Wann denke ich an Tumor ? Zwei Beispiele aus der Praxis v d M: 63J w 24.11.09 Lumbalgie 30.11.09 Schmerz Unterbauch seit 3 Tagen in 8 Wo 10 kg Verlust; Sono Gyn: Flüss. Douglas Ct abdm: Tumor im Pancreas Korpus/Schwanz massive Lebermets. Lymphangiosis CEA: 2407 ug/l < 3,0 CA 19-9 219 621 U/ml < 37 CT abdm Therapie: palliativ mit Gemzar + Tarceva PKMD HMS
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Wann denke ich an Tumor ? Zwei Beispiele aus der Praxis v d M: 63J w 24.11.09 Lumbalgie 30.11.09 Schmerz Unterbauch seit 3 Tagen in 8 Wo 10 kg Verlust;
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Wann denke ich an Tumor ?Zwei Beispiele aus der Praxis
v d M: 63J w 24.11.09 Lumbalgie30.11.09 Schmerz Unterbauch seit 3 Tagenin 8 Wo 10 kg Verlust; Sono Gyn: Flüss. DouglasCt abdm: Tumor im Pancreas Korpus/Schwanz
Begriff DefinitionSensitivität Anteil von Personen mit
Merkmal und pos. Test
Spezifität Anteil von Personen ohneMerkmal und neg. Test
pos. VorhersagewertAnteil von Personen mit pos. Test und dem Merkmal
neg. Vorhersagewert Anteil von Personen mitneg. Test ohne das Merkmal
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Guajak Test oder Haemoccult TestSensitivität: 20% bis 40%Steigerung: durch Wiederholung auf 90%falsch positiv: Fleischkonsum, Naso- Oro- Pharyn.bltgfalsch negativ: Ascorbinsäure (Vitamin C)
Die Sterblichkeitsrate am kolorektalen Karzinom kann durch wiederholten Guajak Test um 20% gesenkt werden
Anspruch: ab 450 J alle 2 J ???Alternativen: Haematoporphyrin Test
Immunologische Tests
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anerkannte Screening VerfahrenSigmoidoskopie / ColoskopieTest auf occultes BlutPapanicolaou-AbstrichSelbstuntersuchung der Brust nicht mehr
01741 192,76 totale Koloskopie01742 28,56 Zuschlag Polypenabtragung01743 12,97 Histologie bei Koloskopie01745 25,99 Früherkennung Hautkrebs01746 19,84 Zuschlag zu 01732 Hautscreening
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Welche Bedeutung haben Herr Hess und seine Arthusritter aus dem Kyphhäuserberg eigentlich für mich als Hausarzt in Minden?
Interessiert mich der EBM überhaupt?
Mein Verhältnis zu Ihnen als Gastroenterologeninteressiert mich sehr wohl: ich will nicht Ihre wertvolle Zeit stehlen.
Medizin nach Wissenschaft und nicht nach GeldPKMD HMS
Wann denke ich an Tumor ?3. der symptomatische Patient
AppetitlosigkeitGewichtsverlustSchwächeSchmerzen FieberSchwitzenJuckreizrektale BlutungKonstipation, Stuhlkalieber klein
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Serum Tumormarker
nicht für Früherkennung undnicht für Primärdiagnostik geeignetnur bei symptomatischen Patientendetection diagnosis managemant in combination with biopsy and us ct mri
zur Prognosestellungzur Therapieüberwachungzur Früherkennung von Rezidiven
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ASCO`s Guideline on Tumormarkers in Gastroinrestinal Cancers
Serum TumormarkerSymbol Name FunktionCEA carcinoembryonic antigen colorectal cancerCA 19-9 cancer antigen 19-9 pancreatic cancerAFP alpha feto protein LebermetastasenPSA prostate specific antigen nicht empfohlenP53 nicht empfohlenRas intrazelluläres Signalprotein siehe TumorimmunologieDCC deleted in colon cancer nicht empfohlenTS Thymidine synthase siehe TumorimmunologieTP Thymidine phosphtase siehe TumorimmunologieDPD Dihydropyrimidine dehydrogenaseMSI microsatellite instability siehe Tumorimmunologie18 q loss of heterogenicity siehe Tumorimmunologie
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Struktur des CEA Gen`s und des CEA Proteins
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Schema des CEA Gen`s und des CEA Proteinswww.journals.cambridge.org/fulltext
• Figure 1. Schematic representation of the human carcinoembryonic antigen (CEA) gene and protein (a) The CEA gene is encoded by a segment of DNA that is 3100 base pairs in length and is derived from eight exons (N domain, A1–A3, B1–B3 and M domain; Ref. 17). (b) The CEA protein product contains a leader sequence and three highly conserved repeat domains (1–3), each comprising 178 amino acids. Each of these three repeat domains can be further divided into two sub-domains (A and B), which share significant sequence homology. Each domain contains four cysteine residues at similar positions, which pair up to form A and B ‘loops’ stabilised by disulphide bridges between the cysteines. (a) The domains and sub-domains in the CEA gene correspond to the labelled domains of the mature protein shown in (b). The CEA protein consists of 668 amino acids, and has a configuration that is similar to that of other members of the immunoglobulin gene superfamily. The protein extends out from the cell membrane into the extracellular space, and is anchored through a hydrophobic C-terminal region (the M domain; Ref. 13). Most of the final molecular weight of CEA is provided by N-linked glycosylation, which occurs at the sites indicated in (b) (fig001hka).
P53 pathwayhttp://p53.free.fr/Crossraod of pathwaysCell growth regulationApoptosisMDM2, COP1, PIRH2, JMKPromote degradation of p53Genotoxic and non-genotoxicStress activates p53 in 2 stepsInhibition of mdm2Overtranslation of p53 RNA
Figure 1. A simplified model of some of the components of p53 signalling. Under normal conditions, the p53 pathway operates on 'standby' mode. Activation occurs in response to a variety of cellular stresses such as DNA damage and expression of activated oncogenes. See [1] for a more detailed description of the pathways activated by specific stresses. Post-translational modifications (such as phosphorylation at the indicated serine residues) activate the protein for DNA binding and transactivation of downstream 'effector' genes that mediate the tumour suppressor actions of p53. The outcome of activation depends on the nature and magnitude of the stress, its transduction via specific upstream kinases, and the resultant programme of p53-dependent gene expression. Transcriptional coactivators such as apoptosis stimulating protein of p53 and BRCA1 (not shown) may further 'fine tune' the response and, in some cases, preferentially promote specific cellular responses such as apoptosis. Many of the components of this signalling pathway are targets for genetic and/or epigenetic changes in breast cancer as described in the text. Not shown is the induction of MDM2, which acts as a negative feedback regulator of the pathway by promoting the degradation of p53. Because of space limitations, other important constituents of the pathway have had to be omitted.
8/06 Rezidiv- Metastase : erneute Resektion Lebermetastase in MHH 4/07 kein Hinweis auf ein Rezidiv
02.10.09 Ileocoloskopie Prof. Gartung: seit 4 Wo peranaler Blutabgang:Bef: GI-Blutung rectosigmoid. Exulcerierender Tumor 10-20 cm ab ano15.10.07 Prof. Gröninger: Abdm-perineal Resek mit TME und Samenbl.pT4, pN0 (0/24), MX, R0 – G2 Stadium IIB
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Wann denke ich an Tumor ?4. Ausgewählte Tumor des GI - Trakte
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Wann denke ich an Tumor ?4. Ausgewählte Tumore des GI - Trakte
1. Esophageal cancer 2. Gastrointestinal stromal tumors 3. Gastric marginal zone lymphoma MALT 4. Primary colon cancer 5. Familial colorectal cancer risk 6. Advanced colorectal cancer 7. Anal cancer 8. Pancreatic cancer 9. Hepatocellular carcinoma10. Prostate cancer11. Biliary cancer
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1. Esophageal cancercrude incidence in Europe 4,5 cases/100 000/year
DX: endoskopic histology according to WHO criteriasmall cell versus squamous cell carcinoma
staging: BC, liver- renal-function test, endoskopy, CTchest and abdomen
TX: surgery only when locally resectablepreoperative radiation?limited versus extensive disease; preop chemo/radiation
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2. Gastrointestinal stromal cancer GISTrare tumors incidence 1.5/100 000/year
DX: small esophago-gastric or duodenal nodule < 2cm > 2cm
DNA mismatch repairs erroneous insertion, deletionand misincorporation of bases; G/T and A/C pairing;during DNA replication and recombination;Repairing DNA damage;
mutational events disrut the superhelical structure
Mismatch repair proteins: MutL, MutS, MutH
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APC: adenomatosis polyposis coli
tumor suppressor gene
Long arm (q) chromosome 5between position 21 and 22Base pair 112.118.468 and 112.209.5322843 aminoacids 311 646 Da
controls number of cell divisionattachment to other cells
on short arm (p) of chromosome 1between position 34.3 and 32.1Between base pair 45.464.007 and 45.475.152
mutation in MUTYH gene causes autosomal recessiv familial adenomatou polyposis
MUTYH-associated polyposis
correction of mistakes in DNA replicationnonfunctioning glycosylase enzymewhen base excision repair is compromisedmutation in other genes, cell overgrowth,and tumor formation
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6. Advanced colorectal cancer412 900 cases in 2006 in Europesuspicion confirmation by US abdm/liver, CT, chest x-raycytology and histology mandatory
treatment: surgery wide resection of primary tumor with alllymphnodes
In T1-4 , N1-2, M0 (stage III, modf. Dukes C1-3) 5-FU5-FU/LV oxaliplatin (FOLFOX) for DFS disease free survival
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7. Anal cancer
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8. Pancreatic cancer10th most frequent, 2,6% of all ca in both sexes,leading cause of death: 65 000 each year
DX: infiltrating ductal adeno, 90%; acinar cell carcinoma;Pancreatoblastoma; no screening recommended;90% of patientes carry a mutation in K-ras oncogenesigns: jaundice, new onset diabetes mellitus, prancreatitis;Spiral CT; ERCP; MRCP; Ca 19-9 of limited diagnostic value
staging:TX:
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9. Hepatocellular cancerHCC 8,29/100 000/year; 5mc in men 8mc in womenrisk factors: ETOH cirrhosis, HBV, HCV