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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.
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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.
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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.
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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.
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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
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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
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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
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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
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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
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