gastroenterology laboratory diagnostics & cases...

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Seminar Seminar Medical Faculty Medical Faculty - - Pra Pra gue gue , , October October 20 20 14 14 GASTROENTEROLOG GASTROENTEROLOG Y Y LABORATORY LABORATORY DIAGNOSTI DIAGNOSTI CS & CASES CS & CASES MUDr.Petr Kocna CSc. http://www.lf1.cuni.cz/~kocna/pkweb1.htm MUDr.Petr Kocna CSc. MUDr.Petr Kocna CSc. http://www.lf1. http://www.lf1. cuni cuni . . cz cz /~ /~ kocna kocna /pkweb1. /pkweb1. htm htm

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Seminar Medical Faculty - Prague, October 2014SeminarSeminar Medical FacultyMedical Faculty -- PraPraguegue, , OctoberOctober 20201414

GASTROENTEROLOGYLABORATORY DIAGNOSTICS & CASES

GASTROENTEROLOGGASTROENTEROLOGYYLABORATORYLABORATORY DIAGNOSTIDIAGNOSTICS & CASESCS & CASES

MUDr.Petr Kocna CSc.http://www.lf1.cuni.cz/~kocna/pkweb1.htm

MUDr.Petr Kocna CSc.MUDr.Petr Kocna CSc.http://www.lf1.http://www.lf1.cunicuni..czcz/~/~kocnakocna/pkweb1./pkweb1.htmhtm

22

HELICOBACTER PYLORIPEPSINOGENS, GASTRITIS

COELIAC SCREENING - THERAPYCHRONIC PANCREATITIS

EXOCRINE PANCREATIC FUNCTIONQUANTITATIVE FIT

COLORECTAL CANCER SCREENING

HELICOBACTERHELICOBACTER PYLORIPYLORIPEPSINOGENPEPSINOGENSS, GASTRIT, GASTRITISIS

CCOOELIAELIACC SCREENING SCREENING -- TTHHERAPERAPYYCHRONIC PANCHRONIC PANCCREATITREATITISIS

EXOEXOCCRINRINEE PANPANCCREATREATIC FUNCTIONIC FUNCTIONQUQUANTITATIVANTITATIVEE FITFIT

CCOLOREOLORECCTTAAL L CANCER SCREENINGCANCER SCREENING

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

33

HELICOBACTER PYLORIPEPSINOGENS, GASTRITIS

COELIAC SCREENING - THERAPYCHRONIC PANCREATITIS

EXOCRINE PANCREATIC FUNCTIONQUANTITATIVE FIT

COLORECTAL CANCER SCREENING

HELICOBACTERHELICOBACTER PYLORIPYLORIPEPSINOGENPEPSINOGENSS, GASTRIT, GASTRITISIS

CCOOELIAELIACC SCREENING SCREENING -- TTHHERAPERAPYYCHRONIC PANCHRONIC PANCCREATITREATITISIS

EXOEXOCCRINRINEE PANPANCCREATREATIC FUNCTIONIC FUNCTIONQUQUANTITATIVANTITATIVEE FITFIT

CCOLOREOLORECCTTAAL L CANCER SCREENINGCANCER SCREENING

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

44

GASTRITIS - CARCINOMA SEQUENCESGASTRITGASTRITIS IS -- CCARCINOMARCINOMA SEQUENCESA SEQUENCES

Hp - IARC 19941.class cancerogen

HpHp -- IARC 1994IARC 19941.1.class cclass cancerogenancerogen

NORMAL MUCOSANORMAL MUCOSANORMAL MUCOSA

ATROPHIC GASTRITISATROPHIC GASTRITISATROPHIC GASTRITIS

INTESTINAL METAPLASIAINTESTINAL METAPLASIAINTESTINAL METAPLASIA

GASTRIC CANCERGASTRIC CANCERGASTRIC CANCER

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

55

Male - J.N. - IT specialist - born 1978in childhood common childhood diseases,

none of injury, none of hospitalization, parents in healthy,severe disease in the family - who do not know.Now does not have any subjective complainrts.

MaleMale -- J.N. J.N. -- ITIT specialisspecialistt -- born born 19719788in childhood common childhood diseasesin childhood common childhood diseases,,

none of injury, none of hospitalizationnone of injury, none of hospitalization,, parents in healthyparents in healthy,,severe disease in the family severe disease in the family -- who do not knowwho do not know..Now does not have any subjective complainrts.Now does not have any subjective complainrts.

CASE: 12-01CASECASE:: 1212--0101

Comes to LG laboratories with requirement for Hp test - UBTComes to LG laboratories with requirement for Hp test Comes to LG laboratories with requirement for Hp test -- UBTUBT

On the internet he found - Hp is cancerogen of the 1.classOn theOn the internetinternet he foundhe found -- HpHp isis ccancerogenancerogen of the of the 11..classclass

On the internet he found - LG laboratory, non-invasive Hp testOn theOn the internetinternet he foundhe found -- LGLG laboratolaboratory, nonry, non--invainvassivivee Hp Hp testtest

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

66

13C-UBT performed on the individual wish (self-paying)Value of 13C DOB – 14.1 ‰, Hp - positive

( Normal values up to DOB 5 ‰ )

1313CC--UBTUBT performed on the individual wish (selfperformed on the individual wish (self--paying)paying)Value of Value of 1313C DOB C DOB –– 14.1 ‰, 14.1 ‰, HpHp -- popossitivitivee

( ( NormNormaall values up to values up to DOB DOB 55 ‰ )‰ )

Comes to GE ambulance with requirement foreradication therapy, which the alone cannot pay

Comes toComes to GE ambulance GE ambulance with requirement forwith requirement foreradieradication cation tthheraperapyy,, which the alone cannot paywhich the alone cannot pay

On the internet he found - suitable eradication therapyOn theOn the internetinternet he foundhe found -- suitablesuitable eeradiradiccaation therapytion therapy

CASE: 12-01 - laboratory dataCASECASE:: 1212--01 01 -- laboratorlaboratoryy datadata

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

European Helicobacter Pylori Study GroupCurrent Concepts in the Management of

Helicobacter pylori InfectionThe Maastricht 2-2000 Consensus Report

September 2000

European Helicobacter PyloriEuropean Helicobacter Pylori StudyStudy GroupGroupCurrent Concepts in theCurrent Concepts in the Management ofManagement of

Helicobacter pylori InfectionHelicobacter pylori InfectionTheThe Maastricht 2Maastricht 2--20002000 ConsensusConsensus ReportReport

SeptemberSeptember 20002000

77

WHO TO TREAT - STRONGLY RECOMMENDED INDICATIONSWHO TO TREAT WHO TO TREAT -- STRONGLY RECOMMENDED INDICATIONSSTRONGLY RECOMMENDED INDICATIONS

DU/GU (active or not, including complicated PUD) 1

MALToma 2

Atrophic gastritis 2

Post-gastric cancer resection 3

Patients - first degree relatives of gastric cancer patients 3

Patients wishes (after full consultation with their physician) 4

DUDU//GUGU ((active oractive or not,not, including complicatedincluding complicated PUD)PUD) 11

MALTomaMALToma 22

AtrophicAtrophic gastritisgastritis 22

PostPost--gastric cancer resectiongastric cancer resection 33

PatientsPatients -- first degree relatives of gastric cancer patientsfirst degree relatives of gastric cancer patients 33

Patients wishesPatients wishes ((after full consultation with their physicianafter full consultation with their physician)) 44

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

HCl HCl

88

HOW TO PREDICT RESULT of Hp INFECTIONHOW TO PREDICT RESULT of Hp INFECTIONHOW TO PREDICT RESULT of Hp INFECTION

HCl HCl

GASTRIN ↑GASTRIN GASTRIN ↑↑ GASTRIN ↑GASTRIN GASTRIN ↑↑

ATROPHYCANCER

ATROATROPHYPHYCANCERCANCER

DUODENALULCER

DUODENDUODENAALLULCERULCER

NODISEASE

NONODISEASEDISEASE

BACTERIAL TRIBE - GENETIC DISPOSITION - ENVIRONMENT - DIETS ?BACTERIAL TRIBE BACTERIAL TRIBE -- GENETIC DISPOSITIONGENETIC DISPOSITION -- ENVIRONMENT ENVIRONMENT -- DIETS ?DIETS ?

H.Pylori + hostH.H.PyloriPylori + + hosthost

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

99

Suspected - Gastritis - Hp infection - Gastric-cancer Suspected Suspected -- Gastritis Gastritis -- HpHp infecinfection tion -- GastricGastric--cancer cancer

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

negative Hp,normal PGI/PGII

normal G-17b

negative Hp,normal PGI/PGII

normal G-17b

positive Hp,normal PGI/PGII

normal G-17b

positive Hp,normal PGI/PGII

normal G-17b

Hp +/-,low PGI/PGIIhigh G-17b

Hp +/-,low PGI/PGIIhigh G-17b

positive Hp,low PGI/PGII

low G-17b

positive Hp,low PGI/PGII

low G-17b

No risk of a stomach disease

No risk of No risk of a a sstomachtomach diseasedisease

Increased risk ofgastric or duodenal

ulcer

IncreasedIncreased risk ofrisk ofgastric or duodenalgastric or duodenal

ulcerulcer

Increased risk ofgastric cancer

IncreasedIncreased risk ofrisk ofgastric cancergastric cancer

detection HpPGI/PGII, G-17b

detection HpPGI/PGII, G-17b

H. pylori gastritisH.H. pyloripylori gastritisgastritis Atrophic gastritis Atrophic gastritiAtrophic gastritis s

Eradicate H. pylori infection + consider gastroscopyEradicateEradicate H.H. pylori infectionpylori infection + + cconsider gastroscopyonsider gastroscopy

Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers. Agréus L, Kuipers EJ, Kupcinskas L, Malfertheiner P, et al.

Scand J Gastroenterol. 2012; 47(2):136-147

Rationale in diagnosis and screeningRationale in diagnosis and screening ofof atrophicatrophic gastritisgastritis with stomachwith stomach--specific specific plasmaplasma biomarkersbiomarkers.. AgréusAgréus L,L, KuipersKuipers EJ,EJ, KupcinskasKupcinskas L,L, MalfertheinerMalfertheiner P,P, et alet al..

ScandScand JJ GastroenterolGastroenterol. 2012; 47(2):136. 2012; 47(2):136--147147

1010

Hp INFECTION DIAGNOSTICHp INFECHp INFECTION TION DIAGNOSTIDIAGNOSTICC

non-invasive test, gold standard, specificity and sensitivity 95% - 13C UBT, breath test with 13C-urea

non-invasive test, if 13C-UBT not available, Hp antigen in stool

rapid urease test (CLO test) - if the gastroscopy clinically indicated, required bioptic samples from at least three different gastro-duodenal positions

IgA-IgG antibodies determination in serum does not have primary diagnostic importance, as positivity to Hp-antibodiesin subjects > 60 years could be 85%

non-invasive test, gold standard, specificity and sensitivity 95% - 13C UBT, breath test with 13C-urea

non-invasive test, if 13C-UBT not available, Hp antigen in stool

rapid urease test (CLO test) - if the gastroscopy clinically indicated, required bioptic samples from at least three different gastro-duodenal positions

IgA-IgG antibodies determination in serum does not have primary diagnostic importance, as positivity to Hp-antibodiesin subjects > 60 years could be 85%

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

1111

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

Statement 14: Validated serological tests for H pylori and markers of atrophy(ie, pepsinogens) are the best available non-invasive tests to identify subjects at

high risk of gastric cancer. Evidence level: 1a Grade of recommendation: B

Statement 14: Validated serological tests for H pylori and Statement 14: Validated serological tests for H pylori and markers of atrophymarkers of atrophy(ie, pepsinogens) are the best available(ie, pepsinogens) are the best available nonnon--invasive tests to identify subjects at invasive tests to identify subjects at

high risk of gastric cancer. Evidence level: 1a Grade of recommehigh risk of gastric cancer. Evidence level: 1a Grade of recommendation: Bndation: B

Statement 4: In patients treated with PPIs: (1) if possible, PPI should be stopped for 2 weeks before testing by culture, histology, rapid urease test, UBT

or stool test. Evidence level: 1b Grade of recommendation: A(2) if it is not possible, validated IgG serology can be performed.

Evidence level: 2b Grade of recommendation: B

Statement 4: In patients treated with PPIs: (1) if possible, PPIStatement 4: In patients treated with PPIs: (1) if possible, PPI should be should be stopped for 2 weeks before testing by culture, histology, rapid stopped for 2 weeks before testing by culture, histology, rapid urease test, UBT urease test, UBT

or stool test. Evidence level: 1b Grade of recommendation: Aor stool test. Evidence level: 1b Grade of recommendation: A(2) if it is not possible, validated IgG serology can be perform(2) if it is not possible, validated IgG serology can be performed.ed.

Evidence level: 2b Grade of recommendation: BEvidence level: 2b Grade of recommendation: B

Statement 1: The diagnostic accuracy of the stool antigen test (SAT) is equivalent to the UBT if a validated laboratory-based monoclonal test is used.

Evidence level: 1a Grade of recommendation: A

Statement 1: The diagnostic accuracy of the Statement 1: The diagnostic accuracy of the stool antigen teststool antigen test (SAT) is (SAT) is equivalent to the UBT if a validatedequivalent to the UBT if a validated laboratorylaboratory--based monoclonal test is used.based monoclonal test is used.

Evidence level: 1a Grade of recommendation: AEvidence level: 1a Grade of recommendation: A

Management of Helicobacter pylori infection - ConsensusManagement of Helicobacter pylori infection Management of Helicobacter pylori infection -- ConsensusConsensus

Management of Helicobacter pylori infection - the Maastricht IV/ Florence Consensus Report.

Malfertheiner P. et all. - The European Helicobacter Study Group (EHSG).Gut 2012; 61: 646 - 664

Management of Helicobacter pylori infection Management of Helicobacter pylori infection -- the Maastricht IV/ Florence the Maastricht IV/ Florence Consensus Report.Consensus Report.

MalfertheinerMalfertheiner P.P. et all. et all. -- The European Helicobacter Study Group (EHSG)The European Helicobacter Study Group (EHSG)..Gut 2012; 61: 646 Gut 2012; 61: 646 -- 664664

1122

HELICOBACTER PYLORIPEPSINOGENS, GASTRITIS

COELIAC SCREENING - THERAPYCHRONIC PANCREATITIS

EXOCRINE PANCREATIC FUNCTIONQUANTITATIVE FIT

COLORECTAL CANCER SCREENING

HELICOBACTERHELICOBACTER PYLORIPYLORIPEPSINOGENPEPSINOGENSS, GASTRIT, GASTRITISIS

CCOOELIAELIACC SCREENING SCREENING -- TTHHERAPERAPYYCHRONIC PANCHRONIC PANCCREATITREATITISIS

EXOEXOCCRINRINEE PANPANCCREATREATIC FUNCTIONIC FUNCTIONQUQUANTITATIVANTITATIVEE FITFIT

CCOLOREOLORECCTTAAL L CANCER SCREENINGCANCER SCREENING

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

1133

Woman - L.J. - born 1972in childhood anemic, asthenic, often in sanatoria,

mother and sister followed for thyreopathyastheny, height 171 cm, weight 52 kg

menarche at 15 years, married,at the time of diagnosis (2005) after 1 spont. abortion 1994

WomanWoman -- L.J. L.J. -- born born 19721972in childhoodin childhood anemicanemic, , asthenicasthenic, , often in sanatoria,often in sanatoria,

mother and sister followed for mother and sister followed for thyreopatthyreopathyhyasthenasthenyy, , heightheight 171171 cm, cm, weightweight 5252 kgkg

menarchmenarchee atat 15 15 yearsyears, , married,married,at the time of diagnosisat the time of diagnosis (2005) (2005) afterafter 1 spont. 1 spont. abortionabortion 19941994

CASE: 12-02CASECASE:: 1212--0202

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

1144

2005 admitted to gastroenterology clinic

with requiremed of colonoscopy for hypochrome anemia

Colonoscopy - normal findings

Histology of bioptical samples - normal findings

2005 2005 admitted to admitted to gastroenterologgastroenterology cy clinilinicc

with requiremed of colonoscopy for with requiremed of colonoscopy for hypochypochhromromee anemianemiaa

CColoolononossccopopyy -- normnormaal l findingsfindings

Histology of bioptical samplesHistology of bioptical samples -- normnormaal l findingsfindings

CASE: 12-02CASECASE:: 1212--0202

Routine laboratory test indicatedRoutine laboratory test indicatedRoutine laboratory test indicated

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

1155

haemoglobin 117 g/l, haematocrit 0.352

albumin 46.6 g/lalkaline phosphatase 1.54 ukat/l

alanine aminotransferase 0.52 ukat/laspartate aminotransferase 0.43 ukat/l

gamma-glutamyl transpeptidase 0.16 ukat/lcalcium 2.35 mmol/l

phosphate 1.22 mmol/lferrum 22.9 mmol/l

total cholesterol 3.19 mmol/ltriglycerides 0.65 mmol/l

hhaaemoglobinemoglobin 117117 g/l,g/l, hhaaematoematoccritrit 0.3520.352

albumin albumin 46.646.6 g/lg/lalkalialkalinene phphososphphatatasease 1.1.5454 ukatukat/l/l

alanine aminotransferalanine aminotransferasease 0.0.5252 ukatukat/l/laspartate aminotransferaspartate aminotransferasease 0.0.4343 ukatukat/l/l

gammagamma--glutamyl transpeptidglutamyl transpeptidasease 0.0.1616 ukatukat/l/lccalciumalcium 2.2.3535 mmolmmol/l/l

phphososphatephate 1.1.2222 mmolmmol/l/lferrumferrum 22.922.9 mmolmmol/l/l

totaltotal cholesterol cholesterol 3.193.19 mmolmmol/l/ltriglyceridtriglycerideses 0.650.65 mmolmmol//ll

CASE: 12-02 - laboratory dataCASECASE:: 1212--0202 -- laboratorlaboratoryy datadata

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

1166

coeliac screening markers - 11/4/05:

IgA anti-transglutaminase 132 U/ml

IgA anti-gliadin 30 U/ml

IgG anti-gliadin 132 U/ml

IgA anti-endomysium - positive

ccooeliaeliac screening markers c screening markers -- 11/4/05:11/4/05:

IgA antiIgA anti--transglutamintransglutaminasease 132 U/ml132 U/ml

IgA antiIgA anti--gliadin 30gliadin 30 U/mlU/ml

IgG antiIgG anti--gliadin 132 gliadin 132 U/mlU/ml

IgA antiIgA anti--endomysium endomysium -- popossitivitivee

Histology - small bowel biopsy:active coeliac, subtotal atrophy, decreased lactase, IEL 50/100

Histology Histology -- small bowel biopsy:small bowel biopsy:active active ccooeliaeliacc, subtot, subtotaal atrol atrophyphy, , decreased decreased lalaccttasease, IEL 50/100, IEL 50/100

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

CASE: 12-02 - laboratory dataCASECASE:: 1212--0202 -- laboratorlaboratoryy datadata

ICEBERG HYPOTHESIS OF COELIAC INCIDENCEICEBERG HYPOTHESIS OF COELIAC INCIDENCEICEBERG HYPOTHESIS OF COELIAC INCIDENCE

POTENTIAL CSPOTENTIAL CS

LATENT CSLATENT CS

SILENT CSSILENT CS

CLINICAL CSCLINICAL CS

HLA DQw2, IEL, γ/δ IELHLA DQw2, IEL, HLA DQw2, IEL, γ/δ γ/δ IELIEL

NORMAL MUSOCA, + MARKERYNORMNORMAALL MUSOCAMUSOCA,, + MARKERY+ MARKERY

MUCOSAL DEFECT, ASYMPTOMATICMUCOSAL DEFECT, ASYMPTOMATICMUCOSAL DEFECT, ASYMPTOMATIC

CLINICAL Dg.CCLINICLINICALAL Dg.Dg.

HISTOLOGY Dg.HISTOLOGYHISTOLOGY Dg.Dg.

SEROLOGY Dg.SEROLOGSEROLOGY Y DgDg..

1177

TRANSIENT CSTRANSIENT CS

ATYPICAL CSATYPICAL CS

((NNONON CS)CS)

INCIDENCE 1:1000INCIDENCE 1:1000INCIDENCE 1:1000

INCIDENCE 1:200INCIDENCE 1:200INCIDENCE 1:200

INCIDENCE 1:100INCIDENCE 1:100INCIDENCE 1:100

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

Dermatitis herpetiformisOsteoporosis, unexplained fracturesUnexplained anaemiaChronic fatigue syndrome Resistent irritable bowel syndromeSpont. abortion and fetal growth retardationUnexplained anaemia (iron, folic acid)HypertransaminasemiaRecurrent aphthous stomatitisDental enamel hypoplasiaDiabetes mellitus type 1.Autoimmune thyroiditisAutoimmune liver diseaseSystemic lupus erythematosusSjögren syndromePrimary biliary cirrhosis or sclerosing cholangitis

Dermatitis herpetiformisOsteoporosis, unexplained fracturesUnexplained anaemiaChronic fatigue syndrome Resistent irritable bowel syndromeSpont. abortion and fetal growth retardationUnexplained anaemia (iron, folic acid)HypertransaminasemiaRecurrent aphthous stomatitisDental enamel hypoplasiaDiabetes mellitus type 1.Autoimmune thyroiditisAutoimmune liver diseaseSystemic lupus erythematosusSjögren syndromePrimary biliary cirrhosis or sclerosing cholangitis

MAIN RISK GROUPSMAINMAIN RIRISK GROUPSSK GROUPS

CD SUSPECTED SYMPTOMSCCDD SUSPECTEDSUSPECTED SYMPTOMSYMPTOMSS

AUTOIMUNNE DISEASESAUTOIMUNNAUTOIMUNNEE DISEASESDISEASES

1818

TARGETED COELIAC SCREENINGTARGETED COELIAC SCREENINGTARGETED COELIAC SCREENING

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

1199

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

C. Briani et al. / Autoimmunity Reviews 7 (2008) 644–650C.C. Briani et alBriani et al. /. / Autoimmunity ReviewsAutoimmunity Reviews 7 (2008) 6447 (2008) 644––650650

Definitive diagnosis of CDDefinitive diagnosis of CD

Gluten free dietGluten free diet

HLA HLA typitypingng,,bbiopsiopsy rey re--evaluationevaluation

IntestinalIntestinalbiopsybiopsy

negative antibodiesnegative antibodiesnegative antibodies

positiveantibodies

popossitivitiveeantibodiesantibodies

IgA deficientIgAIgA deficientdeficient

positiveantibodiespopossitivitivee

antibodiesantibodies

histologichistologic features of CD features of CD

clinical andclinical and histologichistologic improvementimprovement

high clinicalhigh clinicalsuspicionsuspicion

negativebiopsy

negativenegativebiopsybiopsy

Provisional diagnosis of CDProvisional diagnosis of CD

Increased probabilityIncreased probabilityof of ccooeliaeliacscs

Low probabilityLow probabilityof of ccooeliaeliacscs

IgA atTGIgA atTG // IgA EmAIgA EmAaandnd totaltotal IgAIgA

Targeted screeningTargeted screening ofof ccooeliac diseaseeliac disease

IgIgGG atTGatTG ,, IgG EmAIgG EmAoror IgGIgG AGAAGA

Definitive diagnosis of CDDefinitive diagnosis of CD

IgIgAA atTGatTG2 & total 2 & total IgAIgA

Intestinal biopsyIntestinal biopsy

negative HLAnegative HLAnegative HLA positive HLApositive HLApositive HLA

anti TG2> 3x normal

anti TG2anti TG2> 3x normal> 3x normal

ExcludeExclude IgAIgA deficiencydeficiencyLow gluten intakeLow gluten intake

No risk for CDNo risk for CD

HLA DQ2 HLA DQ2 aandnd/or DQ8/or DQ8

AsymptomaticAsymptomatic person at genetic risk forperson at genetic risk for coeliaccoeliac diseasedisease

negative antibodiesnegative antibodiesnegative antibodies

anti TG2< 3x normal

anti TG2anti TG2< 3x normal< 3x normal

Marsh 2 or 3

Marsh Marsh 2 or 32 or 3

EmAnegative

EmAEmAnegativenegative

Marsh 0 or 1Marsh 0 or 1Marsh 0 or 1

Normal dietNormal dietFalse positive testsFalse positive tests

Potential CDPotential CD

Transient falseTransient false pozitpozit..anti TG2anti TG2

Normal dietNormal dietFurther serology testingFurther serology testing

IgA EmAIgA EmA

EmA positiveEmAEmA positivepositive

2020

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

European Society for Pediatric Gastroenterology,Hepatology, and Nutrition Guidelines for the Diagnosis ofCoeliac Disease. Husby S. at al. JPGN 2012; 54: 136–160

European Society for Pediatric Gastroenterology,European Society for Pediatric Gastroenterology,Hepatology, and Nutrition Guidelines for the Diagnosis ofHepatology, and Nutrition Guidelines for the Diagnosis ofCoeliac Disease. Husby S. at al. JPGN 2012; 54: 136Coeliac Disease. Husby S. at al. JPGN 2012; 54: 136––160160

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BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

Old and new serological tests for celiac disease screening.Volta U., Fabbri A., Parisi C. et al. Expert Rev. Gastroenterol. Hepatol. 2010, 4(1)

Old and new serological testsOld and new serological tests forfor celiac disease screeningceliac disease screening..Volta U.,Volta U., FabbriFabbri A., Parisi C.A., Parisi C. et alet al. Expert. Expert RevRev.. GastroenterolGastroenterol.. HepatolHepatol. 2010, 4(1). 2010, 4(1)

ACTUALACTUAL PROTOPROTOCCOLOLANTIBODIES DETERMINATIONANTIBODIES DETERMINATION

(EVIDENCE (EVIDENCE -- BASED)BASED)

PERSPEPERSPECCTIVTIVEE PROTOPROTOCCOLOLANTIBODIES DETERMINATIONANTIBODIES DETERMINATION

((WORKINGWORKING HYPOTHYPOTHESISHESIS))

INCREASE OF IgA atTG SPECIFICITYINCREASEINCREASE OFOF IgA atTGIgA atTG SPECIFICITYSPECIFICITY

INCREASE OF IgA atTG SPECIFICITYCOELIAC DETECTION WITH IgA DEFFICIENCYCOELIAC DETECTION IN CHILDRENS < 2 YR

INCREASE INCREASE OFOF IgA atTGIgA atTG SPECIFICITYSPECIFICITYCOELIAC DETECTION WITHCOELIAC DETECTION WITH IgAIgA DEFDEFFICIENCYFICIENCYCOELIAC DETECTIONCOELIAC DETECTION IN CHILDRENSIN CHILDRENS < 2 YR< 2 YR

COELIAC DETECTION WITHIgA DEFFICIENCY

COELIAC DETECTION WITHCOELIAC DETECTION WITHIgAIgA DEFDEFFICIENCYFICIENCY

COELIAC DETECTIONIN CHILDRENS < 2 YRCOELIAC DETECTIONCOELIAC DETECTIONIN CHILDRENSIN CHILDRENS < 2 YR< 2 YR

IgA atTGIgA atTGIgA atTG IgA atTGIgA atTGIgA atTG

+ IgA EmA++ IgA EmAIgA EmA

+ IgG atTG++ IgG atTGIgG atTG

+ IgA AGA++ IgAIgA AGAAGA

+ IgG DGP++ IgGIgG DGPDGP

+ IgA+ IgA+ IgA

2222

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

INTESTINAL BIOPSY IN THE COELIAC DISEASE DIAGNOSTICSINTESTINAL BIOPSY IN THE COELIAC DISEASE DIAGNOSTICSINTESTINAL BIOPSY IN THE COELIAC DISEASE DIAGNOSTICS

Clinical practice - Coeliac disease - Eur J Pediatr. - online March 2012C. M. Frank Kneepkens & B. Mary E. von Blomberg

ClinicalClinical practicepractice -- Coeliac diseaseCoeliac disease -- EurEur J Pediatr. J Pediatr. -- online Marchonline March 20122012C. M. FrankC. M. Frank KneepkensKneepkens & B. Mary E.& B. Mary E. von Blombergvon Blomberg

Marsh 0 Marsh 1 Marsh 2 Marsh 3a Marsh 3b Marsh 3cMarsh 0 Marsh 1 Marsh 0 Marsh 1 Marsh 2 Marsh 3a Marsh 3b Marsh 3cMarsh 2 Marsh 3a Marsh 3b Marsh 3c

2233

NORMAL MUCOSANORMNORMAL MUCOSAAL MUCOSA

TOTAL ATROPHYTTOTOTAALL ATROATROPHYPHY

NEGATIVE ANTIBODIESNEGATIVE ANTIBODIESNEGATIVE ANTIBODIES

POSITIVE ANTIBODIESPOPOSSITIVITIVE ANTIBODIESE ANTIBODIES

HEALTHY SUBJECTTREATED COELIACHEALTHY SUBJECTHEALTHY SUBJECTTREATED COELIACTREATED COELIAC

FLORID COELIACUNTREATED

FLORID COELIACFLORID COELIACUNTREATEDUNTREATED

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

GLUTEN FREE DIET (GFD) - SCREENING & DIAGNOSTICS GLUTEN FREE DIETGLUTEN FREE DIET (GFD)(GFD) -- SCREENING & DIAGNOSTICS SCREENING & DIAGNOSTICS

TREATED COELIAC ?OTHER AUTOIMMUNITY ?

TREATED TREATED CCOOELIAELIACC ??OTHER OTHER AUTOIAUTOIMMMUNITMUNITYY ??

2244

ENDOSCOPIC MARKERS OF COELIAC DISEASEENDOSCOPIC MARKERS OF COELIAC DISEASE

Normal duodenalmusoca

NormNormaall duodenalduodenalmusocamusoca

EnterscopyEntersEntersccopopyy Mosaic pattern of duodenal mucosaMoMossaiaic pattern of c pattern of duodenal mucosaduodenal mucosa

Chromoendoscopywith indigocarmineChromoendosChromoendosccopopyywith with indigoindigoccarmarmineine

http://www.lfhk.cuni.cz/kcvl/stranky/ENTERO/E-cel1.htmlhttp://www.http://www.lfhklfhk..cunicuni..czcz//kcvlkcvl//strankystranky/ENTERO/E/ENTERO/E--cel1.cel1.htmlhtml

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

2255 http://www.lfhk.cuni.cz/kcvl/stranky/Kapsle/C-CE1.htmlhttp://www.http://www.lfhklfhk..cunicuni..czcz//kcvlkcvl//strankystranky/Kapsle/C/Kapsle/C--CE1.CE1.htmlhtml

CAPSULE ENDOSCOPYCAPSULE ENDOSCOPY

NON-INVASIVE ENDOSCOPICEXAMINATION

NON-INVASIVE ENDOSCOPICEXAMINATION

Normal duodenalmusoca

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

NormNormaall duodenalduodenalmusocamusoca

Mosaic pattern of duodenal mucosaMoMossaiaic pattern of c pattern of duodenal mucosaduodenal mucosa

2266

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

tTGtTG

DEAMIDATION

GASTRIC, PANCREATICPEPTIDASES, PROLYL-ENDOPEPTIDASE

CD4+ TCELL

TH1-CELLTH2-CELL

B-CELL

TISSUETRANSGLUTAMINASE

M. CELLS

INFLAMMATION

MESENCHYMALCELLS

COELIAC VILLUSATROPHY

COELIACCRYPTS HYPERTROPHYANTIBODIESANTIBODIES

IL2, γIFN, TNFIL2, γIFN, TNFIL 4,5,10IL 4,5,10

GLIADINGLIADIN

33-mer PEPTIDE33-mer PEPTIDE WHEAT

according to Mowat AT, Lancet 2003, 361: 1290accordingaccording toto MowatMowat AT, Lancet 2003, 361: 1290AT, Lancet 2003, 361: 1290

2277

COELIAC COELIAC TTHHERAPERAPYY

1. GLUTEN-FREE DIET1. 1. GLUTENGLUTEN--FREE DIETFREE DIET

xx5. NON-TOXIC WHEAT5. N5. NONON--TOXIC TOXIC WHEATWHEAT

4.HLA BLOCATION4.4.HLA BLOHLA BLOCATIONCATION

2. ENZYMES PEP, EP-B22. ENZYM2. ENZYMESES PEPPEP,, EPEP--B2B2xx

3. TG2 INHIBITOR3.3. TG2TG2 INHIBITORINHIBITOR

xx

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

2288

COELIAC THERAPY: ENZYMIC HYDROLYSISCCOOELIAELIACC THTHERAPERAPY: ENZYMICY: ENZYMIC HYDROLHYDROLYSISYSIS

INTRAINTRA--DIGESTIVDIGESTIVEEDETOXIFIDETOXIFICCAATIONTIONPREPRE--GASTRONOMICGASTRONOMIC

DETOXIFIDETOXIFICCAATIONTION

PROLYLPROLYL--ENDOPETIDENDOPETIDASEASELACTOBACILLUSLACTOBACILLUS,, ASPERGILUSASPERGILUS

PROTEPROTEASESASES

BABACCTERITERIAALLPROLYLPROLYL--ENDOPEPTIDENDOPEPTIDASEASE,,

CYSCYS--PEPTIDPEPTIDASE FROMASE FROM BARLEYBARLEY

MODIFICATION OF FOODMODIFICATION OF FOODPERORPERORAALL APAPPPLILICATION OFCATION OFENZYMENZYMESES -- HYDROLHYDROLASESASES

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

Glutenase ALV003 Attenuates Gluten-Induced Mucosal Injury in Patients With Celiac Disease. Lähdeaho ML, Kaukinen K, Laurila K, Vuotikka P, Koivurova OP,

Kärjä-Lahdensuu T, Marcantonio A, Adelman DC, Mäki M. Gastroenterology. 2014 Jun;146(7):1649-1658

Glutenase ALV003 Attenuates GlutenGlutenase ALV003 Attenuates Gluten--Induced Mucosal Injury in Patients With Induced Mucosal Injury in Patients With Celiac DiseaseCeliac Disease. . Lähdeaho ML, Kaukinen K, Laurila K, Vuotikka P, Koivurova OP,Lähdeaho ML, Kaukinen K, Laurila K, Vuotikka P, Koivurova OP,

KärjäKärjä--Lahdensuu T, Marcantonio A, Adelman DC, Mäki M. Lahdensuu T, Marcantonio A, Adelman DC, Mäki M. Gastroenterology. 2014 Jun;146(7):1649Gastroenterology. 2014 Jun;146(7):1649--16581658

2299

WHEAT RYE BARLEY OATS RICE SORGHUM MILLET MAIZEWHEAT RYE BARLEY OATS RICE SORGHUM MILLET MAIWHEAT RYE BARLEY OATS RICE SORGHUM MILLET MAIZEZEGLIADIN SECALIN HORDEIN AVENIN ZEINGLIADIN SECALIN HORDEIN AVENIN GLIADIN SECALIN HORDEIN AVENIN ZEINZEIN

DECREASING PATOGENICITY FOR CS

T cell receptorT cell receptorT cell receptor

DQ2 moleculeDQ2 moleculeDQ2 molecule

DECREASING TEST SENSITIVITY mAb

Gliadinstandard

mAbmAbGliadinGliadin

standardstandard

GLUTEN FREE DIET - CEREALS

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

GLUTEN FREE DIET GLUTEN FREE DIET -- CEREALSCEREALS

3030

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

0

10

20

30

40

50

1 3 5 7 9 11 13 15 17 19 21 23 25 27 290

10

20

30

40

50

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29

day amount - mg gliadin/50kg weightday amount day amount -- mgmg gliadingliadin//50kg 50kg weightweight

Therapy errorFood with high gliadin level

Therapy errorTherapy errorFood with highFood with high gliadingliadin levellevel

250 g gluten free foodhigh - 9,9 mg gliadin

250 g 250 g gluten free foodgluten free foodhigh high -- 9,9 mg9,9 mg gliadingliadin

GLUTEN FREE DIET - DAY QUANTITYGLUTEN FREE DIET GLUTEN FREE DIET -- DAY QUANTITYDAY QUANTITY

Monitoring of Daily Gliadin Intake in Patients on Gluten-free Diets. Gabrovská D., Kocna P., et al.: Prague Medical Report 2011, 112 (1): 5 – 17

Monitoring of Daily Gliadin Intake in Patients on GlutenMonitoring of Daily Gliadin Intake in Patients on Gluten--free Diets. free Diets. Gabrovská D., Kocna P., et al.: Prague Medical Report 2011, 112Gabrovská D., Kocna P., et al.: Prague Medical Report 2011, 112 (1): 5 (1): 5 –– 1717

3131

since 11/2005 complete gluten-free diet2008 gave birth to a healthy daughter, who has not coeliac,

follows the diet - is on remision

sincesince 11/2005 11/2005 completecomplete glutengluten--freefree dietdiet2008 2008 gave birth to agave birth to a healthy daughterhealthy daughter, , who has not coeliac,who has not coeliac,

follows the diet follows the diet -- is on remisionis on remision

coeliac specific antibodies - 24/4/06:

IgA anti-transglutaminase 2 U/ml

IgA anti-gliadin 7 U/ml

IgG anti-gliadin 29 U/ml

IgA anti-endomysium - negative

coeliac specific antibodies coeliac specific antibodies -- 24/4/06:24/4/06:

IgA antiIgA anti--transglutamintransglutaminasease 2 U/ml2 U/ml

IgA antiIgA anti--gliadin 7 U/mlgliadin 7 U/ml

IgG antiIgG anti--gliadin 29 U/mlgliadin 29 U/ml

IgA antiIgA anti--endomysium endomysium -- negativnegativee

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

CASE: 12-02 - THERAPYCASECASE:: 1212--0202 -- THERAPYTHERAPY

CASE: 12-02 - laboratory dataCASECASE:: 1212--0202 -- laboratorlaboratoryy datadata

3322

immunological markers - 24/7/12:

interferron gamma, IFNγ 57,7 (normal up tol 31 %)

tumor necrosis factor, TNFα 74,7 (normal up to 44 %)

interleukin, IL2 - 47,9 (normal up to 28 %)

immunologicalimmunological marmarkkerers s -- 24/7/12:24/7/12:

interfeinterferrron gammaron gamma,, IFNIFNγγ 57,757,7 (norma(normall up tolup tol 31 %)31 %)

tumor necrosis factor,tumor necrosis factor, TNFTNFα α 74,774,7 (norma(normall up toup to 44 %)44 %)

interleukin, interleukin, ILIL22 -- 47,947,9 (norma(normall up toup to 28 %)28 %)

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

CASE: 12-02 - laboratory dataCASECASE:: 1212--0202 -- laboratorlaboratoryy datadata

LIFELONG DISEASE, PERMANENT INTESTINALINTOLERANCE OF GLUTEN, PROLAMIN PROTEINS

GENETIC FACTORS - HLA-B8, HLA-DR3, HLADQ2

INITIALISING FACTORS - GLIADIN OR SIMILAR PEPTIDES

IMMNOLOGY RESPONSE, AUTOIMMUNE TYPE OFDISEASE

DAMAGE OF SMALL INTESTINAL MUCOSA

MALABSORPTION SYNDROME

RESPONSE TO GLUTEN FREE DIET

LIFELONG DISEASE, PERMANENT INTESTINALINTOLERANCE OF GLUTEN, PROLAMIN PROTEINS

GENETIC FACTORS - HLA-B8, HLA-DR3, HLADQ2

INITIALISING FACTORS - GLIADIN OR SIMILAR PEPTIDES

IMMNOLOGY RESPONSE, AUTOIMMUNE TYPE OFDISEASE

DAMAGE OF SMALL INTESTINAL MUCOSA

MALABSORPTION SYNDROME

RESPONSE TO GLUTEN FREE DIET

COELIAC DISEASE SUMMARYCCOEOELIALIAC DISEASE SUMMARYC DISEASE SUMMARY

3333

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

H2/CH4 and 13C - BREATH TESTSHH22/C/CHH44 and and 1313CC -- BREATH TESTSBREATH TESTS

3434

SMALL BOWEL ABSORPTION - FUNCTION TESTSSMALL BOWEL ABSORPTION - FUNCTION TESTS

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

Hydrogen analyserHydrogen analyserLactotest 202Lactotest 202

1313--CC analyseranalyserHeliHeli FANFAN

Regression of lactose malabsorption in coeliac patients after receiving a gluten-free diet.

Scand J Gastroenterol. 2008;43(2):174-177

Regression of lactose malabsorption in coeliac patients Regression of lactose malabsorption in coeliac patients after receiving a glutenafter receiving a gluten--free diet.free diet.

Scand J Gastroenterol. 2008;43(2):174Scand J Gastroenterol. 2008;43(2):174--177177

13C-xylose and 14C-xylose breath tests for the diagnosisof coeliac disease.

Scand J Gastroenterol. 2008;43(2):166-173

13C13C--xylose and 14Cxylose and 14C--xylose breath tests for the diagnosisxylose breath tests for the diagnosisof coeliac disease.of coeliac disease.

Scand J Gastroenterol. 2008;43(2):166Scand J Gastroenterol. 2008;43(2):166--173173

LALACCTTOSEOSE BREATHBREATH TESTTEST20g LA20g LACCTTOSE DOSAGEOSE DOSAGEHYDROGEN DETERMINATIONS HYDROGEN DETERMINATIONS 5 HO5 HOURSURSCUTCUT--OFF OFF VALUEVALUE 20 ppm20 ppm

DD--XYLXYLOSEOSE BREATHBREATH TESTTEST100mg 13C100mg 13C--XYLXYLOSE DOSAGEOSE DOSAGERATIORATIO 12C:13C12C:13C DETERMINATIONDETERMINATIONBREATHBREATH INDEX 30min/210minINDEX 30min/210min

3355

LACTOSE INTOLERANCE DIAGNOSISLACTOSE INTOLERANCE DIAGNOSIS

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

HISTOCHEMICAL DETECTIONOF LACTASE ACTIVITY IN THEENTEROCYTE BRUSH BORDERIMMUNOHISTOCHEMICAL TEST

HISTOCHEMICAL DETECTIONHISTOCHEMICAL DETECTIONOF LACTASE OF LACTASE AACCTIVITYTIVITY ININ THETHEENTEROCYTENTEROCYTE BRUSH BORDERE BRUSH BORDERIMIMMMUNOHISTOCHEMICUNOHISTOCHEMICALAL TESTTEST

MODERN RAPID TESTLACTASE ACTIVITY DETECTIONCHROMOGENIC METHOD

MODERNMODERN RAPID TESTRAPID TESTLACTASE LACTASE AACCTIVITYTIVITY DETECTIONDETECTIONCHROMOGENCHROMOGENICIC METMETHHODOD

3366

HELICOBACTER PYLORIPEPSINOGENS, GASTRITIS

COELIAC SCREENING - THERAPYCHRONIC PANCREATITIS

EXOCRINE PANCREATIC FUNCTIONQUANTITATIVE FIT

COLORECTAL CANCER SCREENING

HELICOBACTERHELICOBACTER PYLORIPYLORIPEPSINOGENPEPSINOGENSS, GASTRIT, GASTRITISIS

CCOOELIAELIACC SCREENING SCREENING -- TTHHERAPERAPYYCHRONIC PANCHRONIC PANCCREATITREATITISIS

EXOEXOCCRINRINEE PANPANCCREATREATIC FUNCTIONIC FUNCTIONQUQUANTITATIVANTITATIVEE FITFIT

CCOLOREOLORECCTTAAL L CANCER SCREENINGCANCER SCREENING

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

3377

Male - A.A. - born 1938history of gallbladder problems - (cholecystolithiasis)

hypertension treatment on Ca blockers, obesityDietary error - goulash, beer

Abdominal pain around the navel broadening in the back, vomitingS-amylase 20,2, C-reactive protein 1.day 5 g/l, calcium 1,85 mmol/l

Abdominal ultrasound - cholecystolithiasa

MMaleale -- AA..AA. . -- bornborn 19381938history of history of gallbladder problemsgallbladder problems -- (cholecystolithias(cholecystolithiasisis))

hypertension treatment on Ca blockers, obesityhypertension treatment on Ca blockers, obesityDietary error Dietary error -- goulash, beergoulash, beer

Abdominal pain around the navel broadening in the back, vomitingAbdominal pain around the navel broadening in the back, vomitingSS--amylase amylase 20,220,2, C, C--reactive protein 1.day 5 g/l, calcium 1,85 mmol/lreactive protein 1.day 5 g/l, calcium 1,85 mmol/l

Abdominal ultrasound Abdominal ultrasound -- cholecystolithiasacholecystolithiasa

CASE: 12-03CASECASE:: 1212--0303

Admitted to surgary clinic – emmergency unitliquid saturation – 5000 ml/24 hrs

Admitted to surgary clinic Admitted to surgary clinic –– emmergency unitemmergency unitliquid saturation liquid saturation –– 5000 ml/24 hrs5000 ml/24 hrs

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

3388

5.day - CT abdomenSevere acute necrotizing pancreatitis (more than 60%)

ATB administration - cefotaxime 10 days, parenteral nutrition, febricity,

25.day – necrosis drainage under CT Complications:

Renal insufficiency, borderline cardiac compensation

5.d5.dayay -- CT abdomenCT abdomenSevere Severe acute necrotizing pancreatitisacute necrotizing pancreatitis (more than 60%) (more than 60%)

ATB ATB administration administration -- cefotaxime 10 days, parenteral nutrition, cefotaxime 10 days, parenteral nutrition, febrifebricitycity, ,

25.d25.dayay –– necrosis drainage under CT necrosis drainage under CT Complications: Complications:

Renal insufficiency, borderline cardiac compensation Renal insufficiency, borderline cardiac compensation

CASE: 12-03CASECASE:: 1212--0303

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

3399

CASE: 12-03 - laboratory dataCASECASE:: 1212--03 03 -- laboratorlaboratoryy datadata

22 33 55 77 4545 9090creatinincreatinin 130130 8888 7979 7373 7575 7575ureaurea 9.29.2 6.66.6 4.34.3 6.96.9 2.52.5 4.74.7albuminalbumin 3939 27.827.8 24.524.5 24.524.5 20.520.5 3838NaNa++ 133133 135135 135135 131 / 135131 / 135 135135 143143KK++ 3.73.7 3.63.6 3.43.4 3.4 / 3.93.4 / 3.9 4.04.0 4.94.9ClCl-- 9898 103103 100100 93 / 9693 / 96 102102 104104pHpH 7.437.43 7.46 / 7.477.46 / 7.47pCOpCO22 5.345.34 6.91 6.91 / 5.58/ 5.58BEBE 2.42.4 10.910.9 / 6.2/ 6.2HCOHCO--

33 26.326.3 34.634.6 / 3.01/ 3.01

1-2 day dehydratation 7 day metabolic alkalosis11--2 day dehydratation 7 day metabolic2 day dehydratation 7 day metabolic alalkkalalosisosis

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

4040

CASE: 12-03CASECASE:: 1212--0303

Transfer to metabolic unit of 2nd. medical clinicTransferTransfer toto metabolicmetabolic unit of 2nd. medical cunit of 2nd. medical clinilinicc

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

45.den abdominal CT native and contrast - enhanced biphasic.In comparison with the presence of 8.9.08 slightly accentuated necrotic deposit in pancreatic body, about 39 x 30 mm, minor

hypodense districts in cauda of the pancreas which is the border width, with unsharp bounded. Pancreatic head not enlarged,

without any deposits. Dc. pankreaticus unextended. Peripancreatical fluid better highlightet, particular cranially

from the pancreas - 100 x 110 mm and anterior to the pancreas 110 x 60 mm, fluid collection up to the front of the left renal fascia.

Cholecystolithiasis. Fluidothrax right posterior 71 x 25 mm.

45.den abdominal CT native and contrast45.den abdominal CT native and contrast -- enhanced biphasic.enhanced biphasic.In comparison with the presence of 8.9.08 slightly accentuated In comparison with the presence of 8.9.08 slightly accentuated necrotic depositnecrotic deposit in pancreatic body, about 39 x 30in pancreatic body, about 39 x 30 mm, minor mm, minor

hypodensehypodense districts in cauda of the pancreas which is the border districts in cauda of the pancreas which is the border widthwidth, , with unsharpwith unsharp bounded. Pancreatic head not enlarged, bounded. Pancreatic head not enlarged,

without any deposits. Dc. pankreaticus unextended. without any deposits. Dc. pankreaticus unextended. Peripancreatical fluid better highlightet,Peripancreatical fluid better highlightet, particular cranially particular cranially

from the pancreas from the pancreas -- 100 x 110 mm and anterior to the pancreas 100 x 110 mm and anterior to the pancreas 110 x 60 mm,110 x 60 mm, fluid collection up to the front of the left renal fascia. fluid collection up to the front of the left renal fascia.

Cholecystolithiasis.Cholecystolithiasis. Fluidothrax right posterior 71 Fluidothrax right posterior 71 x 25 x 25 mmmm..

4141

45.day transfer to metabolic unit of 2nd. medical clinicintroduced naso-jejunal probe, pulled the drain, gradually increased

enteral nutrition to 2200 ml per day (2200 kcal, 85 g protein)Drugs: proton pump inhibitors (omeprazole 2x20 mg),

substituted pancreatic enzymes (Creon 25000j 3 x 1 cps),liquid free, probiotics. Conducted training for home

enteral nutrition and released to home care

45.45.dday transferay transfer toto metabolicmetabolic unit of 2nd. medical cunit of 2nd. medical cliniliniccintroduced nasointroduced naso--jejunal probejejunal probe,, pulled the pulled the drdraiainn, , gradually increased gradually increased

enteralenteral nutrition to 2200 ml per day (2200 kcal, 85 g protein)nutrition to 2200 ml per day (2200 kcal, 85 g protein)Drugs: proton pump inhibitors (omeprazole 2x20 mg),Drugs: proton pump inhibitors (omeprazole 2x20 mg),

substituted pancreatic enzymes (Creon 25000j 3 x 1 substituted pancreatic enzymes (Creon 25000j 3 x 1 cpscps)),,liquid liquid freefree,, probiotics. Conducted training for homeprobiotics. Conducted training for home

enteral nutrition and released to home careenteral nutrition and released to home care

The ICU 52 days, 55 days in the hospital, then home enteralnutrition 93 days, gradual transfer to oral intake.

Proton pump inhibitors discontinued,and patient gradually discontinued probiotics ,

The ICU 52 days, 55 days in the hospital, then home enteralThe ICU 52 days, 55 days in the hospital, then home enteralnutrition 93 days, gradual transfer to oral intakenutrition 93 days, gradual transfer to oral intake..

Proton pump inhibitors discontinued,Proton pump inhibitors discontinued,and and patient gradually discontinued probioticspatient gradually discontinued probiotics ,,

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

CASE: 12-03CASECASE:: 1212--0303

4422

Cholecystectomy performed after 5 months.Continued pancreatic enzyme application,

Creon 25000 - 3 x 1 cps, total 1,5 year with good effect.

CCholecysteholecystecctotomy performed after 5 months.my performed after 5 months.Continued Continued panpanccreatic enzymreatic enzyme application,e application,

CCreon 25000reon 25000 -- 3 x 1 3 x 1 cpscps, , total total 1,5 1,5 year with good eyear with good effffeect. ct.

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

90.day - CT and contrast - enhanced abdominal natively.Conclusion: Compared with the measurement of 19.9.08

increased pancreatic pseudocyst extending peripherally to the mediastinum. Splenic vein thrombosis with colleterals at large

curvature of the stomach. Necrosis of the pancreatic body, relatively less is its head and tail. Small deposit in the liver,

nonspecific appearance. Multiple cholecystolithiasis. Duodenal diverticulum..

90.d90.dayay -- CT and contrastCT and contrast -- enhanced abdominal natively.enhanced abdominal natively.Conclusion: Compared with the measurement of 19.9.08 Conclusion: Compared with the measurement of 19.9.08

increased pancreatic pseudocyst extending peripherally to the increased pancreatic pseudocyst extending peripherally to the mediastinum.mediastinum. Splenic vein thrombosis with colleterals at large Splenic vein thrombosis with colleterals at large

curvature of the stomach.curvature of the stomach. Necrosis of the pancreatic body, Necrosis of the pancreatic body, relatively less is its head and tail.relatively less is its head and tail. Small deposit in the liverSmall deposit in the liver,,

nonspecific appearance.nonspecific appearance. Multiple cholecystolithiasis. Multiple cholecystolithiasis. Duodenal diverticulum..Duodenal diverticulum..

CASE: 12-03CASECASE:: 1212--0303

4433

After 1,5 year executed exocrine pancreatic secretion tests :

FELA (fecal elastase-1) 378 μg/g (normal above 200 μg/g)13C-MTG breath test, 6hr. cPDR - 51 % (normal above 30 %)

After After 1,5 1,5 yearyear executedexecuted exocrineexocrine panpanccreatic sereatic seccreretion teststion tests ::

FELA (FELA (fecal fecal elastelastasease--1) 378 1) 378 μμg/gg/g (normal above 200(normal above 200 μμg/gg/g))1313CC--MTG MTG breath breath testtest,, 6hr. 6hr. cPDR cPDR -- 51 % 51 % (normal above 30(normal above 30 %%))

Pancreatic enzyme substitution discontinued,at this time gall diet without pancreatic substitution.

PPananccreaticreatic enzymeenzyme substitusubstitution tion discontinueddiscontinued,,at this time gall diet without pancreatic substitutionat this time gall diet without pancreatic substitution..

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

CASE: 12-03 - laboratory dataCASECASE:: 1212--03 03 -- laboratorlaboratoryy datadata

4444

CHRONIC PANCREATITIS DIAGNOSTICSCHRONICCHRONIC PANPANCCREATITREATITIS DIAGNOSTICSIS DIAGNOSTICS

EUSEUS ERCPERCP MRCPMRCP

SENSITIVITSENSITIVITYY 56% (4056% (40--72)72) 72% (5872% (58--86)86) 54% (4454% (44--64)64)

SPECIFICITSPECIFICITYY 81% (6881% (68--95)95) 75% (6075% (60--90)90) 78% (7278% (72--83)83)

Diagnosis of mild chronic pancreatitis (Cambridge classification)Sai JK, Suyama M, Kubokawa Y, Watanabe S.

World J Gastroenterol 2008 February 28; 14(8): 1218 - 1221Researchers Test the Value of ERPC for the Detection of Early Chronic Pancreatitis

Frei R. - Gastroent.Endoscop.News 2007, 58, 02

DiagnosisDiagnosis ofof mild chronic pancreatitismild chronic pancreatitis (Cambridge (Cambridge classificationclassification))SaiSai JK,JK, SuyamaSuyama M,M, KubokawaKubokawa Y,Y, WatanabeWatanabe S. S.

WorldWorld JJ GastroenterolGastroenterol 20082008 FebruaryFebruary 28; 14(8): 1218 28; 14(8): 1218 -- 12211221ResearchersResearchers TestTest the Valuethe Value of ERPC forof ERPC for the Detectionthe Detection ofof Early Chronic PancreatitisEarly Chronic Pancreatitis

FreiFrei R. R. -- GastroentGastroent..EndoscopEndoscop..NewsNews 2007, 58, 022007, 58, 02

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

Diagnostic imaging for mild chronic pancreatitisDiagnostic imaging for mild chronic pancreatitisEndoscopic ultrasound (EUS)Endoscopic ultrasound (EUS)

Endoscopic retrograde cholangiopancreatography (ERCP) Endoscopic retrograde cholangiopancreatography (ERCP) Magnetic resonance cholangiopancreatography (MRCP)Magnetic resonance cholangiopancreatography (MRCP)

4455

Quantitative MRCP assessment of pancreatic exocrine reserve and itscorrelation with faecal elastase-1 in patients with chronic pancreatitis

Manfredi R. el al. Radiol med. - DOI 10.1007/s11547-011-0774-6

Quantitative MRCP assessment of pancreatic exocrine reserve and Quantitative MRCP assessment of pancreatic exocrine reserve and itsitscorrelation with faecal elastasecorrelation with faecal elastase--1 in patients with chronic pancreatitis1 in patients with chronic pancreatitis

Manfredi R. el al. Radiol med. Manfredi R. el al. Radiol med. -- DOI 10.1007/s11547DOI 10.1007/s11547--011011--07740774--66

MRCP - SECRETION VOLUMEMATHEMATICAL PROCEDUREPANCREATIC FUNCTION TEST

MRCP MRCP -- SESECCRERETION VOLUMETION VOLUMEMATHEMATICAL PROCEDUREMATHEMATICAL PROCEDUREPANPANCCREATIC FUNCREATIC FUNCTION TESTTION TEST

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

4466

EXOCRINE PANCRAETIC FUNCTION TESTSEXOEXOCCRINRINEE PANPANCCRAETRAETIC FUNCTION TESTSIC FUNCTION TESTS

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

STOOL SAMPLING - 72hr.STOOL SAMPLINGSTOOL SAMPLING -- 7272hr.hr.

STANDARD METHOD FOREXOCRINE PANCREATIC FUNCTION

STANDARDSTANDARD METMETHHODOD FORFOREXOEXOCCRINRINEE PANPANCCREATREATIC FUNCTIONIC FUNCTION

S-CCK TESTSS--CCKCCK TESTTEST

FAT 72 hr.FATFAT 72 72 hrhr..

WITHOUT STIMULATION

WITHOUT WITHOUT STIMULATIONSTIMULATION

FECALELASTASE

FECALFECALELASTASEELASTASE

INDIRECTSTIMULATION

INDIRECTINDIRECTSTIMULATIONSTIMULATION STIMULATING

MEALSTIMULASTIMULATINGTING

MEALMEAL SUBSTRATESUBSTRSUBSTRATEATE

SECRETORY CAPACITYGRADING CHP

SECRETORY CAPACITYSECRETORY CAPACITYGRADING CHPGRADING CHP

DIGESTIVE FUNCTIONOF (LIPID) DIGESTIONDIGESTIVE FUNCTIONDIGESTIVE FUNCTIONOF (LIPID) DIGESTIONOF (LIPID) DIGESTION

4477

250mg13C-MTG250mg250mg

1313CC--MTGMTG

MAIZE BREAD20g FAT

MAIZE BREADMAIZE BREAD20g 20g FATFAT

PANCREATICLIPASE

PANPANCCREATICREATICLIPLIPASEASE

SUBSTITUTIONTHERAPY

SUBSTITSUBSTITUTIONUTIONTTHHERAPERAPYY

PERORAL ADMINISTRATIONPERORAL ADMINISTRATIONPERORAL ADMINISTRATION

DRUGLIPASEDRUGDRUG

LIPLIPASEASE

13C-MARKERANALYSIS

1313CC--MARKERMARKERANALYSISANALYSIS

EXOCRINE PANCRAETIC FUNCTION TESTSEXOEXOCCRINRINEE PANPANCCRAETRAETIC FUNCTION TESTSIC FUNCTION TESTSBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

13C- MTG BREATH TEST 1313CC-- MTG BREATH TEST MTG BREATH TEST

4488

peroraladminitration

peroralperoraladminitrationadminitration

enzymichydrolytic

GIT function

enzymicenzymichydrolytichydrolytic

GIT GIT funcfunctiontion

13C 1313C C

absorptionabsorpabsorptiontion

13C 1313C C

eliminationeliminaeliminationtion

measurementof 13C/12C ratiomeasurementmeasurementof of 1313C/C/1212CC ratioratio

cummulativeCO2 output

ccuummmulmulativeativeCOCO22 outputoutput

cPDRcPDRcPDR

13CO21313COCO22

CO2 excretionCOCO22 excretionexcretion

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

13C-substrate1313CC--substrsubstraattee

meal = bread + fatmeal = bread + fatmeal = bread + fat

4499 Kahl S., Best Pract.Res.Clin.Gastro. 2004KahlKahl SS., ., Best PractBest Pract..ResRes..ClinClin..GastroGastro. . 20020044

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

40 - 120 kIU LIPASE

THERAPY OK

THERAPY OK

COMBINATION WITH PPI

THERAPY OK

MALABSORPTIONSYNDROME

OTHER SOURCES

FAILED THERAPY

PABA, PLT, 13C-MTG TESTWITH SUBSTITUTION

FAILED THERAPY

SUBSTITUTION THERAPY

PANCREAS RESECTION

40 - 120 kIU LIPASE

THERAPY OK

THERAPY OK

COMBINATION WITH PPI

THERAPY OK

MALABSORPTIONSYNDROME

OTHER SOURCES

FAILED THERAPY

PABA, PLT, 13C-MTG TESTWITH SUBSTITUTION

FAILED THERAPY

SUBSTITUTION THERAPY

PANCREAS RESECTION

05

10152025303540

Control CyFi05

10152025303540

Control CyFi

10 mg/kg 13C-MTGcPDR 6 hours1100 mg/kg mg/kg 1313CC--MTGMTGcPDRcPDR 6 hours6 hours

13Carbon mixed triglyceride breath testand pancreatic enzyme supplementation in cystic fibrosis

Amarri S. et al.: Archives of Disease in Childhood 1997; 76: 349–351

13Carbon13Carbon mixed triglyceride breathmixed triglyceride breath testtestand pancreaticand pancreatic enzymeenzyme supplementation in cystic fibrosissupplementation in cystic fibrosis

AmarriAmarri S.S. et alet al.:.: ArchivesArchives ofof Disease in ChildhoodDisease in Childhood 1997; 76: 3491997; 76: 349––351351

CF without enzyme therapy2400 IU lipase/kg/food4800 IU lipase/kg/food

CFCF without enzyme therapywithout enzyme therapy2400 IU lipase2400 IU lipase//kgkg//foodfood448800 IU lipase00 IU lipase//kgkg//foodfood

cPDR 13CcPDRcPDR 1313CC

5050

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

13C-MTG - BREATH TEST WITH MIXED TRIGLYCERIDE13C-MTG - BREATH TEST WITH MIXED TRIGLYCERIDE

0,0

10,0

20,0

30,0

40,0

50,0

60,0

70,0

80,0

-50 50 150 250 350 450 550 650 750 850 9500,0

10,0

20,0

30,0

40,0

50,0

60,0

70,0

80,0

-50 50 150 250 350 450 550 650 750 850 9505151

CUT-OFF FELA: 200 μg/gCUTCUT--OFF FELAOFF FELA: 200 : 200 μμg/gg/g

FELA μg/gFELA FELA μμg/gg/g

CUT-OFF MTG: 30 %CUTCUT--OFF MTGOFF MTG: : 3030 %%

PANCREATITISPAPANCREATITISNCREATITIS

100 μg/g100 100 μμg/gg/gcPDR MTG (%)cPDRcPDR MTG (%)MTG (%)

NORMALNORMALNORMALCHP-ACHP-BCHP-CCHP-DNON-CHP

CHPCHP--AACHPCHP--BBCHPCHP--CCCHPCHP--DDNONNON--CHPCHP

246 BREATH TESTS WITH 13C-MTG160 CHP - 73 CONTROLS (NON-CHP)

CONFORMITY MTG & FELA - 80.2 % (191/238)

246 BREATH246 BREATH TESTTESTS WITHS WITH 1313CC--MTGMTG160 CHP 160 CHP -- 7733 CONTROLS (NONCONTROLS (NON--CHP)CHP)

CONFORMITYCONFORMITY MTG & FELA MTG & FELA -- 8080.2.2 % (% (191911/238/238) )

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

13C-MTG - BREATH TEST & FECAL ELASTASE13C-MTG - BREATH TEST & FECAL ELASTASE

0,0

10,0

20,0

30,0

40,0

50,0

60,0

70,0

80,0

-50 50 150 250 350 450 550 650 750 850 9500,0

10,0

20,0

30,0

40,0

50,0

60,0

70,0

80,0

-50 50 150 250 350 450 550 650 750 850 9505522

CUT-OFF FELA: 200 μg/gCUTCUT--OFF FELAOFF FELA: 200 : 200 μμg/gg/g

FELA μg/gFELA FELA μμg/gg/g

CUT-OFF MTG: 30 %CUTCUT--OFF MTGOFF MTG: : 3030 %%

100 μg/g100 100 μμg/gg/gcPDR MTG (%)cPDRcPDR MTG (%)MTG (%)

NORMALNORMALNORMAL

GROUP OF 28 CHP OF FTN WITH NORMAL VALUES OF BOTH PANCEATIC TESTS

FELA > 200 mg/g MTG > 30.0 %

GROUP OF 28 CHP OF FTN WITH NORMAL GROUP OF 28 CHP OF FTN WITH NORMAL VALUES OF BOTH PANCEATIC TESTSVALUES OF BOTH PANCEATIC TESTS

FELA > 200 mg/g MTG > 30.0 %FELA > 200 mg/g MTG > 30.0 %

SUBSTITUTION THERARYEXCESSED

IN 93 % PATIENTS

SUBSTITUTION THERARYSUBSTITUTION THERARYEXCESSED EXCESSED

IN 93 % PATIENTS IN 93 % PATIENTS

13C-MTG - BREATH TEST & FECAL ELASTASE13C-MTG - BREATH TEST & FECAL ELASTASEBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

5533

HELICOBACTER PYLORIPEPSINOGENS, GASTRITIS

COELIAC SCREENING - THERAPYCHRONIC PANCREATITIS

EXOCRINE PANCREATIC FUNCTIONQUANTITATIVE FIT

COLORECTAL CANCER SCREENING

HELICOBACTERHELICOBACTER PYLORIPYLORIPEPSINOGENPEPSINOGENSS, GASTRIT, GASTRITISIS

CCOOELIAELIACC SCREENING SCREENING -- TTHHERAPERAPYYCHRONIC PANCHRONIC PANCCREATITREATITISIS

EXOEXOCCRINRINEE PANPANCCREATREATIC FUNCTIONIC FUNCTIONQUQUANTITATIVANTITATIVEE FITFIT

CCOLOREOLORECCTTAAL L CANCER SCREENINGCANCER SCREENING

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

5544

Colorectal carcinoma is the most common tumor of the GE tractIn the Czech Republic (2008) was diagnosed 8236 subjects with CRC,

on CRC died 4313 patients, more than 50% of the mortality is due to the high proportion of patients diagnosed in advanced stages III and IV

Screening over 50 years - the target population in the Czech Republic includes 3,782,524 subjects

FOBT/TOKS screening test was carried out in 2010 only in 370,905 persons, ie. 9.8%

FOBT/TOKS + indicated colonoscopyin 2009 found only 618 CRC of 8236 diagnosed CRC, which is only 7.5%

Colorectal carcinoma is the most common tumor of the GE tractColorectal carcinoma is the most common tumor of the GE tractIn the Czech Republic (2008) was diagnosed 8236 subjects with CRIn the Czech Republic (2008) was diagnosed 8236 subjects with CRC, C,

on CRC died 4313 patients, on CRC died 4313 patients, more than 50%more than 50% of the mortality is of the mortality is due to the high proportion of patients diagnosed in due to the high proportion of patients diagnosed in advanced advanced stages III and IVstages III and IV

Screening over 50 years Screening over 50 years -- the target population in the Czech Republic the target population in the Czech Republic includes includes 3,782,524 3,782,524 subjectssubjects

FOBT/TOKS FOBT/TOKS screening test was screening test was carried outcarried out in 2010 only in 2010 only in in 370,905 370,905 persons, iepersons, ie. . 9.8% 9.8%

FOBT/TOKS + indicated FOBT/TOKS + indicated colonoscopycolonoscopyin 2009in 2009 found only 618 found only 618 CRCCRC of of 82368236 diagnosed diagnosed CRCCRC, , which is only 7.5% which is only 7.5%

Recommendations for the Ministry of Health Commission proposes a solution which enables

1. increase the number of subjects with FOBT/TOKS2. increase the detection of early CRC with more accurate test TOKS

regional cooperation with general practitionersand offer quantitative FIT for FOBT/TOKS

Recommendations for the Ministry of Health Commission Recommendations for the Ministry of Health Commission proposes a solution which enablesproposes a solution which enables

1. 1. increase the numbeincrease the number of subjectsr of subjects with FOBT/with FOBT/TOKSTOKS2. 2. increase the detection of early increase the detection of early CCRC RC with more accurate testwith more accurate test TOKSTOKS

regional cooperation with general practitionersregional cooperation with general practitionersand offer quantitative and offer quantitative FIT for FOBT/TOKSFIT for FOBT/TOKS

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

5555

0

20

40

60

80

100

g-FOBT i-FOBT qi-FOBT0

20

40

60

80

100

g-FOBT i-FOBT qi-FOBTHaemoccultHaemoccult

28,728,7%% 56,856,8%% 83,483,4%%

g-FOBT – GUAJAC TEST, HAEMOCCULTgg--FOBT FOBT –– GUAJAGUAJACC TEST, HAEMOCCULTTEST, HAEMOCCULT

gg--FOBT FOBT WITH SENSITIVITY < WITH SENSITIVITY < 30% 30% USED TILL 31.12. 2012USED TILL 31.12. 2012

Commitee of CRC screening at Ministry of health CR, July 2012Commitee of CRC screening at Ministry of health CR, July 2012Commitee of CRC screening at Ministry of health CR, July 2012

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

5566

0

20

40

60

80

100

g-FOBT qi-FOBTi-FOBT0

20

40

60

80

100

g-FOBT qi-FOBTi-FOBTRapid Rapid testtest

28,728,7%% 56,856,8%% 83,483,4%%

i-FOBT QUALITATIVE, RAPID TESTii--FOBT FOBT QUQUALITATIVALITATIVEE,, RAPID RAPID TESTTEST

2 TIMES HIGHER SENSITIVITY OF 2 TIMES HIGHER SENSITIVITY OF ii--FOBTFOBTss TO GUAJAC gTO GUAJAC g--FOBTsFOBTs

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

5757

SAMPLINS SYSTEM - OC SENSOR μSAMPLINS SAMPLINS SYSTSYSTEEMM -- OC SENSOR OC SENSOR μμ

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

ALUMINIUM FOILPERFORATION

ALUMINIUM FOILALUMINIUM FOILPERFORAPERFORATIONTION

FILTRATIONOF SAMPLE EXTRACT

FILTRATIONFILTRATIONOF SAMPLE EXTRACTOF SAMPLE EXTRACT

25 μl INJECTTO CUVETTE25 25 μμll INJECTINJECTTO CUVETTETO CUVETTE

STOOL SAMPLEINSERT

STOOL SAMPLESTOOL SAMPLEINSERTINSERT

TRANSFER of 10 mgSTOOL SAMPLE

TRANSFER of TRANSFER of 10 mg10 mgSTOOL SAMPLESTOOL SAMPLE

5588

Levi Z.,Rozen P.,Hazazi R.,Vilkin A.,Waked A.,Maoz E.,Birkenfeld S.,Leshno M.,Niv Y.Ann Intern Med. 2007;146:244-255

A Quantitative Immunochemical Fecal Occult Blood Test for Colorectal Neoplasia

LeviLevi Z.,Rozen P.,Z.,Rozen P.,HazaziHazazi R.,R.,VilkinVilkin A.,A.,WakedWaked A.,A.,MaozMaoz E.,E.,BirkenfeldBirkenfeld S.,S.,LeshnoLeshno M.,Niv Y.M.,Niv Y.Ann InternAnn Intern Med. 2007;146:244Med. 2007;146:244--255255

AA Quantitative Immunochemical Fecal Occult BloodQuantitative Immunochemical Fecal Occult Blood Test forTest for Colorectal NeoplasiaColorectal Neoplasia

ng Hb/mlng Hbng Hb/ml/ml SYMPTOMATIC SUBJECTS FOR COLONOSCOPYSYMPTOMATIC SUBJECTS FOR CSYMPTOMATIC SUBJECTS FOR COLONOSOLONOSCCOPOPYY

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

0

200

400

600

800

1000

1200

1400

1600

NORMAL ADENOM ADV.ADENOM CANCER0

200

400

600

800

1000

1200

1400

1600

NORMAL ADENOM ADV.ADENOM CANCER

iFOBT - OC Micro - Eikencut-off 75 ng/ml

iFOBT iFOBT -- OC MicroOC Micro -- EikenEikenccutut--offoff 7575 ngng/ml/ml

315 - 654 ng/mlmean 485 ng/ml315 315 -- 654654 ngng/ml/mlmeanmean 485485 ngng/ml/ml

140 - 263 ng/mlmean 202 ng/ml140 140 -- 263263 ngng/ml/mlmeanmean 202202 ngng/ml/ml

25 - 45 ng/mlmean 35 ng/ml25 25 -- 4545 ngng/ml/ml

meanmean 3535 ngng/ml/ml

697 - 1477 ng/mlmean 1087 ng/ml697 697 -- 14771477 ngng/ml/mlmeanmean 10871087 ngng/ml/ml

5959

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

Higher Fecal Immunochemical Test Cutoff LevelsTerhaar sive Droste JS et al. Cancer Epidemiol Biomarkers Prev. 2011; 20(2)

Higher Fecal Immunochemical Test Cutoff LevelsHigher Fecal Immunochemical Test Cutoff LevelsTerhaarTerhaar sive Drostesive Droste JS et al. Cancer JS et al. Cancer EpidemiolEpidemiol Biomarkers Biomarkers PrevPrev. 2011; 20(2) . 2011; 20(2)

75

80

85

90

95

50 75 100 125 150 20075

80

85

90

95

50 75 100 125 150 200

sensitivitysensitivitysensitivity

specificityspecificityspecificity

ngng/ml/ml

Optimization of qFIT cut-off, for indication to colonoscopy: Indicate as much as possible, all pathology - with 15% healthy subjects ?

NOT indicate healthy subjects, but decrease sensitivity about 15% ?

Optimization of qFIT cutOptimization of qFIT cut--off, for indication to off, for indication to colonoscopycolonoscopy: : Indicate as much as possible, all pathology Indicate as much as possible, all pathology -- with with 15% healthy subjects15% healthy subjects ??

NOT indicate healthy subjects, but NOT indicate healthy subjects, but decrease sensitivity about 15%decrease sensitivity about 15% ??

2145 subjects > 40 year2145 subjects > 40 yearwith with colonoscopycolonoscopy

76 x CRC76 x CRC

6060

QUANTITATIVE ANALYSIS of Hb IN STOOLQUANTITATIVEQUANTITATIVE ANALYSIS of HbANALYSIS of Hb ININ STOOLSTOOL

Quantitative determination of Hb in fecesby analyzer Eiken OC-Sensor micro

General University Hospital in Prague15000 analyzes in 5 years (2008-2013)

Data-mining analysis tool I-COPallowed to complete several databasesOpenLIMS, Laboratory data, FIT, Hb in

stool output with National Cancer Registry

Quantitative determination of Hb in fecesQuantitative determination of Hb in fecesby analyzer Eiken by analyzer Eiken OCOC--Sensor microSensor micro

General University Hospital in PragueGeneral University Hospital in Prague15000 analyzes15000 analyzes in 5 years (2008in 5 years (2008--2013)2013)

DataData--mining analysis tool Imining analysis tool I--COPCOPallowed to complete several databasesallowed to complete several databasesOpenLIMSOpenLIMS, Laboratory data, FIT, Hb in , Laboratory data, FIT, Hb in

stool output stool output with with National Cancer RegistryNational Cancer Registry

December 2013DecemberDecember 20132013

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

Kocna P., Májek O., Blaha M., Zima T., Dušek L.: Characteristics of Colorectal Cancer Detected by Quantitative Faecal Haemoglobin

Test in Hospital Opportunistic Screening. Clin Chem Lab Med 2014; 52, Special Suppl, pp S416

Kocna P., Májek O., Blaha M., Zima T., Dušek L.: Kocna P., Májek O., Blaha M., Zima T., Dušek L.: Characteristics of Colorectal Cancer Detected by Quantitative FaCharacteristics of Colorectal Cancer Detected by Quantitative Faecal Haemoglobin ecal Haemoglobin

Test in Hospital Opportunistic Screening. Test in Hospital Opportunistic Screening. Clin Chem Lab Med 2014; 52, Special Suppl, pp S416Clin Chem Lab Med 2014; 52, Special Suppl, pp S416

6611

810 ng/ml(180-1646)810810 ng/mlng/ml((180180--16461646))

969 ng/ml(346-1855)969 969 ng/mlng/ml((346346--18551855))

CRC TUMOUR POSITION - FIT TEST VALUESCRC TUMOUR POSITION CRC TUMOUR POSITION -- FIT TEST VALUESFIT TEST VALUES

FIT Hb ng/ml values are significantly non differentaccording to tumor location

FIT Hb ng/mlFIT Hb ng/ml values values are are significantly significantly non non differentdifferentaccording to tumor locationaccording to tumor location

FIT OC-Sensor method could be usedfor CRC screening in any tumor location

FIT OCFIT OC--SensorSensor method could be usedmethod could be usedfor CRC screeningfor CRC screening in any tumor locationin any tumor location

627 ng/ml(309-1422)627627 ng/mlng/ml((309309--14221422))

1322 ng/ml(695-1580)13221322 ng/mlng/ml((695695--15801580))

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

6262

810 ng/ml(180-1646)810810 ng/mlng/ml((180180--16461646)) 969 ng/ml

(346-1855)969 969 ng/mlng/ml((346346--18551855))

CRC TUMOUR POSITION - FALSE NEGATIVECRC TUMOUR POSITION CRC TUMOUR POSITION -- FALFALSESE NEGATIVNEGATIVEE

627 ng/ml(309-1422)627627 ng/mlng/ml((309309--14221422))

1322 ng/ml(695-1580)13221322 ng/mlng/ml((695695--15801580))

3/163/163/16 5/295/295/29

1/81/81/81/111/111/11

18.7%18.7%

12.5%12.5%9.1%9.1%

17.2%17.2%

False negative False negative -- 15,62%15,62%

SSensitivity for CRC ensitivity for CRC -- 84,38%84,38%

Kelley L, Swan N, Hughes DJ. - Colorectal Dis. 2013 Sep; 15(9): e512-21An analysis of the duplicate testing strategy of an Irish immunochemical FOBT

colorectal cancer screening programme

Kelley L, Swan N, Hughes DJ.Kelley L, Swan N, Hughes DJ. -- Colorectal Dis. 2013 Sep; 15(9): e512Colorectal Dis. 2013 Sep; 15(9): e512--2121An analysis of the duplicate testing strategy of an Irish immunoAn analysis of the duplicate testing strategy of an Irish immunochemical FOBT chemical FOBT

colorectal cancer screening programmecolorectal cancer screening programme

One test used with cutOne test used with cut--off off (75 ng/ml)(75 ng/ml)Percentage of nonPercentage of non--detected CRCdetected CRC 17.6%17.6%

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

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BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

Proteomics of colorectal cancer: overview of discovery studies and identification ofcommonly identified cancer-associated proteins and candidate CRC serum markers.

Jimenez CR, Knol JC, Meijer GA, Fijneman RJ. - J Proteomics. 2010;73:1873-1895

ProteomicsProteomics ofof colorectal cancercolorectal cancer:: overviewoverview ofof discovery studies and identificationdiscovery studies and identification ofofcommonly identified cancercommonly identified cancer--associated proteins and candidateassociated proteins and candidate CRCCRC serum markersserum markers. .

JimenezJimenez CR,CR, KnolKnol JC,JC, MeijerMeijer GA,GA, FijnemanFijneman RJ. RJ. -- JJ ProteomicsProteomics. 2010;73:1873. 2010;73:1873--18951895

5 year survival rate (%)5 year survival rate (%)5 year survival rate (%)

normal adenoma progressive locatized CRC lymph node CRC livercolon adenoma CRC metastasis metastasis

normal normal adenoma progressiveadenoma progressive locatized CRC lymph node CRC liverlocatized CRC lymph node CRC livercolon colon adenoma adenoma CRC metastasis metastasisCRC metastasis metastasis

10 - 15 years10 10 -- 15 years15 years

CRC stage: Dukes I-II Dukes III Dukes IVCRC stage: DCRC stage: Dukes Iukes I--II Dukes III Dukes IVII Dukes III Dukes IV

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MOLECULAR BIOLOGYDNA CHIPs FOR COLORECTAL CANCER SCREENING

MOLEMOLECCULULAARR BIOLOGBIOLOGYYDNA DNA CHIPCHIPss FOR CFOR COLOREOLORECCTTAALL CCAANCER SCREENINGNCER SCREENING

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

PreGen-Plus - DETECTION23 MOLECULAR MARKERS OF CR-CA

21 MUTATIONS - APC, K-ras, p53MIKROSATELLITE INSTABILITY - BAT-26

PreGenPreGen--Plus Plus -- DETECDETECTIONTION23 MOLE23 MOLECCULULAARR MARKERMARKERS OFS OF CCRR--CACA

2121 MUTAMUTATIONS TIONS -- APCAPC, K, K--ras, p53ras, p53MIKROSATELMIKROSATELLITELITE INSTABILITINSTABILITY Y -- BATBAT--2626

http://www1.lf1.cuni.cz/~kocna/glab/glency1.htmhttp://www1.lf1.http://www1.lf1.cunicuni..czcz/~/~kocnakocna//glabglab/glency1./glency1.htmhtm

6655NLM Medline on-line

abstractsNLM Medline onNLM Medline on--lineline

abstractsabstractsDirect link to MZČRNational lab.registryDirect link to MZČRDirect link to MZČRNational lab.registryNational lab.registry

http://gelab.zde.czhttp://http://gegelalab.b.zdezde..czcz

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.

http://www1.lf1.cuni.cz/~kocna/glab/glency1.htmhttp://wwwhttp://www11.lf1..lf1.cunicuni..czcz/~/~kocnakocna//glabglab/glency1./glency1.htmhtm

http://gelab.zde.czhttp://http://gelabgelab..zdezde..czcz

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ON - LINE INTERNET RESOURCESON ON -- LINE INTERNET RESOURCESLINE INTERNET RESOURCES

http://www1.lf1.cuni.cz/~kocna/ginet/index.htmhttp://wwwhttp://www11.lf1..lf1.cunicuni..czcz/~/~kocnakocna/g/ginetinet//indexindex..htmhtm

http://gweb.zde.czhttp://http://gwebgweb..zdezde..czcz

http://www1.lf1.cuni.cz/~kocna/ge_atlas/ge_frames.htmhttp://wwwhttp://www11.lf1..lf1.cunicuni..czcz/~/~kocnakocna/g/ge_atlase_atlas//gege_frames_frames..htmhtm

http://geatlas.zde.czhttp://http://geatlasgeatlas..zdezde..czcz

http://www1.lf1.cuni.cz/ukb/lectures.htmhttp://wwwhttp://www11.lf1..lf1.cunicuni..czcz//ukbukb//lectureslectures..htmhtm

BIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGY Kocna P.BIOCHEMICBIOCHEMICAL DIAGNOSTICS IN GASTROENTEROLOGYAL DIAGNOSTICS IN GASTROENTEROLOGY KocnaKocna P.P.