- sclerotherapy)
Procedure:
-1- proof balloons with water (gastric : 250 ml;
esophageal: about 80 ml)
-2- Patient should be intubated and the head of the bed up
at 45 degrees.
-2- insert through nose or mouth using anesthetic gel till 50–55 cm
JOáBUFUIFHBTUSJDCBMMPPO<CSPXO>XJUINMPGBJSBOEDPOUSPM
position (x-ray or endoscopically) complete with additional 200 ml
PGBJSBOEDMBNQUIFHBTUSJDQPSU>
-5- traction: with 500 ml bag of saline solution, then reduce to 250 ml
<NBSLUIFUVCFBUUIFOPTFFOUSZ>
BJSQSFTTVSFJOUIFFTPQIBHFBMCBMMPPO<ZFMMPX>
mNN)H<DMBNQUIFFTPQIBHFBMQPSU>
-7- test tube with water (F).
* Air pressure: H0-H6 : 35-45 mmHg ; H6-H24: 30-35 mmHg; >H24 : 25-30 mmHg
NB: Every 6 hours esophageal balloon pressure to 0 for 5 min (risk of mucosal
necrosis).
[Senstaken RW and Blakemore AH. Balloon tamponage for the control of
hemorrhage from esophageal varices. Ann Surg 1950;131:781–89]
50
Corrosive injury
Algorithm for corrosive injuries

in the esophagus and/or stomach
acute corrosive management of circulation & airway

injury MBSZOHFBMFEFNB ĺ tracheostoma
perforation,
CT scan chest & abdomen mediastinitis,
physical examination peritonitis
within 12 h
no
lesions EGD grade 4
discharge grading? /
prognosis?
grade 1 & 2 A
no treatment
grade i.v. antibiotics,
liquid diet 2B&3 surgery
after 24 hrs normal diet
ICU, observation
i.v. antibiotics & PPI; NPO and nutrition with a duodenal
tube; after 48 hrs, liquid diet if no odynophagia; EGD after
1 – 3 wks (in case of dysphagia also after yrs)
laparoscopy optional (if deterioration occurs)
[Modified from Sleisenger 8th ed.]
51
Esophagus
Corrosive injury
Prognosis of corrosive injuries in the

esophagus and/or stomach
complete 70 – 100% 65% early

recovery strictures or mortality
pyloric stenosis
~100% esopha-
geal resection
with jejunal
or colonic inter-
position
Grade 1 Grade 2 A Grade 3 A Grade 4

B B
[Modified from Zargar SA et al. Gastrointestinal Endoscopy 1991

and from Cheng HT et al. BMC Gastroenterol 2008]
Complications of corrosive injuries in the

1. perforation (acute)
2. esophago-tracheal or -bronchial fistulas
3. esophageal motility disorder
4. pyloric stenosis (mths – yrs)
5. stenosis / strictures (from grades 2B to 3) (2 wks – 5 yrs)
therapeutic options:
frequent multiple dilations (bougie or balloon)
retrievable metal and plastic self expanding stents
ĺ possible problems: migration > 40%,
long-term success < 50%
6. esophageal cancer (after – 30 yrs)

1000 x fold risk of developing esophageal cancer compared to gene-
ral population ĺ begin endoscopic surveillance 15 yrs after ingestion
(generally not performed more than every 1– 3 yrs)
52
Corrosive injury
Pseudodiverticulosis
7FSZSBSFTZOESPNDBSBDUFSJTFECZNVMUJQMF áBTLTIBQFE
outpouchings of pinhead size in the wall of the esophagus.
Dilatation of excretory ducts of the esophageal submucosal
glands. Unknown physiopathology. May be associated with
HBTUSPFTPQIBHFBMSFáVY TUSJDUVSFT XFCT IFSQFTPSDBOEJEBN
esophagitis and esophageal neoplasm.
dx: endoscopy or radiological evaluation.

Symptoms: dysphagia.
Treatment: dilatation of stricture and treatment of oesophagitis.
[Attila T1, Marcon NE. Esophageal intramural pseudodiverticulosis with food
impaction. Can J Gastroenterol. 2006 Jan;20(1):37-8.]
Corrosive injury
Grading of corrosive injuries in the

Grade 1 Grade 2 A Grade 3 A Grade 4

edema & friability, bleeding, multiple ulcera- perforation
hyperemia of erosions, blisters, tions and small
the mucosa whitish membranes, scattered areas
exudates, and of necrosis
superficial ulcers B
B multiple ulcerati-
grade 2A plus deep ons and extensive
discrete or circum- necrosis
ferential ulceration
53
Stomach
Dyspepsia
Endoscopy Algorithm Dyspepsia
Dyspepsia
Age > 55 years Age < 55 years*1

Alarm signal No alarm signal
H. pylori H. pylori
prevalence < 10% prevalence ≥ 10%
H. pylori test
PPI therapy trial and if necessary,
therapy
Endoscopy
Alarm signals:
Age > 55 years, newly occurring symptoms
Family anamnesis for malignancy of the upper gastrointestinal tract
Past history of peptic ulcer disease
Unintentional weight loss
Gastrointestinal bleeding or iron deficiency anemia
Increasing dysphagia or odynophagia
Persistent vomiting
Icterus
Tumor in abdomen, lymphadenopathy
[Prevalence of H. pylori infection in adults is approximately 12% in Switzerland [8].]
[Talley NJ, et al: American gastroenterological association technical review on the
evaluation of dys-pepsia. Gastroenterology 2005]
[Talley NJ, et al: Guidelines for the management of dyspepsia.
Am J Gastroenterol 2005]
*1 Age might vary according to local guidelines
54
Metaplasia
Algorithm Metaplasia
Atrophic gastritis / intestinal

metaplasia Dysplasia
Helicobacter pylori eradication
Chromoendoscopy / Narrow Band Imaging (NBI),

if available
Distribution Dysplasia grade*
Atrophy Atrophy or
(mild/ intestinal Low grade High grade
moderate) metaplasia
or intestinal in antrum
metaplasia and corpus
in antrum
No Every After After

follow-up 3 years 12 months 6 months
* In the case of visible macroscopic lesions: consider staging and resection.

Sampling: take * 2 biopsies from the antrum, corpus, large and small curvature
[Dinis-Ribeiro M, et al. guideline from the European Society of Gastrointestinal Endo-
scopy (ESGE), European Helicobacter Study Group (EHSG), European Society of
Pathology (ESP), and the Sociedade Portuguesa de En-doscopia Digestiva (SPED).
Endoscopy. 2012 Jan; Epub 2011]
55
Stomach
Gastritis
Gastritis – endoscopic classification
Erythematous / Erythematous / Flat erosive Elevated erosive

exudative exudative
Atrophic Hemorrhagic 3FáVY Rugal /

hyperplastic
Endoscopic follow-up
r /05XJUIEVPEFOBMVMDFS
r (BTUSJDVMDFSBGUFSXFFLT mPGBMMTUPNBDIVMDFST
are malignant)
r 'PSZPVOHQBUJFOUTXJUIOPTVTQJDJPVTTUPNBDIVMDFSBOESJTL
status (H. pylori, ASS/NSAID), re-endoscopy can be waived.
[McColl Ke. Am J Gastroenterol. 2009] [Lanza FL, et al. Am J Gastroenterol 2009]
Gastritis
Sidney classification – Endoscopy
Morphology
r &SZUIFNBUPVTFYVEBUJWFHBTUSJUJT
r (BTUSJUJTXJUIGMBUFSPTJPOT
r (BTUSJUJTXJUIQPMZQPJEFSPTJPOT
r "USPQIJDHBTUSJUJT
r )FNPSSIBHJDHBTUSJUJT
r 3FGMVYHBTUSJUJT
r .ÊOÊUSJFShTEJTFBTF jHJBOUSVHBMGPMETvHBTUSJUJT
Localization
r 1BOHBTUSJUJT DPSQVTHBTUSJUJT BOUSVNHBTUSJUJT
56
Gastritis
Sidney Classification – Histology

Acute gastritis Cause
r"DVUFIFNPSSIBHJDFSPTJWF ĺ Medication, intoxication
gastritis
r"DVUF)QZMPSJHBTUSJUJT ĺ H. pylori
r"DVUFQIMFHNPOPVTHBTUSJUJT ĺ Sepsis
Chronic gastritis Cause
r/POBUSPQIJDHBTUSJUJT ĺ H. pylori (Type B gastritis)
r"USPQIJDHBTUSJUJT ĺAutoimmunity (Type A gastritis)

- Autoimmune gastritis ĺ H. pylori, environmental factors
- Multifocal atrophic gastritis
r4QFDJBMGPSNT ĺ chemical irritation, NSAID/
- Chemical gastritis medication, bile (Type C
- Radiation gastritis gastritis)
- Lymphocytic gastritis ĺ Irradiation
ĺ Immune mechanisms, gluten,
H. pylori, idiopathic
- Granulomatous, not ĺ Crohn's disease, sarcoidosis,
infectious M. Wegener / other vasculiti-
des, foreign bodies, idiopathic
- Eosinophilic gastritis ĺ food allergies, other allergies
- Infectious gastritis ĺ bacteria, viruses, fungi,
parasites
Grading
r-ZNQIPDFMMVMBSJOGJMUSBUJPO - normal
r*OGMBNNBUJPOBDUJWJUZ - low-grade
(neutrophilic leucocytes)
r"USPQIZ - moderate
r*OUFTUJOBMNFUBQMBTJB - high-grade
[Dixon MF, et al. International Workshop on the Histopathology of Gastritis, Houston

1994. Am J Surg Pathol. 1996 Oct;20(10)]
[Tytgat GN. J Gastroenterol Hepatol. 1991]
57
Stomach
Gastritis (Helicobacter pylori)
Diagnostics
Method Sensitivity (%) Specificity (%)

Non-invasive methods
Serology 70-90 70-90
13C breath test 90-95 90-95
Stool antigen 85-95 85-95
Invasive methods
Fast urease test 90-95 90-95
Histology* 80-98 90-98
Culture 70-90 100
PCR-analysis 90-95 90-95
* Sydney recommendation: 6 biopsies (2x antrum, 2x corpus, large/small curvature)

Test result
False positive: serology (previous infection, cross-reactive
antibodies), atrophic gastritis / achlorhydria, bacterial
overgrowth of the stomach
False negative: after partial gastrectomy, with acute gastrointestinal
bleeding, with / after (< 2 weeks) PPI therapy, with /
after (4 weeks) antibiotic therapy
Management of H. pylori eradication therapy

Please consider risks and benefits of any eradication treatment before
starting the medication. H pylori infection is the most consistent risk
factor for gastric cancer. Its elimination is therefore the most promising
strategy to reduce the incidence of gastric cancer. Global prevalence
of H. pylori is about 50% or higher. In CH, H. pylori prevalence is
approximately 25% (1 of 4 persons), in south-eastern Europe H. pylori
prevalence rises to 40–70%.
Confirmed indication
r"DUJWFQFQUJDVMDFSEJTFBTF
r."-5MZNQIPNBPGUIFTUPNBDI
r"USPQIJDHBTUSJUJT
r1SFWJPVTQBSUJBMHBTUSFDUPNZEVFUPHBTUSJDDBSDJOPNB
r1PTJUJWFGBNJMZIJTUPSZ HSBEFSFMBUJWFXJUIHBTUSJDDBSDJOPNB

r%ZTQFQTJB
r1BUJFOUSFRVFTU
58
r .PSCVT.ÊOÊUSJFS
r *EJPQBUIJDUISPNCPDZUPQFOJDQVSQVSB *51

r -ZNQIPDZUJDHBTUSJUJT
r 'VUVSF
UIFSBQZXJUI/4"*%
r 'VUVSF
UIFSBQZXJUIBTQJSJO "4"
JOQBUJFOUTXJUIIJTUPSZPGQFQUJD
ulcer disease
r0UIFSXJTFVOFYQMBJOFEJSPOEFàDJFODZBOFNJB
Helicobacter pylori
Controversial indication with tendency towards
H. pylori eradication:
r 'VODUJPOBMEZTQFQTJB OVNCFSOFFEFEUPUSFBU

«better than every other treatment»
r-POHUFSNMPXEPTFBTQJSJO "4"
JOUBLF FTQFDJBMMZJOUIFFMEFSMZ
(> 65 years)
r0UIFSHBTUSPUPYJDESVHT FH1SFEOJTPOF
JODPNCJOBUJPOXJUI
low-dose aspirin (ASA) intake
r-ZNQIPDZUJDHBTUSJUJT
r1SFWJPVTQBSUJBMHBTUSFDUPNZ BGUFSmZFBST
Weak indication:
r7JUBNJO#EFàDJFODZ
r"TUINBBOEBUPQZ
r0CFTJUZBOESFMBUFEJMMOFTTFT
No evidence:
r 5IFSFJTOPFWJEFODFUIBU)QZMPSJFSBEJDBUJPODBOMFBEUPSFHSFTTJPO
of intestinal metaplasia.
r0OBWFSBHF )QZMPSJTUBUVTIBTOPFGGFDUPOTZNQUPNTFWFSJUZ
symptom recurrence and treatment efficacy in GERD. H pylori
eradication does not exacerbate pre-existing GERD or affect
treatment efficacy.
H. pylori therapy
1) PPI (PPI standard dose)
Esomeprazole 20 mg ~ Pantozole 40 mg ~
Lansoprazole 30 mg ~ Rabeprazole 20 mg ~ Omeprazole 20 mg
PPI should be given as «1 – 0 – 1» regime during 7–10 (–14) days.
A higher PPI dose (e.g. doubled IPP dose with respect to the
«standard» dose) may increase cure rates by 8–12%.
59
Stomach
2) Antibiotics
Consider regional clarithromycin resistence levels
(«Clari-R» prevalence) before starting H. pylori treatment.
rMPXMFWFM QSFWBMFODF
JG$MBSJ3
rIJHIMFWFM QSFWBMFODF
JG$MBSJ3
In Switzerland (CH) and Germany, Clari-R is considered to be below

20 %. In many parts of Italy, Clari-R is considered to be above 20 %.
The following therapy schemes are used in CH.
In case of failure of first-line treatment, second-line treatment is

selected without resistance testing, whereas with further failure,
third-line treatment should be chosen based on H. pylori cultures
and antibiotic susceptibility testing.
FIRST LINE THERAPY

Clarithromycin 2 x 500 mg/d AND Amoxicillin 2 x 1000 mg/d 7 days
In case of proven intolerance/allergy to penicillin:
Clarithromycin 2 x 500 mg/d AND Metronidazole 2 x 500 mg/d 7 days
plus PPI (various drugs, see above)
These two regimens are considered equivalent. Extending the

duration of PPI-clarithromycin-containing triple therapies from
7 to 14 days improves the eradication success by about 5 %
and may be considered.
OR
Bismuth Quadruple Therapy

rYDBQTVMFTE QPTUQSBOEJBMJOUBLF
EBZT
plus Omeprazole 20 mg 1 – 0 – 1
(for 10 days; not proven with other PPI)
60
SECOND LINE THERAPY

Bismuth Quadruple Therapy plus Omeprazole (see above)
10 days
OR
-FWPáPYBDJOYNHE "NPYJDJMMJOYNHE
7 – 14 days
3JTJOHSBUFTPGMFWPáPYBDJOSFTJTUBODFTIPVMECFUBLFOJOUPBDDPVOU
THIRD LINE THERAPY

based on susceptibility testing only (!)
61
Stomach
H. pylori in clinical practice
H. pylori testing under PPI therapy:

PPI should be stopped for 2 weeks before testing by culture,
histology, rapid urease test, urea breath test or stool Ag test.
If it is not possible, validated IgG serology can be performed.
H. pylori and peptic ulcer disease:

In uncomplicated duodenal ulcer, prolonging acid inhibition with PPI
is not recommended after completion of H. pylori treatment. In gastric
ulcer and complicated duodenal ulcer, prolonging PPI therapy is
recommended.
H. pylori eradication treatment should be started at reintroduction of

oral feeding in cases of bleeding ulcer.
H. pylori – tests to control eradication success:

The urea breath test or a laboratory-based validated monoclonal (Ag)
stool test are both recommended as non-invasive tests for
determining the success of eradication treatment. There is no
role for serology. The time for testing the success of H. pylori
eradication after the end of treatment should be at least 4 weeks
(> 4 weeks after the last antibiotic dose, > 2 weeks after the last
PPI intake).
Possible causes for H. PYLORI TREATMENT FAILURE (relapse):

1. Low medication adherence (compliance)
2. Resistance of the specific H. pylori strain
3. Smoking, bacterial virulence, low absorption of antibiotics/PPI, etc.
Reinfection with H pylori after eradication is rare in developed

countries but more common in developing countries at around 13 %.
[Federico A et al., World J Gastroenterol 2014 January 21; 20(3): 665-672. Malfertheiner
P et al., Gut 2012;61:646-664 («Maastricht IV»). Fischbach W, et al., S3-guideline
‘Helicobacter pylori and gastroduodenal ulcer disease’]. Z Gastroenterol 2009; 47:
68–102]
62
Gastric Ulcers
Peptic Ulcer Disease

PPI therapy duration (standard dose):
Erosive gastritis/duodenitis: 4 weeks
Gastric/duodenal ulcer: 8 weeks
Differential diagnosis: H. pylori-negative,

NSAID-negative peptic ulcer disease (approx. 10%)
r 'BMTFOFHBUJWF)QZMPSJUFTU VOEFS11*UIFSBQZ
after antibiotic therapy)
r 6OEJTDPWFSFE"4"/4"*%JOUBLF
r 6MDFSPHFOJDNFEJDBUJPO CJTQIPTQIPOBUF JSPOQSFQBSBUJPOT
r 4UPNBDIDBSDJOPNB MZNQIPNB
r *#% $SPIOhTEJTFBTF
r )IFJMNBOOJJ
r 4ZTUFNJDNBTUPDZUPTJT
r ;PMMJOHFS&MMJTPOTZOESPNF
r )JTUPSZPGQBSUJBMTUPNBDISFTFDUJPO
r )JTUPSZPGSBEJPUIFSBQZ
Strategy for long-term NSAID therapy

Risk factors for NSAID-associated peptic ulcer disease
Gastrointestinal risk
r "HFZFBST IJHIEPTF/4"*%UIFSBQZ IJTUPSZPGQFQUJDVMDFS
disease, co-medication with aspirin cardio, corticosteroids,
or anticoagulation
r -PXSJTLOPSJTLGBDUPSTNPEFSBUFSJTLSJTLGBDUPSTIJHISJTL
> 2 risk factors
Cardiac risk
r -PXZFBSNPSUBMJUZ )JHIZFBSNPSUBMJUZö
Gastrointestinal risk
Low Moderate High
Low NSAID NSAID + PPI NSAID + PPI
cardiac risk COX-2 COX-2 + PPI
High Naproxen + PPI Naproxen + PPI No NSAID/COX-2

cardiac risk
Cycloxygenase-2-inhibitors (COX-2); proton-pump inhibitor (PPI).
63
Stomach
Upper Gl bleeding
Peptic ulcers are described using the Forrest classification:
Forrest Preval- Relapse Fatality

Classification: ence: bleeding rate* Rate*
Ia (Spurting 10% 90% 26%
hemorrhage)
Ib (Oozing 10% 10 – 20% 10%
hemorrhage)
IIa (Visible vessel) 25% 50% 11%
IIb (Adherent clot) 10% 25 – 30% 7%
IIc (Hematin on 10% 10% 3%

ulcer base)
III (No signs of 35% < 5% 2%

recent hemorrhage)
* without endoscopic therapy

[Adapted from: Forrest JA: Lancet 1974; Laine L: N Engl J Med 1994; Katschinski B:
Dig Dis Sci 1994]
64
Upper Gl bleeding
Risk stratification:
The use of risk stratification tools is recommended by the International
Consensus Upper Gastrointestinal Bleeding Group
[Barkun AN et al.: Ann Intern Med 2010]
The Rockall score predicts mortality from gastrointestinal

ulcer bleeding:
Risk marker: Score value:

Age (years): < 60 0
60–79 1
≥ 80 2
Shock index: No shock 0
Pulse >100, SBP* >100 1
SBP* <100 2
Comorbidity: No major comorbidity 0
Major comorbidity 2
Renal failure, Liver failure,
metastatic cancer 3
Endoscopic Mallory-Weiss tear 0
diagnosis: all other diagnoses 1
GI malignancy 2
Evidence of None 0
bleeding: Blood, adherent clot,
spurting vessel 2
[Rockall TA, Logan RFA et al.: Lancet 1996]

Online Calculator: http://www.bsg.org.uk/rockall-score-calculator.html
Score: Relapse bleeding: Mortality:

<3 5% 1%
3–5 15% 5%
>6 > 30% > 15%
CAVE: The Rockall score underscores the rate of recurrent bleeding

*SBP = Systolic blood pressure [Church NI et al.: Gastrointest Endosc 2006]
65
Stomach
Upper Gl bleeding
Glasgow-Blatchford Score (GBS):

Need for intervention in suspected upper GI bleeding
Risk marker: Score value:

Blood urea: (mmol/L) 6.5 – 7.9 2
8 – 9.9 3
10 – 24.9 4
≥ 25 6
Hemoglobin: ƃ (g/L) 120 – 129 1
100 – 119 3
< 100 6
Hemoglobin: Ƃ (g/L) 100 – 119 1
< 100 6
Systolic blood pressure: 100 – 109 1
(mm Hg) 90 – 99 2
< 90 3
Pulse ≥ 100 /min 1
Melaena 1
Syncope 2
Hepatic disease 2
Cardiac failure 2
r The GBS is based only on clinical and laboratory variables and can
be assessed in the ER without endoscopy
[Blatchford O, Murray WR, Blatchford M: Lancet 2000]
r A low-risk cohort (score value = 0) has a negative predictive value

of 100% for rebleeding, endoscopic intervention, and death
[Stanley AJ et al: Lancet 2009]
r In the validation group, scores of 6 or more were associated with

a greater than 50% risk of needing an intervention
Online Calculator:
http://www.mdcalc.com/glasgow-blatchford-bleeding-score-gbs
66
Upper Gl bleeding
Recommendations for the management of upper

gastrointestinal bleeding:
r *NNFEJBUFMZFWBMVBUFBOEJOJUJBUFBQQSPQSJBUFSFTVTDJUBUJPO
r $MPTFMZNPOJUPSWJUBMTJHOTBOEBJSXBZ
r (JWFOPUIJOHCZNPVUI
r 5XPMBSHFDBMJCFS HBVHFPSMBSHFS
QFSJQIFSBMDBUIFUFST
or a central venous line
r 1SPWJEFTVQQMFNFOUBMPYZHFOBOEDSZTUBMMPJEáVJE
r 5SBOTGVTFJGIFNPHMPCJOmH-JOIJHISJTLQBUJFOUTPSH-
in low-risk patients. (MEMO: Avoid over-transfusion in variceal
bleeding, be restrictive)
r 1SPHOPTUJDTDBMFTBSFSFDPNNFOEFEGPSFBSMZTUSBUJàDBUJPOPG
patients into low-and high-risk categories for rebleeding and mortality
r "DJETVQQSFTTJPOXJUI11*FH1BOUPQSB[PMFNHCPMVTGPMMPXFE
by 8 mg/h infusion
r 1SPLJOFUJDT FSZUISPNZDJOFNHJWJOTBMJOFTPMVUJPOPWFS
15 minutes, >30 minutes before endoscopy) can improve gastric
visualization
r &BSMZFOEPTDPQZ XJUIJOIPVSTPGQSFTFOUBUJPO
JTSFDPNNFOEFE
for most patients with acute upper gastrointestinal bleeding
r 4FMFDUFEQBUJFOUTXJUIBDVUFVMDFSCMFFEJOHXIPBSFBUMPXSJTLGPS
rebleeding on the basis of clinical and endoscopic criteria may be
discharged promptly after endoscopy
r 3PVUJOFTFDPOEMPPLFOEPTDPQZJTOPUSFDPNNFOEFE
r "TFDPOEBUUFNQUBUFOEPTDPQJDUIFSBQZJTHFOFSBMMZSFDPNNFOEFE
in cases of rebleeding
r *OQBUJFOUTXIPSFDFJWFMPXEPTF"4"BOEEFWFMPQBDVUFVMDFS
bleeding, ASA therapy should be restarted as soon as the risk for
cardiovascular complication is thought to outweigh the risk for
bleeding
r *OQBUJFOUTXJUIQSFWJPVTVMDFSCMFFEJOHXIPSFRVJSFDBSEJPWBTDV
lar prophylaxis, it should be recognized that clopidogrel alone has
a higher risk for rebleeding than ASA combined with a PPI.
[Barkun AN et al.: Ann Intern Med 2010]
67
Stomach
Functional GI disorders
Rome III Criteria
Functional Gastrointestinal Disorders

B. Functional gastroduodenal disorders
B1. Functional dyspepsia
B1a. Postprandial distress syndrome
B1b. Epigastric pain syndrome
B2. Belching disorders
B2a. Aerophagia
B2b. Unspecified excessive belching
B3. Nausea and vomiting disorders
B3a. Chronic idiopathic nausea
B3b. Functional vomiting
B3c. Cyclic vomiting syndrome
B4. Rumination syndrome in adults
Rome III Criteria: Functional Dyspepsia

One or more of the following:
rBothersome postprandial fullness rEarly satiation
rEpigastric pain rEpigastric burning
AND
No evidence of structural disease (including at the upper endoscopy)
that is likely to explain the symptoms.These criteria should be
fulfilled for the last three months with symptom onset at least six
months before diagnosis
[Tack J et al. Gastroenterology 2006]
Rome III Criteria: Irritable Bowel Syndrome

> 12 weeks in the past 12 months
of continuous or recurrent abdominal pain or discomfort,
has its onset at least 6 months prior to diagnosis and includes
at least two of the following:
r 3FMJFWFEXJUIEFGFDBUJPO
r "TTPDJBUFEXJUIBDIBOHFJOGSFRVFODZPGTUPPM
r "TTPDJBUFEXJUIBDIBOHFJODPOTJTUFODZPGTUPPM
Symptoms that cumulatively support the diagnosis of IBS:
r "COPSNBMTUPPMGSFRVFODZ EBZPSXFFL
r "COPSNBMTUPPMGPSN MVNQZIBSEPSMPPTFXBUFSZ
r "COPSNBMTUPPMQBTTBHF TUSBJOJOH VSHFODZ PSGFFMJOHPG

incomplete evacuation)
r 1BTTBHFPGNVDVT
r #MPBUJOHPSGFFMJOHPGBCEPNJOBMEJTUFOUJPO
[Data from Thompson WG et al,18 and Longstreth GF, Thompson G,Chey WD, et al.
Functional bowel disorders. Gastroenterology.2006;130(5):1480-1491]
68
Alarm symptoms for further workup

r "COPSNBMCMPPETUVEJFT
r "OFNJB
r "OPSFYJB
r #MPPEJOTUPPMT
r 'BNJMZIJTUPSZPGDPMPODBODFSPSJOáBNNBUPSZCPXFMEJTFBTF
r 'FWFS
r .BMOVUSJUJPO
r /PDUVSOBMTZNQUPNT
r 0OTFUJOQBUJFOUTZ
r 1BMQBCMFBCEPNJOBMPSSFDUBMNBTT
r 1FSTJTUFOUEJBSSIFBPSTFWFSFDPOTUJQBUJPO
r 3FDFOUBOUJCJPUJDVTF
r 3FDUBMCMFFEJOH
r 8FJHIUMPTT
Heterotopic gastric mucosa of the esophagus or inlet patch:
Definition:
Island of ectopic gastric mucosa in the proximal esophagus. Most
accepted etiology is con-genital. Can be colonized with
H. pylori. Incidence 1–14 % of endoscopy.
Localization: typically on the lateral walls a few cm distal to the upper
esophageal sphincter
Size: mm to 3–5 cm. Unique or multiple.
Clinico-pathological Classification:
Typ I: Asymptomatic (most patients)
Typ II : Symptomatic without morphologic changes (regurgitation,
dysphagia, hoarseness, globus, throat discomfort and chronic
cough)
Typ III: Symptomatic with morphologic changes (benign complications:
strictures, ulcers, webs, stenoses, fistula)
Typ IV: Intraepithelial neoplasia (dysplasia) (low-grade/high-grade)
Typ V: Invasive adenocarcinoma (extremely rare)
Treatment:
Typ I: No.
Typ II: And III PPI-Therapy. Stenosis can be dilated. Biopsy is
mandatory to rule out neoplasia.
Typ IV: Few cases no standard care. Endoscopic surveillance is
recommended. Argon-plasma. Resection.
[Chong VH. World J Gastroenterol. 2013 Jan 21;19(3):331-8.Clinical significance
of heterotopic gastric mucosal patch of the proximal esophagus.] [von Rahden BH1,
Stein HJ, Becker K, Liebermann-Meffert D, Siewert JR.Am J Gastroenterol. 2004
Mar;99(3):543-51. Heterotopic gastric mucosa of the esophagus: literature-re-
view and proposal of a clinicopathologic classification]
69
Intestine
Operation Techniques
Biliopancreatic diversion with duodenal switch
Stomach
Biliopancreatic limb
Alimentary limb
Common channel } 2.5 meter
Sleeve gastrectomy
Stomach
Resected
Stomach
70
Roux-en-Y Gastric Bypass
Gastric pouch
Stomach
Antecolic Roux
limb (150 cm)
Biliopancreatic limb
(50 cm from Treitz)
Gastric surgery 1
Billroth I Billroth II
71
Intestine
Gastric surgery 2
Roux-en-Y Roux-en-Y
gastro-jejunostomy esophago-jejunostomy
Jejuno-jejunostomy Jejuno-jejunostomy
Pylorus preserving Pancreaticoduodenectomy

Pancreaticoduodenectomy (Whipple Operation) with
Braun's anastomosis
72
Source of infectious diarrhea
Noninvasive pathogens Invasive diarrhea

(small intestine) (ileocolonic)
Viruses Viruses
Rotavirus Cytomegalovirus
Calicivirus (norovirus, Herpes simplex virus type II
Norwalk agent)
Adenovirus (enteric)
Astrovirus
Bacteria Bacteria
Vibrio cholera Campylobacter species
Salmonella Salmonella species
Toxigenic E. coli Shigella species
(ETEC, EPEC, EAEC) E. coli 0157:H7 (EHEC)
Aeromonas hydrophila Yersinia
Listeria monocytogenes Clostridium difficile
Tuberculosis NoncholeraVibrio
Aeromonas hydrophila
Plesiomonas shigelloides
EIEC
Listeria monocytogenes
Tuberculosis
Parasites Parasites
Giardia lamblia Ameba
Cryptosporidia Trichuris trichiura
Isospora belli Balantidium coli
Cyclospora cayetanensis Blastocystis hominis
(facultative pathogen)
ETEC, enterotoxigenic E. coli; EPEC, enteropathogenic E. coli; EAEC,
enteroaggregative E. coli; EHEC, enterohemorrhagic E. coli; EIEC,
enteroinvasive E. coli.
[Adapted from DDSEP®7 Digestive Diseases Self-Education Program®
(published by AGA 2013)]
73
Intestine
Acute Diarrhea
Assessment of patients with diarrheal disease

Panel 1: Adequately assess the patient and determine the level of
dehydration. Important factors include duration of illness;
alertness, skin turgor, mucous membrane dryness, sunken
eyes or fontanelles, and postural hypotension all indicate
moderate or severe hypovolemia and dehydration; signs of
JOáBNNBUJPOJODMVEFGFWFS CMPPEZTUPPM BOEUFOFTNVT
Panel 2: In cases of dehydration (panel 2), patients can be rehydrated

CZPSBMBENJOJTUSBUJPOPGáVJETUIBUDPOUBJOHMVDPTF TVHBSPS
starch, and electrolytes. If patients are unconscious or
WPNJUJOH áVJETTIPVMECFSFQMBDFEJOUSBWFOPVTMZ
Consider loperamide.
Panel 3: Epidemiologic and clinical clues can be used to identify

the infectious agent. Consider immunoglobulin A deficiency,
which predisposes to giardiasis, and immunosuppression
(particularly in patients with AIDS), which can lead to proto-
zoal infections, Mycobacterium avium complex, and
intestinal cytomegalovirus infections. Clinical features can
also be used to identify the infectious agent. Bloody diarrhea
is associated with Shiga toxin-producing E. coli, Shigella
and E. histolytica infections; abdominal pain with Yersinia
and some C. difficile infections; dysentery with Shigella or
Campylobacter infection; wasting with Giardia or Cryptospo-
SJEJVNJOGFDUJPOBOEGFDBMJOáBNNBUJPOXJUI4IJHFMMB
Campylobacter, Salmonella, and some E. coli and C.
difficile infections.
74
Acute Diarrhea
1. Assess
r%VSBUJPO EBZ
r%FIZESBUJPO
r*OáBNNBUJPO
- Fever
- Blood
- Tenesmus
2. Dehydration
r'MVJUTDPOUBJOJOHHMVDPTF TUBSDI
r&MFDUSPMZUFT
r #JTNVUITVCTBMJDZMBUF
r -PQFSBNJEF
3. Clues to causes
Epidemiological Clinical
r'PPE r#MPPEZEJBSSIFB
r"OUJCJPUJDT r"CEPNJOBMQBJO
r4FY r%ZTFOUFSZ
r5SBWFM r8BTUJOH
r%BZDBSF r'FDBMJOáBNNBUJPO
r0UIFSJMMOFTTFT
r0VUCSFBLT
[Gastroenterology 2009;136:1874-86]
75
Intestine
Acute Diarrhea
Algorithm for severe acute bloody, inflammatory,

or outbreak-related infectious diarrhea
Depending on the epidemiologic setting involved and likely causes,
specific diagnostic tests are suggested as discussed in the text.
Specific bacteria such as Campylobacter, Shigella, or C. difficile
and protozoa such as Cryptosporidium, Giardia, or Cyclospora may
require specific antibacterial or antiparasitic agents, respectively.
Empiric antimicrobial therapy, while awaiting laboratory test results,
is usually appropriate for these pathogens. However, antibacteri-
al treatment may worsen diarrhea secondary to EHEC (eg, E coli
)
XIJDIVTVBMMZQSFTFOUTXJUIOPOJOáBNNBUPSZ CMPPEZ
EJBSSIFB*OBEEJUJPOUPUIFNBOBHFNFOUPGáVJEBOEFMFDUSPMZUF
imbalances
76
Acute Diarrhea
1. Obtain fecal specimen for one or more panels, if

severe, bloody, inflammatory or outbreak suspected
A. B. C.
Community- Nosocomial diarrhea Persistent diarrhea
acquired or (onset > 3 d of (> 7 d)
travelers's diarrhea hospitalization)
Culture and test for: Test for: Consider protozoa:

Salmonella, Shigella, C difficile toxins A+B Giardia, Cryptospori-
Campylobacter +, if outbreak, dium, Cyclospora,
+ (if blood or HUS) > 65 yo with Isosopra belli +
E coli O157:H7 + comorbidity, JOáBNNBUPSZ
SLT + C difficile immunocompro- screen
toxins A+B (esp if mised, neutropenic
recent antibiotics, or suspected syste-
chemotherapy, or mic enteric infection D.
recent hospitalization) add: Salmonella, If immunocompro-
Shigella, mised
Campylobacteer (especially HIV+)
r$POTJEFSFNQJSJD and, if bloody, add:
áVPSPRVJOPMPOF EHEC
therapy for adults or (as in Panel A)
sulfa-trimethoprim- Microsporidia
sulfamethoxazole for Mycobacterium
children with r%JTDPOUJOVFBOUJNJ avium complex
JOáBNNBUPSZNPEJGZ crobials if possible
therapy as needed r$POTJEFSFNQJSJD
following testing metronidazole or r5SFBUQFSUFTUSFTVMUT
results. if illness is severe or r$POTJEFSFNQJSJD
r$POTJEFSFSZUISPNZ patient is immuno- metronidazole or
cin or azithromycin compromised consi- tinidazole if suspec-
for suspected Cam- der oral vancomycin ted Giardia infection
pylobacter infection.
r"WPJEBOUJNPUJMJUZ
quinolone and
sulfatrimethoprim
if suspected EHEC
infection (afebrile,
bloody diarrhea).
2. Consider antimicrobial therapy for specific pathogens
[Gastroenterology 2009;136:1874-86]
77
Intestine
Chronic Diarrhea
Definition: Decreased stool consistency up to > 4 weeks
Differential diagnosis – chronic diarrhea

s/SMOTICDIARRHEA s3ECRETORYDIARRHEA
- Laxative abuse (osmotic) - Laxative abuse (not osmotic)
- Nutritional (Mg2+, PO43-, SO42-) - Chologenic diarrhea
- Carbohydrate malabsorption (terminal ileum,
s3TEATORRHOEA postcholecystectomy)
- Malabsorption syndrome - Bacterial toxins
- Short bowel syndrome - Inflammatory bowel disease
- Celiac disease - Ulcerative C. / Crohn's disease
- Bacterial overgrowth - Microscopic colitis
- Mesenterial ischemia - Diverticulitis
- Maldigestion syndrome - Vasculitis
- Pancreas insufficiency - Medications / toxins
- Excess bile acids - Motility disorder
s)NFLAMMATORYDIARRHEA - Post-vagotomy diarrhea
- Inflammatory bowel disease - Post-sympathectomy
- Ulcerative C. / Crohn's disease diarrhea
- Microscopie colitis - Diabetic autonomic
- Ulcerative jejunoileitis neuropathy
- Infectious diarrhea - Hyperthyroidism
- Pseudomembranous colitis - Irritable bowel syndrome
- Invasive bacteria (Yersinia, - Neuroendocrine tumors
tuberculosis) - gastrin, VIP, somatostatin
- Ulcerative viruses (CMV, HSV) - mastocytosis, carcinoid
- Invasive parasites (amoebas) - medullary thyroid carcinoma
- Ischemic colitis - Neoplasms
- Irradiating colitis - colon carcinoma, lymphoma
- Neoplasms - villous adenoma
- colon carcinoma, lymphoma - M. Addison
- Diverticulitis - Hereditary
- Idiopathic
78
79
Intestine
Chronic Diarrhea
Differential diagnosis – medication

antibiotics, antidepressives, antihypertensives (beta blockers,
ACE-inhibitors), diuretics, anticonvulsives, lipid lowering drugs,
antidiabetics (biguanides), H2-blockers / PPIs, theophylline,
chemotherapy, alcohol
Differential diagnosis – infections

Bacteria: Clostridium difficile, Campylobacter sp.,
Salmonella sp., Tropheryma whipplei,
Aeromonas, Plesiomonas shigelloides
Parasites: Giardia lamblia, Entamoeba histolytica,
Cryptosporidium, Microsporidia, Isospora
belli, Ascaris, Strongyloides stercoralis
[Fine KD, et al. AGA technical review on the evaluation and management of
chronic diarrhea. Gas-troenterology. 1999]
Anamnesis Suspected diagnosis

Nutrition sweeteners, allergies, intolerances, milk
products, caffeine, fibrous material, mint,
fruits, seafood
Weight loss malabsorption, pancreatic insufficiency,
M. Whipple, neoplasia, abdominal angina
Pain IBD, IBS, stenosis, abdominal angina
Extraintestinal symptoms hyperthyroidism, diabetes mellitus, vasculi-
tis, M. Whipple, IBD, mastocytosis,
tuberculosis
Personal anamnesis radiotherapy, operation, antibiotic therapy,
chemotherapy
80
Chronic Diarrhea
Initial examinations
Blood Hemogram with mechanical differentiation,
INR/Quick, TSH, resorption parameters
(i.e. potassium, calcium, phosphate, zinc
(if applicable), albumin, cholesterol, ferritin,
folic acid, vitamin B12, alkaline phospha-
tase, 1,25-OH vitamin D)
Stool bacteriology, C. difficile toxin/culture,
parasites (1 x native, 2 x SAF), calprotectin
Further diagnostics
Blood Tissue transglutaminase antibodies, endo-
mysium antibodies, total IgA (celiac disease)
Chromogranin A, gastrin, calcitonin
(neuroendocrine tumor)
IgE tryptase (food intolerances)
Stool Elastase, Chymoptrypsin (pancreas
insufficiency)
Bisacodyl and phenolphthalein, if appli-
cable (laxative abuse)
Others H2-lactose breath test (lactose intolerance)
Gastroscopy with small intestinal biopsies
and fluid (SIBO)
ileocolonoscopy with biopsies from all
segments (microscopic colitis)
Secretin stimulation test (pancreatic
insufficiency)
Anthrachinone in urine (laxative abuse)
Fecal collection for 72 hours
as an important diagnostic tool for
clarification of chronic diarrhea
81
Intestine
Chronic Diarrhea
Stool Osmolar/
Osmotic Gap: stool osmolal gap = stool osm – (2 * (Na + K) )
> 50 mosmo/kg suggests osmotic diarrhea
< 50 mosmol/kg suggests secretory diarrhea
(The stool osmolality is usually not directly
measured, and is often given a constant in
the range of 290 to 300)
Causes of osmotic
diarrhea include: r#JMFTBMUEFGJDJFODZ
r1BODSFBUJDJOTVGGJDJFODZ
r$FMJBD5SPQJDBM4QSVF
r8IJQQMFhTEJTFBTF
r*OUFTUJOBM-ZNQIPNB
r.FEJDBUJPOT
r-BDUPTF*OUPMFSBODF
r-BYBUJWFBCVTF EFQFOEJOHPO
the type of laxative)
Causes of secretory
diarrhea include: r-BYBUJWFBCVTF EFQFOEJOHPO
the type of laxative)
r)PSNPOBM &OEPDSJOF5VNPST
82
Chronic Diarrhea
Nonspecific chronic diarrhea (> 4 weeks)
3FEáBHT Age > 50 y,

blood in stool, postexposure Endoscopy
to antibiotics, anaemia
Calprotectin in stool Inflammatory diarrhea
Stool bacteriology, check

stool for parasites (3x), Infectious diarrhea
small bowel biopsy, small
CPXFMáVJEBTQJSBUJPO
> 300 g/24 h Stool weight < 300 g/24 h
Pseudo diarrhea
Genuine diarrhea Incontinence, irritable
bowel syndrome
< 7 g/24 h Stool fat > 7 g/24 h
No Steatorrhoea Steatorrhoea
Evaluation: pancreas
MR/CT-enteroclysis
> 50 mOsmol/kg Osmotic gap < 50 mOsmol/kg
Fasting test, if applicable
Osmotic diarrhea Secretory diarrhea
Special tests according to differential diagnosis
83
Intestine
Chronic Diarrhea
Microscopic Colitis
Diagnostic Triad
r$ISPOJD XBUFSZEJBSSIFB QPUFOUJBMXFJHIUMPTT TUPNBDIQBJO
r.BDSPTDPQJDBMMZOPSNBMDPMPTDPQZ
r1BUIPMPHJDIJTUPMPHZ
Abnormal immune response to luminal antigen in predisposed

individuals. Common: medication (i.e. acarbose, aspirin, lansoprazole,
NSAID, ranitidine, sertraline). Cumulative in autoimmune diseases
(e.g. Hashimoto's thyroiditis, celiac disease!).
Differential diagnosis – chronic diarrhea

r "-8":4CBTFEPOIJTUPMPHZ öCJPQTJFT BUMFBTU
1 biopsy per colon segment)
r /PSFMFWBODFGPSQSPHOPTJT DMJOJDBMBTTFTTNFOU
PSTFWFSJUZ
Lymphocytic colitis Collagenous colitis

r*OUSBFQJUIFMJBMMZNQIPDZUPTJT r#SPBEFOFETVCFQJUIFMJBM
(> 20 / epithelial cells) collagen band 7–100 μm
r.JYFEJOáBNNBUPSZJOàMUSBUF r*OUSBFQJUIFMJBMMZNQIPDZUPTJT
in the lamina propria possible
r*NQBJSNFOUPGFQJUIFMJBMDFMMT r*NQBJSNFOUPGFQJUIFMJBMDFMMT
áBUUFOJOHPGFQJUIFMJBMDFMMT áBUUFOJOHPGFQJUIFMJBMDFMMT
vacuolization and detach- vacuolization and detachment)
ment) r.JOJNBMDSZQUBSDIJUFDUVSF
r.JOJNBMDSZQUBSDIJUFDUVSF dysfunction possible
dysfunction possible
Prognosis / Progression
rTQPOUBOFPVTIFBMJOH rDISPOJDJOUFSNJUUFOU
r/PJODSFBTFENPSUBMJUZ progression
r/PJODSFBTFESJTLPGDPMPO r/PJODSFBTFENPSUBMJUZ
carcinoma r/PJODSFBTFESJTLPGDPMPO
carcinoma
84
Chronic Diarrhea
Therapy of microscopic colitis
Active Microsopic Colitis
Consider drug-induced MC,

Consider smoking cessation
Loperamide
Budesonide 9 mg/d,
Colestyramine
6 – 8 weeks
Bismuth
Nonresponse/Intolerance Relapse
Reconfirm MC diagnosis
Consider
differential diagnoses
Budesonide 9 mg/d, followed

by Budesonide low-dose
(up to 6 mg/d) + Calcium/Vitamin D
Æ evidence-based
...Æempirical
Nonresponse/Intolerance
Adalimumab, Infliximab
Ileostomy
Azathioprine/6-MP
[Figure 4 Algorithm for the treatment of Microscopic Colitis proposed by the

European Microscopic Colitis Group (EMCG) Münch A. et al., J Crohn Colitis
2012; 6: 932–45]
85
Intestine
Chronic Diarrhea
SMALL BOWEL BACTERIAL OVERGROWTH (SIBO)

SIBO syndrome: diarrhea, steatorrhoea, vitamin B12 deficiency,
hypoproteinemia
Most common bacteria: Streptococcus sp. (71%), E. coli (69%),
Staphylococcus sp. (25%), Micrococcus (22%), Klebsiella (20%)
Promoting factors
Intestinal stasis – anatomical
Small intestinal diverticula, operations (Billroth II, gastric bypass),
strictures (Crohn's disease, after operation)
Intestinal stasis – dysmotility

Diabetic autonomic neuropathy, sclerodermatitis, amyloidosis,
idiopathic intestinal pseudo-obstruction, after radiotherapy,
Crohn's disease
Achlorhydria
Chronic atrophic gastritis, proton pump inhibitor, older patients
Immunological factors
Hypo-/agammaglobulinemia, AIDS, immunosuppression
Multifactorial
Liver cirrhosis, kidney insufficiency, chronic pancreatitis,
enterocolic fistula
86
Chronic Diarrhea
Diagnosis
Invasive
r 4NBMMJOUFTUJOBMáVJEBTQJSBUF
Diagnosis: >105 CFU/mL (contraindication: approximately 60% of
UIFJOUFTUJOBMáPSBDBOOPUCFDVMUJWBUFE MPXSFQSPEVDJCJMJUZ
Noninvasive
r 9ZMPTFCSFBUIUFTU
- 14C-Xylose: (standard in USA, radioactive isotope)
- 13C-Xylose (expensive)
r )CSFBUIUFTU
- Glucose-H2 (most often used in Europe, but up to 15% false
negatives due to non-hydrogen producers)
- Lactulose-H2
Therapeutic approach
r 1PTTJCMF CVUOPTUBOEBSEJ[FEEJBHOPTUJDDSJUFSJB
Therapy
1. Treatment/correction of triggering factors
2. Treatment of bacterial overgrowth
3. Treatment of malabsorption syndrome
Antibiotic therapy over 7-10 days

r $JQSPáPYBDJO YNHE
OPSáPYBDJO YNHE

metronidazole (3 x 250 mg/d), trimethoprim/sulfamethoxazole
(2 x 160/800 mg/d), doxycycline (2 x 100 mg/d), amoxicillin/clavu-
lanic acid (2 x 500 mg/d), rifaximin (1200 mg/d) – not yet available
in Switzerland
Return of bacterial growth: antibiotic therapy over 5 – 10 days

every 4 weeks using various medications.
[Quigley, E. M. M. & Quera, R. Small intestinal bacterial overgrowth: roles of anti-
biotics, prebiotics, and probiotics. Gastroenterology 130, 2006.]
87
Intestine
Treatment of Irritable Bowel Syndrome:

Cave:
Some of the agents have not been studied in randomised
controlled trials in IBS and their efficacy may be limited.
Symptom Treatment Active

pharmaceutical
ingredient
Constipation Fiber Psyllium, Bran
Osmotic laxatives Polyethylene
gylcol/Macrogol
Stimulant laxatives Senna
Bisacodyl
Sodium picosulfate
Prokinetic Agents Prucalopride
Lubiprostone
Diarrhea Antidiarrheal agents Loperamide

Probiotics Lactobacillus casei
Bifidobacterium lactis
Enterococcus faecalis
Abdominal Pain Spasmolytics Butylscopolamine
Mebeverine
Pinaverium bromide
Tricyclic Amitriptylin
antidepressants
Selective serotonin Escitalopram
re-uptake inhibitors Citalopram
(SSRI) Sertralin
Bloating Simethicon
Dimethicon
Dyspepsia Phytotherapeutics STW 5
Artichoke extract
Peppermint oil
88
Pharmacological Approaches
Dose per day Comments
individual
1-2 sachets
12-150 mg
5-10 mg
5-10 mg
1-2 mg Not licensed for IBS
with constipation
2x 24 μg Not licensed for IBS
with constipation
2-16 mg
individual Dosing should
be high and long
enough
10-100 mg
200-400 mg
50-200 mg
50-150 mg
10-20 mg Start with low doses

20-40 mg
50-200 mg May cause diarrhea
41-82 mg
1-3 tablets
3x 20 drops
3x 320 mg
3x 187 mg
89
Intestine
Constipation
Rome III criteria for chronic constipation

Criteria fulfilled for the last 3 months and symptom onset at
least 6 months prior to diagnosis
Presence of ≥2 of the following symptoms:
r-VNQZPSIBSETUPPMTJOöPGEFGFDBUJPOT
r4USBJOJOHEVSJOHöPGEFGFDBUJPOT
r4FOTBUJPOPGJODPNQMFUFFWBDVBUJPOGPSöPGEFGFDBUJPOT
r4FOTBUJPOPGBOPSFDUBMPCTUSVDUJPOCMPDLBHFGPSö
of defecations
r.BOVBMNBOFVWFSTUPGBDJMJUBUFöPGEFGFDBUJPOT
EJHJUBMNBOJQVMBUJPOT QFMWJDáPPSTVQQPSU
rFWBDVBUJPOTQFSXFFL
Loose stools rarely present without the use of laxatives
Insufficient criteria for irritable bowel syndrome
[Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC.
Functional bowel disorders. Gastroenterology. 2006;130:1480–91]
90
Causes of secondary constipation

Organic Colorectal cancer, extraintestinal mass,
QPTUJOáBNNBUPSZ JTDIFNJDPSTVSHJDBM
stenosis
Neurological Spinal cord injury, Parkinson's disease,

paraplegia, multiple sclerosis, autonomic
neuropathy, Hirschsprung's disease,
chronic intestinal pseudo-obstruction
Myogenic Myotonic dystrophy, dermatomyositis,

scleroderma, amyloidosis, chronic intestinal
pseudo-obstruction
Anorectal Anal fissure and strictures, IBD, proctitis
Endocrine, Diabetes mellitus, hypothyroidism, hypercal-

metabolic cemia, porphyria, chronic renal insufficiency,
panhypopituitarism, pregnancy
Drugs Opiates, antihypertensive agents, tricyclic

antidepressants, iron preparations,
anti-epileptic drugs, anti-Parkinsonian agents
(anticholinergic or dopaminergic)
Diet, lifestyle Low fiber diet, dehydration, inactive lifestyle
[Eoff JC. Optimal treatment of chronic constipation in managed care: review and
roundtable discussion. J Manag Care Pharm. 2008;14:1–15]
91
Intestine
Three Main Types of Primary (idiopathic) Constipation
Normal-transit Most common Frequently overlaps

constipation subtype with IBS-C
Mostly characte-
Slow-transit rized by reduced Common
constipation phasic colonic in woman
motor activity
Poor coordination Considerable

1FMWJDáPPS
PGQFMWJDáPPSBOE overlap with STC
dysfunction
anal sphincter and NTC
[Tack J et al. Diagnosis and treatment of chronic constipation – a European perspec-

tive. Neurogastroenterol Motil. 2011 August; 23(8): 697–710]
92
Guideline-supported General Treatment Pathways

1. Exclude other pathologies and secondary causes
2. Begin treatment with dietary and lifestyle adjustments
3. Move to osmotic laxatives, stool softeners and bulk-forming
agents (no consensus on the order in which these should
be tried)
4. Move to stimulant laxatives, suppositories and/or enemas
5. Surgery should be used as a last resort or to treat identified
disorders that require surgical correction
[Tack J et al. Diagnosis and treatment of chronic constipation – a European perspec-

tive. Neurogastroenterol Motil. 2011 August; 23(8): 697–710]
93
Intestine
Enterokinetic treatment algorithm
Patient with chronic

constipation (infrequent or Education: lifestyle
hard stools or difficult to and dietary measures
pass stools)
History and physical

examination
No Constipating No Chronic
"MBSNGFBUVSFT
ESVHT functional
constipation
Yes Yes
(Rome III
Technical criteria)
Stop drugs
examinations
if possible
as indicated
"EFRVBUFSFMJFG No
Yes
Drug-induced
constipation
No
Abnormality
JEFOUJàFE
Yes
Organic disease with
constipation, treat
accordingly
[Tack J et al. Diagnosis and treatment of chronic constipation – a European

perspective. Neurogastroenterol Motil. 2011 August; 23(8): 697–710]
94
Initial or subsequent
addition of laxatives
No Yes
Long-term
"EFRVBUFSFMJFG
management
No
Add /switch laxative
Yes
Long-term
"EFRVBUFSFMJFG
management
No
Stop laxative and commence

with enterokinetic drug
(prucalopride)
Yes
Long-term
"EFRVBUFSFMJFG
management
No
Refractory constipation
Refer for additional testing

following Rome guidelines
for refractory constipation
and difficult defecation
95
Intestine
Functional GI disorders: Constipation
Refractory constipation and difficult defecation
1 2
Refractory constipation: Physiological testing:
no improvement with anorectal manometry,
high-fiber diet, laxatives rectal balloon expulsion,
and prucalopride and colonic transit
3
Yes Are anorectal manometry
and balloon expulsion
CPUIOPSNBM
5 4 6
Yes No Functional
Slow transit Is colonic
constipation
constipation USBOTJUTMPX
with normal transit
No
[Tack J et al. Diagnosis and treatment of chronic constipation – a European

perspective. Neurogastroenterol Motil. 2011 August; 23(8): 697–710]
96
7
No Are both tests
BCOPSNBM
No
Yes
9 8
Functional
Assess barium or
defecation
MR defecography
disorder
Yes
10 11
Does Is colonic
defecography USBOTJUTMPX
reveal disordered No Yes
EFGFDBUJPO
13 12
Functional Functional
defecation defecation
disorder with disorder with
normal transit slow transit
Yes No
14
Does slow transit normalize
after correcting defecation
EJTPSEFS
97
Intestine
Chronic constipation: New treatment approaches

Substance Prucalopride
Mode of action Potent, selective, high-affinity
agonist at the 5-HT4 receptor
Indication Constipation resistant to dietary and lifestyle adjustments,

osmotic laxatives, stool softeners, bulk-forming agents
and stimulant laxatives
Dosage once-daily 1–2 mg
Administration orally
Resorption / yes / partially hepatic / renal
Metabolism /
Elimination
Contraindications Bowel obstruction / hepatic and renal
insufficienc / pregn.
Side effects headache, nausea, diarrhea,
and abdominal pain
Effect over 3 bm / week
(vs placebo) in 24 % (vs 13)
CH / EU / USA +/+/+
[Adapted from:
UÊ À`Ê
Ê>`Ê-Õ>ÀiÃÊ
\Ê vviVÌÊvÊ>Ý>ÌÛiÃÊ>`Ê«>À>V}V>ÊÌiÀ>«iÃÊÊVÀV
idiopathic constipation: systematic review and meta-analysis. Gut 2011;60:209e218.
UÊ À>Ê °Ê>VÞÊiÌÊ>°Ê
ÀVÊVÃÌ«>Ì\Ê iÜÊ`>}ÃÌVÊ>`ÊÌÀi>ÌiÌÊ>««À>ViÃ°
Therap Adv Gastroenterol. 2012 July; 5(4): 233–247]
98
Lubiproston Linaclotide Methylnaltrexone

Direct (luminal) stimulation Direct stimulation of intestinal peripherally-acting
of chloride channels guanylate cyclase type-C μ-opioid antagonist
(GC-C) receptors
Laxative-resistant
opioid Induced
Constipation (OIC)
2 x 24 ug 1 x 290 ug /d 1 x 12 mg (> 62 kg)
IBS-C: 2 x 8 ug 1 x 8 mg (< 62 kg)
orally orally orally
Minimally / oxidation in Minimally / no / little hepatic metabolism
stomach and duodenum metabolization / esp. renal
bowel obstruction, Bowel obstruction, Pregnancy, Renal insufficiency

pregnancy, breastfeeding breast-feeding (relative ci) (dose reduction)
Diarrhea, nausea, Diarrhea headache, nausea,
abdominal pain diarrhea
Spontaneous defecation Improvement of frequency defecation within 4 h
within 24 h in 60 % (vs 35) of bm in 20 % (vs 5) in 60 % (vs 14)
+/-/+ -/+/+ +/-/+
99
Intestine
Treatment
Laxative Active Indication
pharmaceutical
ingredient
Bulk laxative Psyllium Stool softener

in constipation,
for long term use
Sterculiae gum
Osmotic Symptomatic treatment

laxative / poorly of constipation,
absorbed for regular use
sugars
Lactulose
Lactitol
Polyethylene
glycol /
Macrogol
Stimulant
laxative
100
Mechanism of action Dose / Commonest Contraindication

maximum adverse events
recommended
dose
Increases colonic residue, Titrate up to Bloating and Ileus, acute

stimulating peristalsis; ~20 g; should áBUVT FTQFDJBMMZ constipation,
Natural fibers that undergoes be taken with at the onset of stool impaction
bacterial degradation, plenty of water treatment
increases colonic residue, to avoid intesti-
stimulating persistalsis nal obstruction
Colonic retention of water,

due to osmotic effect of
poorly absorbed sugars,
stimulating peristalsis
Synthetic disaccharide Lactulose: Gas and bloating, Ileus, abdominal

consisting of galactose and 15 – 45 ml once especially at the pain
fructose linked by bond or twice (initial onset of treatment of unknown origin
resistant to disaccharidases; 3 days), then
not absorbed by the small dose reduction
intestine; undergoes bacterial to 10 – 25 ml
fermentation in the colon Lactitol: 30 ml
with formation of (= 20 g) once
short-chain fatty acids a day (initial
4 – 5 days),
then reduce to
maintenance
dose 15 ml
(10 g) once
daily
Organic polymers that are 6 – 36 g once Bloating and Ileus, IBD, toxic
poorly absorbed and not or twice a cramping (less megacolon, bowel
metabolized by colonic day, can be than other poorly perforation
bacteria mixed with absorbed sugars)
noncarbonated
beverages
Stimulates intestinal motility

or secretion, effect within
6 –12 hours
101
Intestine
Treatment
Anthraqui- Senna Acute constipation,
nones for occasional use
Diphenyl- Bisacodyl Acute constipation, for

methane short term use or prolonged
derivatives use under medical
supervision
Sodium Acute constipation, for

picosulfate short term use or prolonged
use under medical super-
vision in opioid induced
constipation
Prokinetic Prucalopride Chronic constipation in wo-

agents man after failure of dietary
(Benzofuran) restrictions and 2 laxatives
within 9 months, prescribed
only by gastroenterologists
102
Converted by colonic 12 –150 mg Abdominal cram- Ileus,spastic

bacteria to their active form; daily before ping, diarrhea, constipation,
colonic stimulation by active bedtime nausea, may abdominal pain
secretion of electrolytes into cause melanosis of unknown origin,
the lumen and inhibition of coli, a benign hypokalemia
reabsorption condition that is
usually reversible
within 12 months
after the cessation
of laxative use; no
definitive asso-
ciation between
anthraquinones
and colon cancer
or myenteric nerve
damage has been
established
Hydrolyzed by endogenous 5 –10 mg Abdominal Ileus, colonic

esterases; stimulates directly every night cramping, pain, obstruction, acute
active secretion of water and diarrhea appendicitis,
electrolytes into the lumen dehydration,
and inhibition of water and hypokalemia
electrolyte reabsorption,
stimulates motility of small
intestine and colon
Hydrolized to its active form 5 –10 mg Diarrhea, abdo- Ileus, colonic

by colonic bacterial enzy- every night minal cramping, obstruction,
mes; affects only the colon pain, nausea acute appendicitis,
dehydration,
hypokalemia
Selective, high affinity 5-HT4 1 – 2 mg once Headache, End-stage renal

(serotonin) receptor agonist, daily, stop if no abdominal pain, disease and hemo-
altering colonic motility effect with nausea, diarrhea dialysis, End-stage
patterns 2 mg daily liver disease
within 4 weeks (Child C cirrhosis),
bowel perforation,
IBD, toxic
megacolon, colonic
obstruction, Ileus,
no contraception
103
Intestine
Terminal ileitis differential diagnosis
inflammatory bowel disease

r $SPIOhTEJTFBTF NPTUDPNNPO
r CBDLXBTIJMFJUJTEVFUPVMDFSBUJWFDPMJUJT
infectious colitis
r :FSTJOJBTQQ
r:FSTJOJBFOUFSPDPMJUJDB
r:FSTJOJBQTFEVPUVCFSDVMPTJT
r 4BMNPOFMMBTQQ
r $MPTUSJEJVNEJGàDJMF
r UZQIJMJUJT OFVUSPQBFOJDFOUFSPDPMJUJT
r .ZDPCBDUFSJBMTQQ
r.ZDPCBDUFSJVNUVCFSDVMPTJT
r.ZDPCBDUFSJVNBWJVN
r "DUJOPNZDPTJT
r "OJTBLJBTJT
r $ZUPNFHBMPWJSVT
r )JTUPQMBTNBDBQTVMBUVN
spondyloarthropathies
r BOLZMPTJOHTQPOEZMJUJT
r SFBDUJWFBSUISJUJT
r QTPSJBTJT
vascular
r WBTDVMJUJEFT
rTZTUFNJDMVQVTFSZUIFNBUPTVT 4-&
rQPMZBSUFSJUJTOPEPTB 1"/
r)FOPDI4DIÕOMFJOQVSQVSB
r#FIÉFUhTEJTFBTF
rPUIFSWBTDVMJUJEFT$IVSH4USBVTTTZOESPNF SIFVNBUPJEBSUISJUJT
Wegener granulomatosis, lymphomatoid granulomatosis, giant-cell
arteritis, Takayasu arteritis, thromboangiitis obliterans
r TNBMMCPXFMJTDIBFNJB
104
Terminal ileitis differential diagnosis
small-bowel neoplasms
r BEFOPDBSDJOPNBPGUIFTNBMMCPXFMDBFDVN
r MZNQIPNBMZNQIPNBPGUFSNJOBMJMFVN
r DBSDJOPJEUVNPVS
r NFUBTUBUJDDBODFS
drug-related
r /4"*%FOUFSPQBUIZ JTPMBUFEUFSNJOBMJMFBMVMDFSBUJPOT *5*6
r PUIFSESVHT,$MUBCMFUT QBSFOUFSBMHPMEUIFSBQZ PSBM

contraceptives, ergotamine, digoxin, diuretics, antihypertensives
infiltrative
r FPTJOPQIJMJDFOUFSJUJT
r TBSDPJEPTJT
r BNZMPJEPTJT
r TZTUFNJDNBTUPDZTUPTJT
others: endometriosis, radiation enteritis, lymphoid nodular

hyperplasia
[Dilauro S, Crum-cianflone NF. Ileitis: when it is not Crohn's disease. Curr Gastroen-
terol Rep. 2010;12 (4): 249-58]
105
Intestine
IBD Therapy
Equivalent anti-inflammatory doses

of different oral corticosteroids
Prednisone Other corticosteroids
10 mg Prednisolone
40 mg Hydrocortisone
10 mg Prednisone
are equivalent to 8 mg Methylprednisolone
1.6 mg Dexamethasone
1.6 mg Betamethasone
106
107
Intestine
IBD Therapy, CD
Therapy algorithm for Crohn's disease based on

ECCO Guidelines 2010 and IBD Ahead treatment
recommendations*.
Dosage of Therapeutics
Substance Dosage
5-ASA Mesalazine 3–4.5 g/d
Corticosteroide Budesonide 9–12 mg/d
Prednisone 0.75–1 mg/kg/d
Immunosuppressors Azathioprine (AZA) 2–2.5 (max. 3) mg/kg/d
6-Mercaptopurine (6-MP) 1–1.5 mg/kg/d
Methotrexate (MTX) 15–25 mg, 1 x / week
Antibiotics Metronidazole 1000–1500 mg/d
Ciprofloxacin 1000 mg/d
Biologics Adalimumab Subcutaneous
Week 0: 160 mg
Week 2: 80 mg
Week 4: 40 mg
Then every 2 weeks: 40 mg
Infliximab Infusion over 1– 2 hours
Week 0: 5 mg/kg
Week 2: 5 mg/kg
Week 6: 5 mg/kg
Then every 8 weeks: 5 mg/kg
Certolizumab Pegol Subcutaneous
(off-label in certain countries) Week 0: 400 mg
Week 2: 400 mg
Week4: 400 mg
[*This therapy algorithm has been developed in 2012 by: Prof. C. Braegger, Dr. Ph. de Saussure, Prof. F. Froehlich,
Dr. C. Gaia, Prof. P. Michetti, PD Dr. C. Mottet, Prof. G. Rogler, Prof. B. Sauter, PD Dr. A. Schöpfer, Prof. F. Seibold,
Prof. A. Straumann, PD Dr. S. Vavricka.]
108
IBD Therapy, CD
Moderately active Crohn's disease*
Budesonide Prednisone
+ Antibiotics if sepsis Multiple
+/– or +/–
predictors for
AZA/6-MP/MTX AZA/6-MP/MTX is assumed
severe course
5B 5B#
Evaluation of effectiveness after 1–2 weeks
Induction therapy
Response: Tapering of steroids
Relapse within No response after

12 weeks during 2–4 weeks
tapering of steroids
1
Response Steroid Steroid-refractory
Step
dependent Steroid-intolerant
5C 6D 5H
Maintenance therapy
anti-TNF
Exceptional
AZA/6-MP/MTX +/–
No medication
AZA/6-MP/MTX
6A 6A 5H
Monitoring every 10 –12 weeks Monitoring every 10 –12 weeks
2
Response Primary
Step
Therapy failure unsatisfactory or non-response Non-response

response failed Intolerance
anti-TNF
Consider – Reduction of Alternative Consider
anti-TNF
surgery intervall anti-TNF surgery
Relapse-therapy/
– Dosage increase
Therapy failure
6B 6B 5J 5J 6B
3
* Moderately active localised ileocaecal Crohn's disease: CDAI >150-300, no previous surgeries /
Step
Therapeutic pathway: is valid for luminal Crohn's disease, no stenosis, no fistulas.

# This data refers to ECCO statements.
109
Intestine
IBD Therapy, CD
Severely active localised ileocaecal Crohn's disease
Prednisone
+
AZA/6-MP/MTX
5C#
Induction therapy
Response: Tapering of Prednisone
Relapse within 12 weeks No response after

during tapering of steroids 2–4 weeks
1
Response Steroid dependent Steroid-refractory
Step
Steroid-intolerant
5C 6D 5H
Monitoring
every
Maintenance therapy
anti-TNF
AZA/6-MP/MTX 10 –12 weeks. +
For therapy AZA/6-MP/MTX
failures:
5C 5C
Monitoring every 10 –12 weeks
2 Primary
Response
Step
unsatisfactory or non-response
loss of response Intolerance
anti-TNF
– Reduction of Alternative Consider
intervall anti-TNF surgery
Relapse-therapy/
– Dosage increase
Therapy failure
5J 5J
3
Step
110
IBD Therapy, CD
Colonic disease
Mild disease Moderate to severe disease

Mesalazine or Prednisone
salazopyrin (sulfasalazine) +
topical or p.o. AZA/6-MP/MTX
5D# 5D

Induction therapy
Relapse within 12 weeks No response after

during tapering of steroids 2–4 weeks
1
Steroid dependent Steroid-refractory
Response
Step
5C Steroid-intolerant
6D 5H
Monitoring every
10 –12 weeks.
Maintenance therapy
anti-TNF
AZA/6-MP/MTX Therapy failure: +
after min. AZA/6-MP/MTX
12 weeks
5C 5C
Monitoring every 10 –12 weeks
2
Response Primary
Step
response failed Intolerance
anti-TNF
– Reduction of Alternative Response Consider
intervall anti-TNF unsatisfactory or surgery
Relapse-therapy/
– Dosage increase loss of response

Therapy failure
5J 5J
3
Step
111
Intestine
IBD Therapy, CD
Extensive small bowel disease*
Prednisone
+
AZA/6-MP/MTX
5E#
Induction therapy
Response: Tapering of Non-response

Prednisone after 2–4 weeks
1
Response Steroid-refractory
Worsening
Step
Steroid-intolerant of symptoms
5C 5H
Consider
Maintenance therapy
AZA/6-MP/MTX
AZA/6-MP/MTX Hospitalization
+
anti-TNF and steroids i.v.;
in-depth
6C 5E anamnesis
Monitoring every 10 –12 weeks 5E

Monitoring every
10 –12 weeks
2 Primary
Response
Step
loss of response Intolerance
anti-TNF
AZA/6-MP/MTX
– Reduction of Alternative
+
intervall anti-TNF
Relapse-therapy/
anti-TNF
– Dosage increase
Therapy failure
5E 5J 5J
3
* Extensive small bowel disease: >50 cm or >1 segment affected,
Step
with or without colonic involvement.

112
IBD Therapy, CD
Fistulating Disease
Symptom free perianal fistula
Therapy optional
Induction therapy
Simple perianal fistula* Complex perianal fistula*

Exclude perinanal abcess or treat
immediately if present (9F) and/or or
Antibiotics Seton° Antibiotics

and/ Seton° and anti-TNF
(Metronidazole or
or
1 or Ciprofloxacin) Fistulotomy AZA/6-MP
Step
9G# 9H 9J 9K
Maintenance therapy
AZA/6-MP
and/
and/or Seton°
or
anti-TNF
9M
2
Step
Exclude abcess and/or

stenosis
Seton° AZA/6-MP/MTX
or + and/or + Antibiotics or Stoma
Relapse-therapy/
surgery anti-TNF
Therapy failure
9N
3
* Simple fistula: Perianal fistula without branching/ Complex Fistula: Perianal branched
Step
fistula system
° Seton: Non-cutting Seton. / # This data refers to ECCO statements.
113
Intestine
IBD Therapy, CD
Monitoring of efficacy and safety 4, 7
Recommendations for general IBD monitoring4

Mandatory Clinical examination:
Number of bowel movements per day
Level of abdominal pain
Extra-intestinal symptoms
Fever
Other medications
Laboratory:
CRP
Complete blood count
Transaminases
Recommended Imaging to be discussed according to
clinical symptoms:
Endoscopy
CT scan or MRI
Check on vaccination status
Calprotectin7
Fecal calprotectin for the management

of Crohn’s disease7
Monitoring disease activity Faecal calprotectin levels correlate well with
endoscopic and histological disease activity. In
Crohn’s disease, the correlation is better for colonic
than for ileal disease.
Monitoring response to treatment Low faecal calprotectin levels after treatment
indicate response of endoscopic disease activity
better among adult than paediatric patients.
Establishing mucosal healing Mucosal healing seems to indicate controlled IBD
activity. It has been associated with sustained clinical
remission as well as reduced rates of hospitalisation
and surgical resection. Data on faecal calprotectin
as a surrogate marker of MH are emerging, but
the evidence is not yet conclusive.
Prediction of IBD relapse Faecal calprotectin levels <150 μg/g indicate IBD
remission with a low risk of relapse. Reports
from prospective intervention studies using
calprotectin-guided therapy strategies to investigate
the long-term outcome of IBD are not yet available.
114
IBD Therapy, CD
Risk for severe disease course: predictive factors
Patients with poor prognosis benefit most of an

early therapeutic begin with immunosuppressiva
or biologics (5F)1
Predictive factors Disease course References
s Age < 40 – Chronically active L Beaugerie et al.; Gastroenetrol 2006;
s Steroids at disease 130:650-56
first episode – Hospitalization C Loly et al.; Scand J Gastroenterol 2008;
s Perianal disease – Surgery 43:948-54
– Steroid-dependence
s Weight loss (> 5 kg) and – Complex perinanal C Loly et al.; Scand J Gastroenterol 2008;
strictures (B2 according disease 43:948-54
Montreal Classification) – Resection of colon
– Small bowel
resection
– Stoma
s Disease of Ileum – Strictures L Henckaerts et al.; Clin Gastroenterol
(L1 according Montreal – Surgery Hepatol 2009; 7:972-80
Classification) – Penetrating E Louis et al.; Gut 2003j 52: 552-557
disease
s Deep ulcerations (Infe- – Penetrating disease M Allez et al.; Am J Gastroenterol 2002;
station of the surface – Colonectomy 97:947-53
within one bowel
segment > 10%
s Smoker – Surgery, fistula E Lindberg; Gut 1992; 33: 779-782

(> 10 cigarettes/day) and abcesses
[References: 1. Dignass A et al., The second European evidence-based consensus
on the diagnosis and management of Crohn’s disease: Current management, Journal
of Crohn’s and Colitis (2010). 2. Van Assche G et al., The second European evidence-
based Consensus on the diagnosis and management of Crohn’s disease: Special
situations, Journal of Crohn’s and Colitis (2010) 4, 63–101. 3. Ferrante M et al.,
Physician perspectives on unresolved issues in the use of conventional therapy in
Crohn’s disease: Results from an international survey and discussion programme,
Journal of Crohn’s and Colitis (2012) 6, 116–131. 4. Pache I et al., TNF-␣ blockers
in inflammatory bowel diseases: Practical consensus recommendations and a user’s
guide, Swiss Med Wkly. 2009; 139 (19–20): 278–287. 5. www.embryotox.de, Infor-
mationsseite des Pharmakovigilanz- und Beratungszentrums für Embryonaltoxikologie
Deutschland. 6. Beglinger C et al., Screening for tuberculosis infection before initiation
of anti-TNF-a therapy, Swiss Med Wkly 2007;137:621-622. 7. Burri E and Beglinger C,
Faecal calprotectin – a useful tool in the management of inflammatory bowel disease,
Swiss Med Wkly. 2012;142:w13557. 8. Von Wagner M and Zeuzem S, Prophylaxis
and therapy of reactivation of hepatitis B in immunosuppressed patients, Dtsch Med
Wochenschr 2009;134: 255–258. 9. Mahadevan U et al., The London Position
Statement of the World Congress.of Gastroenterology on Biological Therapy for IBD
With the European Crohn ’ s and Colitis Organization: Pregnancy and Pediatrics,
Am J Gastroenterol. 2011 Feb;106(2):214-23.]
115
Intestine
IBD Therapy, CD
Treatments during pregnancy

Class of product Products FDA Classification
Glucocorticoids Prednisolone C
Budesonide B
Antibiotics Metronidazole B
Ciprofloxacin C
Immuno-modulators Azathioprine D
6-MP
Methotrexate X
TNF-a Antibody Adalimumab B
Infliximab B
Certolizumab9 B
Category A: Appropriate and well-controlled studies have not shown any risk to the fœtus during
the first three months of pregnancy (and there is no sign of risk in the later weeks of pregnancy).
Category B: Reproductive studies carried out in animals have not shown any risk to the
fœtus; however no appropriate or well controlled study exists in pregnant women. Category C:
Reproductive studies carried out in animals have shown a harmful effect for the fœtus; however
no appropriate or well controlled study exists in humans. The use of this medication in pregnant
women can however be justified when the potential benefit to the latter outweighs the potential risks.
116
Pregnancy Breast Feeding
st
1 Trimester: a slightly inceased risk of cleft palate No risk for the breastfed baby, even
cannot be excluded if used during sensitive phase between if high-dose treatment over a short
8–11 weeks of pregnancy. period of time.
2nd-3rd Trimester / Perinatal: depending on the duration
of treatment, dose and indication, a intra-uterine growth
retardation, premature delivery, transient hypoglycaemia,
hypotonia and electrolyte abnormality in the new-born
have been shown.
1st Trimester: No risk reported for the breastfed baby, not even In around 60 infants breastfed whilst
if high dose treatment for a short period of time, no evidence for the mother was on Metronidazole,
mutagenic or carcinogenic effects if intra-uterine exposure. no harmful effect was seen.
Possible effects on cartilage formation (ciprofloxacin)
2nd-3rd Trimester / Perinatal: No evidence for feto-toxic risk.
1st Trimester: no teratogenic risk in >1500 pregnant women In infants that are completely breast-
treated orally fed and after maternal absorption of
2nd-3rd Trimester / Perinatal: on several occasions a reduced Aziathioprine during breast-feeding,
birth weight and an increased number of premature births have as a general rule no symptoms have
been observed. been observed
1st Trimester: teratogen potential with a variable pattern of No reports for breastfed babies
malformations; dose-dependent. A dose <10mg/week does not available.
seem to be teratogenic.
2nd-3rd Trimester / Perinatal: can lead to intra-uterine growth
retardation, bone marrow suppression and in very rare cases
foetal intra-uterine death.
1st Trimester: no teratogenic effect in >100 assessed High molecular weight and
pregnancies. low oral availability: absorption
2nd-3rd Trimester / Perinatal: Only individual case reports of by the newborn unlikely.
exposure during 2–3 trimester. Diaplacental transfer presumed No clinical abnormalities reported.
in case of more mature placenta.
1st Trimester: No data available, but experience from company In the few case reports to date no
registries and case reports: no embryotoxic risk. side effects have been described in
2nd-3rd Trimester / Perinatal: Only case reports. In case of a the breastfed baby.
more mature placenta, transfer to the foetus via an active process
and can reach maternal therapeutic serum concentrations.
1st Trimester: Potential concern that Fab' fragment can pass the
placenta by passive diffusion. One case report: no serum level
2nd-3rd Trimester / Perinatal: Only case reports. Probably lower detectable in breast milk.
diaplacental transfer compared to other anti-TNF␣ antibodies
(shown in rats).
Category D: Data on the secondary effects coming from observations or clinical or post-
marketing studies carried out in humans clearly show risks for the human fœtus. The use of
this medication in pregnant women can however be justified when the potential benefit to the
latter outweighs the potential risks. Category X: Studies carried out on animals or on humans
have showed malformations in the fœtus and/or, on the basis of data on the secondary effects
coming from clinical or post-marketing observations, show risks for the human fœtus, the risks
outweighing by far the potential benefits.
117
Intestine
IBD Therapy, CD and UC
Screening before anti TNF-Therapy

Contra-indications or warnings for Anti-TNF-therapy with respect to
findings during screening before treatment.
Evaluation If yes
1. Serious infection (incl. active TB) or sepsis Contra-indicated
2. In case of flare:
a. Clostridium difficile toxin positive in stools Contra-indicated
b. CMV infection proven by biopsies Contra-indicated
c. Parasites in stool Contra-indicated
3. Cardiac insufficiency NYHA III or IV Contra-indicated
4. Neurological disease Use with caution
5. History of malignancy Use with caution
6. Latent TB (i.e. positive IGRA test or abnormal x-ray Treatment with isoniazid
suggestive of past TB not adequately treated or 300 mg/d for 9 months or
history of prior exposure to TB) rifampicin 10 mg/kg daily
for 4 months; TNF-therapy
can be started after 1 month
of preventive therapy
7. HIV-positive, uncontrolled disease Contra-indicated
8. Positive HBV serology Start anti-viral agents HBV

a. HBsAg positive DNA should be assessed every
b. positive HBcAb and negative HBsAg 2 – 3 months but antiviral
therapy is not recommended
unless HBV-DNA is detected
9. Chronic HCV infection Use with caution
10. Abnormal transaminase levels Further evaluations
11. Women: last gynecological examination >1 year Obtain exam
Vaccinations:
Check vaccination status prior to initiation of Anti-TNF-therapy,
follow BAG recommendations on www.bag.admin.ch/impfungen
118
IBD Therapy, UC
Therapy algorithm for Ulcerative Colitis based on

ECCO Guidelines 2012 and published literature*.
Dosing of therapies
Substance Dosage
5-ASA Mesalazine 2 – 4.8 g/d (oral)

1 – 2 g/d (rectal)
Corticosteroids Budesonide 2 mg/d (rectal)

Prednisone 0.75 – 1 mg/kg/d
Immunosuppressives Azathioprine (AZA) 2 – 2.5 (max. 3) mg/kg/d

6-Mercaptopurine (6-MP) 1–1.5 mg/kg/d
Cyclosporine 2 mg/kg/24 hours i.v.
Tacrolimus Target serum concentration:
10 – 15 ng/ml
Biologics Adalimumab Subcutaneous

Week 0: 160 mg
Week 2: 80 mg
Week 4: 40 mg
Golimumab Subcutaneous
Week 0: 200 mg
Week 2: 100 mg
Week 4: 50 mg
(100 mg for patients > 80 kg)
Infliximab Infusion over 1– 2 hours

Week 0: 5 mg/kg
Week 2: 5 mg/kg
Week 6: 5 mg/kg
Then every 8 weeks: 5 mg/kg
[* This therapy algorithm has been developed in 2014 by: Christoph Beglinger, Janek Binek,
Elmar Christian, Pascal Juillerat, Michael Manz, Pierre Michetti, Christian Mottet, Carl Oneta,
Gerhard Rogler, Bernhard Sauter, Alain Schoepfer, Frank Seibold, Stephan Vavricka.]
119
Intestine
IBD Therapy, UC
Mild to moderate Ulcerative Colitis
Acute flare with no evidence for infectious disease
Proctitis Left-sided colitis Extensive colitis
Rectal 5-ASA: Rectal 5-ASA: Oral 5-ASA * 2 g

1 g suppository enema or foam * 2 g and
rectal 5-ASA * 2 g
Evaluate response Evaluate response Evaluate response

after 2 weeks; remission after 2 weeks; remission after 2 weeks; remission
after 4 – 8 weeks after 4 – 8 weeks after 4 – 8 weeks
Add on
Maintenance Maintenance
Maintenance Optimize oral
with rectal with oral
with Rectal steroids 5-ASA dose
and/or +/–
rectal 5-ASAa,b (up to 4.8 g/d)
oral 5-ASAa,b rectal 5-ASAa
Add on
Oral 5-ASA Mild to moderate UC

(up to 4.8 g/d) not responding to 5-ASA
Response/remission
No response/no remission
a Maintenance treatment recommended for all patients, on-demand treatment
only possible for patients with mild disease
b In case of intolerance to 5-ASA, E.coli Nissle may be used as alternative for
maintenance treatment
120
IBD Therapy, UC
Mild to moderate Ulcerative Colitis

not responding to 5-ASA
1st flare 2nd flare within a year

not responding to 5-ASA not responding to 5-ASA
(infection excluded) (infection excluded)
Oral steroids Oral steroids + AZA/6-MP
Evaluate response after 2 weeks Evaluate response after 2 weeks
Taper steroids Steroid-refractory ulcerative colitis: Taper steroids

within 6 –12 active disease despite oral steroids within 6 –12
weeks (up to 0.75 mg/kg/d prednisolone) weeks
over 4 weeks
Steroid-dependent ulcerative colitis: Maintenance

Maintenance
Fail to taper steroids within 16 weeks with AZA/6-MP
with oral (* 2 g)
or +/–
and/or
Relapse within 12 weeks after 5-ASA/rectal
rectal 5-ASAa,b
steroids stop steroids
Response/remission
a Maintenance treatment recommended for all patients, on-demand treatment
only possible for patients with mild disease
b In case of intolerance to 5-ASA, E.coli Nissle may be used as alternative for
maintenance treatment
121
Intestine
IBD Therapy, UC
Steroid-dependent Ulcerative Colitis
Fail to taper steroids within 16 weeks or

Relapse within 12 weeks after stop of steroids Exclude infection
Steroid-intolerance
Anti-TNF
AZA/6-MP
(+/– AZA/6-MP)
Fail to taper
Taper steroids steroids within ,]HS\H[LLMÄJHJ`
HUKL]HS\H[LLMÄJHJ` 16 weeks after up to 14 weeks
after 12 weeks or
relapse
within 12 weeks
after steroid stop
AZA/6-MP Increase dose/ Maintenance

intolerance decrease inter- with Anti-TNF
val of Anti-TNFa (+/– AZA/6-MP)
Loss of
response
Maintenance Switch to other Maintenance Switch to
with AZA/6-MP thiopurine with Anti-TNF alternative
or to anti-TNF (+/– AZA/6-MP) Anti-TNFa
Response/remission
In case of severe flare, consider hospitalization and treatment with intravenous
steroids or surgery
Consider drug level/metabolite testing to guide dose increases or modification
a Consider endoscopy before switching to a different Anti-TNF therapy
122
IBD Therapy, UC
Steroid-refractory Ulcerative Colitis
Active disease despite prednisolone Exclude infection

up to 0.75 mg/kg/day over 4 weeks (incl. C. diff, CMV)
Anti-TNF (+/– AZA/6-MP)

or AZA/6-MPa
,]HS\H[LLMÄJHJ`
after up to 14 weeks
Exclude
infection
Maintenance with
Increase dose/decrease
Anti-TNF or AZA/6-MP
interval of Anti-TNF
or combination
Loss of
response
Increase dose/decrease
Switch to alternative Anti-TNFb
interval of Anti-TNF
Response/remission
In case of severe flare, consider hospitalization and treatment with intravenous
steroids or surgery
Consider drug level testing to guide dose increases or modifications
a Also consider treatment with tacrolimus; AZA/6-MP monotherapy only if no
need for rapid induction
b Consider endoscopy before switching to a different Anti-TNF-therapy
123
Intestine
IBD Therapy, UC
Severe Ulcerative Colitis
Mandatory hospital admission in case of:

s bloody diarrhea * 6/day and
sone or more signs of systemic toxicity:
– tachycardia > 90 bpm
– fever > 37.8 °C
– Hb < 10.5 g/dL
– ESR > 30 mm/h
– CRP > 30 mg/L
Exclude infection
Methylprednisolone
i.v. corticosteroids
60 –125 mg/24 h
Assess response after 3 days

Discuss treatment options including colectomy
Switch
AZA to oral Prior AZA
naive steroids failure
and taper
Choice of
Anti-TNFa or Ciclosporineb ZWLJPÄJ
or Tacrolimus 2nd line treatment
AZA/6-MP Anti-TNFa depends on
Assess response after clinical setting
4-7 days
3rd line immuno-

Maintenance
Maintenance Maintenance suppressive
with Anti-TNF
with AZA/6-MP with Anti-TNF therapy
or AZA/6-MP
or colectomyc
Response/remission
Consider drug level testing to guide dose increases or modifications
a Data for hospitalized patients only available for Infliximab.
b Exclude low Mg/Cholesterol.
c 3rd line immunosuppressive therapy restricted to specialized centers
124
IBD Therapy, UC
Monitoring efficacy and safety

General recommendations for monitoring of ulcerative colitis patients
Mandatory Clinical examination
s.UMBEROFBOWELMOVEMENTSPERDAY
s,EVELOFABDOMINALPAIN
s%XTRA INTESTINALSYMPTOMS
s&EVER
s/THERMEDICATIONS
Laboratory:
s#20
s#OMPLETEBLOODCOUNT
s4RANSAMINASES
s)RONSTATUS
s6IT$AND"
Recommended Clinical examination
s#ALPROTECTIN
s%NDOSCOPYACCORDINGTOCLINICALSYMPTOMS
s#HECKVACCINATIONSTATUSFOLLOW"!'RECOMMENDATIONS
on www.bag.admin.ch/impfungen)
s0!0 4ESTYEARLY
s$ERMATOLOGICALCONTROLYEARLY
s"ONEDENSITOMETRY
Fecal calprotectin (FC) for the management of ulcerative colitis
Fecal calprotectin (FC) Mucosal healing is associated with lower hospitalization

for the management rates, a reduced need for surgery, a lower relapse rate
of Ulcerative Colitis and a lower risk of colorectal cancer in UC. FC reflects
endoscopic activity of UC more accurately than clinical
activity or other laboratory markers and may be used as
surrogate marker for mucosal healing.
Monitoring disease A FC-guided treatment strategy may be advantageous
activity compared to a treatment strategy based on clinical sym-
ptoms alone, however, prospective data are lacking.
Response to Anti-TNF Anti-TNF-therapy leads to a sharp decline of FC levels and
therapy normal FC () 100 μg/g) after induction therapy has been
shown to predict clinical remission at 1 year.
125
Intestine
IBD Therapy, UC
Colon cancer screening
Proctitis Left-sided/extensive colitis
No evidence of previous or current endoscopic

Determine risk profile
and/or
6 – 8 years after first
microscopic inflammation proximal
manifestation
to the rectum: no regular surveillance
High risk*: Low risk*:

colonoscopy colonoscopy
every 1– 2 years every 3 – 4 years
from the 8th year from the 8th year
after first after first
manifestation manifestation
In cases with concurrent PSC, surveillance colonoscopies should be carried out yearly
from the point of PSC diagnosis irrespective of disease activity and extent.
Post-proctocolectomy:
Endoscopic surveillance is recommended for patients with dysplasia or cancer
before or at the time of proctocolectomy.
* Risk stratification mainly depends on extent of disease, severity of endoscopic

and/or histological inflammation, pseudopolyps, concurrence of PSC,
and family history of CRC.
PSC = Primary sclerosing cholangitis
126
IBD Therapy, UC
Treatments during pregnancy

Class of SubstanceFDA Use during Use during
product pregnancy pregnancy breast feeding
category
5-ASA Mesalazine B 1st trimester: no signs for No abnormalities
teratogenic effects, confirmed by in breast-fed
clinical studies. 2nd/3rd trimester: infants have been
clinical studies have not shown described.
any fetotoxic effects to date.
Cortico- Budesonide B 1st trimester: no teratogenic Rectal or oral use
steroids effects expected. 2nd/3rd trimester: is unproblematic
no feto-toxic risk known and not due to low oral
expected. availability.
Prednisone C 1st trimester: a slightly increased No risk for the
risk of palatoschisis cannot be breast-fed baby,
excluded if used during sensitive even for high-dose
phase between 8 –11 weeks treatment over a
of pregnancy. 2nd/3rd trimester: short period of time.
depending on the duration
of treatment, dose and indication,
intra-uterine growth retardation,
premature delivery, transient
hypoglycemia, hypotonia and
electrolyte abnormality in the
newborn have been shown.
Immuno- Azathioprine D 1st trimester: no teratogenic risk in In infants that
suppressives 6-Mercapto- >1500 pregnant women treated are completely
purine orally. 2nd/3rd trimester: no breastfed as a
evidence for fetotoxic risk. general rule no
symptoms have
been observed.
st
Biologics Adalimumab B 1 trimester: no teratogenic effect High molecular
Infliximab has been shown. 2nd/3rd trimester: weight and low oral
active diaplacental transfer in availability: absorp-
case of more mature placenta. tion by the newborn
Theoretical concerns regarding unlikely. No clinical
development of immune system abnormalities in
and reduced immunity of the case reports.
newborn.
Golimumab B Only case reports available22 No data published
Category A: Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester
of pregnancy (and there is no evidence of risk in later trimesters). Category B: Animal reproduction studies have
failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.
Category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate
and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women
despite potential risks. Category D: There is positive evidence of human fetal risk based on adverse reaction data
from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the
drug in pregnant women despite potential risks. Category X: Studies in animals or humans have demonstrated
fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from inves-
tigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh
potential benefits. (http://depts.washington.edu/druginfo/Formulary/Pregnancy.pdf)
127
Intestine
IBD Therapy
Treatment protocol / monitoring of Azathioprine
Frequency of
laboratory check by
primary care physician:
(blood count + liver
Dose Duration enzymes*)
1. 50 mg /day 2 weeks Æweekly for 2 weeks
if ok then
2. 100 mg /day 2 weeks Æweekly for 2 weeks
if ok then
3. Increase dose 2 weeks Æweekly for 2 weeks
(50 mg
every time)
Æ Up to target ÆCycle (3.) repeat until target

(2–2.5 mg / kg) dose is reached
4. Steady dose Long-term Æmonthly
therapy for 2 months
Æevery 2 months
for 1 year
5. Regular check-up Æevery 3 months
* an active Hepatitis B or an inactive carrier of the Hepatitis B virus should have

been already exclused.
128
IBD Therapy
ADA, low serum albumin, high CRP (baseline), male sex (higher drug
clearance), high BMI (may increase clearance), high baseline anti-TNF
concentration (amount of drug cleared per time increases with the
amount present in serum).
When is measurement of through-levels and ADA indicated?

r MPTTPGSFTQPOTFPSJOTVGàDJFOUMZDPOUSPMMFEEJTFBTFBDUJWJUZ FJUIFS
derived by clinical parameters, endoscopy or radiology)
r BNCJHVPVTTZNQUPNTEVSJOHPSTIPSUMZBGUFSJOGVTJPOPG*'9
suggestive of an immediate or delayed infusion reaction
r QPUFOUJBMMZBGUFSQSPMPOHFEBOUJ5/'NPOPPSDPNCJUIFSBQZXIFO
treatment de-escalation is considered
r QPUFOUJBMMZQSJPSUPJOJUJBUFBOBOUJ5/'JOQBUJFOUTUIBUQSFWJPVTMZ
have been exposed to the very same drug
r QPUFOUJBMMZBMXBZTBGUFSDPNQMFUJPOPGUIFJOEVDUJPOQIBTF GPS
JOTUBODFXJUIJOáJYJNBCBUXFFLQSJPSUPUIFUIEPTF
r QPUFOUJBMMZBMSFBEZTPPOFS QSJPSUPUIFUIJSEPSFWFOTFDPOEJOGVTJPO

JODBTFPGBIJHIMZBDUJWFEJTFBTFXJUITVCTUBOUJBMJOáBNNBUPSZ
burden, e.g. in the event of acute severe colitis
129
Intestine
IBD Therapy
Guidelines for Chromoendoscopy in UC: SURFACE
S trict patient selection.

r1BUJFOUTXJUIIJTUPMPHJDBMMZQSPWFOVMDFSBUJWFDPMJUJTBOE
at least eight years’ duration in clinical remission.
r"WPJEQBUJFOUTXJUIBDUJWFEJTFBTF
Unmask the mucosal surface.

r&YDFMMFOUCPXFMQSFQBSBUJPOJTOFFEFE3FNPWFNVDVTBOE
remaining fluid in the colon when necessary.
Reduce peristaltic waves.

r8IFOESBXJOHCBDLUIFFOEPTDPQF BTQBTNPMZUJDBHFOU
should be used (if necessary).
Full length staining of the colon.

r1FSGPSNGVMMMFOHUITUBJOJOHPGUIFDPMPO QBODISPNPFOEPTDPQZ

in ulcerative colitis rather than local staining
A ugmented detection with dyes.

r*OUSBWJUBMTUBJOJOHXJUIJOEJHPDBSNJOFPS
methylene blue should be used to unmask flat lesions more
frequently than with conventional colonoscopy.
Crypt architecture analysis.

r"MMMFTJPOTTIPVMECFBOBMZ[FEBDDPSEJOHUPUIFQJU
pattern classification.
r8IFSFBTQJUQBUUFSOUZQFT*m**TVHHFTUUIFQSFTFODFPG
nonmalignant lesions, staining patterns III–V suggest the
presence of intraepithelial neoplasia and carcinomas.
Endoscopic targeted biopsies.

r1FSGPSNUBSHFUFECJPQTJFTPGBMMNVDPTBMBMUFSBUJPOT QBSUJDV
larly of circumscript lesions with staining patterns indicative
of intraepithelial neoplasia and carcinomas (pit patterns III–V).
[Kiesslich R, Neurath MF. Chromoendoscopy: an evolving standard in

surveillance for ulcerative colitis. Inflamm Bowel Dis 2004;10:695–6]
130
IBD Therapy
Simplified dosage regimen for intravenous iron

(iron sucrose, ferric carboxymaltose1, iron isomaltose)
Total iron quantity ferric carboxymaltose
Hb (g/dl) Body weight <70 kg Body weight ≥70 kg
≥10 1000 mg 1500 mg
7–10 1500 mg 2000 mg
The total iron quantity was administered in individual weekly infusions of

500 mg or 1000 mg ferric carboxymaltose.
Patients with a body weight of less than 67 kg received individual doses of 500 mg.
* This dosage regimen is not yet approved in Switzerland.

[1 Evstatiev R et al. FERGIcor, a Randomized Controlled Trial on Ferric
Carboxymaltose for Iron Deficiency Anemia in Inflammatory Bowel Disease.
Gastroenterology. 141.3 (2011): 846–53]
Max. Dilution 2
Iron quantity ** ferric Maximum quantity Minimum Means for the
carboxy- of 0.9% NaCl solution infusion time of filling infusion
maltose for infusion dilution
500 mg 10 ml 100 ml* 6 minutes 2 ml syringe

and blue (23G)
or pink (18G) Catheter
needle
blue (22G)
or
1000 mg 20 ml 250 ml* 15 minutes 10 ml syringe
and pink (20G)
pink needle
(18G)
* Please observe the dilution: ≥2 mg iron per ml

** Refer to Swiss Drug Compendium for other iron dosages
[2 Swiss Drug Compendium]
131
Intestine
IBD Therapy
Disease activity in UC – Truelove and Witts

Patients characteristics Mild
Light clinical symptoms, but
which can be worsened by the
subjective perception of the
patient
Especially urgencies contribute
to a more severe perception of
the disease Localization of the
disease is important as topical
treatments will have to be adju-
sted accordingly
Bloody stools per day <4

Pulse <90 bpm
Temperature $
Hemoglobin >11.5 g/dl
ESR <20 mm/h
CRP normal
Mayo Classification for endoscopical disease activity

0 = remission 1 = mild 2 = moderate 3 = severe
erythema + ++ +++
vascular pattern È absent
bleeding contact, friability spontaneous
lesions none erosions ulcerations
[Schroeder KW, et al. N Engl J Med. 1987.]
132
IBD Therapy
Moderate Severe
Increased clinical symptoms but Severe active ulcerative colitis
only mild systemic symptoms is best defined by Truelove
and Witts Criteria
Steroid use is a good criterion to Patients should be admitted to

classify a patient as moderate or hospital for intensive treatment
severe
Presence of mucosal friability

(bleeding on light contact with the
rectal mucosa on sigmoidoscopy
>4 >6
=90 bpm >90 bpm
<37.5$ $
>10.5 g/dl <10.5 g/dl
<30 mm/h >30 mm/h
<30 mg/L >30 mg/L
133
Intestine
IBD Therapy
Pouchitis
$JQSPáPYBDJOPS.FUSPOJEB[PMFYXLT
Responded
Infrequent Relapse Frequent Relapse
Antx-responsive Pouchitis Antx-dependent Pouchitis
Probiotic or Antibiotic
Antibiotics prn
$BSCPO.JDSPTQIFSF
134
IBD Therapy
Pouchitis
$JQSPáPYBDJOPS.FUSPOJEB[PMFYXLT
Not Responded
Metronidazole or
$JQSPáPYBDJO
x 2 more wks
Responded Not Responded
Antx-refractory Pouchitis
$JQSPáPYBDJO.FUSPOJEB[PMF
or Rifaximin or Tinidazole
x 4 wks
Not Responded
5-ASA /steroids /
Immunomodulators /
#JPMPHJDT
135
Intestine
Fistula
Anal Fistulas:
r.PTUTQPSBEJDàTUVMBBSFBSFTVMUPGDSZQUPHMBOEVMBSJOGFDUJPO
r5IFàTUVMBSFQSFTFOUTUIFDISPOJDQSPDFTTXIFSFBTUIFBCTDFTT
JTUIFBDVUFJOáBNNBUPSZFWFOU
rPGBOPSFDUBMBCTDFTTFTBSFBSFTVMUPGDSZQUPHMBOEVMBS
infection
Classification:
r.PTUIFMQGVMJTJODMJOJDBMSPVUJOFBDMBTTJàDBUJPOXIJDIEFTDSJCFT
the Fistula according to their relationship to the anal sphincter
1. Intersphincteric
2. Transphincteric
3. Suprasphincteric
4. Extrasphincteric
5. Subanodermal
5 2
3
1
Diagnosis:
r$ISPOJDJOáBNNBUPSZCPXFMEJTFBTFTIPVMECFSVMFEPVU
(Different therapy)
r"TTFTTNFOUPGTQIJODUFSGVODUJPO
r%JHJUBMFYBNJOBUJPOBOEQSPCJOHEZFJOHQSFPQFSBUJWFJOUSBPQFSBUJWFMZ
plus anal endosonography is helpful for showing the relation of the
fistula tract to the anal sphincter (Correlation both is better than 90%)
r*ODBTFPGSFDVSSFOUPSDPNQMFYàTUVMB.3*JNBHJOHTIPVMECF
considered
136
Fistula Therapy
Treatment:
Diagnosis of anal fistula is usually an indication for surgery
Low fistula: Subanodermal fistula

Intersphincteric fistula Fistulotomy
(Healing rate upto 100%)
Distal transsphincteric
fistula
High fistula: Proximal

transsphincteric fistula
Suprasphincteric fistula Surgical reconstruciton/
Biomaterial
Extrasphincteric fistula (Lower healing rate and
impaired sphincter function)
Surgical options for high fistula:

1. Surgical reconstruction
B"EWBODFNFOUáBQ5IFBJNJTBOFYDJTJPOPGUIFàTUVMBBOEUIF
cryptoglandular focus and a following closure of the inner fistula
DBWJUZCZEJGGFSFOUáBQUFDIOJRVFT
b. Fistula excision with direct sphincter reconstruction:
After excision of the fistula and reconstruction of the divided
sphincter
2. Biomaterial:
a. Fibrin glue: after curettage the tract is filled with fibrin glue
as a biomatrix for the body`s own tissue to grow in.
b. Anal fistula plug: The anal fistula plug is a biomedical product
made of e.g. porcine small – intestinal submucosa which
is brought into the tract as a biomatrix. It could be combined
XJUIBNVDPTBMáBQBOEBDVSFUUBHF
[Ommer A et al: S3 Leitlinie: Kryptoglanduläre Analfisteln: coloproctology 2011]
137
Intestine
%NQUVTKFKWOFKHƂEKNGVJGTCR[
Initial episode
Preferred: metronidazole 500 mg orally three times daily
or 250 mg four times daily for 10 to 14 days
Alternative:
vancomycin 125 mg orally four times daily for 10 to 14 days
First relapse
Confirm diagnosis (see text)
If symptoms are mild, conservative management
may be appropriate
If antibiotics are needed, repeat treatment as in initial
episode above
Second relapse1, 2
Tapering and pulsed oral vancomycin (below), with or without
probiotics (Saccharomyces boulardii 500mg orally twice daily).
The probiotics may be overlapped with the final week of the
taper and continued for two additional weeks in the absence
of antibiotics.
125 mg orally four times daily for 7 to 14 days

125 mg orally twice daily for 7 days
125 mg orally once daily for 7 days
125 mg orally every other day for 7 days
125 mg orally every 3 days for 14 days
Alternative: fidaxomicin 200mg orally twice daily for 10 days4
Subsequent relapse3, 4
Vancomycin 125 mg orally four times daily for 14 days, followed by
rifaximin 400 mg twice daily for 14 days
Alternative: fidaxomicin 200 mg orally twice daily for 10 days
[1. Tedesco FJ, Gordon D, Fortson WC. Am J Gastroenterol 1985]
[2. Cohen SH, Gerding DN, Johnson S et al.
Infect Control Hosp Epidemiol 2010]
[3. Johnson S, Schriever C, Galang M et al. Clin Infect Dis 2007]
[4. Louie TJ et al: N Engl J Med 2011]
138
Celiac disease
Presenting symptoms of adult celiac patients
Symptoms or signs Frequency (%)

fatigue 82
abdominal pain or discomfort 77
gas or bloating 73
anemia 63
weight loss 55
diarrhea 52
depression, irritability or anger 46
nausea, cramping or vomiting 46
muscle, joint or bone pain 42
confusion or memory loss 37
hair loss 29
[Modified from Zipser RD et al. Digestive Diseases and Sciences 2003]
Diagnostics in celiac disease
Clinical symptoms Intention Preferred procedure

asymptomatic people screening serology
antiendomysial antibodies
or tissue transglutaminase
antibodies
unspecific symptoms case serology
finding antiendomysial antibodies
or tissue transglutaminase
antibodies
strong suspicion of diagnostic > 3 duodenal biopsies,
celiac disease 1 biopsy from the bulbus,
exclude heliobacter pylori
139
Intestine
Celiac disease
Table Sensitivity, Specificity of serological tests

Antibody Sensitivity Specificity Comment
(%) (%)
Gliadin IgA 70 –90 85–94 Should be
abandoned
completely, due
to insufficient
accuracy
Gliadin IgG 69–85 88–92 Similar as above,
formerly the only
reliable test in
the event of IgA
deficiency
Gliadin, 80–95 90–100 Considerably
deamidated higher accuracy
then former gliadin
antibodies; also
accurate in IgA
deficiency
Trans- 90–98 94–97 Comparably high
glutaminase (IgA) sensitivity to
endomysial
antibody, more
expensive, worse
specificity
Endomysial (IgA) 75–98 98–100 Excellent speci-
ficity, laborious,
expensive
140
Celiac disease
HLA:
HLA-DQ2 is present in more than 90% of patients with celiac disease,
while almost the complete rest of HLA-DQ2 negative patients is
positive for DQ8 (combined negativity for both is extremely rare
in true CD). Thus, excellent sensitivity renders this test an ideal tool
to exclude CD. However, due to relatively high costs and also
inaccurate specificity, HLA should only be performed in the following
exceptional constellations:
Patient already on gluten-free diet; (strong) familial history of CD, in

order to rule out potential to develop frank CD in the future; histology
suspicious for CD with no clearcut serological constellation.
Due to high prevalence of DQ2 or DQ8 of roughly 30-40% in the gene-

ral population, the specificity of this test is «lousy».
Celiac disease
HLA DQ2 or DQ8
General Population
141
Intestine
Celiac disease
Range of clinical presentations in celiac disease

Silent celiac disease
rQBUJFOUTXIPEPOPUDPNQMBJOPGBOZTZNQUPNTBOEEPOPUTFFL
medical advice
rNPTUPGUIFTFQBUJFOUTBSFSFMBUJWFTPGQBUJFOUTXJUILOPXODFMJBD
disease or members of the general population found to be positive
in the search for antiendomysial antibodies or tissue transgluta-
minase antibodies
Minor celiac disease

r QBUJFOUTDPNQMBJOJOHPGUSJWJBM USBOTJFOU PSBQQBSFOUMZVOSFMBUFE
symptoms (i.e. dyspepsia, abdominal discomfort and bloating, mild
or occasional altered bowel habit without malabsorption mimicking
irritable bowel syndrome, unexplained anemia, isolated fatigue,
cryptic hypertransaminasemia, infertility, peripheral and central neu-
rologic disorders, osteoporosis, short stature, dental enamel de-
fects, dermatitis herpetiformis) or of isolated symptoms of autoim-
mune diseases often reported in association with celiac disease
rNPTUPGUIFTFQBUJFOUTBSFCJPQTJFEBGUFSBQPTJUJWFTFBSDIPG
antiendomysial antibodies or tissue transglutaminase antibodies
Major celiac disease

r QBUJFOUTDPNQMBJOJOHPGGSBOLNBMBCTPSQUJPOTZNQUPNT JF
diarrhea which is often nocturnal and with incontinence, steator-
rhoea suggested by loose discoloured, greasy, and frothy stools
UIBUBSFEJGàDVMUUPáVTIBXBZ XFJHIUMPTTBOEPUIFSGFBUVSFTPG
malnutrition, cramps, tetany, and peripheral oedema due to electro-
lyte and albumin depletion); symptoms of other autoimmune
diseases may be associated
rNPTUPGUIFTFQBUJFOUTBSFCJPQTJFEPOMZPOUIFCBTJTPGTZNQUPNT
[Modified from Di Sabatino A et al. Lancet 2009]
In unclear cases of celiac disease, consider olmesartan-

induced enteropathy.
[Mayo Clinic Proceedings 2012;87:732]
142
Intestine
Mid Gl Bleeding
Main causes of mid gastrointestinal bleeding:
Bleeding source: Frequency:

Angiodysplasia 20 – 60%
Ulcerations (IBD, NSAIDs etc.) 10 – 40%
Neoplasia 1 – 10%
[Elfa GH et al.: Gastrointest Endosc 2004]

r #MFFEJOHTPVSDFTJOUIFTNBMMCPXFMBSFSBSF
(only 1 to 5% of all gastrointestinal bleedings)
[Okazaki H et al.: J Gastroenterol 2009]
r j1VTIBOEQVMMvFOUFSPTDPQZBOETNBMMCPXFMDBQTVMFFOEPTDPQZ
have comparable sensitivity for the detection of a bleeding source
in the small bowel
[Pasha SF et al.: Clin Gastroenterol Hepatol 2008]
r "QQSPYJNBUFMZUPPGUIFàOEJOHTJODBQTVMFFOUFSPTDPQZ
have been missed by EGD and colonoscopy
[Kitiyakara T, et al.: Gastrointest Endosc 2005; Delvaux M, et al.: Endoscopy 2004]
143
Intestine
Lower Gl Bleeding
Causes of lower gastrointestinal bleeding:
Bleeding source: Frequency:

Diverticula 30%
Colitis (ischemic, IBD) 15%
Carcinoma, Polyps 13%
Angiodysplasia 10%
Anorectal diseases 11%
Upper gastrointestinal bleeding 10%
Unknown (consider NSAIDS) 2– 8%
[Elta GH et al.: Gastrointest Endosc 2004]

r 0WFSBMMNPSUBMJUZPGMPXFS(*#JTMPX BQQSPY

[Strate LL et al.: Clin Gastroenterol Hepatol 2008]
r 6QUPPGQBUJFOUTXJUITVTQFDUFEMPXFS(*CMFFEJOHIBWF
a bleeding source proximal to the ligament of Treitz
[Strate LL et al.: Gastroenterol Clin North Am 2005]
r 6SHFOUDPNQBSFEUPFMFDUJWFDPMPOPTDPQZJNQSPWFTEFUFDUJPO
rate of bleeding source, but has no effect on mortality and relapse
bleeding rate
[Green BT et al.: Am J Gastroenterol.2005]
144
Intestine
Polyps
Recommendations for surveillance

after colonoscopic polypectomy
[Adapted from recommendations of the Swiss Society of Gastroenterology]
Preconditions:
r complete colonoscopy, optimally cleansed colon, complete
resection of all polyps (so-called clearing colonoscopy), complete
recovery of the resected specimens for histological examination
please note: after piecemeal-resection of sessile polyps or in case
of equivocal completeness of resection, a check colonoscopy is
recommended within 3 months
r estimated life expectancy > 10 years
r no evidence of hereditary cancer syndromes (FAP, HNPCC,
Peutz-Jeghers) or other conditions with increased risk for colorectal
DBODFS DISPOJDJOáBNNBUPSZCPXFMEJTFBTF BDSPNFHBMZFUD
145
Intestine
Polyps
Risk Polyp histology &

category secondary criteria
I Tubular adenoma
rmQPMZQTand
rTJ[FõDNand
rOPIJHIHSBEFEZTQMBTJBand
rOFHBUJWFGBNJMZIJTUPSZ TUEFHSFFSFMBUJWFT
II Tubular adenoma
rQPMZQTor
rTJ[FDNor
rIJHIHSBEFEZTQMBTJBor
rQPTJUJWFGBNJMZIJTUPSZ TUEFHSFFSFMBUJWFT
(Tubulo-) villous adenoma or serrated adenoma

rBOZOVNCFSBOETJ[F
rBOZHSBEFPGEZTQMBTia
III pT1 /carcinoma in situ within the polyp

rQPMZQFDUPNZFOEPTDPQJDBMMZDPNQMFUFand
rSFTFDUJPONBSHJOTIJTUPMPHJDBMMZGSFFPGDBSDJOPNB
and
rXFMMPSNPEFSBUFMZEJGGFSFOUJBUFE ((
Bnd
rOPJOWBTJPOPGMZNQIBUJDBOEPSWFOPVTWFTTFMT
IV pT1 /carcinoma in situ within the polyp

rQPMZQFDUPNZFOEPTDPQJDBMMZOPUDPNQMFUFor
rSFTFDUJPONBSHJOTIJTUPMPHJDBMMZOPUGSFFPG
carcinoma or
rQPPSMZEJGGFSFOUJBUFEPSVOEJGGFSFOUJBUFE ((
or
rJOWBTJPOPGMZNQIBUJDBOEPSWFOPVTWFTTFMT
Hyperplastic polyps
proximal to the rectosigmoid or size > 1 cm or > 20 polyps
in the rectosigmoid and size ≤ 1 cm
146
Colonoscopy Colonoscopy interval
interval when findings normal
5y stop surveillance
3y 5y
≤3 months for examination 5y

of the polypectomy site;
then 3 y
ĺ surgical resection generally indicated
3y 5y
no surveillance
147
Intestine
Polyps
Paris Classification of Colon-Polyps

Endoscopic Paris Description
appearance class
Ip Pedunculated
polyps
Protruded Ips Subpedunculated

lesions polyps
Is Sessile polyps
Flat elevation
0–IIa of mucosa
Flat elevated
lesions
Flat elevation
0–IIa /c with central
depression
0–IIb Flat mucosal

change
Flat lesions 0–IIc Mucosal

depression
Mucosal
0–IIc / IIa depression with
raised edge
[The Paris endoscopic classification of superficial neoplastic lesions: esophagus,

stomach, and colon November 30 to December 1, 2002
VOLUME 58, NO. 6 (SUPPL), 2003 GASTROINTESTINAL ENDOSCOPY]
148
Polyps
Kudo – Classification of Polyps
(a) Pit pattern type I
(b) Pit pattern type II
(c) Pit pattern type III S
(d) Pit pattern type III L
(e) Pit pattern type IV
I – Round pits (f) Pit pattern type V

II – Stellar or papillary pits
IIIS – Small tubular or roundish pits
IIIL – Large tubular or roundish pits
IV – Branch-like or Gyrus-like pits
V – Unstructural pits
Types I and II are benign and show regular round or star-shaped pits,
Types III to V are malignant and are more disordered and chaotic, with different
sizes and more tubular and irregular pits.
[S. Kudo, S. Tamura et al. Diagnosis of colorectal tumorous lesions by magnifying

endoscopy, Gastrointest. Endosc., 44 (1996), 8–14]
149
Intestine
CRC
Recommendations for surveillance after curative

surgery for colorectal cancer
[Adapted from recommendations of the Swiss Society of Gastroenterology]
Preconditions:
r QPTUPQFSBUJWFTUBHF***** 5PS/ .
JOQBUJFOUTXIPXPVME
qualify for treatment of recurrence or metastases, judged on the
basis of age and general condition
r TVSWFJMMBODFJTBOJOUFSEJTDJQMJOBSZUBTL DPPSEJOBUFECZPOFJOTUJ
tution in permanent contact with the involved physicians (surgeon,
general practitioner, gastroenterologist, radio-/oncologist etc.)
r BCBTFMJOFDPNQMFUFDPMPOPTDPQZJTNBOEBUPSZQSFPQFSBUJWFMZ
(or postoperatively within 3 months) along with preoperative staging
by imaging, usually by a CT scan of chest and abdomen
(with additional pelvic CT in cases of rectal cancer)
r IFSFEJUBSZDPMPSFDUBMDBODFSTZOESPNFT '"1 )/1$$ 1FVU[
Jeghers) or other high risk conditions for colorectal cancer (chronic
JOáBNNBUPSZCPXFMEJTFBTF BDSPNFHBMZFUD
BSF/05JODMVEFEJO
these recommendations and require special surveillance
Months postoperatively
6 12 18 24 36 48 60
Clinical examination1 quarterly twice a year
& CEA levels2 within within 2nd + +
1st year and 3rd year
Colonoscopy + +3
CT scan of chest & abdomen4 + + + + +
In case of rectal cancer: + + + +

rectosigmoidoscopy & EUS
1) in cases of low (extraperitoneal) rectal cancer, treated with total mesorectal
excision (TME), quarterly rectal exam (by the responsible surgeon)
2) preoperative analysis of CEA levels routinely recommended; in case of
postoperative elevation, imaging studies are recommended
3) once findings are normal, change to 5 years interval
4) triple contrast (oral-rectal-intravenous) CT scan of chest & abdomen
(supplemented with a pelvic CT in case of rectal cancer) is standard;
liver ultrasound plus chest X-ray is an alternative; chest CT scan is
beneficial in rectal cancer
150
151
Intestine
HNPCC
Amsterdam-II-Criteria (All must be fulfilled)

The Amsterdam Criteria have been highly successful, with estimated
sensitivity and specificity of 60% and 70%, respectively. Certain
deficiencies, however, have become increasingly recognized. For
example, the original Amsterdam Criteria did not take into account
extracolonic cancers, patients with new MMR mutations were not
addressed, and some families with multiple polyps but without profuse
polyposis were erroneously classified as having putative HNPCC.
Therefore the Amsterdam Criteria II (see below) were introduced in
1999 with estimated sensitivity of 78% and specificity of 61%.
r "UMFBTUSFMBUJWFTXJUI)/1$$BTTPDJBUFEDBODFS
(colorectum, endometrium, small bowel, ureter or renal pelvis) AND
r 0OFTIPVMECFBàSTUEFHSFFSFMBUJWFUPUIFPUIFSUXP
r "UMFBTUUXPTVDDFTTJWFHFOFSBUJPOTTIPVMECFBGGFDUFE
r "UMFBTUPOFTIPVMECFEJBHOPTFECFGPSFBHF
r 'BNJMJBMBEFOPNBUPVTQPMZQPTJTTIPVMECFFYDMVEFE
r 5VNPSTTIPVMECFWFSJàFECZQBUIPMPHJDBMFYBNJOBUJPO
Vasen, H., Watson, P., Mecklin, J.-P., & Lynch, H. (1999). New clinical criteria for he-
reditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the
International Collaborative Group on HNPCC. Gastroenterology, 116(6), 1453–1456.
[1Syngal S, Fox EA, Eng C, et al: Sensitivity and specificity of clinical criteria for here-
ditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1. J
Med Genet 37:641-645. 2000]
152
HNPCC
Tumors from individuals should be tested for MSI

(microsatellite instability) in the following situations
(Bethesda guidelines)
1. colorectal cancer diagnosed in a patient who is less than 50 y
2. presence of synchronous, metachronous colorectal, or other
HNPCC-associated tumors*, regardless of age
3. colorectal cancer with the MSI-H† like histology‡ diagnosed in
a patient who is less than 60 y§
4. colorectal cancer diagnosed in a patient with one or more 1st
degree relatives with an HNPCC-related tumor, with one of the
cancers being diagnosed under age 50 y
5. colorectal cancer diagnosed in a patient with two or more 1st
or 2nd degree relatives with HNPCC-related tumors, regardless
of age
* Hereditary nonpolyposis colorectal cancer (HNPCC)-related tumors include

colorectal, endometrial, stomach, ovarian, pancreas, ureter and renal pelvis,
biliary tract, and brain (usually glioblastoma as seen in Turcot syndrome),
sebaceous gland adenomas and keratoacanthomas in Muir–Torre syndrome,
and carcinoma of the small bowel.
† MSI-H: microsatellite instability–high in tumors refers to changes in two or
more of the five National Cancer Institute-recommended panels of
microsatellite markers.
‡ Presence of tumor infiltrating lymphocytes, Crohn’s-like lymphocytic reaction,
mucinous/signet-ring differentiation, or medullary growth pattern.
§ There was no consensus among the workshop participants on whether
to include the age criteria in guideline 3 above; participants voted to keep less
than 60 years of age in the guidelines.
[Adapted from Umar A et al. J Natl Cancer Inst 2004]
153
Intestine
High risk colorectal cancer conditions
Characteristic features of High Risk Colorectal Cancer

Condition/Inheritance Gene Lifetime cancer risks
Lynch-Syndrome hMLH1 & 2 colon

autosomal-dominant hMSH6 endometrium
hPMS2 stomach
EpCAM ovary
hepatobiliary tract
upper urinary tract
pancreatic
small bowel
CNS (glioblastoma)
Familial adenomatous APC colon

polyposis (FAP) duodenum/periampullary
autosomal-dominant stomach
pancreas
thyroid
liver (hepatoblastoma)
CNS (medulloblastoma)
Attenuated FAP APC colon
autosomal-dominant duodenum/periampullary
thyroid
MUTYH-associated MUTYH colon
polyposis duodenum
autosomal-recessive
Peutz-Jeghers STK11 breast

syndrome colon
autosomal-dominant pancreas
stomach
ovary
lung
small bowel
uterine/cervix
testicle
Juvenile polyposis SMAD4 colon
syndrome BMPR1A stomach, pancreas and
autosomal-dominant small bowel
Hyperplastic polyposis colon

inheritance unknown
[Adapted from Jasperson KW et al. Gastroenterology 2010]
154
Conditions
% Nonmalignant features
Non-poly posis
50 – 80 physical or nonmalignant features – besides
40 – 60 keratoacanthomas and sebaceous adenomas/
11– 19 carcinomas – are rare
9 – 12
2 –7
4 –5
3 –4
1– 4
1– 3
Adenomatous polyposis
100 100s to 1000s of colorectal adenomas gastric
4 – 12 fundic glands and duodenal adenomatous polyposis
<1 congenital hypertrophy of the retinal pigment
2 epithelium; epidermoid cysts; osteomas
1– 2 dental abnormalities
1– 2 desmoid tumors
<1
70 <100 colonic adenomas
4 – 12 upper gastrointestinal polyposis similar to FAP
1–2 other non-malignant features are rare in attenuated FAP
80 colonic phenotype similar to attenuated FAP;
4 duodenal polyposis
Hamartomatous polyposis
54 mucocutaneous pigmentation
39 gastrointestinal hamartomatous
11– 36 (Peutz-Jeghers) polyps
29
21
15
13
9
<1
39 gastrointestinal hamartomatous (juvenile) polyps
21 features of hereditary hemorrhagic telangiectasia;
congenital defects
Hyperplastic polyposis
> 50 hyperplastic polyps, sessile serrated polyps,
traditional serrated adenomas and mixed adenomas
155
Intestine
Management recommendations for High Risk Colorectal

Condition Cancer
Lynch-Syndrome colon
endometrium/ovary
upper urinary tract

upper GI tract
other
Familial adenomatous colon
polyposis (FAP)
upper GI tract
other
MUTYH-associated colon
polyposis
duodenum
Peutz-Jeghers colon
syndrome breast
pancreas
stomach/small bowel
cervix/uterus/ovary
testes
Juvenile polyposis colon
syndrome stomach
Hyperplastic colon
polyposis
[Adapted from Jasperson KW et al. Gastroenterology 2010]
156
Ca ncer Conditions
Recommendations
colonoscopy every 1– 2 y, start at 20 – 25 y
consider prophylactic hysterectomy & bilateral salpingo-
oophorectomy after childbearing complete; gynecological
cancer screening
consider annual urinalysis, beginning at 30 – 35 y
consider EGD (incl. side view endoscope) every 1– 2 y, start at age 30 – 35 y
BOOVBMQIZTJDBMFYBNJOBUJPOJODMVEJOHTLJO TFCBDFPVTDBSDJOPNB
colonoscopy every 1– 2 y, start at 10 – 12 y (for attenuated FAP

at 18 – 20 y)
prophylactic colectomy when polyps become unmanageable
(if remaining rectum or ileal pouch, screen every year)
EGD every 1– 3 y, start at 20 – 25 y
annual physical examination, including thyroid
colonoscopy every 2 – 3 y, start at 25 y
EGD every 1– 3 y, start at 20 – 25 y
colonoscopy every 2 – 3 y, start with symptoms or latest at 18 – 20 y
annual mammogram & breast MRI, start at 25 y
MRCP and/or EUS every 1– 2 y, start at 30 y
EGD and abdominal CT with oral contrast every 2 – 3 y, start at 10 y
annual pelvic examination, pap smear and transvaginal US, start at 18 y
annual testicular examination, start at 10 y
colonoscopy every 2– 3 y, start with symptoms or latest at 18 – 20 y
EGD every 1– 3 y
colonoscopy every 1– 2 y
157
Intestine
Suggested flow chart for investigation and diagnosis

of possible hereditary nonpolyposis colon cancer
(HNPCC) families.
Family referred Clinicopathologic

data collected
8IJDIUVNPSTBWBJMBCMF *GQPTTJCMF
test youngest affecteds with colorectal
tumor or endometrial ca.)
One One
≥ 2 tumors None
cancer adenoma
IHX
.4* yes
MPTT
no
Not
Any loss of
HNPCC
MSH2 or MSH6
or ≥ 2 with loss
yes
PG.-)
no
no Any MSI+
no tumor retains
yes
.-)
≥ 2 with MSI
yes
[Lipton L et al. JCO 2004;22:4934-4943]
158
Run model 1UISFTIPME
Constitutional
DNA from suitable yes no Not HNPCC
BGGFDUFE
Perform MSI and IHX on available

colorectal tumors and endometrial
yes no cancers. HNPCC diagnosed, if,
1 One or more tumors with absent
MSH2 and/or MSH6 protein or
2 A colorectal adenoma MSI+ or
3 one or more tumors MSI+ with
retention of MLH1 expression, or
4 All cancers (minimum of two) MSI+
and/or MLH1-absent, or
5 Two of three cancers MSI+ and/or
MLH1-absent
– Possible HNPCC
Mutation screen
(targeted if poss.)
+ HNPCC
Not
HNPCC
159
Intestine
Ogilvie syndrome
Acute colonic pseudo-obstruction (Ogilvie’s syndrome)
definition r Gross dilatation of the cecum and right

hemicolon (occasionally extending to the
rectum) in the absence of a stenosis
etiology r Trauma; recent surgery; electrolyte

abnormalities
r Obstetric / gynecologic diseases
r Medications (NSAIDs, opiates,
antidepressants)
clinical symptoms r Abdominal distention

r Nausea & vomiting; abdominal pain
r Constipation or paradoxically diarrhea
rx r Clearly dilated colon
diagnosis r Diagnosis can be made only after

excluding the presence of toxic megaco-
lon or mechanical obstruction
treatment r Conservative management

(algorithm next page) r Neostigmine
r Endoscopic decompression or surgery
160
Ogilvie syndrome
Treatment algorithm in Ogilvie’s syndrome
conservative r /10 *7' /(TVDUJPO

management r If no response…
evaluation r &WBMVBUFBOEUSFBUSFWFSTJCMFDBVTFT
(e.g. electrolyte abnormalities)
r *GOPSFTQPOTFw
neostigmine r mNH*7 PWFSNJO

VOEFS
cardiovascular monitoring (atropine
bedside!)
r CONTRAINDICATIONS: bronchial
asthma, recent myocardial infarction,
beta-blockers, bradyarrhythmias,
hyperthyroidism, intestinal stenosis
r *GOPSFTQPOTFw
endoscopic r "UUIFMBUFTUJGDFDVNDN
decompression r *GOPSFTQPOTFw
surgery or PEC r &OEPTDPQJDQFSDVUBOFPVTFOEPTDPQJD

colostomy (PEC)
r 4VSHFSZDFDPTUPNZPSDPMFDUPNZ
161
Intestine
Diverticulitis
Classification and management

Classification: Hansen Hinchey Mortality Management:
& Stock
Asymptomatic 0 - 0% Conservative:
Acute, I 0 - Fasting for
uncomplicated solids
Acute, II I-IV - Antibiotics
complicated - Regular
- Confined IIa Ia reassessment
pericolic within 48 h
JOáBNNBUJPO
phlegmon
- Confined IIb Ib < 5% Abscess
pericolic drainage and
abscess possibly surgery
- Pelvic or IIb II Early elective
distant surgery
abscess
- Purulent IIc III 13% Emergency
peritonitis surgery
- Fecal 43%
peritonitis IV
Chronic III - Elective surgery
recurrent in stenosis
diverticulitis
[Adapted from: Hinchey EJ: Adv Surgery 1978; Hansen O: Langenbecks Arch Chir
1999; Kaiser AM: Am J Gastroenterol 2005; Jacobs D: N Engl J Med 2007]
162
Diverticulitis
Diagnosis:
r $5IBTIJHIFTUTFOTJUJWJUZBOETQFDJàDJUZGPSEJWFSUJDVMJUJT
[Lohrmann D: Eur J Radiol 2005]
r $MBTTJàDBUJPOTPG)BOTFO4UPDLBOE)JODIFZDPSSFMBUFUPQSPHOPTJT
[Kaiser AM: Am J Gastroenterol 2005]

r 4FSJPVTDPVSTFJOJNNVOPDPNQSPNJTFEQBUJFOUT
[Chapman J: Ann Surg 2005]
r "WPJEPQJBUFT TUFSPJET "4" /4"*%

[Humes DJ: Gut 2011; Strate LL: Gastroenterology 2011]
r $POUSPWFSTJBMFGàDBDZPGàCFSTVQQMFNFOUBUJPO
[Peery AF: Gastroenterology 2012]
163
Intestine
Malabsorption
Differential Diagnosis
Phase and nature of Example

malabsorptive defect
Luminal phase
A. Substrate hydrolysis
1. Digestive enzyme deficiency Chronic pancreatitis
2. Digestive enzyme inactivation Zollinger-Ellison syndrome
3. Dyssynchrony of enzyme Post Billroth II procedure
release, inadequate mixing
B. Fat solubilization
1. Diminished bile salt secretion Cirrhosis
2. Impaired bile secretion Chronic cholestasis
3. Bile salt deconjugation Bacterial overgrowth
4. Increased bile salt loss Ileal disease or resection
C. Luminal availability of
specific nutrients
1. Diminished gastric acid Atrophic gastritis – vitamin B12
2. Diminished intrinsic factor Pernicious anemia – vitamin B12
3. Bacterial consumption Bacterial overgrowth –
of nutrients vitamin B12
Mucosal (absorptive) phase
A. Brush border hydrolysis*
1. Congenital Sucrase-isomaltase deficiency
disaccharidase defect
2. Acquired Lactase deficiency
disaccharidase defect
B. Epithelial transport
1. Nutrient-specific defects Hartnup’s disease
in transport
2. Global defects in transport Celiac sprue
Postabsorptive,
processing phase
A. Enterocyte processing Abetalipoproteinemia
B. Lymphatic Intestinal lymphangiectasia
164
Protein loosing enteropathy
␣-1-AT-Clearance
Stool volume (/3d) x Stool ␣1-AT
Formula: ␣1-AT-Clearance (ml/d) =
Serum ␣1-AT
Normal values. <24 ml/d without diarrhea; <56 ml/d with diarrhea.
Interpretation. In the case of marked albumin loss syndrome,
values exceeding 200 ml/d are possible.
Sources of error
- Diarrhea
- ␣1-Antitrypsin is degraded at gastric pH levels <3.5
TPUIFUFTUJTPGMJNJUFEWBMVFJO.ÊOÊUSJFSTEJTFBTF

- Blood in faeces leads to misleading high ␣1–antitrypsin levels.
165
Intestine
Malabsorption
Diagnosis Evaluations
Test Impaired
intraluminal Digestion
Stool fat (qualitative, quantitative) Increased (concentration
usually > 9.5%)
Stool
Stool elastase Low in moderate and severe

pancreatic exocrine insufficiency
Stool ova and parasites and May be positive in parasitic biliary
specific parasitic antigens cholangiopathy
Serum carotene Decreased
Serum cholesterol Decreased

Laboratory (serum)
Serum albumin Usually normal, except with bacterial

overgrowth
Prothrombin activity Decreased if severe
Serum calcium Usually normal if pancreas is the cause

Serum 25-OH vitamin D Decreased
Serum iron Normal
Serum folate Normal
Xylose absorption Normal, except with bacterial overgrowth
Stimulation tests
Absorption/
Lactose absorption Normal, except in some instances of

(lactose tolerance test or breath bacterial overgrowth
hydrogen after lactose load)
Vitamin B12 absorption Decreased in bacterial overgrowth and
(Schilling test) exocrine pancreatic insufficiency
Lactulose and glucose breath Early appearance of H2 in breath in
hydrogen test bacterial overgrowth
Secretin/cholecystokinin Abnormal in chronic pancreatic exocrine

stimulation tests insufficiency
IgA anti-tissue transglutaminase Absent
IgA antiendomysial antibody
IgA antibodies to deaminated gliadin
Endoscopy
Endoscopic intestinal biopsy Normal except in severe bacterial

overgrowth
Wireless capsule endoscopy Usually normal
[Current – Diagnosis and treatment; Lange, 2011]

166
Malabsorption
Useful laboratory tests in evaluation of intestinal malabsorption.
Mucosal Lymphatic Limitations

Disease Obstruction
Increased Increased False-negative result if inadequate ingestion
(concentration usually of dietary fat or recent barium ingestion;
<9.5%) false-positive result with castor oil or mineral
oil ingestion
May be low due Usually Low specificity for pancreatic disease if small
to dilution normal intestinal disease is present
May diagnose Giardia, Negative
Isospora, cryptospo-
ridia, microsporidia,
tapeworms
Decreased Decreased Low values may occur in normal subjects
who ingest little dietary carotene
Decreased Decreased May be normal or increased in patients with
untreated lipoprotein abnormality
Often decreased Often
decreased
Decreased if severe Decreased May also be decreased in liver disease but
if severe parenterally administered vitamin K should in-
duce normalization if caused by malabsorption
Decreased Decreased .BZSFáFDUIZQPBMCVNJOFNJB
Decreased Decreased
Often decreased Normal
Often decreased Normal
Abnormal, unless Normal Requires normal gastric emptying and renal
disease confined to function
distal small intestine
Increase in plasma Normal May be abnormal in all categories if patient
glucose <20 mg/dL; has primary intestinal lactase deficiency;
increased breath H2 requires normal gastric emptying
Decreased in Normal Requires good renal function
extensive ileal disease
Normal Normal Requires normal gastric emptying; false-
positive results may occur in patients with
rapid small intestinal transit
Normal Normal Relatively low sensitivity, cumbersome and
labor intensive
Present in Absent Lower sensitivity in infants and all ages in
celiac sprue mild disease, false negative results in IgA
deficiency
Often abnormal Often May miss patchy mucosal disease
abnormal
Often abnormal Often Labor intensive, cannot biopsy lesions, may
abnormal obstruct strictured intestine
167
Intestine
Malabsorption
Enteral tube feeding

Indication e.g.
GI stenoses Fresubin® original fibre,
no tolerance to fibers Osmolite®
Longterm feeding, maintenance of Fresubin original fibre®,
GI function, diabetes, constipation Jevity®
Energy requirement , Fresubin® energy fibre,
fluid intake Jevitiy Hical®, Osmolite Hical®
Diarrhea (and constipation) -
Maldigestion, -absorption, Perative®,
short bowel, deep position Survimed (OPD)®
of feeding tube
Acute and chronic Nepro®,
kidney failre Fresumin Hepa®
Critical care patients Oxepa®,
Reconvan®,
Intestamin®
Increased demands Zn, Se, Cu
(e.g. fistulas, burn) or tube feeding
< 1500 ml/Tag
Tube feeding < 1500 ml/day Supradyn®,
Berocca®,
Benerva®
Deficiencies P, K, Ca, Mg
168
Malabsorption
Tube feeding
High caloric Isocaloric without fibers
tube feeding (1 kcal/ml)
with fibers
High caloric with/

(>1- max. 2 kcal/ml) without fibers
soluable fibers
Low molecular Main nutrition as monomeric or easy
tube feeding resorbable components
Metabolism-adapted High caloric, low electrolyte,

tube fedding ev. low protein
Immun-modulated Pharmacologic effect (as aminoacids,
tube feeding Omega 3-FS, nucleotides, Vitamin C and E,
trace elements)
Supplements Trace elements
Vitamines
Electrolytes
169
Intestine
Malabsorption
Therapeutic options and algorithm

in short bowel syndrome
Small bowel length > 60-80 cm Ileocecal region
preserved Colon (partially) preserved
Yes No
r51/EVSJOHBDVUFQIBTFPOMZ r51/EVSJOHBDVUFQIBTFPOMZ
rJTPUPOJDTBMUHMVDPTFTPMVUJPOT rJTPUPOJDTBMUHMVDPTFTPMVUJPOT
rDPOUSPMBOEDPNQFOTBUJPOPG rDPOUSPMBOEDPNQFOTBUJPOPG
electrolyte and water deficiencies electrolyte and water deficiencies
r)2-blocker/PPI for the first r)2-blocker/PPI for the first
6 months 6 months
r"OUJEJBSSIFBMESVHT r"OUJEJBSSIFBMESVHT
r"EFRVBUFOVUSJFOUTVQQMZ r"EFRVBUFOVUSJFOUTVQQMZ
r.$5 r.$5
r"WPJEBODFPGPYBMBUFJOEJFU r"WPJEBODFPGPYBMBUFJOEJFU
rNHDBMDJVNQP rNHDBMDJVNQP
Reduction and termination of parenteral nutrition (if possible)

tolerated Not tolerated
r$POUJOVBUJPOPGPSBMOVUSJUJPOBOE r$POUJOVBUJPOPG QBSUJBM

QBSFOUFSBM
above mentioned measures nutrition and above mentioned
r$POUSPMBOETVCTUJUVUJPOPGWJUBNJO measures
and trace element deficiencies r$POUSPMBOETVCTUJUVUJPOPGWJUBNJO
r"OOVBMNFBTVSFNFOUTPGCPOF and trace element deficiencies
density r"OOVBMNFBTVSFNFOUTPGCPOF
density
In case of complications:
Hepatobiliary system : cholestasis, steatosis, liver failure Æ oral nutrition,
reduce dextrose and fat content of TPN; cholelithiasis Æ cholecystectomy
Bones : check calcium and vitamin D, if necessary substitute
bisphosphonate i.v. Infections : improve handling of catheter Catheter
PDDMVTJPOUSZUPáVTI BEBQUBUJPOPG51/TPMVUJPO BOUJDPBHVMBUJPO
Improvement No improvement
Continuation of above Small bowel (and liver)

mentioned measures transplantation
170
Malabsorption
Management of the short bowel syndrome

after extensive small bowel resection
Definition and principles:

r HMPCBMNBMBCTPSQUJPOTZOESPNFEVFUPJOTVGàDJFOUBCTPSQUJWF
capacity and/or disturbed gastrointestinal regulation resulting from
extensive bowel resections.
r 4#4JTPCMJHBUPSZBGUFSSFTFDUJPOPGNPSFUIBOPGUIFTNBMM
intestine or if less than 100 cm of small bowel are left.
r "EEJUJPOBMSFTFDUJPOTPGUIFJMFPDFDBMSFHJPOPSUIFDPMPOJODSFBTF
severity.
r -PTTFTPGUIFEVPEFOVNPSUIFUFSNJOBMJMFVNJNQBJSBCTPSQUJPO
much more than loss of other parts of the small bowel because
specific absorptive and regulatory functions of these intestinal sites
cannot be replaced by other parts of the small bowel.
r "CTPSQUJPOPGNBKPSGPPEDPNQPOFOUTWBSJFTJO4#4'BU
malabsorption is usually particularly severe, not compensated by
colonic mechanisms and associated with deficiencies of the fat
soluble vitamins A, D, E and K.
r %FàDJFODJFTPGUIFXBUFSTPMVCMFWJUBNJOT# # #BOE$
are relatively rare.
r )ZQFSPYBMVSJBXJUIBOJODSFBTFESJTLPGOFQISPMJUIJBTJTJT
observed in 60%.
r $BMDJVN NBHOFTJVNBOEJSPOBTXFMMBTGPMJDBDJEEFàDJFODJFT
are a typical consequence of expanded proximal small bowel
resections.
r 5IFMPTTPGUIFJMFVNMFBETUPWJUBNJO#EFàDJFODZBOEUP
spill-over of unabsorbed bile acids into the colon, which causes
cholerheic diarrhea and increase the risk of gallstone formation
(cholesterol and pigment stones).
r *OQBUJFOUTXJUI$SPIOTEJTFBTFGVODUJPOBMMPTTFTEVFUPDISPOJD
JOáBNNBUJPONBZGVSUIFSJNQBJSBCTPSQUJWFGVODUJPOTFWFOJGTNBMM
bowel resection is limited.
r "EBQUBUJPOPGUIFSFNBJOJOHJOUFTUJOFSFRVJSFTFYQPTVSFUPNBDSPOV
trients. Adaptive responses develop over 1–2 years following inte
stinal resection and increase absorptive capacity by several hundred
percent as a result of increased mucosal surface, increased
absorptive capacity per surface and slowed intestinal motility.
r *NQPSUBOUOFVSPIPSNPOBMNFEJBUPSTJOWPMWFEBSFHMVDBHPOMJLFQFQUJ
de 1 and 2 (GLP-1 and GLP-2), peptide YY (PYY) and neurotensin.
171
Intestine
Malabsorption
Intestine Malabsorption Pathophysiology

nutrient and Symptoms
Duodenum Calcium, Anemia, Osteoporosis
Magnesium,
Phosphate,
Iron, Folic acid
Jejunum Electrolytes Secretion of intestinal
(Na, K), Glucose, hormons¶
Amino acids, Æ gastric acid secretion µ
watersoluble Æ peptic ulcers
Vitamines, Cholezystokinin und sekretin ¶
Micronutrients Æ gall bladder contraction ¶
Æ risk for bile stones µ
Ileum Vit. B12, bile acids, Discontinuation of the entero-
fat/essential fatty hepatic circulation of bile acids
acids, fatsoluble Æ steatorrhea, diarrhea, loss
vitamins of electrolytes, colitis, formation
of bile stones
Resection > 50 cm of Ileum:
Vit.-B12-resorption ¶
Ileocoecal Vitamin B12 Vit.−B12−malabsorption
valve Bacterial synthesis of
D−Lactate Æ Lactate acidosis
Deconjugation of bile acids Æ
Diarrhea, Steatorrhea
Colon water, electrolytes In case of steatorrhea “lime
(Na, Mg, Ca), soap” formation Æ Oxalate µ
middle-chain Æ Hyperoxaluria Æ nephroli-
triglycerides (MCT) thiasis
Dehydratation, electrolyte
disturbances
172
Malabsorption
Incidence:
r mQFS JOIBCJUBOUT
Etiology:
r SFQFUJUJWFCPXFMSFTFDUJPOTJO$SPIOTEJTFBTF
r DPOTFRVFODFPGWBTDVMBSEJTPSEFSTJOBEVMUT JOUFTUJOBMJOGBSDUJPO

r DPOHFOJUBMWBTDVMBSBCFSSBUJPOTJODIJMESFO
r DPNQMJDBUJPOTBGUFSBCEPNJOBMTVSHFSZ
r 7PMWVMVT
r NVMUJQMFJOUFTUJOBMàTUVMBT
r JOUFTUJOBMJSSBEJBUJPO
r BCEPNJOBMUSBVNB
r CBSJBUSJDTVSHFSZ
Assessment:
r EFHSFFPG TNBMM
CPXFMMPTT
r GVODUJPOBMEJTUVSCBODFT
Regular lab test:

(initially as often as appropriate, later on every 3–6 months,
after 12 months yearly)
Na, K, Cl, Ca, Mg, phosphate, urea, creatinine, iron, ferritin,

transferrin, glucose, pre-albumin,
Albumin, ALAT, ASAT, GGT, AP, Bilirubin, CRP
Bicarbonate (blood gas analyses), lactate
RBC (incl. thrombocytes)
Quick or INR
Vitamin: Folic acid, Vit. B12 and B1, Vitamins A, D, E
Micronutrients: Fe, Zn, Se
173
Intestine
Malabsorption
3 phases of postoperative adaptation process
Acute Phase
Begin Immediately after resection
Duration Generally less than 4 weeks
Goal to stabilise the patient
Main losses Fluid, electrolytes
Main clinical massive diarrhea

problem
Treatment parenteral nutritional support, gastric acid
secretion inhibitors and, in severe cases,
the somatostatin-analogue octreotide
Nutrition Energy:
32–35 kcal/kg/d
Glucose:
max. 4–6 g/kg/d
Fat:
1.2-1.8 g/kg/d (30-50% of energy supply)
Amino acids:
1.0-1.5 g/kg/d (to be increased
to max. 2 g/kg/d)
174
Malabsorption
Adaptation Phase Maintenance Phase
1–2 years
to induce maximal adapta- To individualise permanent dietetic
tion by gradually increasing maintenance nutrition, dependent
nutrient exposure on extent and quality of nutritive
deficits effective therapy of acute
exacerbations and optimal mainte-
nance therapy of Crohn’s disease
average malabsorption of 30% of
nutrients ingested
for a target absorption rate of

30–40 kcal/kg/d (ideal body
weight), about 45–60 kcal/kg/d
must be ingested
Adequate and regular supplemen-
tation of vitamins, minerals and
trace elements.
If no distal ileum is left, vitamin B12
must be supplemented parenterally.
Calcium should be given generously
by mouth (800–1200 mg/d)
175
Intestine
Malabsorption
3 phases of postoperative adaptation process
1) Acute Phase
1./2. postoperative day:

Infusion therapy using Ringer, glucose and
amino acid solutions, substitution of water
soluble vitamins and trace elements
Start of total parenteral nutrition

Oral/enteral nutrition with gradually
increasing nutrient loads: isoosmolar
salt–glucose-solutions, tea, carbohydrate
solutions, medium chain triglycerides,
amino acids
176
Malabsorption
2) Adaptation Phase 3) Maintenance Phase

Drug Therapy (Table)
Oral/enteral nutrition Oral nutrition in stable patients:
with gradually increasing many small meals, high fat diet,
nutrient loads to 30–40 small amounts of medium chain
kcal/kg/d: isoosmolar triglycerides in patients with pre-
salt–glucose-solutions, tea, served colon, fluids can usually be
carbohydrate solutions, taken with meals, substitution of
medium chain triglycerides, vitamins and minerals as needed, in
amino acids. particular calcium.
Frequent small solid meals Avoidance of nutrients rich in oxala-
are advisable. If this is te if distal small intestinal resection.
not sufficient to ensure
adequate energy supply or
not tolerated continuous
enteral nutrition can be
used.
Predominantly long chain
triglycerides, free fatty
acids, small amounts of
medium chain triglycerides
in patients with preser-
ved colon, saccharose,
maltose, glutamine, pectin,
substitution of vitamins
and minerals as needed, in
particular calcium.
Growth hormone (and
GLP-2) may improve the
adaptive process.
177
Intestine
Malabsorption
Recommended dietetic treatment
Colon present No colon

Carbohydrates 50–60% 40–50 %
Fat 20–30 % MCT/LCT 30–40% LCT
Proteins 20–30 % 20–30%
Fibre soluble No
Fluids isotonic or hypotonic isotonic
Oxalate avoid No limitation
it appears possible to treat even some patients with very short bowel,
i.e. less than 50 cm of small intestine left, with oral nutrition, only.
Still, a considerable proportion of patients will need long-term paren-

teral nutrition.
These patients require 30-40 kcal/kg/d; 32 kcal/kg/d are recommen-
ded for total parenteral nutrition.
In addition, electrolytes, minerals, vitamins and trace elements must
be supplemented.
Prevention of nephrolithiasis
Supplementation of Vitamin B6
(=Coenzyme for Oxalate degradation) 300 mg/d
4VGàDJFOUPSBMáVJET
(and urine production at least 2000 ml urine/d)
Avoid Oxalate excess
Calcium inriched nutrition
(800–1200 mg/d) or Calcium supplementation during main meals
In case of hyperoxaluria: Calcium 3 g/d to the main meals,
increase to 4 g/d if necessary
In case of hypocitraturia: Potassium citrate
Substitution of MCT if necessary (reduces Oxalate absorption)
In case of increased uric acid in urine. Supplement alkalinisating
sparkling water or Potassium citrate
Laboratory treatment goals (in urine):

Oxalate: < 32 umol/mmol Creatinine
Citrate: 107 mmol/mmol Creatinine,
(better > 200 mmol/mmol Creatinine)
178
Malabsorption
Calcium: < 7,5 mmol/mmol Creatinine

Sodium: < 287 mmol/mmol Creatinine
Uric acid: < 2500 umol/24 h
Prevention of nephrolithiasis
Substitution of vitamins and trace elements

in short bowel syndrome
Vitamin A 10,000–50,000 U/d if liver function is normal
Vitamin B12 300 mg s.c. per month following resection of terminal ileum
Vitamin C 200–500 mg/d
Vitamin D 1600 U/d
Vitamin E 30 IU/d
Vitamin K 10 mg/week
Selenium 60–100 mg/d
Zinc 220–440 mg/d
Doses given above are for orientation, only. The exact individual requirements
must be evaluated and doses adjusted according to regularly performed
appropriate laboratory measurements.
Drug therapy in short bowel syndrome
Drug Recommended
dose per day*
Loperamide 4–16 mg
(and codeine to slow transit)
H2-antagonists (to reduce gastric (acid)
secretion)
- Ranitidine 300–600 mg
- Famotidine 40–80 mg
PPI (to reduce gastric 20–40 mg
(acid) secretion)
Octreotide (to reduce gastric 2–3 x 50–100 ug
(acid) secretion) subcutaneously
Cholestyramine (to reduce 4–16 g
cholerheic diarrhea) (may deteriorate steatorrhea)
Pancreatin (to improve digestion) 25,000–40,000 U per meal
Metronidazole (in bacterial overgrowth) 800 –1200 mg
*Oral application if not stated otherwise.
[Ref.: 1.Keller J et al. Management of the short bowel syndrome after extensive
small bowel resection. Best Pract Res Clin Gastroenterol 2004; 18(5):977-92 2.
Leuenberger M et al. Das Kurzdarmsyndrom: Eine interdisziplinäre Herausforderung.
Aktuel Ernaehr Med 2006; 31:235-42]
179
Intestine
Lactose intolerance
Primary lactose intolerance is caused by a down-regulation in the

expression of lactase along the villous membranes of the enterocyte.
Secondary lactose intolerance results from the reduction of entero-

cytes (e.g. post-infectious, celiac disease, Crohn's disease, etc.) or the
early degradation of lactose in the small intestine by bacteria (e.g.
bacterial overgrowth) or parasites (e.g. Giardia, Ascaris, Cestodes, etc.).
Reduced lactase expression (i.e. primary lactose intolerance) is

associated with the „single-nucleotide polymorphisms“ C13910T or
G22018A. The LCT13910 gene test can be performed within the daily
clinical routine. Patients with the genotype CC have reduced lactase
activity, and those with the genotypes CT and TT have normal enzyme
activities. The LCT13910 gene test has a sensitivity ranging from
61-97% and a specificity of between 93-98% in the diagnosis of an
abnormal H2-lactose breath test.
Algorithm for the evaluation of lactose intolerance
Symptoms
lactose intolerance
+ Lactose H2-Breath test –
LCT 13910 LCT 13910

+ – + –
Gene test+ Gene test- Gene test+ Gene test-

H2-breath test+ H2-breath test+ H2-breath test- H2-breath test-
False negative
Primary Secondary LI No
Breath test
LI bacterial LI
asymptomatic
overgrowth
deficiency
180
Lactose intolerance
Biohit® rapid lactase test:

Test:
r QPTUCVMCBSEVPEFOBMCJPQTZ
r JODVCBUJPOPGEVPEFOBMCJPQTZNBUFSJBMXJUIMBDUPTFJOBQMBUFJO
which a strong colour reaction develops within 20 min if lactase
activity is present and if glucose appears in the test cup from
hydrolysed lactose
Interpretation:
Severe Hypolactasia: Symptomatic hypolactasia very likely.
Duodenal lactase activity <10 U/g protein. C/C genotype common.
DD: Celiac disease.
Mild Hypolactasia: Symptomatic hypolactasia unlikely (20%).

Duodenal lactase activity 10 U/g protein or more in 80% at least.
C/T genotype common.
Normolactasia: Symptomatic hypolactasia impossible. Duodenal lac-

tase always 10 U/g protein or more. TT genotype common. Untreated
celiac disease impossible.
sensitivity 93.8%, specificity 94.1%

[Orlandi M, Netzer P, Inauen W. IDENTIFYING LACTOSE INTOLERANCE WITH A
NOVEL BIOPSY-BASED RAPID LACTASE TEST, Gut 2006; Vol 55 (suppl V): A98]
181
Intestine
Lactose intolerance
Lactose-Intolerance-Tests
H2-breath Lactose Genetic test of Lactase activity
test tolerance –13910 C/T at jejunal brush
test polymorphism border
Test principle Increase of H2 Increase of Genetic Enzymatic
in respiratory blood sugar Polymorphism activity of actase
air after lactose after lactose 13910 upstream enzyme in
challenge challenge of lactase gene biopsy sample
Cut off >20 ppm <1.1 mmol/l 13910C/C <17–20 IU/g
within 3 hours within indicates lactase
3 hours non-persistence
Availability Good Excellent Variable Rare
False positives Rapid GI-transit, Rapid Rare (<5%) in Probably rare
(malabsorption small intestinal GI-transit, im- Caucasians
incorrectly bacterial paired glucose
diagnosed) overgrowth tolerance
False Non-H2- Fluctuations All causes of Patchy enzyme
negatives producers. in blood secondary expression
(malabsorption Full colonic sugar lactose
wrongly adaptation malabsorption
excluded)
Secondary Cannot be Cannot be Cannot be Can be excluded
causes excluded, excluded excluded (histopathology
kinetic of H2- obtained
increase can at same
be suggestive procedure)
Assessment Possible Possible Not possible Not possible
of symptoms/
lactose
tolerance
Comment Method of Rarely Definitive test Reference
choice for performed for lactase standard for
assessment due to inferior non-persistence detection of
of lactose sensitivity in Caucasians. lactase
malabsorption and specificity Less suitable in deficiency
and intolerance other populations. (primary or
Not suitable in secondary)
patients with
intestinal disease
at risk of se-
condary lactase
deficiency
Cost Low Lowest High Highest
[Misselwitz et al: Lactose malabsorption and intolerance: pathogenesis, diagnosis
and treatment, 2013]
182
Small intestine bacterial overgrowth
Lactulose H2-Breath Test (bacterial overgrowth)

Principle of the lactulose H2-breath test
Lactulose
(Disacharose)
$PMPOáPSB
H2, CH4 etc.
Lactulose
(Disacharose) Lung
Liver
The human intestine cannot metabolize lactulose (disaccharide).

Approximately 90 – 120 min after oral ingestion, undigested lactulose
enters the colon (normal orocecal transit time), where it is metabolized
CZMPDBMJOUFTUJOBMáPSB5IFSFTVMUJOHHBTFT )2, CH4) are transported
via the portal venous system through the liver unmetabolized, and
are expelled out via the lungs. An increase in the concentrations of
H2 and CH4 of greater than 20 ppm and 8 ppm over the normal value
respectively, after oral ingestion of 30 g lactulose, is normal. An early
increase (i.e. 60 or even 30 min after oral ingestion of lactulose) is
indicative of bacterial overgrowth in the small intestine.
183
Intestine
Proctology hemorrhoids
Definition
Hemorrhoids
Grade I Grade II Grade III Grade IV

Protrusion in Emerging towards Emerging Spontaneous
proctoscope outside with towards prolapse
pressing; outside with without
spontaneous pressing; reposition
reposition digital
reposition
r 1MFYVTIFNPSSIPJEBMJTJOUFSOVT
r /PSNBMIFNPSSIPJEBMDVTIJPOQBEEJOH
Thrombosed hemorrhoids
Thrombosed external Perianal hematoma caused

hemorrhoids by vein rupture
r 1MFYVTIFNPSSIPJEBMJTFYUFSOVT
r /PSNBMOPUWJTJCMF
[Banov, J S C Med Assoc 1985]
184
Treatment for internal hemorrhoids
Grade I Grade II-III Grade (III)-IV

Symptom-based (small Grade III) Thrombosed
incarceration
–
Fibers* Fibers* + BL Surgery
–
–
BL
BL = Band ligation
[*Diet, stool regulation (stabilizing agent)BL = Band ligation
AGA. Gastroenterology 2004]
Hemorrhoids:
Classification of Hemorrhoids (Goligher et al 1983):

First degree Cushions bulge into the lumen of the anal
canal but do not prolaps below the dentate
line on straining
Second degree Cushions prolapse while straining or
defecation and can be seen at the exterior.
They disappear spontaneously
Third degree Cushions prolapse while straining or
defecation and can be seen at the exterior.
They can only be replaced digitally into the
anal canal
Fourth degree The prolapse of the cushions is permanent
and irreducible
185
Intestine
Therapie:
First degree Second degree Third degree
Conservative Dietary and lifestyle Dietary and lifestyle

Treatment:
Dietary and lifestyle + +
Modifications:
r "EFRVBUFGMVJEJOUBLF Rubber band Stapled Hemor-
and high fiber diet rhoidopexy
r 'JCSFTVQQMFNFOU
r %JPTNJO
2 x 500 mg/day or or
Stapled hemorrhoi- Excisional Hemor-

dopexy rhoidectomy
(Ferguson)
If conservative or or
treatment fails:
Rubber band Hemorrhoidal Arte- Hemorrhoidal Arte-

ry Ligation (HAL) ry Ligation (HAL)
or or or
Sclerotherapy (Sclerotherapy) (Rubber band)
after Intervention/ after Intervention/

suergery: surgery:
Diosmin Diosmin
2 x 500 mg/d 2 x500 mg/d
(14 d) (14 d)
* when additional symptomatic skin tags
186
Fourth degree Acute Prolaps with thrombosis
Dietary and lifestyle Dietary and lifestyle
+ +
Excisional Hemorrhoi- Initial conservative inpatient treatment:

dectomy* r "OBMHFUJD5IFSBQZXJUI
(Ferguson) NSAID/Morphin
r -JEPDBJO(FM
r %JPTNJOYNH
or r $PMEQBDL
(Stapled Hemorroido- early surgery:

pexy)
excisional hemorrhoidectomy
or
(stapled hemorrhoidopexy)
after Intervention/
surgery:
Diosmin
2 x 500 mg/d
(14 d)
187
Intestine
Rubber Band Ligation:

+ Low complication rate - High recurrence rate
Easy office procedure
Low Pain
Repetitive application possible
Sclerotherapy
+ Low complication rate - High recurrence rate
Easy office procedure Low evidence
Little Pain
Hemorrhoidal Artery Ligation (HAL)

+ Low complication rate - Low evidence
Little pain
Low recurrence rate
Stapled Hemorrhoidopexy
+ High evidence - Higher recurrence rate
Low recurrence rate in Grad IV Hemorrhoids
Little pain
Excisional Hemorrhoidectomy
+ Low recurrens rate - postoperative pain
High evidence
[M. Grandel, FH Hetzer: Evidence basierte Therapie des Hämorrhoidalleidens:
Therapeutische Umschau 2013]
Thrombosed external Hemorrhoids
Symptoms < 72 h Symptoms < 72 h

Operative Treatment Conservative Treatment
Excision (No Incision!!!) Diosmin 3 x 1000 mg (Day 1 – 3)
Diosmin 2 x 500 mg (14 days) Diosmin 2 x 500 mg (Day 4 – 14)
NSAID (2–3 days) NSAID (2–3 days)
topical Lidocaine Gel
Stool softeners – e.g. Stool softeners – e.g.
Macrogol, Psyllium Macrogol, Psyllium
188
Fissure-in-ano
r 1SJNBSZGJTTVSFJOBOP PWFSPGBMMDBTFT

- Location: 90% at posterior midline, 10% at anterior midline
(most of those are female)
- Etiology: unclear
- Benign longitudinal ulcer of the lower third of the anal canal distal
from the dentate line.
r BDVUFGJTTVSFJOBOP4ZNQUPNTMBTUJOHOPUMPOHFSUIBOmXFFLT
- simple tear of the anoderm with sharp margins
r DISPOJDGJTTVSFJOBOP4ZNQUPNTMBTUJOHMPOHFSUIBOmXFFLT
- Ulcer with edema and fibrosis. Edges are indurated and
under mined. Visible internal sphincter. With or without a so
called «sentinel pile» at its lower end.
r 4FDPOEBSZGJTTVSFJOBOP
- Location: atypical at lateral position
- Aetiology: In association with other diseases: Crohn`s disease;
anal tuberculosis, AIDS, STD, iatrogen, anal carcinoma
- Treatment: Therapie of the underlying pathology
Symptoms: Pain and bleeding during and particulary after defecation
189
Intestine
2TQEVQNQI[ƂUUWTGU
Diagnosis: Patient history. Physical examination by simply spreading

the buttocks. No anoscopy, no digital rectal examination because of
the severe pain.
Therapy of Primary acute fissure-in-ano:
Fissure Therapy
Nifedipine 0.2% two weeks (2–3 times/day)
+ –
Stool softener
Macrogol o. Psyllium
Painkillers/NSAID
Continue with Nifedipine 0.2%

for another 4 weeks
Healing unchanged 1) (Botox® 2x20 E i.m.)

80–90 % symptomatic 2) Balloon dilatation
(chronic fissure) 3) Fissurectomy
Therapy of Secondary chronic fissure-in-ano:

Mostly operative treatment required. Conservative treatment fails in over
50% of all cases. No more sphincterotomy (High rate of incontinence).
Fissurectomy (with or without Botulinum toxin)
Stool softener
Macrogol o. Psyllium
Painkillers/NSAID
[Hetzer FH et al: Praxis 2000; Hetzer FH: procto workshop 2012]
190
2TQEVQNQI[ƂUUWTGU
Fissure – Drug treatment
Nitro- Ca-channel Botulinum

glycerine blocker toxin
Drug Glyceryl Nifedipine 0.2% Botulinum toxin
trinitrate 0.2% Diltiazem 2% Typ A
Method Intrasphincter Intrasphincter Rev. sphincter
pressure pressure paresis 2 – 3 months
Healing rate 27– 85% 45 – 95% 25 – 96%
Recurrence 0 – 43% 4% 4%
Advantage(s) Inexpensive Inexpensive Single injection
80% of patients
pain-free
after 7–10 day
Disadvantage(s) Headache Compliance Patient costs
20 – 70% Less experience (Botox 100 E
Compliance Headache Painful injection
0-20% Perianal thrombosis
5 – 10%
Reversible inconti-
nence 3 – 12%
a
Evidence Grade I b
I c
I
[AGA technical review. Gastroenterology 2003]
191
Intestine
Proctology Incontinence score
Stool – Incontinence – Scores

Wexner Score – Dis Colon Rectum 1993; 36: 77–97
Type of
incontinence Never Rarely Sometimes Usually Always
Solid 0 1 2 3 4
Liquid 0 1 2 3 4
Gas 0 1 2 3 4
Wears pad 0 1 2 3 4
Lifestyle 0 1 2 3 4
alteration
Never 0; rarely <1/month; sometimes <1/week, >1/month;
Usually <1/day, >1/week,
Always >1/day.
O = perfect, 20 = complete incontinence
192
Proctology: Fecal incontinence
Stool – Incontinence – Score

Vaizey Score Gut 1999; 44: 77–80
Type of
incontinence Never Rarely Sometimes Weekly Daily
Solid 0 1 2 3 4
Liquid 0 1 2 3 4
Gas 0 1 2 3 4
Wears pad 0 1 2 3 4
Lifestyle 0 1 2 3 4
alteration
No Yes
Need to wear a pad or plug 0 2
Taking constipating medicines 0 2
Lack of ability to defer defecation for 15 min 0 4
Never: no episodes in the past 4 weeks;
Rarely: 1 episode in the past 4 weeks;
Sometimes: >1episode in the last 4 weeks but <1/week;
Weekly: 1 or more episodes a week but <1/day;
Daily: 1 or more episodes a day
Add one score from each row: minimum score = 0
= perfect continence
Maximum score = 24
= total incontinence
193
Intestine
Proctology: Fecal incontinence
Fecal Incontinence (FI) of the adult
«Alarm symptoms» Basic examination «Alarm symptoms»

Patient history,
physical examination
Exclusion: Immediate
Incontinence induced
Surgery:
by medication
no Rectal prolapse
Incontinence in
«Alarm symptoms» Rectovaginal fistula
assosiciation with
Acute anal
IBD Therapy of the
sphincter injury
underlying disease
Education
of the patient:
Nutrition counseling:
Persisting FI constipation nutrition Persisting FI
Evacuation of stool with
e.g. colonic irrigation
Toilet access
(map of public toilets)
Persisting FI
Additional:
Loperamide 0.5–2 mg/day
Stool bulking agents: e.g.
Psyllium
Further
Diagnostics:
Anorectal Manometry Persisting FI
Endoanal Ultrasound
MRI Defecography
Additional: Persisting FI
Biofeedback Therapy
for 3 month
BIG SPHINCTER
NO SPHINCTER
DEFECT SMALL SPHINCTER
DEFECT
DEFECT
SPHINCTER STOMA
REPAIR SACRAL NERVE DYNAMIC
GRACILOPLASTY
STIMULATION ARTIFICIAL
Persisting FI
BOWEL
Persisting FI SPHINCTER
[Hetzer FH: Procto workshop 2012]
194
Proctology: Condylomata acuminata
(Swiss recommendation)
Location perianal Endoanal

Size < 5 mm ≥ 5 mm
1st line Imiquimod CO2Laser#- / CO2Laser#- /
Therapy cream Scalpel incision Scalpel incision
5% topical
application*<>
Adjuvant Linola® Sept## b.i.d Imiquimod anal

Therapy for 2 weeks tampon**<>
followed by
Imiquimod
cream
5% topical
application*<>
Follow-up 3 months
* 3x/week until inflammatory demarcation (usually at least for 12 weeks), follow-up
after 12 weeks. Application before bedtime, skin exposure for 6–10 hours, rinse skin
the following morning with mild soap and water [1,2]
#
In high-risk patients ( HIV.positive, carcinogenic HPV-positive, post-transplant pati-
ents) histology mandatory (for HPV-typing & to rule out dysplasia, malignancy)
##
not available in CH (= 0.5 g Clioquinol per 100 g Crème)
** 3x/week before bedtime for 12 weeks, keep anal tampon until the following
morning and rinse with water [3]
HIV-patients: Aldara is indidicated and effective in HIV-Patienten too. [4]
[[1] L. Edwards, A. Ferency, L. Eron et al., Self-administered topical 5% imiquimod

cream for external anogenital warts. Arch Dermatol 1998; 134:25–30]
[[2] Carrasco D, van der Straten M, Tyring SK. Treatment of anogenital warts with
imiquimod 5% cream followed by surgical resection of residual lesions. J Am Acad
Dermatol 2002; 47: S212-16]
[[3] Kaspari M, Gutzmer R, Kaspari T, Kapp A, Brodersen JP. Application of imiquimod
by suppositories anal tampons) efficiently prevents recurrences after ablation of anal
canal condyloma. Br J Dermatol 2002; 147:757-9 ]
[[4] Cusini M, Salmaso F, Zerboni R, Carminati G, Vernaci C, Franchi C, Locatelli
A, Alessi E. 5% Imiquimod cream for external anogenital warts in HIVinfected patients
under HAART therapy. Int J STD AIDS 2004; 15:17-20]
[D. Hahnloser, F. Hetzer (modified)]
195
Hepatology
Liver segments
Sonographic Dimensions of Abdominal Organs

and Vessel
Liver: Craniocaudal diameter < 140 mm, anteroposte-
rior diameter < 120 mm
Liver: Angle of inferior border left lobe < 30°
and right lobe < 45°
Gallbladder: Length < 120 mm, width < 40 mm, wall
thickness < 4 mm
Bile ducts: Normal width of DHC < 6mm, after cholecy-
stectomy < 9 mm, intrahepatic ducts < 4 mm
Spleen: Length < 110 mm, thickness < 40 mm
Appendix: Diameter < 6 mm, wall thickness < 2 mm
Kidneys: Length 100–120 mm, width 50–70 mm,
width of parenchyma 13–25 mm
Kidneys: Parenchyma-Pyelon Index: >1.6:1 (< 30 years),
1.2-1.6:1 (31-60 years), 1.1:1 (> 60 years)
Adrenal gland: < 10 mm
Pancreas: Head < 30 mm, body < 25 mm, tail < 25 mm,
pancreatic duct < 2 mm
Prostate: Width < 45 mm, Depth < 35 mm,
Length < 35 mm, Volume 25 mL
Thyroid gland: Width 40–70 mm, Depth 10–30 mm,
Length 10–20 mm, Volume 20–25 mL
Urinary bladder: Volume < 750 mL (male)/ < 550 mL (female),
residual urine < 50 mL wall thickness < 4 mm
(filled bladder), < 8 mm (empty bladder)
Aorta: Suprarenal part < 25 mm, infrarenal part < 20 mm
Vena cava: < 20 mm
Portal vein: < 13 mm
Hepatic veins: < 7 mm
Splenic vein: < 10 mm
196
Liver segments
Liver segments I
Anterior view Inferior view

right cranial left
right ventral left
caudal
Lobus caudatus
dorsal
Liver segments II Subcostal cut
IVb III
III IVb III
IVa II IVa II IVb
V V V
VIII I
VI
VII VI VII VI
Subcostal cut cranial Subcostal cut median Subcostal cut caudal

Longitudinal cut
III III / IVb IVb IVb / V V / VI

IVa VI
II
II / IVa IVa / VIII VII / VIII VII
I
VII
Left lobe Left lobe Both liver Right liver Right liver Right liver
lateral paramedian lobes lobe lobe lobe
left Longitudinal Paramedian Portal vein wide lateral
cut v.cava right cut
197
Hepatology
Liver segments
CEUS – contrast-enhanced ultrasound

r$POUSBTUIBSNPOJDJNBHJOH $)*
Analysis:
0-30 s: early arterial phase
30-90 s: portal venous phase,
followed by an investigational break to avoid early
disintegration of bubbles
3-5 min: late (venous) phase
Interpretation: (after completing the CEUS-investigation)
1. Rate ultrasound contrast of focal lesion in late phase first

2. Rate ultrasound contrast of focal lesion in arterial phase next
3. Rate finally ultrasound contrast of focal lesion in portal phase
198
Liver segments
1. Late 2. Arterial 3. Portal suggestive

venous phase phase for:
phase
HypOechoic Hyperechoic Iso- / hypOechoic HCC =
(chaotic vessels) Hepatocellular
carcinoma
Iso- / hyperechoic Hypervascular
metastasis
HypOechoic HypOechoic HypOvascular
metastasis
Rim enhancement HypOechoic CCC = Cholan-
Non-enhancement Non-enhancement gio-carcinoma
Isoechoic Hyperechoic Hyperechoic FNH
(centrifugal filling,
spoke wheel pattern,
central scar, feeding
artery)
Hyper-/ Isoechoic Haemangioma
(centripetal filling,
central non-enhance-
ment, thrombosis)
Isoechoic Hyper-/ Isoechoic Adenoma
(in B-mode not
detectable)
Isoechoic Regenerative
(in B-mode not Nodule
detectable)
Isoechoic Rim enhancement Hypoenhancement / Abscess
(central non- rim enhancement /
enhancement) central non-
enhancement, septa
199
Hepatology
Hepatopathy
Hepatopathy
Increased transaminases (< 5x ULN)
obesity, alcohol, hepatotoxic medication
Hematology: hemoglobin, MCV, MCHC, leucocytes

+ differentiation, thrombocytes INR
Chemistry: alk. phosphatase, y-GT, bilirubin,
ferritin, transferrin saturation, albumin,
Serology: hepatitis A (HAV-AB), hepatitis B
(HBsAg, HBcAB), hepatitis C (HCV-AB)
purely hepatocellular cholestatic
Laboratory: ANA, auto-

antibodies (SMC, LKM,
SLC), ceruloplasmin, Laboratory: AMA, auto-
Į1-antitrypsin deficiency, antibodies (SMC, LKM,
transglutaminase-AB, SLC), ANCA
endomysium-AB, serum
electrophoresis,
genetics (HFE)
Ultrasound – abdomen Ultrasound – abdomen
Liver biopsy MRCP / ERCP
200
Hepatopathy
Hepatocellular Hepatopathy
Slightly increased transaminases (< 5x the upper normal value)

r )FQBUJD"-"5"4"5
- Non-alcoholic fatty liver disease (NAFLD)
- Non-alcoholic steatohepatitis (NASH)
- Medication/toxins (see separate list)
- Chronic hepatitis B/C/D
- Acute viral hepatitis (A-E, CMV, EBV)
- Hemochromatosis
- Autoimmune hepatitis
-Į1-Antitrypsin deficiency
- Morbus Wilson
r )FQBUJD"4"5"-"5
- Alcohol
- Non-alcoholic fatty liver disease (NAFLD)
- Non-alcoholic steatohepatitis (NASH)
- Liver cirrhosis
r &YUSBIFQBUJD
- Celiac disease
- Hemolysis
- Muscle disease
- Thyroid disease
- Endurance sport (Marathon)
Markedly increased transaminases (> 15x the upper normal value)

r "DVUFWJSBMIFQBUJUJT "& )FSQFT
r .FEJDBUJPOUPYJOT TFFTFQBSBUFMJTU
r *TDIFNJDIFQBUJUJT
r "VUPJNNVOFIFQBUJUJT
r "DVUFCJMFEVDUPCTUSVDUJPO
r "DVUF#VEE$IJBSJTZOESPNF
201
Hepatology
Hepatopathy
Medication / Toxins / Drugs

r "OBCPMJDTUFSPJET r (PMETBMUT
r "MMPQVSJOPM r *NJQSBNJOF
r "NPYJDJMMJODMBWVMBOJDBDJE r *OEJOBWJS
r $BQUPQSJM r *QSJOEPMF
r $BSCBNB[FQJOF r /FWBQJSJO
r $IMPSQSPQBNJEF r .FUIZMUFTUPTUFSPOF
r $ZQSPIFQUBEJOF r &DTUBTZ NFUIZMFOFEJPYZ/
r %JMUJB[FN methylamphetamine)
r &SZUISPNZDJO r 0YBQSP[JO
r &TUSPHFOT r 1J[PUZMJOF
r 'MPYVSJEJOF r 2VJOJEJOF
r 'MVDMPYBDJMMJO r 5PMCVUBNJEF
r 'MVQIFOB[JOF r 5SJNFUIPQSJNTVMGBNFUIPYB[PMF
Medication Herbs/Alternative medicine
r 1BSBDFUBNPM r $SFPTPUFCVTI -BSSFBUSJEFOUBUB
r "MQIBNFUIZMEPQB r &QIFESB &QIFESBTJOJDB
r "NPYJDJMMJO r #BDIGMPXFST (FOUJBOB
Clavulanic acid r (FSNBOEFS 5FVDSJVNGSVUJDBOT
r "NJPEBSPOF r +JO#V)VBO )FSCB-ZDPQPEJJ

r "[BUIJPQSJOF Serrati)
r $BSCBNB[FQJOF r $BSPCMPDVTUCFBO 4FOOBBMFY
r %BOUSPMFOFTPEJVN andrina)
r %JTVMàSBN r ,BWB,BWB 1JQFSNFUIZTUJDVN
r &USFUJOBUF r 4LVMMDBQT 4DVUFMMBSJB
r 'MVDPOB[PMF r 4IBSLDBSUJMBHF
r (MJCFODMBNJEF r 7JUBNJO"
r )BMPUIBOF
r )FQBSJO
r *TPOJB[JEF Drugs
r ,FUPDPOB[PMF r "OBCPMJDTUFSPJET
r -BCFUBMPM r $PDBJOF
r .FUIPUSFYBUF r &DTUBTZ NFUIZMFOFEJPYZ/
r /JDPUJOJDBDJE methylamphetamine)
r /JUSPGVSBOUPJO r 1$1 1IFODZDMJEJOF
r /POTUFSPJEBM
antirheumatics
r 1IFOZMCVUB[POF Toxins
r 1IFOZUPJO r 5FUSBDIMPSPNFUIBOF $$M
r 1SPUFBTFJOIJCJUPST r 5SJDIMPSNFUIBOFDIMPSPGPSN
r 4VMGPOBNJEF (CHCl3)
r 1SPQZMUIJPVSBDJM r %JNFUIZMGPSNBNJEF $)/0
r 1IFOQSPDPVNPO r %JNFUIZMOJUSPQSPQBOF $)/0
r 4UBUJOT r )ZESB[JOFEJBNJEF /)
r 5SB[BEPOF r $IMPSPGMVPSPDBSCPO $'$
r 7BMQSPBUF r 5SJDIMPSPFUIZMFOF $)$M
r ;BàSMVLBTU r 5PMVFOF $) $)$)
202
Hepatopathy
Cholestatic Hepatopathy
Unconjugated Conjugated
hyperbilirubinemia hyperbilirubinemia
r (JMCFSU.FVMFOHSBDIU r &YUSBIFQBUJDDIPMFTUBTJT
syndrome r )FQBUJUJT WJSBM BVUPJNNVOF
r /FPOBUBMKBVOEJDF alcoholic)
(Icterus neonatorum) r -JWFSDJSSIPTJT
r )FNPMZTJT r 4FQTJT
r )FNBUPNB r 5PYJDIFQBUPQBUIZ
r $SJHMFS/BKKBSTZOESPNF (see separate list)
r *OFGGFDUJWFFSZUISPQPJFTJT r /FPQMBTJB IFQBUJD
(thalassemia, metastases, lymphoma)
megaloblastic anemia) r 1SJNBSZTDMFSPTJOHDIPMBOHJUJT
(PSC)
r %VCJO+PIOTPOTZOESPNF
r 3PUPSTZOESPNF
r 7BOJTIJOHCJMFEVDUTZOESPNF
r #FOJHOSFDVSSFOUJOUSBIFQBUJD
cholestasis (BRIC)
r )ZQFSFNFTJTHSBWJEBSVN
r )&--1TZOESPNF
203
Hepatology
Hepatopathy
Increased alkaline phosphatase

r )FQBUPCJMJBSZ
- Bile duct obstruction
- Primary biliary cirrhosis (PBC)
- Primary sclerosing cholangitis (PSC)
- Medication (see separate list)
- Hepatitis (viral, autoimmune, alcoholic)
- Liver cirrhosis
- Vanishing bile duct syndrome
- Benign recurrent intrahepatic cholestasis (BRIC)
- Venoocclusive disease
r *OGJMUSBUJPOPGUIFMJWFS
- Granulomatous diseases (sarcoidosis, tuberculosis)
- Neoplasia (hepatic, metastases, lymphoma)
- Fungal infection
- Amyloidosis
r &YUSBIFQBUJD
- Bone metabolism (growth, bone diseases)
- Pregnancy
- Chronic kidney insufficiency
- Heart insufficiency
- Infection
[Green R, et al. Gastroenterology (2002)]

204
Ascites-SBP-HRS
Ascites
Degree of severity
Grade I (mild): sonographic; Grade II (moderate): moderate abdominal
distension; Grade III (severe): severe abdominal distension
Diagnostic
Cell count with differentiation (leucocytes), albumin (as well as in
serum), total protein, LDH (as well as in serum), glucose, culture
(aerobic, anaerobic). In special cases: amylase, bilirubin, triglyceride,
cholesterol, tuberculosis culture, cytology.
SAAG > 11 g/L SAAG < 11 g/L

Liver cirrhosis (80%) Malignant ascites (10%)
(often hemorrhagic; LDH,
lactate, increased cholesterol/
triglyceride)
Alcoholic hepatitis, fulminant Ileus, pancreatitis, serositis
hepatic failure, right heart with collagenosis, peritoneal
failure, metastatic liver, portal tuberculosis, mesenteric
vein thrombosis, Budd-Chiari infarct, chylous ascites, biliary
syndrome, acute fatty liver of ascites, nephrotic syndrome,
pregnancy, nephrotic syndro- exudative enteropathy
me, exudative enteropathy
Serum Ascites Albumin Gradient (SAAG) = Albumin Serum – Albumin Ascites
Therapy
General measures
Salt restriction (in addition, avoid using salt, no convenience foods),
áVJESFTUSJDUJPOUPMJUFSE POMZXJUI/B+ < 125 mmol/L), no NSAID
First-time ascites
1. Spironolactone: initially 100 mg/d, then increase weekly up to 400 mg/d
Side effects: hyperkalemia (stop at K+ > 6 mmol/L),
gynecomastia
2. Torasemide: with therapy failure (< 2 kg/week weight reduction)
initially 10 mg/d, slowly increase up to a maximum
of 40 mg/d
Side effects: hypokalemia, kidney insufficiency
205
Hepatology
Ascites-SBP-HRS
Recurring ascites
Direct combination spironolactone 100 mg/d + torasemide 10 mg/d.
Increase to 400 mg/d + 40 mg/d depending on therapy response
Therapy-resistant ascites (5 – 10%)

Paracentesis: albumin substitution (20 g per 2 L ascites)
TIPS (Transjugular Intrahepatic Portosystemic Shunt)
- Indication:
paracentesis > 3x/month, contraindication for paracentesis
(adhesions), hepatic hydrothorax
- Contraindication: severe heart insufficiency, sepsis, portal vein
thrombosis, Child score > 12 points, hepatic encephalopathy
(SBEFm NBMJHOBOUMJWFSUVNPST SFUSPHSBEFQPSUBMWFOPVTáPX
- Discontinue diuretics in the case of: encephalopathy,
Na+NNPM-EFTQJUFáVJESFTUSJDUJPO SFOBMJOTVGàDJFODZ
(creatinine > 133μmol/L)
[Ginès et al. J Hepatol 53, (2010)]
Spontaneous Bacterial Peritonitis (SBP)

1– 4% in the outpatient department, 10–30% for hospitalized cirrhosis
patients with ascites (50% community-acquired, 50% nosocomial)
Diagnosis
Absolute neutrophil count > 250/mL ± positive ascites culture
(positive in 60%)
Bacteria
E. coli (37%), C. pneumoniae (17%), S. pneumoniae (12%), S. viridans
(9%), other Gram +ve bacteria (15%), other Gram –ve bacteria (10%)
Risk factors
Medical history of SBP (70% recurrence rate), systemic infection
(typical UTI), GI bleeding, high Child-Pugh score, low total protein
in ascites (<10 g/L)
206
Ascites-SBP-HRS
Therapy
SBP, empirical therapy
- Ceftriaxone 2 g/d IV for 5 days (alternative: amoxicillin/
clavulanic acid)
- Albumin IV: 1.5 g/kg on Day 1 and 1 g/kg on Day 3
Control paracentesis after 48 h: neutrophilic decrease > 50%,
otherwise adjust antibiotic therapy
Secondary prophylaxis after SBP

/PSáPYBDJONHEQP BMUFSOBUJWFUSJNFUIPQSJN
sulfamethoxazole 800/160 mg) Risk of recurrence
without prophylaxis = 70%, with prophylaxis = 20%
Primary prophylaxis
"TDJUFTQSPUFJOH-$IJME1VHITDPSFQPJOUTOPSáPYBDJO
2x400 mg/d as longterm therapy
- Acute gastrointestinal bleeding: ceftriaxone 2 g/d IV for 5 days or
OPSáPYBDJOYNHEGPSEBZT
Hepatorenal Syndrome (HRS)
Type I: Doubling of creatinine in < 2 weeks (typically

after infection, GI bleeding)
Type II: Slower increase in creatinine (typically with
therapy-resistant ascites)
Diagnosis
r -JWFSDJSSIPTJTXJUIBTDJUFT
r $SFBUJOJOFçNPM- PSNHEM
r /PTIPDL IZQPWPMFNJD TFQUJD PUIFS
r /PJNQSPWFNFOUBGUFSEJTDPOUJOVBUJPOPGEJVSFUJDTWPMVNF
expansion (albumin 1 g/kg, maximal 100 g/d) over 2 days
r /POFQISPUPYJDNFEJDBUJPO
207
Hepatology
Ascites-SBP-HRS
r /POFQISPQBUIZ VSJOFQSPUFJOHE FSZUISPDZUFTWJTVBM

field, normal sonography)
Therapy
General measures
Cave: Hydration ĺ hyponatremia, ascites/edema, stop diuretics, no
NSAID, paracentesis (+ albumin IV 20 g 2 L)
Hepatorenal syndrome (HES) Typ I

Primary Terlipressin: initial 1 mg IV 4-6x/d serum creatinine
< 133 μmol/L => stop therapy
creatinine decrease <25% after 3 days
=> increase up to 2 mg IV 6x/d
creatinine decrease < 50% after 7 days
=> stop therapy
creatinine decrease > 50% after 7 days
=> continue until max. 14 days
Cave: tachyarrhythmia, ischemia (cardial,
peripheral)
Albumin: 1 g/kg on Day 1
thereafter 20–40 g/d
if serum albumin > 45 g/L => stop therapy
(lung edema)
Secondary TIPS (Transjugular Intrahepatic Portosystemic Shunt)
HRS Typ II
Terlipressin + albumin or TIPS, although limited data
With HRS, always evaluate liver transplantation

(poor longterm survival).
[Ginès et al. J Hepatol 53, (2010)]
208
CHILD-PUGH-Score
Parameter / Points 1 2 3
PT s > contr. <4 4–6 >6
Quick % > 70 40 – 70 < 40
INR < 1.7 1.7 – 2.3 > 2.3
Bilirubin μmol/l < 35 35 – 50 > 50
mg/dl <2 2–3 >3
in PBC μmol/l < 70 70 – 170 > 170
mg/dl <4 4 – 10 > 10
Albumin g/l > 35 28 – 35 < 28
g/dl > 3.5 2.8 – 3.5 < 2.8
Ascites none mild moderate to
(response severe
to diuretics) (refractory
to diuretics)
Encephalopathy none Grades 1– 2 Grades 3 – 4
Point CHILD-Stage 1st year 2nd year

score survival rate survival rate
5–6 A – compensated 100% 85%
7–9 B – impaired 80% 60%
10 – 15 C – decompensated 45% 35%
1. Hepatic encephalopathy.
West Haven Criteria for Semiquantative Grading of Mental State
Grade 1
r 5SJWJBMMBDLPGBXBSFOFTTFVQIPSJBPSBOYJFUZ
r TIPSUFOFEBUUFOUJPOTQBO
r JNQBJSFEQFSGPSNBODFPGBEEJUJPO
Grade 2
r -FUIBSHZPSBQBUIZ
r NJOJNBMEJTPSJFOUBUJPOGPSUJNFPSQMBDF
r TVCUMFQFSTPOBMJUZDIBOHF
r JOBQQSPQSJBUFCFIBWJPVS
Grade 3
r 4PNOPMFODFUPTFNJTUVQPS CVUSFTQPOTJWFUPWFSCBMTUJNVMJ
r $POGVTJPO
r HSPTTEJTPSJFOUBUJPO
Grade 4
r $PNB VOSFTQPOTJWFUPWFSCBMPSOPYJPVTTUJNVMJ
[Ferenci P, Lockwood A, Mullen K, et al. Hepatic encephalopathy—definition, nomen-

clature, diagnosis, and quantification: final report of the working party at the 11th World
Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002;35:716–721]
209
Hepatology
HCC Hepatocellular carcinoma
Barcelona Clinic Liver Cancer (BCLC)
Stage Tumour characteristics

Stage A (early HCC)
A1 PST 0 Single tumour
A4 PST 0 3 tumours, all < 3 cm
Stage B (intermediate HCC) Large multinodular
PST 0
Stage C (advanced HCC) Vascular invasion
PST 1-2 or extrahepatic spread
Stage D (end stage HCC) Any
PST 3-4
[Bruix and Sherman, Hepatology, 2011]

Barcelona Clinic Liver Cancer (BCLC) Staging and Treatment Strategy
Stage 0 Stage
PST 0, Child A PST 0-2,
Very early stage (0) Early stage (A)

Single <2 cm Single or 3 nodules
Carcinoma in situ ≤3 cm PS 0
Single 3 nodules ≤3 cm
Portal pressure
/Bilirubin
Associated diseases
Increased
Normal No Yes
Resection Liver transplantation RF/PEI
Curative treatment (30 – 40%) Median Overall survival
> 60 months; 5-year survival 40 – 70%
Abbreviations: OS: Overall survival, PST: Performance status, PEI: percutaneous
ethanol injection, RF: radiofrequency ablation
210
Associated liver features
No portal hypertension and normal bilirubin level

Portal hypertension, normal bilirubin level
Portal hypertension and abnormal level
Child-Pugh A-B
Child-Pugh A-B
Child-Pugh A-B
Child-Pugh C
A-C Stage D
Child A-B PST >2, Child C*
Intermediate stage (B) Advanced stage (C) Terminal stage (D)

Multinodular, Portal invasion,
PS 0 N1, M1, PS 1-2
TACE Sorafenib Best supportive care

Target 20% OS 20 Target 40% OS 11 Target 10% OS
months (45 – 14) months (6-14) <3 months
[Modified after EASL Clinical Practice Guidelines, 2011]
211
Hepatology
Portal vein thrombosis (PVT)
PVT Algorithm
Chronic (> 60 d)/

Acute (< 60 d)* cavernous
transformation
&UJPMPHZ
Upper
endoscopy –
7BSJDFT
In patients with gastroesophageal
varices, do not initiate anticoagulation
until after adequate prophylaxis for variceal
bleeding
has been instituted
min.3 month Treat underlying
anticoagulation disease
Discuss permanent anticoagulation therapy

with permanent prothrombotic conditions
*Possible criteria defining acute stage of portal vein thrombosis:

r Recent abdominal pain
r /PFWJEFODFPGDISPOJDQPSUBMIZQFSUFOTJPO JFHBTUSPJOUFTUJOBM
bleeding, ascites, collateral porto-systemic circulation or
hypersplenism)
r $POUSBTUFOIBODFE$5PSEVQMFY%PQQMFSVMUSBTPVOETIPXJOH
no porto-portal collaterals at the porta hepatis
212
Portal vein thrombosis (PVT)
Etiology of PVT
r $JSSIPTJT
r 5SBOTKVHVMBSJOUSBIFQBUJDQPSUPTZTUFNJDTIVOU
r Infection: abdominal sepsis, omphalitis, pylephlebitis
r Local Inflammation: appendicitis, diverticulitis, pancreatitis, cholecy-
stitis, trauma, retroperitoneal fibrosis, endoscopic sclerotherapy,
collagen vascular diseases (e.g. lupus), Behcet's disease, inflamm-
atory bowel disease
r Malignancy: hepatocellular carcinoma, pancreas carcinoma,
lymphoma, cholangiocarcinoma, compression or invasion of the
portal vein by tumor (e.g. pancreatic cancer)
r Acquired: oral contraceptives, pregnancy, other malignancy,
myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria,
hyperhomocysteinemia, antiphospholipid syndrome
r Congenital: factor V Leiden, protein C or protein S deficiency, pro
thrombin gene mutation, antithrombin deficiency, MTFR gene
mutation that raises homocysteine, myeloproliferative disorders,
increased factor VIII levels
[Condat B, et al., Hepatology. 2000]
Portal hypertensive gastropathy
2-category classification system
1. Mild 2. Severe
r snake skin pattern of gastric r TOBLFTLJOQBUUFSOBOESFE
mucosa marks, cherry red spots
r risk of bleeding: 5 – 31% r SJTLPGCMFFEJOH – 62%
Patients with portal hypertensive gastropathy-associated bleeding:
β-blockers should be used for prevention of recurrent bleeding.
Baveno V workshop 2010
[McCormack TT. Gut 1985.26:1226 and Yoo HY. Gastrointest Endosc 2002]
213
Hepatology
TIPS
Indications for TIPS

Efficacy determined by controlled trials
r 4FDPOEBSZQSFWFOUJPOBOEQPTTJCMFUSFBUNFOUPGBDVUFCMFFEJOH
r 3FGSBDUPSZDJSSIPUJDBTDJUFT
Efficacy assessed in uncontrolled series

r 3FGSBDUPSZBDVUFCMFFEJOHWBSJDFT
r 1PSUBMIZQFSUFOTJWFHBTUSPQBUIZ
r #MFFEJOHHBTUSJDWBSJDFT
r (BTUSJDBOUSBMWBTDVMBSFDUBTJB
r 3FGSBDUPSZIFQBUJDIZESPUIPSBY
r )FQBUPSFOBMTZOESPNF5ZQFTBOE
r #VEE$IJBSJTZOESPNF
r 7FOPPDDMVTJWFEJTFBTF
r )FQBUPQVMNPOBSZTZOESPNF
Contraindications to TIPS placement Absolute

r 1SJNBSZQSFWFOUJPOPGWBSJDFBMCMFFEJOH
r $POHFTUJWFIFBSUGBJMVSF
r .VMUJQMFIFQBUJDDZTUT
r 6ODPOUSPMMFETZTUFNJDJOGFDUJPOPSTFQTJT
r 6OSFMJFWFECJMJBSZPCTUSVDUJPO
r 4FWFSFQVMNPOBSZIZQFSUFOTJPO
Relative
r )FQBUPNB FTQFDJBMMZJGDFOUSBM
r 0CTUSVDUJPOPGBMMIFQBUJDWFJOT
r 1PSUBMWFJOUISPNCPTJT
r 4FWFSFDPBHVMPQBUIZ */3
r 5ISPNCPDZUPQFOJBPG DN
r .PEFSBUFQVMNPOBSZIZQFSUFOTJPO
Complications of TIPS
Complications Frequency (%)
r 5*14EZTGVODUJPO
r 5ISPNCPTJT m
r 0DDMVTJPOTUFOPTJT m
r 5SBOTDBQTVMBSQVODUVSF
r *OUSBQFSJUPOFBMCMFFE m
r )FQBUJDJOGBSDUJPO
r 'JTUVMBF SBSF
r )FNPCJMJB
r 4FQTJT m
r *OGFDUJPOPG5*14 SBSF
214
TIPS
r )FNPMZTJT m
r &ODFQIBMPQBUIZOFXXPSTF m
r &ODFQIBMPQBUIZDISPOJD m
r 4UFOUNJHSBUJPO m
* = measure point for

@ Duplex sonography
(halfway between the
TQMFOPQPSUBMDPOáV
ence and entry of the
TIPS in the portal vein)
Hepatic vein TIPS Portal vein
TIPS US-Doppler Control

Measurements:
r .BJOQPSUBMWFJOWFMPDJUZ .17
DNTFD
r %JTUBMTUFOUWFMPDJUZ %47
DNTFD
r 1FBLTUFOUWFMPDJUZ 147
DNTFD
r *OEJSFDUTJHOT
P )PNPHFOáPXJO5*14
P 1PSUBMWFJOáPX.BJOQPSUBMWFJOTIPVMECFIFQBUPQFUBM
Flow direction in the entire portal system is towards the portal vein
FOEPGUIFTUFOUXJUIJOWFSTJPOPGQPSUBMWFJOáPXJOJOUSBIFQBUJD
1PSUBMWFJOT JOáPXJO5*14BOEPVUáPXGSPN5*14
*GSFDBOBMJ[FE
para-umbilical vein is present (with blood shunting away from
UIFMJWFS
áPXJOUIFMFGUQPSUBMWFJOXJMMCFIFQBUPQFUBMEFTQJUF
normal TIPS function
Surveillance suggestion: Doppler sonograms between 3 and 6
months after TIPS; repeat at 6-month intervals for the first two
years
Ultrasonographic findings suggesting TIPS dysfunction or

recurrence of the complication of portal hypertension that led
to the initial TIPS, should be followed by repeat shunt veno-
graphy and intervention
[Abraldes et al. Am J Gastroenterol 2005
Boyer TD, Haskal Z. AASLD Practice Guidelines HEPATOLOGY, Vol. 51, No. 1, 2010]
215
Hepatology
Aethylic hepatitis
online: www.unos.org/resources/MeldPeldCalculator.asp?index=98
[Discrimination factor or Maddrey Score (Maddrey, 1988):

DF = 4.6 x (Prothrombin time [TP] – control-TP [sec]) +
bilirubin [mg/kl] > 32]
Liver cirrhosis, MELD Score

MELD Score: Model of End Stage Liver Disease
r Serum creatinine, total serum bilirubin, and INR within the MELD
TDPSFGPSNVMBSFáFDUUIFTFWFSJUZPGMJWFSEZTGVODUJPOJODJSSIPTJT
(Kamath PS et al, Hepatology 2001):
r .&-%4DPSF¤MO(Creatinine) + 3.78× ln (Bilirubin)

+ 11.20× ln (INR) + 6.43
r Best predictor of 3-month mortality in hospitalized patients

with liver cirrhosis:
- MELD ≥ 40 points: 100% mortality
- MELD 30 – 39 points: 83% mortality
- MELD < 10 points: 4% mortality
r Online MELD score calculator: https://sasl.unibas.ch/1
1calculators-MELD.php
216
MELD Score
Indications for liver transplantation evaluation

r After first major hepatic decompensation in patients with liver
cirrhosis (i.e. ascites, variceal bleeding, hepatic encephalopathy)
- or -
r $)*-%4DPSFö
- or -
r .&-%4DPSFö
- or -
r )FQBUPDFMMVMBSDBSDJOPNBXJUIJO.JMBODSJUFSJB MFTJPOVQUPDN
3 lesions not larger than 3 cm), no vascular invasion, no regional
nodes or distal metastasis
- or -
r "DVUFMJWFSGBJMVSF TFF,JOHAT$PMMFHFDSJUFSJB$MJDIZDSJUFSJB

-or-
r Other rare indications & under certain circumstances to consider:
i.e. hepatopulmonary syndrome, portopulmonary hypertension,
hemangioblastoma, hepatoblastoma, nodular regenerative
hyperplasia, Budd-Chiari syndrome, familial amyloidosis, primary
hyperoxaluria, polycystic liver disease, neuroendocrine tumors,
glycogen storage disease
217
Hepatology
Alcoholic hepatitis
Treatment algorithm in alcoholic steatohepatitis

according to EASL guidelines (2012)
Patients with decompensated ALD and active drinking
Suspect ASH
r3BQJEEFUFSJPSBUJPOPGMJWFSGVODUJPO IJHICJMJSVCJOMFWFMT
r/FXPOTFUPGDMJOJDBMEFDPNQFOTBUJPO
Prognostic assessment r.BEESFZT%'

r.&-%
r"#*$
r(MBTHPXTDPSF
High risk Low risk
Consider Nutrition assessment

transjugular +
treatment of complications
biopsy in cirrhotic patients
ASH confirmed ASH not confirmed
Before starting corticosteroids or pentoxifylline, it is recommended:

r4DSFFOJOHGPS)#7 )$7BOE)*7
r"CEPNJOBMVMUSBTPVOEUPFYDMVEFPUIFSDBVTFTPGKBVOEJDF
r4ZTUFNBUJDCBDUFSJBMJOGFDUJPOTDSFFOJOHBOECMPPE BTDJUFTBOEVSJOFDVMUVSF
r4DSFFOPGSFOBMGBJMVSFBOEFBSMZUSFBUNFOUPGIFQBUPSFOBMTZOESPNF
r1SPQFSDPOUSPMPGIZQFSHMZDFNJB
Consider clinical parameters such as severe sepsis, active bleeding or local
clinical guidelines to choose between prednisolone and pentoxifylline.
or
Pentoxifylline Prednisolone
(400 mg TID for 4 wk) (40 mg QD for 4 wk)
Continue treatment Lille model 7 days Stop prednisolone*

3 more wk <0.45 ≥0.45 Consider early OLT in
higlhly selected patients
* A Lille score * 0.45 indicating non-response and increased risks of infection and death.
In non responders, the interruption of corticosteroids is recommended particularly in those
classified as null responders (Lille score >0.56)
218
Alcoholic hepatitis
Maddrey’s Alcoholic Hepatitis

Discriminant Function
Equation:
Discriminant = 4.6 x (Patient PT – 11.8 s) +
Plasma Bilirubin (umol/L)/17
PT = Prothrombin Time
A value more than 32 implies poor outcome

with one month mortality ranging between
35% to 45%.
[Reference: Maddrey WC et al: Corticosteroid therapy of
alcoholic hepatitis” Gastroenterology, 1978.]
Conversion Quick (%) to Prothrombin Time (s):

100 % ≈10.1 s 50 % ≈15.2 s
90 % ≈10.7 s 45 % ≈16.4 s
80 % ≈11.3 s 40 % ≈17.6 s
70 % ≈12.3 s 35 % ≈19.6 s
60 % ≈13.5 s 30 % ≈21.8 s
55 % ≈14.2 s 25 % ≈25.4 s
219
Hepatology
Acute Liver Failure
Prognostic Model for Acute Liver Failure:

King’s College Hospital Criteria
Potentially helpful indicators of poor prognosis in patients

with acute liver failure (sensitivity 68-69% and specificity
82-92%):
Acute liver failure secondary to paracetamol overdose:

r Grade 3 or 4 hepatic encephalopathy
r pH < 7.30 or arterial lactate > 3.0 mmol/L after fluid
resuscitation
r INR > 6.5 (PT > 100 seconds) and serum creatinine
> 300 μmol/L (> 3.4 mg/dL)
Non-paracetamol associated acute liver failure:

r INR > 6.5 (PT > 100 seconds), or
r any 3 of the following:
- age between 10 and 40 years
- duration of jaundice before hepatic encephalopathy
> 7 days
- INR ≥ 3.5 (PT > 50 seconds)
- serum bilirubin > 300 μmol/L (> 17.6 mg/dL)
- unfavorable etiology: seronegative hepatitis, or
idiosyncratic drug reaction or Wilson disease
[Modified from: AASLD Position Paper: The Management of Acute Liver
Failure, Update 2011]
Prognostic Model for Acute Liver Failure:

Clichy Criteria
Potentially helpful indicators of poor prognosis in patients
with acute liver failure (positive predictive value 82%, negative
predictive value 98%):
Presence of hepatic encephalopathy and factor V level:

r Factor V < 20% of normal in patients < 30 years of age, or
r Factor V < 30% of normal in patients > 30 years of age
[Modified from: AASLD Position Paper: The Management of Acute Liver
Failure, Update 2011]
220
Hemochromatosis
Target Population
Symptomatic** Asymptomatic* Adult 1st degree

relative of HH
Step 1
Serum transferrin saturation and ferritin
TS < 45% and normal TS > 45% and/or

ferritin elevated ferritin
Step 2
No further evaluation HFE Genotype
Compound hete- C282Y/C282Y

rozygote C282Y/
H63D C282Y
heterozygote or Ferritin < 1000 μg/L Ferritin > 1000 μg/L
non-C282Y and normal liver or elevated liver
enzymes enzymes
Exclude other liver

Step 3
or hematologic + –
+ Liver biopsy for
Therapeutic
diseases ± liver HIC and
phlebotomy
biopsy histopathology
[Bacon et al. Hepatology, Vol. 54, No. 1, 2011]
221
Hepatology
Hemochromatosis
Asymptomatic*
Abnormal serum iron studies on routine screening chemistry panel
Evaluation of abnormal liver tests
Identified by family screening
Nonspecific, systemic symptoms**

Weakness
Fatigue
Lethargy
Apathy
Weight loss
Specific, organ-related symptoms
Abdominal pain (hepatomegaly)
Arthralgias (arthritis)
Diabetes (pancreas)
Amenorrhea (cirrhosis)
Loss of libido, impotence (pituitary, cirrhosis)
Congestive heart failure (heart)
Arrhythmias (heart)
Treatment of hemochromatosis
Hereditary hemochromatosis
r 0OFQIMFCPUPNZ SFNPWBMPGN-CMPPE
XFFLMZPSCJXFFLMZ
r $IFDLIFNBUPDSJUIFNPHMPCJOQSJPSUPFBDIQIMFCPUPNZ
r "MMPXIFNBUPDSJUIFNPHMPCJOUPGBMMCZOPNPSFUIBOPGQSJPSMFWFM
r $IFDLTFSVNGFSSJUJOMFWFMFWFSZQIMFCPUPNJFT
r 4UPQGSFRVFOUQIMFCPUPNZXIFOTFSVNGFSSJUJOSFBDIFTNH-
r $POUJOVFQIMFCPUPNZBUJOUFSWBMTUPLFFQTFSVNGFSSJUJOCFUXFFO
50 and 100 mg/L
r "WPJEWJUBNJO$TVQQMFNFOUT
Secondary iron overload due to dyserythropoiesis

r %FGFSPYBNJOFBUBEPTFPGmNHLHCPEZXFJHIU
per day
r %FGFSBTJSPYHJWFOPSBMMZ
r $POTJEFSGPMMPXVQMJWFSCJPQTZUPBTDFSUBJOBEFRVBDZ
of iron removal
r "WPJEWJUBNJO$TVQQMFNFOUT
222
Wilson Disease
Diagnostic Methods for Wilson Disease

r Serum ceruloplasmin (< 0.1 g/L)
r Serum „free“ (non-ceruloplasmin bound) copper (> 200 μg/L)
r 24-hour urinary copper excretion (> 1.6 μmol/24 h, > 100 μg/24 h)
r Presence of Kayser-Fleischer rings by slit lamp examination
r Liver biopsy (histology, Rhodanine stain, Orcein stain)
r Hepatic parenchymal copper concentration (> 4 μmol/g dry weight)
r Genetic testing for ATP7B mutations
r MRI of the brain with hyperintense basal ganglia in T2
Wilson Disease Scoring System (Leipzig Score)

s 3ERUMCERULOPLASMIN
< 0.1 g/L = 2 0.1-0.2 g/L = 1 > 0.2 g/L = 0
s HOURURINARYCOPPEREXCRETION
> 2x ULN = 2 1-2x ULN = 1 Normal = 0
s 0RESENCEOF+AYSER &LEISCHERRINGS
Present = 2 Absent = 0
s .EUROLOGICSYMPTOMS

Severe = 2 Mild = 1 Absent = 0
r Liver copper** (no cholestasis present):
>4 μmol/g = 2 0.8-4 μmol/g = 1 <0.8 μmol/g = -1
s 'ENETICTESTINGFOR!40"MUTATIONS
2 chromosomes = 4 1 chromosome = 1
s #OOMBS NEGATIVEHEMOLYTICANEMIA
Present = 1 Absent = 0
Score interpretation:
≥ 4 points: diagnosis established
3 points: diagnosis possible, but more tests needed
≤ 2 points: diagnosis very unlikely
* or typical abnormalities at brain MRI
** Rhodanine-positive granules if no quantitative liver copper available
223
Hepatology
Hepatitis B
Diagnosis and progression
HBc HBe HBs DNA

AB Ag AB Ag AB Interpretation
+ + - + - + Acute hepatitis
+ - + + - + Chronic hepatitis
(HBeAg negative)
+ - +/- + - + Chronic hepatitis
(HBeAg positive)
+ - - + - + Chronic hepatitis
(pre-core mutant)
- - - + - + Chronic hepatitis (immunode-
ficiency, perinatal infection)
+ - + - + - Status after hepatitis B
+ - - - - - Status after hepatitis B
- (HBc-only )
+ - + - - Status after hepatitis B
- - - - + - Hepatitis B vaccination
Progression
65%
HBV infection Asymptomatic Healed
infection
Acute hepatitis
10% 25%
1%
Fulminant
hepatitis
20%
Cirrhosis
Chronic hepatitis
Virus
HCC
persistence
HBs carrier
80%
224
Hepatitis B
Indication for therapy
s ("6 $.!)5M,ANDORINCREASED!,!4
s -ODERATEINmAMMATIONlBROSISINLIVERBIOPSY
(Metavir * A2 or * F2)
ALWAYS treat patients with liver cirrhosis
Pregnancy and Hepatitis B

.PUIFS r 3JTLPGUSBOTNJTTJPOWBSJFT)#F"HQPTJ
tive (70%), HBeAg negative (2–10%, HBc
only (1%))
r 8JUIIJHIFSWJSVTMPBE 7 IU/mL),
antiviral therapy should be undertaken in
the 3rd trimester (Lamivudine, Telbi-
vudine, Tenofovir)
r 8JUIBOUJWJSBMUIFSBQZĺ no breastfeeding
$IJME r "DUJWF BGUFS BOENPOUIT
BOEQBT
sive* (200 IE HBsAb always after 0–12 h)
immunization postpartum
r 4FSPMPHJDBMUFTUJOHBGUFSmNPOUIT
(HBsAg, HBcAK and HBsAK with a titer
goal of >100 IE)
* in Switzerland: Hepatect CP, Hepatitis B Immunoglobulins Behring
[EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol
50, (2009). Cornberg, M. et al. Z Gastroenterol (2011)]
225
Hepatology
Hepatitis B
Treatment
Management of antiviral-resistant HBV
Prevention
r "WPJEVOOFDFTTBSZUSFBUNFOU
r *OJUJBUFUSFBUNFOUXJUIQPUFOUBOUJWJSBMUIBUIBTMPXSBUFPGESVH
resistance or with combination therapy
r 4XJUDIUPBMUFSOBUJWFUIFSBQZJOQBUJFOUTXJUIQSJNBSZOPOSFTQPOTF
Monitoring
r 5FTUGPSTFSVN)#7%/" 1$3BTTBZ
FWFSZNPOUITEVSJOH
treatment
r $IFDLGPSNFEJDBUJPODPNQMJBODFJOQBUJFOUTXJUIWJSPMPHJD
breakthrough
r $POGJSNBOUJWJSBMSFTJTUBODFXJUIHFOPUZQJDUFTUJOH
Treatment
Lamivudine-resistance ĺ Add adefovir or tenofovir
Stop lamivudine, switch to Truvada*^
Adefovir-resistance ĺ Add lamivudine#
Stop adefovir, switch to Truvada*^
Switch to or add entecavir#^
Entecavir-resistanceĺ Switch to tenofovir or Truvada^
Telbivudine –resistance+ ĺ Add adefovir or tenofovir
Stop telbivudine, switch to Truvada
* Truvada= combination pill with emtricitabine 200 mg and tenofovir 300 mg
#
Durability of viral suppression unknown, especially in patients with prior lamivudine
resistance
^ In HIV coinfected persons: scanty in vivo data in non HIV infected persons
+
Clinical data not available
226
Hepatitis C
Definitions of virological response patterns

Rapid virological
response (RVR) Undetectable1 HCV RNA at week 4
Extended RVR (eRVR) Undetectable HCV RNA at weeks 4 and 122
RVR8 Undetectable HCV RNA at week 83
Early virological
response (EVR) >2 log drop of HCV RNA at week 12
Complete EVR (cEVR)4 Undetectable HCV RNA at week 12
Partial EVR (pEVR) >2 log drop but still detectable HCV RNA
at week 12
Delayed virological
response (DVR)5 >2 log drop but still detectable HCV RNA at
week 12, but undetectable at week 24
Partial response (PR) >2 log drop of HCV RNA at week 12 but
detectable at weeks 12 and 24
Null response (NR) <2 log drop of HCV RNA at week 12
Breakthrough (BT) Reappearance of HCV RNA at any time

during treatment
Sustained virological
response (SVR) Undetectable HCV RNA 24 weeks after the
end of treatment
Relapse HCV RNA undetectable at end of treatment

but detectable within 24 weeks of follow-up
1 The term «undetectable» in this paper refers to HCV RNA below the limited of
detection (as opposed to the limit of quantitation) of a sensitive real-time PCR assay.
2 Relates to triple therapy comprising telaprevir.
3 Relates to triple therapy comprising boceprevir, including a 4-week lead-in phase of
pegylated interferon-т and ribavirin.
4 Designated as early virological response in the recent EASL Clinical Practice Guidelines (ref. 2).
5 Formerly designated as slow virological response.
[Modified from: SASL, Treatment of chronic hepatitis C genotype 1 with triple therapy
comprising telaprevir or boceprevir, Swiss Med Wkly 2012]
227
Hepatology
Hepatitis C
Hepatitis C Therapy – Definitions
Null response
Relapse
Non response
HCV RNA level
Breakthrough
2 log10 drop
Partial response
Detection limit
Treatment
0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72
Weeks
[Adapted from Shiffman M. Curr Gastroenterol Rep 2006;8:46–52

Neumann A, et al. Science 1998; De Bruijne J, et al. Neth J Med 2008]
228
Hepatitis C
Treatment options according to 2014 EASL practice

guidelines for chronic HCV infection GT1
r 12 weeks PEG + RBV + Sofosbuvir

r 12 weeks PEG + RBV + Simeprevir°
followed by 12 or 36* weeks of PEG + RBV
r 12 weeks PEG + RBV + Daclatasvir
followed by 12 weeks of PEG + RBV
r 24 weeks RBV + Sofosbuvir
r 12 weeks Sofosbuvir + Simeprevir ± RBV
r 12 or 24** weeks Sofosbuvir + Daclatasvir ± RBV
* In prior partial or null responders.

** In treatment-experienced patients.
RBV: Daily weight-based ribavirin (1000 or 1200 mg in patients

<75 kg or *75 kg, respectively).
PEG: pegylated interferon-alpha,
with interferon without interferon.
°Not recommended in GT1a with Q80K substitution.

r 12 or 20* weeks RBV + Sofosbuvir
r 12 weeks PEG + RBV + Sofosbuvir*
* In cirrhosis and/or treatment-experienced patients.

with interferon without interferon
229
Hepatology
Hepatitis C

r 24 weeks RBV + Sofosbuvir°

r 12 or 24* weeks Sofosbuvir + Daclatasvir ± RBV
* In cirrhosis and/or treatment-experienced patients.

<75 kg or *75 kg, spectively).
° Not recommended in treatment-experienced cirrhotic patients.


r 12 weeks PEG + RBV + Simeprevir
followed by 12 or 36* weeks of PEG + RBV
r 12 weeks PEG + RBV + Daclatasvir
followed by 12 weeks** of PEG + RBV
r 12 weeks Sofosbuvir + Simeprevir ± RBV
r 12 weeks or 24** weeks Sofosbuvir + Daclatasvir ± RBV
* In prior partial or null responders.

** Daclatasvir should be continued in combination with PEG + RBV an additional
12 weeks (total duration 24 weeks) in patients who do not achieve an HCV RNA
level <25 IU/ml at week 4 and undetectable at week 10.
°Not recommended in GT1a with Q80K substitution.
230
Hepatitis C

guidelines for chronic HCV infection GT5 and GT6

231
Hepatology
Autoimmune hepatitis
Simplified diagnostic criteria for autoimmune

hepatitis (AIH)
Variable Cutoff Points Cutoff Points
ANA or SMA* ≥ 1:40 1 ≥ 1:80 2
,+- ≥ 1:40
SLA positive
IgG > ULN 1 > 1.1 x ULN 2
Histology Compatible with AIH 1 Typical of AIH 2
Absence of
viral hepatitis Yes 2
Score interpretation: ≥ 6 points: Probable autoimmune hepatitis
≥ 7 points: Definite autoimmune hepatitis
* Maximal number of points for all autoantibodies is 2; AIH score maximum is 8.
[Modified from: Choi et al., Hepatology 2008]
232
Indications for immunosuppressive treatment

in autoimmune hepatitis
Absolute Relative No
indications indications indication
Serum AST ≥ 10 Symptoms (fatigue, Asymptomatic with
fold ULN normal or near normal
arthralgia, jaundice)
serum Ȗ-globulin
levels
Serum AST ≥ 5 fold Serum AST and/or Inactive cirrhosis
ULN and Ȗ-globulin Ȗ-globulin less than or mild portal
≥ 2 fold ULN absolute criteria hypertension (portal
hepatitis)
Bridging necrosis Interface hepatitis Severe leucopenia
or multiacinar Osteopenia, emotio- (< 2.5 x 109/L or
necrosis on nal instability, hyper- thrombocytopenia <
histology tension, diabetes 50 x 109/L or known
complete deficiency
of TPMT activity
precludes treatment
with azathioprine
Incapacitating Leucopenia Vertebral compressi-
symptoms (≤ 2.5 x 109/L) on, psychosis, brittle
Thrombocytopenia diabetes, uncon-
≤ 50 x 109/L) trolled hypertension,
known intolerances
to prednisone or
azathioprine
Abbreviations: AST = aspartate aminotransferase levels; ULN = upper limit
of normal range; TPMT = thiopurine methyltransferase.
[Modified from: AASLD Practice Guidelines: Diagnosis and Management of
Autoimmune Hepatitis, Manns et al., Hepatology 2010]
233
Hepatology
Monotherapy Combination therapy

Prednisone Prednisone Azathioprine
(mg/day) (mg/day)* (mg/kg/day)
Week 1 60 30 1–2
Week 2 40 20 1–2
Week 3 30 15 1–2
Week 4 30 15 1–2
Maintainance 20 and below 10 1–2
until endpoint
Reasons for Cytopenia Postmenopausal state
preference Thiopurine Osteoporosis
methyltransferase Brittle diabetes
deficiency Obesity, acne
Pregnancy Hypertension
Malignancy Emotional lability
Short course
(<6 months)
* Alternative: Oral budesonide (3mg, three or two times daily) in combination with
azathioprine can induce and maintain remission in patients with noncirrhotic AIH,
with a low rate of steroid-specific side effects (Manns et al. Gastroenterology 2010)
[Modified from: AASLD Practice Guidelines: Diagnosis and Management of
Autoimmune Hepatitis, Manns et al., Hepatology 2010]
234
Autoimmune hepatitis – Classification

Type 1 (~80%) Type 2 (~20%)
Age of onset 10–20 45–70 < 15
Gender distribution 78% female 89% female
Characteristic ANA LKM-1
antibodies SMA (F-actin) LC-1
SLA
pANCA
IgG increase µ +++ +
Steroid response +++ ++
[Modified from: AASLD Practice Guidelines: Diagnosis and Management of
Autoimmune Hepatitis. Manns et al.,Hepatology 2010]
Revised Original Scoring System of the

International Autoimmune Hepatitis Group
Score
Sex Female +2
AP: AST (or ALT) >3 -2
ratio < 1.5 +2
Ȗ-globulin or IgG >2.0 +3
level above normal 1.5 - 2 +2
1.0 - 1.5 +1
<1 0
ANA, SMA > 1:80 +3
or anti-LKM1 titers Â Â 1:80 +2
Â Â 1:40 +1
< 1:40 0
AMA Positive -4
Viral markers Positive -3
Negative +3
Drugs Yes -4
No +1
Alcohol < 25 g/day +2
>60 g/day -2
[Alvarez et al. J of Hepatol 1999]
235
Hepatology
Autoimmune hepatitis – Recommendations for treatment
Remission induction – Aim: Transaminase and IgG levels
In patients who are particularly

predniso(lo)ne, e.g. with diabetes,
High-dose therapy osteoporosis (e.g. post-menopause),
with predniso(lo)ne tolerate a potential cosmetic
Cushing syndrome, hirsutism)
Start with predniso(lo)ne Remission induction with lower

(60 mg/day) dosage of predniso(lo)ne
with subsequent stepwise (30 mg/day)
tapering of dosage following plus
decline of transaminase levels azathioprine (1–2 mg/kg bw/day)
From 30 mg/day additional stepwise tapering of dosage
azathioprine of predniso(lo)ne following
(1–2 mg/kg bw/day) decline of transaminases
Maintenance of remission

Duration of treatment: normally lifelong

Consider treatment-free interval:
(transaminase and IgG levels within normal range), repeatedly
documented histological remission (liver biopsy).
Continue the remission Continue the remission

maintenance therapy with maintenance therapy with
azathioprine (1–2 mg/kg bw/day) azathioprine (1–2 mg/kg bw/day)
If required, combination of If required, combination of
azathioprine (1–2 mg/kg bw/day) azathioprine (1–2 mg/kg bw/day)
with prednis(ol)one with prednis(ol)one
(ⱕ 7.5 mg/day) (ⱕ 7.5 mg/day)
or or
in patients without liver cirrhosis in patients without liver cirrhosis
with budesonide (2 x 3 mg/day) with budesonide (2 x 3 mg/day)
In the case of relapse during maintenance therapy

Increase dosage of/reintroduce therapy with predniso(lo)ne
and, if required, increase of azathioprine dosage
236
within normal range
sensitive to adverse
Growing/ effects of
changing In patients with azathioprine
fatty liver character
disease/NASH, intolerance or contraindication
glaucoma or in patients who do not (leukopenia/thrombocytopenia,
impairment (acne, weight gain) cholestatic hepatitis,
gastrointestinal adverse effects,
pancreatitis)
In patients without liver Remission induction
cirrhosis remission induction with predniso(lo)ne
with budesonide monotherapy (60 mg/day)
(3 x 3 mg/day) or
plus in patients without liver
azathioprine cirrhosis budesonide
(1–2 mg/kg bw/day) monotherapy (3 x 3 mg/day)
only in cases of complete biochemical/immunological remission

verified over a minimum period of 2 years and simultaneously
Taper budesonide and Continue the remission

continue the remission maintenance therapy with low
maintenance therapy with dosage predniso(lo)ne
azathioprine (1–2 mg/kg bw/day) (ⱕ 7.5 mg/day)
or or
continue combination therapy with in patients without liver cirrhosis
budesonide (2 x 3 mg/day) with budesonide (2 x 3 mg/day)
plus or
azathioprine (1–2 mg/kg bw/day) possibly off-label with
mycophenolate mofetil
(2 x 1 g/day)
or budesonide with subsequent stepwise tapering of dosage

(up to 2 mg/kg bw/day)
237
Hepatology
If response to treatment is inadequate

Check compliance, diagnosis and for presence of an
overlap syndrome with PBC or PSC

If there is suspected inadequate compliance during
prednis(lo)one therapy due to adverse effects
(in patients without liver cirrhosis):
switch to budesonide (3 x 3 mg/day) and taper predniso(lo)ne

After excluding the above factors, prediso(lo)ne 60 mg/day
or 30 mg/day in combination with azathioprine
(1–2 mg/kg bw/day) for a longer period (minimum of 4 weeks)
Stepwise tapering of predniso(lo)ne dosage following decline
of transaminase levels

Second line treatment options*:
Supplement or substitute the standard therapy with
mycophenolate mofetil, cyclosporin A or tacrolimus (off-label)
in consultation with a hepatological center

Third line treatment options*:
Supplement or substitute the standard therapy with rituximab
of infliximab** (off-label)
in consultation with a hepatological center
* Consider patient-specific factors such as concomitant diseases, tolerance, drug

interactions/toxicity and responce to treatment following initiation.
** Can induce AIH.
[Author: Prof. Dr. med. Heike Bantel, Department of Gastroenterology,
Hepatology and Endocrinology, Hannover Medical School,
Carl-Neuberg-Str. 130625, Hannover, Germany
E-Mail: bantel.heike@mh-hannover.de]
238
239
Hepatology
Liver and pregnancy
Biochemical changes during normal pregnancy

hemoglobin (from 2nd trimester)
white cell count
platelets unchanged
prothrombin time unchanged
transaminases (ALT, AST) unchanged
alkaline phosphatase (ALP)
gGT unchanged
albumin
bilirubin unchanged
alpha-fetoprotein
cholesterol
uric acid
Pregnancy-related liver diseases
Diagnosis Onset (trimester)

Hyperemesis 1st
Gravidarum
Pre-Eclampsia/ 2nd and/or 3rd

Eclampsia
HELLP 2nd to 3rd or

postpartum
Acute fatty liver 3rd

of pregnancy
Intrahepatic cholestasis 3rd

of pregnancy
Liver 3rd or postpartum

hematoma or rupture
240
Symptoms Therapy Prevalence (%)
nausea, vomiting, weight loss supportive 0.3 – 1.0
> 5%, dehydration, electrolyte
abnormalities
headache, visual disturban- supportive, 5–7
cies, RUQ pain, hypertension, prompt delivery
edema, proteinuria, (with
seizures: eclampsia)
nausea, vomiting, headache, supportive, 0.2 – 0.6
RUQ pain, edema, weight prompt delivery
gain
anorexia, nausea, vomiting, immediate 0.005 – 0.010
headache, RUQ pain, liver delivery
failure, encephalopathy
pruritus, mild jaundice ursodeoxycholic 0.1 – 0.3
acid (10-15 mg/
kg), delivery after
fetal maturity
RUQ pain, pre-eclampsia, surgery 1 (in patients with
hypotension, shock HELLP)
241
Hepatology
Liver and pregnancy
Diagnostic laboratory features in pregnancy-related liver diseases
Diagnosis ALT Bilirubin

Hyperemesis 2–4 x up to 4 x
Gravidarum
Pre-Eclampsia/ 10 – 50 x 2–5 x
Eclampsia
HELLP 10 – 20 x 2–4 x
Acute fatty liver 5 – 10 x 6–8 x

of pregnancy
Intrahepatic cholestasis 1 – 10 x up to 6 x
of pregnancy
Liver 10 – 50 x 2 – 10 x
hematoma or rupture
242
Bile Acids Prothrombin Time Platelets
= = =
= =/ =/
= =/
= =/
= / () =
= =/
243
Hepatology
Liver and pregnancy
Disorders severely affected by pregnancy
Disorder Mechanisms of effect

of Pregnancy
Hepatitis E particularly severe during
pregnancy (especially 3rd
trimester), possibly related
to immunologic changes
Hepatic increased growth of
Adenoma adenoma because of
hyperestrogenemia
Budd-Chiari thrombosis promoted by

syndrome increased gestational serum
levels of estrogen and de-
crease in AT III levels
Splenic artery can rupture during pregnancy

syndrome because of compression by
gravid uterus
Acute symptoms worsened by

intermittent hyperestrogenemia
porphyria
Choledochal cyst compression by gravid

cysts uterus can lead to cyst
rupture or cholangitis
244
Clinical Diagnosis Therapy
Presentation
malaise, anorexia, nau- IgM antibody and supportive therapy for
sea, vomiting, abdominal PCR analysis of acute infection
pain and jaundice blood or feces for may require liver
hepatitis E transplant
nausea, vomiting and abdominal US observe if size < 5 cm
RUQ pain surgery if size > 5 cm
or symptomatic or in-
tralesional hemorrhage
RUQ pain, hepatomegaly doppler abdomi- selective thrombolytic
and ascites nal US, hepatic therapy, surgical shunt
venography or or TIPS anticoagu-
MR-angiography lation with heparin
because warfarin is
contraindicated in
pregnancy
abdominal pain, pulsatile abdominal surgical removal or an-
left upper quadrant mass doppler US giographic occlusion
and abdominal bruit
in patient with portal
hypertension
abdominal pain, vomi- increased urinary discontinue precipi-
ting, constipation, pa- porphobilinogen, tating drugs, avoid
resthesias in extremities, and prolonged fasting, and
mental status changes, ⌬-aminolevulinic administer hematin
tachycardia, and ileus acid and glucose to prevent
attacks
abdominal pain, abdominal US, frequently requires
jaundice, and may require surgery: cystectomy
abdominal mass cholangiography and cholecystectomy
with either Roux-en-Y
hepaticojejunostomy
oder choledochojeju-
nostomy
245
Hepatology
Liver nodule
Diagnostic algorithm for suspected HCC in cirrhosis
Liver
< 1 cm
Repeat US at 3 months
Growing/ changing
Stable
character
Investigate
according to size
Abbreviations: CT, computed tomography; MDCT, multidetector CT;

MRI, magnetic resonance imaging; US, ultrasound.
[Bruix and Sherman, Hepatology, 2011]
246
nodule
> 1 cm
4-phase MDCT/ dynamic

contrast enhanced MRI
Arterial hypervascularity
AND venous or delayed
phase washout
Other contrast enhanced

Yes study (CT or MRI) No
Arterial hypervascularity
HCC AND venous or delayed Biopsy
phase washout
Yes No
247
Hepatology
Non-Alcoholic Steatohepatitis
Lille Model
s 'OALEarly identification of non-response to steroids after 7 days in

patients with severe alcoholic hepatitis
s Lille model combines six reproducible variables (age, creatinine,

albumin, prothrombin time/INR, bilirubin, and evolution of
bilirubin at day 7) and is highly predictive of death at 6 months
s 3URVIVALPROBABILITYATMONTHSISDEFINEDBYTHE CUTOFF
6-month survival probability of patients with a Lille model above
0.45 is about 25% contrary to patients with a Lille model below
this cutoff (85%)
s #ALCULATION,INK www.lillemodel.com
[Louvet, A et al.: The Lille Model: a new tool for therapeutic strategy in patients
with severe alcoholic hepatitis treated with steroids. Hepatology, 2007]
248
Non-Alcoholic Fatty Liver Disease Activity Score

(NAS)
Steatosis (%) ≤5 0
5-33 1
33-66 2
≥66 3
Lobular none 0
JOáBNNBUJPO ≤2 foci 1
(per 200x field) 2-4 foci 2
≥4 foci 3
Hepatocellular none 0
ballooning few, mild ballooning 1
prominent ballooning 2
Fibrosis no fibrosis 0
zone 3 perisinusoidal fibrosis 1a
(special fibrosis staining
required to identify)
zone 3 perisinusoidal fibrosis 1b
(easily seen on H&E)
periportal/portal fibrosis only 1c
zone 3 with periportal/portal 2
fibrosis
as previous with bridging 3
fibrosis
cirrhosis 4
[Kleiner, DE et al.: Design and validation of a histological scoring system for nonalco-
holic fatty liver disease. Hepatology, 2005]
249
Hepatology
HOMA-IR: Homeostasis model assessment

for insulin resistance
s 'OALApproximating equation for insulin resistance
s &ORMULAFasting insulin (mIU/L) x Fasting glucose (mmol/L) / 22.5
s #ALCULATION,INK https://sasl.unibas.ch/11calculators-HOMA.php
HOMA-IR Score (Unit: mIU/L x mmol/L)

<3 Normal insulin resistance
3-5 Moderate insulin resistance
>5 Severe insulin resistance
[Matthews, DR et al.: Homeostasis model assessment: insulin resistance and

beta-cell function from fasting plasma glucose and insulin concentrations in
man. Diabetologia. 1985.]
250
Acute Porphyria
Diagnosis
of acute porphyria
Clinical suspicion of acute porphyria

in a symptomatic patient
Rapid test for porphobilinogen

(PBG) in spot urine
Porphobilinogen Porphobilinogen
normal elevated
24-hour urine 24-hour urine

collection (PBG, ALA) collection (PBG, ALA,
only in strong porphyrins)
clinical suspicion and start treatment
Define type of
acute porphyria
251
Hepatology
Epidemiology PSC and PBC
Epidemiology
Primary biliary cirrhosis Primary sclerosing
(PBC) cholangitis (PSC)
Sex 80–95 % females 60–80 % males
Age 35–50 years 30–60 years
Special Independent of *OáBNNBUPSZCPXFM
character- social class diseases in 70–80 %
istics and/or race (85–90 % ulcerative colitis,
10–15 % Crohn’s disease)
Children and Children and adolescents
adolescents only are often affected; often
rarely affected overlap with autoimmune
hepatitis
Staging
Stage Clinical features Histology
I Pruritus; elevated GGT, 1PSUBMJOáBNNBUJPO
AP (significant), AST, bile duct destruction and
ALT (mild), antimito- bile duct proliferation
chondrial antibodies in the portal tracts
(AMA)
II Same as stage I, Same as stage I,
increase in IgM and JOáBNNBUPSZJOàMUSBUJPO
further elevation of hepatic parenchyma
of above mentioned (piecemeal necrosis
parameters possible), beginning fibrosis
III Same as stage I and II, Rarefication of bile ducts,
mild increase in serum SFEVDFEJOáBNNBUJPO
bilirubin possible increasing fibrosis
IV Jaundice, ascites, Complete cirrhotic
portal hypertension transformation
252
Epidemiology PSC and PBC
Symptoms and findings
Fatigue
Xanthelasmas and xanthomas
Pruritus (especially at night, later also

during the day; cause unkown. Pruritus
is very common = main symptom)
Jaundice (in late stages)
Hepato-and splenomegaly
(moderate to significant)
Signs of liver cirrhosis
(varices, ascites, etc.)
Steatorrhea
(due to cholestasis and pancreatic
insufficiency: Sicca syndrome)
... and
More rarely, vitamin deficiencies

(due to cholestasis and steatorrhea);
night blindness, coagulation
disorders
253
Hepatology
5[ORVQOUƂPFKPIUCPFVTGCVOGPVQRVKQPU
PBC and PSC
Symptoms and findings

sWeight loss 25–80 % sAP, GGT, ALT 90–95 %
and AST Ç
sJaundice 25–70 % sBilirubin Ç 70 %
sRecurrent fever 20–30 % sIgG Ç 40 %
sPruritus 10–70 % sIgM Ç 35 %
sUpper abdominal 40–75 % sAlbumin È 25–30%
complaints
sVariceal hemorrhage 9% sANA positive 10–80%
sAscites 6% sAMA negative > 90 %
sDiarrhea unkown spANCA positive 65–80 %
7–50 % of patients
are believed to be
asymptomatic
Treatment options PBC

Basic drug therapy
Ursodeoxycholic acid 14 ± 2 mg/kg body weight/day
Combination therapy (in trials)

Ursodeoxycholic acid + budesonide 3 x 3 mg/day
Ursodeoxycholic acid + prednisone 10 mg/day

+ azathioprine 100 mg/day
End stage
Liver transplantation
254
5[ORVQOUƂPFKPIUCPFVTGCVOGPVQRVKQPU
PBC and PSC
Treatment options PSC

Basic drug therapy
Ursodeoxycholic acid* 15–20 mg/kg body weight/day
Inflammatory flares
Antibiotics, if necessary
Interventions on the bile duct

Endoscopic dilatation of competent stenoses
End stage
Liver transplantation
* Ursodeoxycholic acid is not approved for the treatment of PSC.
[Bowlus CL & Gershwin ME Autoimmun Rev. 2014; 13: 441–4]

[Yimam KK & Bowlus CL Autoimmun Rev. 2014; 13: 445–50]
255
Biliary Diseases
Gallbladder polyps
Gallbladder Polyps
Polyp on ultrasound
10 – 5–
> 2 cm < 5 mm
20 mm 10 mm
laparo-
«extended»
scopic asympto- sympto- asympto-
cholecy-
cholecy- matic matic* matic
stectomy
stectomy
no repeat
gallstones
gallstones ultrasound at
6 and 12
months
repeat
ultrasound at
6 and 12 increased
stable
months in size
increase reassure
stable
in size
repeat
ultrasound cholecy-
every stectomy
12 months
* Symptoms: Biliary type pain, common duct obstruction, cholangitis, or recurrent

pancreatitis. Dyspepsia is not an indication for surgery.
256
Gallbladder polyps
Benign polyps
Cholesterol polyps 60%
Adenomyomas 25%
Inflammatory polyps 10%
Adenomas 4%
Miscellaneous 1%
Leiomyomas
Fibromas
Lipomas etc.
Malignant polyps
Adenocarcinoma 80%
Miscellaneous 20%
Mucinous cystadenomas
Squamous cell carcinoma
Adenocanthomas
257
Biliary Diseases
Choledocholithiasis
Predictors for choledocholithiasis:
Clinical predictor:
Very strong CBD stone in transabdominal ultrasound
Clinical ascending cholangitis
Bilirubin > 4 mg/dL or > 68 μmol/L
Strong Dilated CBD on ultrasound

(> 6 mm with gallbladder in situ)
Bilirubin level 1.8 - 4.0 mg/dL (= 31 – 68 μmol/L)
Moderate Abnormal liver biochemical test other than bilirubin

Age older than 55 years
Clinical gallstone pancreatitis
[Maple JT et al.: Gastrointest Endosc 2010]
Likelihood of choledocholithiasis:
Likelihood: Management:
High: Presence of any very strong Preoperative ERCP
predictor or both strong
predictors
Intermediate: All other patients Preoperative EUS or

MRCP or laparoscopic
ultrasound
Low: No predictors present Laparoscopic chole-

cystectomy without
cholangiography
[Maple JT et al.: Gastrointest Endosc 2010]
258
Choledochal cysts
Todani classification of bile duct cysts
Normal Type I Type II
Type III Type IV Type V

Choledochal cysts
[www.radiopaedia.org, Dr. Frank Gaillard]
259
Pancreas
Pancreas cysts
Pancreas cysts
Serous cystadenoma Cystic endocrine neoplasm
Usually found incidentally but May have clinical features of solid

can cause abdominal pain pancreatic endocrine neoplasm
and a palpable mass if large
Microcystic with a Unilocular cyst occupies most
«honeycomb» appearance; of neoplasm
rarely has a macrocystic com-
ponent; central calcification
Thin, clear to zero sanginous Thin, clear
Cuboidal epithelium that Monomorphic endocrine tumor cells;
stains positive for glycogen stains positive for chromagranin and
synaptophysin
Almost none (rare reports) Yes

[Catalano et al. Gastrointest Endosc. 2009]
260
Solid pseudopapillary Ductal adenocarcinoma
neoplasm with cystic degeneration
Usually found incidentally; rarely Presents with painless
causes abdominal discomfort jaundice, abdominal/back
pain or rarely pancreatitis
Solid and cystic components Primarily solid mass with
cystic spaces
Bloody + necrotic debris Bloody ± debris

Monomorphic cells with round nuclei Malignant adenocarcinoma
and eosinophilic or foamy cytoplasm; may be seen, but varying de-
stains positive for vimentin and grees of atypia may be present
Į-1-antitrypsin in the specimen
Yes Already present
261
Pancreas
Pancreas cysts
Pancreatic cystic neoplasia and pancreatic pseudocysts
Intraductal papillary Mucinous cystic

mucinous neoplasia neoplasia (MCN)
(IPMN)
- main duct (MD)-IPMN
- branch duct (BD)-IPMN
- mixed type IPMN
Gender predominance ~55% female >95% female

Age (decade) 6.–7. 4.–5.
Symptoms Common when large ~50%
(pancreatitis)
Location (%body/tail) 30% (70% head!) 95%
Common capsule No Yes
Calcification No Rare, curvilinear in the
cyst wall
Gross appearance Grape-like Orange-like
Multifocality Yes No
Internal structure Cyst by cyst Cysts in cyst
Main pancreatic duct Normal, or dilated to >5 Normal or deviated

mm, suggesting MD-IPMN
or combined type
Communication to main Always (though not always Infrequent
pancreatic duct demonstrable)
Malignant / >40(-50)% / 31% 30–50% / <15%
invasive Carcinoma MD-IPMN: >62% / 44% no malignancy in MCNs
BD-IPMN: >24% / 17% of <4 cm without
Mixed type: >58% / 45% mural nodules
«String sign» Pos. Pos.
CEA (in cystic fluid) >192-200 Æ mucinous* >192-200 Æ mucinous*
<OHNM>
Amylase (in cystic fluid) High (i.e. 300) Low (i.e. <100)***
N/A not applicable

* distinguishes with an accuracy of ~80% mucinous from nonmucinous cysts, but not
benign from malignant cysts
** does not exclude a mucinous cyst
*** may also exhibit elevated amylase levels
[Ref.: International consensus guidelines 2012 for the management of IPMN and
MCN of the pancreas; Tanaka M et al., Pancreatology 2012; 12(3):183-97]
262
Solid papillary neoplasia Serous cystic Pseudocyst
(«young women») neoplasia (SCN)
- polycystic SCN
- honeycomb SCN
- oligocystic SCN
- microcystic SCN
- macrocystic SCN
87% female ~70% female <25% female (>75% male)
3. 6.–7. 4.–5.
Rarely ~50% Nearly always
(pancreatitis)
50% 65%
Yes N/A
30–40%, central No
round, well-demarcated, Spongy or Variable

with solid and cystic honeycomb-like
areas with hemorrhage
No Rare
Microcystic and/or Unilocular
macrocystic
No Normal or deviated Normal or irregularly dila-
ted, may contain stones
No No Common
Rarely (10%) Rarely (< 5%) 0
Neg. Neg.
<192 Æ non-mucinous** <192 Æ non-mucinous**
DD BD-IPMN
Low (i.e. <100) High (i.e. 300)
263
Pancreas
Pancreas cysts
Main duct (MD), Branch duct (BD) and mixed type

intraductal papillary mucinous neoplasia (IPMN):
Definitions
MD-IPMN
r TFHNFOUBMPSEJGGVTFEJMBUJPOPGUIFNBJOQBODSFBUJDEVDU .1%

of >5 mm without other causes of obstruction.
r .1%EJMBUJPOPGmNNjXPSSJTPNFGFBUVSFv
r .1%EJBNFUFSPGöNNjIJHISJTLTUJHNBUBv
BD-IPMN
r 1BODSFBUJDDZTUTPGNNJOEJBNFUFSUIBUDPNNVOJDBUFXJUIUIF
MPD DD pseudocyst (PC) for patients with a prior history of
pancreatitis.
Reliable distinguishing features of BD-IPMN:

r NVMUJQMJDJUZBOE
r WJTVBMJ[BUJPOPGBDPOOFDUJPOUPUIF.1% BMUIPVHITVDIB
connection is not always observed.
Mixed type
r DSJUFSJBNFUGPSCPUI.%*1./BOE#%*1./
[International consensus guidelines 2012 for the management of IPMN and MCN of
the pancreas; Tanaka M et al., Pancreatology 2012; 12(3):183-97]
264
Acute pancreatitis
Ranson’s Criteria
At admission or diagnosis
Age > 55 years
WBC >16,000/mm3
Blood glucose >200 mg/dL
Lactate dehydrogenase >350 IU/L
AST > 250 IU/L
Within 48 hours after presentation

Hematocrit decrease >10%
Blood urea nitrogen increase >5 mg/dL
Serum calcium < 8 mg/dL
Base deficit > 4 mEq/L
Fluid sequestration > 6 L
PaO2 < 60 mmHg
Scoring 1 point for each criterion

r m.JME
r m.PEFSBUF NPSUBMJUZm
r m4FWFSF NPSUBMJUZ
[Ranson JH. Etiological and prognostic factors in human acute pancreatitis:
a review. Am J Gastroenterol. 1982]
265
Pancreas
Acute pancreatitis
APACHE II Scale
Diagnosis:
Equation includes these factors: age, rectal temperature, mean
arterial pressure, heart rate, PaO2, arterial pH, serum potassium,
sodium, creatinine, hematocrit, WBC count, Glasgow coma scale
score, chronic health status
Scoring calculation available at http://www.mdcalc.com/
apache-ii-score-for-icu-mortality/ (accessed May 2012)
[Larvin M. et al. APACHE-II score for assessment and monitoring
of acute pancreatitis. Lancet 1989]
CT Severity Index (Balthazar Score)

Grade of pancreatitis on CT
A Normal pancreas (0 points)
B Pancreatic enlargement (1 point)
C Pancreatic enlargement with peripancreatic inflammation (2 points)
D Extrapancreatic changes plus 1 fluid collection (3 points)
E More than 1 fluid collection (4 points)
[Balthazar E, Robinson D, Megibow A, Ranson J. Acute pancreatitis: value
of CT in establishing prognosis. Radiology. 1990]
266
Acute pancreatitis
Factors causing acute pancreatitis

Toxic Infectious
Alcohol Viral
Scorpion toxin Mycoplasms
Worms
Metabolic
Hypertriglyceridemia Vascular
Hypercalcemia Circulatory shock
Hyperuricemia Ischemia-reperfusion
Celiac disease Embolic
Hypothermia
Drugs (with best proof) Malignant hyperthermia
Azathioprine Autoimmune vasculitis
Sulfonamides
Thiazides Hereditary
Furosemide SPINK1
Pentamidine PRSS1
Didanosine CFTR
Methyldopa [Adapted from Waldthaler A et al., Dig Dis. 2010]
Tetracycline
Estrogens
Valproic acid
Sulindac
6-mercaptopurine
5-aminosalicylic acid
L-asparaginase
Mechanical
Gallstones
Neoplastic process
Periampullary diverticulum
Sphincter of Oddi dysfunction
Blunt abdominal trauma
After abdominal operation
Post endoscopic retrograde
cholangiopancreatography
267
Pancreas
Increase of Amylase and Lipase
Causes of Increased Amylase and Lipase Levels

Amylase Lipase
Acute pancreatitis Acute pancreatitis
Diseases that might mimic

acute pancreatitis
Pancreatic pseudocyst Pancreatic pseudocyst
Chronic pancreatitis Chronic pancreatitis
Pancreatic carcinoma Pancreatic carcinoma
Biliary tract disease Biliary tract disease
(cholecystitis, cholangitis, (cholecystitis, cholangitis,
choledocholithiasis) choledocholithiasis)
Intestinal obstruction, Intestinal obstruction,
pseudo-obstruction, ischemia, pseudo-obstruction, ischemia,
or perforation or perforation
Acute appendicitis Acute appendicitis
Ectopic pregnancy
Other disorders
Renal failure Renal failure
Parotitis Treatment with heparin
Macroamylasemia
Ovarian cyst or cystic neoplasm
Carcinoma of the lung
Diabetic ketoacidosis
Human immunodeficiency
virus infection
Head trauma with intracranial
bleeding
[Adapted from AGA Institute Technical Review on Acute Pancreatitis.
Gastro 2007]
268
269
Pancreas
Chronic pancreatitis
Chronic Pancreatitis
Definition
Chronic pancreatitis is a progressive inflammatory disorder
in which pancreatic secretory parenchyma is destroyed and
replaced by fibrous tissue (large duct vs small duct disease)
Causes (TIGAR-O classification,
in increasing order of prevalence)
r5PYJD.FUBCPMJD BMDPIPM TNPLJOH IZQFSDBMDFNJB
hyperparathyroidism, hyperlipidemia
r*EJPQBUIJD FBSMZPSMBUFPOTFU USPQJDBMQBODSFBUJUJT
r(FOFUJD $'53134441*/,NVUBUJPOT
r"VUPJNNVOF
r3FDVSSFOUBDVUFQBODSFBUJUJT
r0CTUSVDUJPO DBODFS EVDUPCTUSVDUJPO QBODSFBT
divisum
r*OGFDUJPVT )*7 NVNQTWJSVT DPYTBDLJFWJSVT
echinococcus
r.JTDFMMBOFPVT HBMMTUPOFT BGUFSUSBOTQMBOU
after irradiation
90-95% of patients have alcoholic or idiopathic disease
Clinical Features
r"CEPNJOBMQBJOBDVUFPSDISPOJD
r&OEPDSJOFQBODSFBUJDJOTVGGJDJFODZEJBCFUFTNFMMJUVT
r&YPDSJOFQBODSFBUJDJOTVGGJDJFODZEJBSSIFB TUFBUPSSIFB
weight loss, malabsorption (vitamin deficiency, osteoporosis)
r1PTTJCMFTJHOTPGMPDBMDPNQMJDBUJPOTQTFVEPDZTUT
obstruction of adjacent organs, vascular thrombosis
Diagnosis
r$PNCJOBUJPOPGQBODSFBUJDGVODUJPOUFTUBOEJNBHJOH
tests (goldstandard of histology is rarely available)
r'VODUJPOBMUFTUTGPSFYPDSJOFQBODSFBUJDJOTVGGJDJFODZ
− Fecal elastase in the stool: <200 μg/g
− Secretin test: endoscopic collection of pancreatic juice
and analysis of bicarbonate concentration after stimulation
with secretin
r*NBHJOHUFTUT
− Modalities: CT, (secretin-enhanced) MRI/MRCP, EUS
− characteristic findings: atrophy, dilated/irregular pancreatic
duct, calcifications, pseudocysts
Management
r1BJO
− With signs of obstruction (dilated pancreatic duct ≥6mm):
r relieve obstruction: ERCP with stricture dilation/stenting,
270
Chronic Pancreatitis
sphincterotomy, stone extraction, lithotripsy, surgery (lateral
pancraeticojejunostomy (modified Puestow operation),
duodenum-preserving pancreatic head resection
(Frey operation), Whipple operation).
− No signs of obstruction:
r alcohol/smoking abstinence, analgesics (opioids), pain
modulators (tricyclic antidepressants, SSRI, gabapento-
ids), pancreatic enzymes, nerve block or neurolysis
r&YPDSJOF*OTVGGJDJFODZ
− 2000 IU lipase per gram of fat ➔ 20’000-40’000 IU for a main
meal and 10’000 IU for a snack (max. dose of lipase per day
A*6QFSLHPGCPEZXFJHIU
− split the lipase dose: before/during/after the meal

− adjust the enzyme dose based on its effects (steatorrhea,
body weight, levels of fat-soluble vitamins)
− consider adding a PPI if inefficient (although most lipase
preparations are acid resistant)
− supplementation of fat-soluble vitamins (vitamin D/E/K/A)
r&OEPDSJOF*OTVGGJDJFODZ
− Cave: patients are prone to treatment-induced hypoglycemia
− simple insulin regimens
Autoimmune Pancreatitis
rmPGDBTFTPGDISPOJDQBODSFBUJUJT
r5ZQFQBSUPGBNVMUJTZTUFNBVUPJNNVOFEJTFBTF
(IgG4-pos.), Type 2: affects pancreas alone
r4ZNQUPNTPCTUSVDUJWFKBVOEJDF EJBCFUFT MFTTQSPOPVODFE
abdominal pain
r%JBHOPTJT
− laboratory analysis: ½ IgG (predominanantly IgG4, only
elevated in Type 1), ANA
− CT/MRI/MRCP: characteristic diffusely enlarged pancreas
(«sausage-shaped»)
− ERCP: long or multiple strictures in the distal bile duct or
sclerosing cholangitis
− improvement on a trial of steroids
− goldstandard: histology
r5SFBUNFOU
− Prednisolone 30-40 mg per day: tapering over 3 months
while monitoring symptoms, serum IgG and imaging fin
dings, followed by maintenance dose of 5-7.5 mg per day
[Quellen: Management of Chronic Pancreatitis. Forsmark. Gastroenterology 2013;

144: 1282-1291.Chronic pancreatitis. Braganza. Lancet 2011; 377: 1184-97]
271
Pancreas
Score
HLA DR3 or DR4 +1
Immune disease Thyreoiditis, colitis, others +2
Other markers Anti SLA, anti-actin, anti-LC1, +2
pANCA
Histological Interface hepatitis +3
features Plasmacytic +1
Rosettes +1
None of above -5
Biliary changes -3
Other features -3
Treatment Complete +2
response Relapse +3
Pretreament Definite diagnosis >15
aggregate score Probable diagnosis 10 – 15
Posttreament Definite diagnosis >17
aggregate score Probable diagnosis 12 – 17
[Modified from: AASLD Practice Guidelines: Diagnosis and Management of Autoim-
mune Hepatitis. Manns et al.,Hepatology 2010]
272
273
Oncology
Tumor staging
Are any of the following high-risk stigmata of

malignancy present?
i) obstructive jaundice in a patient with cystic
lesion of the head of the pancreas
ii) enhancing solid component within cyst,
iii) main pancreatic duct >10 mm in size
Yes No
Consider Are any of the following wor-
surgery, risome features present?
if clinically Clinical: Pancreatitis*
appropriate Imaging: i) cyst ≥3 cm ii) thik-
kened/enhancing cyst walls
iii) main duct size 5-9 mm, iii)
non-enhancing mural nodule
iv) abrupt change in caliber
of pancreatic duct with distal
pancreatic atrophy
Yes No
Perform EUS: What is the
Are any of these size of
features present? largest cyst?
i) Definite mural nodule(s)**
Yes ii) Main duct features No
suspicious for involvement***
iii) Cytology: suspicious
or positive for malignancy Inconclusive
<1 cm 1–2 cm 2–3 cm >3 cm

CT/MRI
EUS in 3–6 Close surveil-
yearly x2 years,
then lengthen
months, then lance every
CT/MRI
interval if no
lengthen interval 3–6 months
CT/MRI change x 2
yearly alternating MRI alternating
in years, then with EUS. MRI with EUS.
2–3 years lengthen Consider surgery Strongly
interval if in young, fit consider
no change patients with need surgery in
for prolonged young,
surveillance fit patients
274
* Pancreatitis may be an indication for surgery for relief of symptoms.
** Differential diagnosis includes mucin, which can
- move with change in patient position,
- may be dislodged on cyst lavage and
- does not have Doppler flow.
Features of true tumor nodule include
- lack of mobility,
- presence of Doppler flow and
- FNA of nodule showing tumor tissue
*** Presence of any one of - thickened walls,
- intraductal mucin or - mural nodules
is suggestive of main duct involvement. In their absence main duct
involvement is incolclusive.
275
Oncology
Tumor staging
-cancer Tumor- CT Thorax/ MRI EUS PET-CT

marker Abdomen
Esophageal- x x x
Gastric - CA72-4 x x x
Colon- CEA x
Rectum- CEA x X Pelvis x
Anal- x x
Pancreatic- CA 19-9 x x x
Cholangio- CA 19-9 x MRCP x
GIST x x
NET Chromo- x Ga-
granin A Dotatoc
Gastro- x x
intestinal
Lymphoma
276
Esophageal Cancer
Primary tumor (T)

T1 Tumor invades lamina propria, muscularis mucosae,
or submucosa
T1a Tumor invades lamina propria or muscularis mucosae
T1b Tumor invades submucosa
T2 Tumor invades muscularis propria
T3 Tumor invades adventitia
T4 Tumor invades adjacent structures
T4a Resectable tumor invading pleura, pericardium,
or diaphragm
T4b Unresectable tumor invading other adjacent structures,
such as aorta, vertebral body, trachea, etc.
Esophageal cancer
T1a uT1b-2 N0 T1b N+ T4b N0/+ T3-4a N0/+
EMR/ Surgery distal Ca proximal ChemoRx Definitive

ESD Ca Squamous-Ca ChemoRx
and Adeno Ca
ChemoRx
if resectable tumor
Surgery
277
Oncology
Esophageal Cancer
Esophageal cancer
After R0 Resection without ChemoRx
Nodal negative Nodal positive
Squamous- Squamous-Ca
Age Ca Adeno-Ca Adeno-Ca Age
pT1-T2 Observe
pT3-4 ChemoRx
Structure Endosonographic view
Epithelium
Lamina propria 1st layer
Muscularis mucosae 2nd layer
Submucosa 3rd layer
Muscularis propria 4th layer
Adventitia 5th layer
Adjacent viscera
278
Esophageal Cancer
Esophageal cancer uT1
279
Oncology
Esophageal Cancer
280
Esophageal Cancer
Siewert classification of adenocarcinoma

of the esophagogastric junction (AEG)
Type I: Type II:

Adenocarcinoma of the True carcinoma of the
distal esophagus with cardia. Tumor center
tumor center more than between 1 cm above to
1 cm above the endo- 2 cm below cardia. Arising
scopic cardia (Z-line). from cardiac epithelium
Generally originates from or a short segment with
Barrett’s metaplasia. intestinal metaplasia.
Type III:
Subcardial gastric carcinoma
infiltrating the cardia ± distal
cm esophagus from below (tumor
center 2 – 5 cm below cardia)
5
{ 1
AEG I adenocarcinoma of the distal esophagus
AEG II cardia carcinoma
{ 0
2
AEG III subcardiac gastric cancer
{
5
[Adapted from HJ Stein, M Feith, JR Siewert. Cancer of the esophagogastric junction.

Surgical Oncology 9 2000]
281
Oncology
Esophageal Cancer
Esophageal cancer – SIEWERT I
Tumor extension Distance from Z-Line
Esophageal cancer – SIEWERT II
Antegrade Retroflexion
Extension above Z-Line Extension below Z-Line
282
Esophageal Cancer
Esophageal cancer – SIEWERT III
Antegrade Retroflexion
283
Oncology
Early Gastric Cancer
Criteria for curative endoscopic resection

in early gastric cancer
Mucosal cancer Submucosal cancer
No ulcer Ulcer present Sm1 Sm2
(< 500 um) (> 500 um)
Size (mm) < 20 > 20 < 30 > 30 < 30 Any size
Differen- EMR ESD ESD Surgery ESD Surgery
tiated
cancer
Undiffe- Surgery Surgery Surgery Surgery Surgery Surgery
rentiated considered
cancer
[EMR: endoscopic mucosal resection; ESD: endoscopic submucosal dissection;

Sm1: submucosal layer 1; Sm2: submucosal layer 2]
284
Gastric Cancer
Medically fit patients
Neoadjuvant treatment Adjuvant treatment
pTis or pT1a EMR/ ESR Surveillance
cT1b N0 M0 Surgery
cT2 N0 M0 (Radio-/) (Radio-/)
Chemotherapy + Surgery Chemotherapy
cTx Nx M1 Herceptin Clinical FU
(Her2-positive) + Chemo
or best-supportive-care
Medically unfit patients

Treatment Follow up
pTis or pT1a EMR/ ESR Surveillance
cTx Nx M0 Radio-/Chemo or Herceptin Clinical FU
(Her2-positive) + Chemo +
pTx Nx M1 Herceptin (Her2-positive) Clinical FU
285
Oncology
Colon Cancer
Operation Adjuvant treatment

T1 N0 M0 Endoscopic resection* observe
pT1-3 pN0 M0 Surgery observe
pT 4 pNx M0 Surgery Chemo
T1-3 pN1 M0 Surgery Chemo
Tx Nx M1 Metachrone or synchrone Chemo (+ optional
surgery: primary tumor Neoadjuvant)
+ metastasis
* pT1 pN0 + risk features (R1, L1, G3): secondary surgery
286
Rectum Cancer
Neoadjuvant Operation Adjuvant

treatment treatment
uT1 N0 no EMD/ESD* observe
T1-2 N0 M0 no Transanal / LAR observe
T3 N0 M0 no LAR observe
T1-4 N+ M0 Radio-/Chemo LAR observe
T4 Nx M0 Radio-/Chemo LAR observe
Tx Nx M1 Radio-/Chemo Metachrone or Chemo
synchrone
surgery:
primary tumor +
metastasis
LAR: Low anterior Resection
*pT1 pN0 + risk features (R1, L1, G3): secondary LAR
287
Oncology
Anal Cancer
Primary tumor (T)

T1 Tumor diameter ≤ 2 cm
T2 Tumor diameter ≥ 2 cm-≤ 5 cm
T3 Tumor diameter ≥ 5 cm
T4 Tumor invades adjacent structures
Lymph node (N)

N0 No Lymph Nodes
N1 Perirectal Lymph Nodes
N2 Para iliacal and/or inguinal unilateral
N3 Para iliacal and inguinal and/or parailiacal /inguinal bilateral
Anal cancer – Follow-up

Intervall Local examination Endoscopy EUS
(months) (anal, inguinal) (flexible RS)
3 +
6 + + +
9 +
12 + + +
18 + + +
24 + + +
30 + + +
36 + + +
48 + + +
60 + + +
288
Anal Cancer
Anal Cancer
Analborder Carcinoma Anal canal Carcinoma
uT1N0 > T1 Any T
Local Excision Radio/Chemo
Complete Partial
pT1N0G1 Remission Remission
R1: Surgery or Abdomino perineale

observe
Radiochemo Rectumexstirpation
289
Oncology
Pancreatic Cancer
Not resectable in curative intention

Tumor Lymphnodes Metastasis
Encasement Any Lymph node Distant Metastasis
of vessels metastasis
Resectable Not resectable
Palliative Stenting Palliative Pain

Whipple procedure
if jaundice treatment
R1 R0 Palliative Chemo
Adjuvant Chemo Gastric outlet obstruction
Stenting or
Gastroenterostomy
290
291
Oncology
Cholangiocarcinoma Diagnosis
Painless Jaundice
CT: bile duct dilatation with/without associated mass
ERCP with IgG4 positive

cytology brushing
Cytology negative
Cytology positve
No mass
no distant Repeat studies

metastasis in 3 months
Operation depending Trial of corticosteroid

on location therapy
292
Cholangiocarcinoma
Resectable Not resectable
Operation depending on location Livertrans- Palliative

plantation in Stenting if
selected cases jaundice
R1 R0
Palliative Chemo
Optional
observe
adjuvant Chemo
293
Oncology
Gallblader Cancer
Treatment
r5B $IPMFDZTUFDUPNZ àWFZFBSTVSWJWBMSBUF
r5C $IPMFDZTUFDUPNZ àWFZFBSTVSWJWBMSBUFm

± segmental resection
IVb und V, N1 LK- resection
r5 $IPMFDZTUFDUPNZTFHNFOUBMSFTFDUJPO*7CVOE7 /
LK- resection (five-year survival rate 50–100%)
r5 4VSHFSZPOMZJG3QPTTJCMF
Hepatectomy + pancreaticoduodenectomy
(five-year survival rate 0–30%)
Overall five-year survival rate approx. 60%. TNM-Stage >T1bN0:

adjuvant combined radiation and chemotherapy has a survival benefit.
294
Neuroendocrine Cancer
Suspected Histology
Biochemical
NET differentiation,
profile:
grade,
Chromogranin A
chromogranin,
24 h urinary 5 HIAA
synaptophysin,
calcium CT Thorax/
Ki67
Abdomen
If negative:
Tumor resection
or biopsy
Consider familial:
MEN-1, VHL, NF Consider PET Scan: Ga DotaToc
nomenclature mitosis Ki-67/MIB-1

(10 HPF) index (%)
NET Grade 1 (G1-NET) = carcinoid <2 ≤2
NET Grade 2 (G2-NET) 2–20 3–20
NEC (G3-NET), large-/small cell >20 >20
295
Oncology
Gastro-intestinal-Stroma Tumor (GIST)
Tumor Risk for progressive disease %

parameter based on site of origin
Mitotic rate Size Stomach Jejunum/ Duodenum Rectum
Per 50 HPF Ileum
≤5 ≤2 None (0%) None (0%) None (0%) None (0%)
>2-<5 - Very low Low Low Low
(1.9%) (4.3%) (8.3%) (8.5%)
> 5 - ≤ 10 Low Moderate Nk Nk
> 10 Moderate High (52%) High (34%) High (54%)
>5 ≤2 None High Nk High
>2-<5 - Moderate High High High
> 5 - ≤ 10 High High Nk Nk
> 10 High High High High
WHO classification of gastroenteropancreatic

endocrine tumors
Site Well differentiated endocrine Well differentiated endocrine
tumor (benign behavior) tumor (Uncertain behavior)
Pancreas Confined to pancreas <2 cm Confined to pancreas <2 cm
<2 mitoses per 10 HPF >2 mitoses per 10 HPF

<2% Ki-67 positive cells, no >2% Ki-67 positive cells or
vascular invasion vascular invasion
Stomach Confined to mucosa- Confined to mucosa-

submucosa submucosa
<1 cm, no vascular invasion >1 cm or vascular invasion
Duodenum, Confined to mucosa- Confined to mucosa-
upper submucosa submucosa
jejunum <1 cm, no vascular invasion >1 cm or vascular invasion
Ileum, Confined to mucosa- Confined to mucosa-
Colon, submucosa submucosa
Rectum <1 cm (small intestine) >1 cm (small intestine)
Appendix Non-functioning Enteroglucagon-producing
Confined to appendiceal wall Confined to subserosa
<2 cm, no vascular invasion >2 cm or vascular invasion
296
Well differentiated endocrine Poorly differentiated endocrine
carcinoma (Low grade malignant) carcinoma (High grade malignant)
Well to moderately differentiated Small cell carcinoma
Gross local invasion and/or Necrosis common
metastases
Mitotic rate often higher >10 mitoses per 10 HPF
(2-10 per 10 HPF) >15% Ki-67 positive cells
Ki-67 index >5% Prominent vascular and/or
perineural invasion
Invasion to muscularis propria
or beyond or metastases
Invasion to mesoappendix or
beyond or metastases
297
Oncology
Intestinal Lymphoma
Stadium systems of primary intestinal Lymphoma

Ann-Arbor- Lugano- TNM- Lymphoma
System System Classification Location
E*I1 I1 T1N0M0 Mucosa, Submucosa
EI 2 I2 T2N0M0 Muscularis propria,
Subserosa
EI 2 I2 T3N0M0 Serosa penetration
EI 2 IIE** T4N0M0 Continous infiltration
of adjectant organs or
tissue
EII 1 II1E T1-4N1M0 Infiltration regional
Lymph nodes
E II 2 II 2E T1-4N2M0 Infiltration other than
regional Lymph nodes
including mesenteric,
paraortal or
retroperitoneal
III - T1-4N3M0 Infiltration of Lymph
nodes on both sides
of the diaphragma
IV IV T1-4N0-3M1 Generalisation of the
Lymphoma
* E= primary extranodal localisation

** E= continuous, through the stomach infiltration in other tissue
298
299
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Essentials in

Stephan Vavricka Reviewed by:

FALK FOUNDATION e.V.

CHILD PUGH score 209

Stable vital signs for at least 1 hour

Quality Indicators for Screening Colonoscopy:

[Schrag SP et al., J Gastrointestin Liver Dis 2007; 16 (4): 407-418]

Attention should be paid to these possible risk factors:

Cardiopulmonary complications may occur in 0.9% of colonoscopic

Absolute and relative contraindications of PEG:

Chromoendoscopy for screening

Larger 2 Ampullas 50 ml of 0.1% 50 ml of 0.1 %

60 to 100 ml solution are needed for the whole colon

[Kiesslich R, Neurath M.; Gastroenterol Clin North Am. 2012 Jun;41(2):291-302]

Bleeding Intervention: Continue Continue Continue

[Boustiere C et al.: Endoscopy 2011 and www.sggssg.ch]

[Boustiere C et al.: Endoscopy 2011 43(5): 445–461]

Dabigatran 1.8 % / year High risk intervention*: 24 h–72 h**

Apixaban 0.8 % / year CAVE creatinine

Prasugrel 7—10 days 24 h–72 h**

* assuming normal renal function

Plastic stents are not used anymore.

r #SFBUIJOHNBOFVWFST 7BMTBMWBNBOFVWFS CSFBUIIPMET

- Stimulation of soft palate, Uvula

Baclofen 3 x 5–20 mg p.o.

Reﬂux esophagitis: Los Angeles

Grade A Grade B Grade C Grade D

Reﬂux esophagitis: Savary-Miller

Grade I Grade II Grade III Grade IV Grade V

Reﬂux esophagitis: MUSE

Stage Metaplasia Ulcer Stricture Erosions

[Sharma P. Gastroenterology 2006;131:1392–1399]

GERD A presumptive diagnosis of GERD

SI= Symptom Index

SAP=Symptom Association Probability

Reﬂux symptoms refractory to PPI

Algorithm for management of patients

Failure of PPIs twice daily

Functional Hyper- NERD Positive Negative

Pain - TLOSR inhibitors Pain

Important facts to remember:

r 4XBMMPXFEUPQJDBMTUFSPJETBTst line therapy:

EoE Treatment Algorithm 2013

Swallowed topical steroid (syrup or powder)

Swallowed topical steroid 1FSTJTUFOUJOáBNNBUJPO

[Straumann A. et al. NATURE Review 2012]

Include into study

White exudates, edema Pinpoint-shaped white exudates

Linear furrows (railroad track), Concentric rings (trachealization)

Prescription for a budesonide syrup for the pharmacist:

Application technique for Eosinophilic Esophagitis

1. Force the red cover apart

2. With a screwdriver, crack the orange container open

3. Take out the blister with the

4. Pull blister open and position powder

[Courtesy of Prof. A. Straumann]

Eosinophilic gastroenteritis (EGE)

Treatment (based on case reports and small case series):

Classiﬁcation of Eosinophilic Gastrointestinal

Conventional manometry – per swallow analysis

Lower esophageal sphincter (LES)

Conventional manometry – per swallow analysis

Upper esophageal sphincter (UES)

r 4XBMMPXFEUPQJDBMTUFSPJETBTst line therapy: