Presentasi sedang didownload. Silahkan tunggu

Presentasi sedang didownload. Silahkan tunggu

LABORATORY EXAMINATION OF ABDOMINAL MALIGNANCY Dr.. dr.Siti Muchayat, MS, Sp PK (K)

Presentasi serupa


Presentasi berjudul: "LABORATORY EXAMINATION OF ABDOMINAL MALIGNANCY Dr.. dr.Siti Muchayat, MS, Sp PK (K)"— Transcript presentasi:

1 LABORATORY EXAMINATION OF ABDOMINAL MALIGNANCY Dr.. dr.Siti Muchayat, MS, Sp PK (K)

2 ONCOGENESIS Growth promoting oncogenes Growth promoting oncogenes Tumor suppressor genes Tumor suppressor genes Transformation Uncontrolled growth, Abn biol behaviour Maturation arrest Abnormal diff Transformation Uncontrolled growth, Abn biol behaviour Maturation arrest Abnormal diff Activation Amplific Mutations Inactivation Mutations Care taker genes

3 CELLULAR ALTERATIONS IN NEOPLASTIC CELLS New tumor associated Ag - viral - oncofetal Loss of adhesion Loss of normal Ag Loss of contact inhibition Loss of cohesian Surface changes - electrical charge - surface glycoprot Cytopl changes - loss of microtubules - synthesis of tumor products Nuclei : -hyperchromatic -enlarged nucleus -enlarged nucleoli Karyotypic Changes: -oncogene -aneuploidy -marker chromosome

4 Setiap sel mempunyai mekanisme pertahanan ► untuk tidak menjadi sel kanker ► dengan beberapa gene independent. Tumor dapat berkembang ► o.k. Mutasi yang berulang pada semua gene dalam sel. Lesi prakanker ► dapat sembuh menjadi tumor jinak menjadi tumor ganas

5

6 TUMOR DEVELOPMENT AND METHODS OF DETECTION Diagnostic threshold “early” “late” Long “invisible” preliminary stage months to many years Immunological methods Biophysical methods 1 mcg 10 3 cells 1 mg 10 6 cells 1 g 10 9 cells g cells 1 kg cells

7 BIOKIMIA SEL TUMOR Perubahan dalam inti sel  Perubahan struktur kromosom Perubahan protein yang berkaitan dengan DNA Modifikasi t-RNA Pola enzim terdiferensiasi Perubahan dalam sitoplasma  Terbentuk (sintesa) protein oncofetal  masuk sirkulasi Perubahan pada permukaan sel  Terbentuk Ag baru Hilang nya Ag lama Perubahan struktur glikoprotein (shg mengubah transpor ke dalam sel & permeabilitas sel) Communication between cells is reduced (thus changing the power of adhesion and inhibit contact between cells)

8

9 PENANDA TUMOR Senyawa spesifik (dalam sirkulasi) yang dihasilkan  sel-sel ganas atau produk sekunder akibat pertumbuhan sel ganas. Penanda tumor yang Ideal Berkaitan dg proses keganasan Mempunyai korelasi dg masa tumor Dapat menunjukkan tipe, lokasi, dan stadium tumor Bisa menggambarkan efek terapi Mampu meramalkan prognosis penyakit Dapat meramalkan terjadinya kekambuhan/ metastasis Sampai saat ini belum ada PT ideal o.k. Heterogenitas dan komplexitas pertumbuhan sel ganas.

10 Pananda Tumor Dibedakan: 1. Produk yang dihasilkan oleh sel tumor itu sendiri Contoh: - Carcinoembryonic Antigen (CEA) - Alfa fetoprotein (AFP) Senyawa jg dihasilkan sel normal tp dgn jlh yg kecil 2. Produk yang menyertai proses keganasan Senyawa yg dibtk sekunder sbg akibat proses keganasan Contoh: - Carbohydrate Antigen 19-9 (CA 19-9) - Cancer Antigen 125 (CA 125)

11 Penanda tumor Produk Asal Tumor Produk Penyerta Tumor Hasil Sintesa Substansi aktif Parameter serum enzim jaringan metabolik berubah sehat masuk sirkulasi Onkofetal Ag (AFP, CEA, TPA) Enzim (GGT, LDH, ALP, AP) CA 19-9 Ag Onkoplacental (HCG, SP1) Hormon (Gastrin, insulin) CA 125 Ag Ektopik (enzim; glikolisis Metabolit (feritin, β2-mikroglobulin) MCA Sintesa protein, sintesa as.nukleat) PAP

12

13 HCC

14 Sampai saat ini tes yang mampu untuk surveilance HCC adalah Serum αfetoprotein dan hepatic ultrasonografi. Kadar AFP mempunyai sensitivitas dan spesifisitas rendah. Ultrasonografi ; tergantung dan terbatas kemampuannya membedakan HCC dengan non neoplastik. Dikembangkan biomarker sebagai indikator proses biologi’: selular, biokimia, molekular, perubahan genetik Selama tahun dikembangkan 2784 penelitian; gene dan protein expression microarray, proteomic, tumor imunologi,

15 PENDAHULUAN Hepatocellular carcinoma (HCC) keganasan banyak terdapat di dunia. Insiden : range <10 kasus per 100,000 populasi di North America dan Western Europe seperti di Iran, Iraq dan India 50 – 150 kasus per 100,000 populasi di bagian Africa dan Asia. HCC : Sebagian besar mengakibatkan kematian. Dengan meningkatnya insiden dan mortalitas HCC, merefleksikan peningkatan prevalensi hepatitis C virus (HCV) infeksi.

16 Major etiologies of HCC. Chronic hepatitis B, C, and D Toxins (e.g., alcohol, tobacco, aflatoxins) Hereditary metabolic liver diseases (e.g., hereditary hemochromatosis, a 1 antitrypsin deficiency) Autoimmune hepatitis State of insulin resistance Overweight in males Diabetes mellitus Nonalcoholic steatohepatitis (NASH) or nonalcoholic Fatty liver disease (NAFLD)

17 Hepatocarcinogenesis

18

19

20

21

22

23 Single Marker Α Fetoprotein * Fetal globulin disintesa sbgn besar di jaringan hati embryonal dan sel yolk sac di sekresi ke serum semasa janin. AFP hilang ses bayi berumur 6 minggu dan  pd orang normal. Prinsip Pem: Cara immunodifusi kepekaan sampai 5  g/l. Cara counter imunoelektroforesis kepekaan sampai 100 mg/ml. Cara pasive haemagglutinasi 30 ng/ml. RIA 2-5 ng/ml.

24 AFP Positip pada; - primer hepatoma 40-80% (imunodifusi), 80-90% (RIA). - Juga pd teratoblastoma gonad, ataxia telengiectasis, hepatitis infeksiosa, Ca hati metastatik, Ca lambung. - Prognosa pd Tx surgikal, radiasi, chemoterapi dari hepatoma. - Pada sirosis meramal adanya hepatoma. - Meningkat pd regenerasi yang hebat dari sel-sel hati, mis; hepatektomi partial, hepatitis yang parah

25 AFP ☻ Sensitivitas antara 39%-65%, spesifisitas 76%-97% Variasi sangat tinggi o.k. Pada penelitian yang berbeda menggunakan cut-off yang berbeda dan juga penelitian yang retrospektif. ☻ Dapat diandalkan dengan menggunakan cut-off > 400 IU/ml, nilai ini sangat tinggi  persentase sangat kecil kejadian HCC. ☻ Penting disini batasan dari marker ini.

26 AFP- L3  Varian fucosylat ( tambahan a1-6 fucose residu) dari glikoprotein AFP yang mempunyai affinitas tinggi pada rantai glukosa dari lens culinaris.  Dipakai diagnosis HCC sebagai; Lens culinaris agglutinin-reactive α-fetoprotein.  AFP- L3 adalah AFP-L3% (rasio AFP-L3 : total AFP) secara lectin- affinity elektrophoresis, band diukur dg densitometer.  Mempunyai korelasi dengan staging HCC Berkorelasi dengan prognosis penderita HCC Berhubungan dengan menurunnya fungsi hati, differensiasi yang buruk, karakteristik biologi dari HCC.  HCC yang kecil < 2 cm follow-up perjalanan penyakit & evaluasi terapi

27

28 Sensitivitas dan Spesifisitas Cut-off 10%  sensi 36,1%  spesi 93,4% 15%  sensi 30,9%  spesi 99,5% 15%  sensi 55,3%  spesi 93,9% 35%  sensi 75%  spesi 83% Penelitian terakhir : Cut-off 15% sensi 96% dan spesi 92% Inkonsistensi hasil karena sulit menstandarkan hasil konversi data kualitatif dari imunobloting dg densitometer

29 Carcino Embryonic Antigen CEA * Glycoprotein yang dihasilkan jaringan embryonal & jaringan neoplastik sistem GI. * Prinsip pem: Cara RIA * Harga normal < 2,5 ng/ml.

30 * Interpretasi - Me  pd ; kronik aktiv hepatitis (22%), hepatoma (63%), sirosis alkoholik (88%). - Ada korelasi dg derajat gangguan fungsi hati (ALP, GOT). - Tertinggi pd Ca colon, Ca pankreas (50%) 4X nilai N. Utk prognosa post reseksi Ca colorectal. Metastase ke hati CEA 4X nilai N.

31

32 ANTI p 53 Antibodi P53 adalah protein tumor suppressor yang diproduksi gene p53. Pada keganasan didapatkan konsentrasi tinggi p53 protein mutasi dengan paruh waktu terpanjang. Diawali dengan mutasi protein jangka waktu lama  terbentuk auto antibodi yaitu anti-p53. Kelemahan anti p53: Tidak sensitif untuk HCC 20-25% 100% positif pada Cholangiocarcinoma, juga pada keganasan: gaster, pancreas, esofageal, dan colon.

33 Des-Gamma Carboxy Prothrombin (Protein induced by vitamin K absence or antagonist-II /PIVKA_II) Pada HCC : terjadi penurunan aktivitas  -glutamyl carboxylase (GGC) tanpa defisiensi vit K, dg abnormal prothrombin time. Defek post-translational yang didapat pada prekursor prothrombin. Pada orang normal prothrombin diproduksi hepatosit ; dg konversi 10 glutamic asid (Glu) residu didekat domain NH2- terminal dari prekursor prothrombin, menjadi  -carboxyglutamic acid (Gla) oleh enzim vit K dependent carboxylase dg  -carboxylasi.

34 bile duct cancer Risk factors  Patients with chronic ulcerative colitis who develop primary sclerosing cholangitis are prone to cholangiocarcinoma. The lifetime risk of developing this cancer is 10-20% with primary sclerosing cholangitis. Some patients with Crohn's disease may also be at risk.ulcerative colitissclerosing cholangitisCrohn's disease  Infection with the liver flukes Clonorchis sinensisand Opisthorchis viverrini have been causally linked. Ascaris lumbricoides infection has also been implicated.Opisthorchis viverriniAscaris lumbricoides  Industrial chemical exposure: chemicals used in the aircraft, rubber and wood-finishing industries have been implicated  Thorium exposure is associated with an increase in cases of cholangiocarcinoma. [  Congenital abnormalities of the bile ducts, eg choledochal cysts.  Caroli's disease (a rare congenital disorder of the intrahepatic bile ducts associated with autosomal recessive polycystic kidney disease where the bile ducts become chronically dilated).autosomal recessive polycystic kidney disease  Recently implicated potential risk factors for the intrahepatic form include hepatitis C,HIV, cirrhosis and diabetes.hepatitis CHIVcirrhosisdiabetes

35 bile duct cancer The patient usually presents with the following symptoms  jaundice (yellowness of the skin)  poor appetite, Weight loss is variable and weakness and fatigue.Weight loss  hepatomegaly. hepatomegaly  Abdominal pain, right upper quadrant, in advanced disease. Abdominal pain  Pale-coloured stools, passage of dark urine, upper gastrointestinal pain (dull ache in the upper right quadrant), weight loss, anorexia and general malaise are common features.  Pruritus Pruritus  Splenomegaly is present if prolonged biliary obstruction has caused secondary biliary cirrhosis. Splenomegalybiliary cirrhosis  The presence of a palpable gallbladder (Courvoisier's sign) may occur with tumours distal to the cystic duct.

36 Investigations  Diagnosis: radiological investigations (including CT or MRI) and pathological assessment from a biopsy, fine needle aspiration or biliary brush cytology. [2]2  LFTs: elevated conjugated bilirubin. Cholestatic picture with markedly elevated alkaline phosphatase, gamma-GT elevated with aminotransferases affected minimally. LFTs  Prothrombin time and INR may be prolonged.  Tumour markers: carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen(CEA) tumour markers may be raised (also found in other causes of obstructive jaundice). Tumour markerscarcinoembryonic antigenobstructive jaundice  Alpha-fetoprotein is not produced by cholangiocarcinoma.

37 Differential diagnosis  Acute cholecystitis. Acute cholecystitis  Bile duct strictures.  Extrabiliary tumour compressing biliary system.  Biliary adenoma.  Primary biliary cirrhosis. Primary biliary cirrhosis  Primary sclerosing cholangitis. Primary sclerosing cholangitis  Ascending cholangitis. Ascending cholangitis  Obstructive choledocholithiasis.choledocholithiasis  Pancreatic tumours. Pancreatic tumours  Choledochal cysts. Choledochal cysts  Acute hepatitis. Acute hepatitis

38 Complications  The risk of biliary tract sepsis is increased and may cause a deterioration which is amenable to antibiotic therapy.  Secondary biliary cirrhosis occurs in 10-20% of patients.

39 Prognosis  Progressive deterioration with average survival of months from diagnosis. The overall survival rates are low because many patients present with unresectable or metastatic disease.  Even in patients undergoing aggressive surgery, five-year survival rates are 10-40% for cholangiocarcinoma.  Prognosis is much better for those with extrahepatic tumours who are suitable for early surgical intervention.  Intrahepatic lesions carry the worst prognosis.

40 Types of bile duct tumors Two major types of bile duct tumors are found  Distal bile duct tumors: tumors affecting the bottom half of the bile duct  Klatskin's tumors: Tumors affecting the upper part of the bile duct Unresectable distal bile duct cancer  In patients with advanced distal bile duct cancer that is not surgically removable

41 Klatskin's tumors  Bile duct cancer of the upper part of the bile duct is also called Klatskin's tumor.  Klatskin's tumors involve the upper part of the bile duct as divides to enter the right and the left parts of the liver. The bile ducts in the liver are called right and left hepatic ducts.  The tumor may involve one or both right and left sides of the hepatic ducts as they enter the liver. The hepatic ducts are closely associated with the blood vessels that supply blood to the liver.  Klatskin’s tumors are closely associated with liver and as they grow invasion into the blood vessels that supply blood to the liver

42 Treatment of Klatskin's tumor  Complete removal of the tumor is the only effective and potentially curative treatment for cancers of the upper bile duct. Klatskin's tumors are removable if:  Blood supply to one side of the liver is not affected by the tumor: Klatskin’s tumors are closely associated with liver and as they grow invasion into the blood vessels that supply blood to the liver is often found. If the blood supply to one side of the liver is free of tumor then the portion of the liver invaded by the tumor can be removed.  The bile duct to one side of the liver is free of tumor: Unresectable Klatskin's tumor  Klatskin's tumor is unresectable if it invades the blood supply to both sides of the liver and/or the hepatic duct to the both sides of the livertherapy treatments are used. In general these tumors respond poorly to treatment

43 Stomach CANCER

44 Signs and symptoms of stomach cancer :  Fatigue  Feeling bloated after eating  Feeling full after eating small amounts of food  Heartburn that is severe and persistent  Indigestion that is severe and unrelenting  Nausea that is persistent and unexplained  Stomach pain  Vomiting that is persistent  Weight loss that is unintentional

45 GASTRIC CANCER Factors that increase your risk of stomach cancer include:  A diet high in salty and smoked foods  A diet low in fruits and vegetables  Eating foods contaminated with aflatoxin fungus  Pickled foods, the use of refrigeration for preserving foods  Family history of stomach cancer  Infection with Helicobacter pylori  Long-term stomach inflammation (chronic gastritis)  Pernicious anemia  Smoking  Stomach polyps

46 Causes Stomach cancer  In general, cancer begins when an error (mutation) occurs in a cell's DNA.  The mutation causes the cell to grow and divide at a rapid rate and to continue living when normal cells would die.  The accumulating cancerous cells form a tumor that can invade nearby structures.  And cancer cells can break off from the tumor to spread throughout the body.

47

48 It is well known that Helicobacter pylori infection is one of the major risk factors for gastric cancer, And that low values of the pepsinogen (PG) I-to-II ratio can be a marker for atrophy of the gastric mucosa, as well as a marker for gastric cancer risk. Therefore, the prevalence of H. pylori infection and the frequency of gastric mucosal atrophy may influence the incidence of gastric cancer.

49  FOBT (Fecal Occult Blood Test): * darah tersamar  untuk m’deteksi adanya darah yang tersembunyi (tu. pd usus) Indikasi: Ca Colon / lambung, Adenoma. Colitis ulcerativa. Diverticulitis. Ulcus lambung. Hernia diapragmatika  CA19-9 *  CA19-9 is a monoclonal antibody generated against a colon carcinoma cell line to detect a monosialoganglioside found in patients with gastrointestinal adenocarcinoma.  It is found it to be elevated in 21 to 42% of cases of gastric Ca 20 to 40 % of colon Can, & 71 to 93 % of pancreatic Ca.  Has been proposed to differentiate benign from malignant pancreatic disease, but this capability remains to be established.

50 alpha 4GnT  the quantitative RT-PCR method targeted to alpha 4GnT mRNA will be useful for the detection of circulating gastric cancer cells in the peripheral blood. CA72-4 *  more important than CA19-9 as a tumor marker in gastric cancer patients.  The CA 72-4 test recognizes the presence in serum of mucin-like tumour associated glycoprotein TAG 72 (M W daltons)  the use of serum CA 72-4 measurements may be more useful than other tumor markers in the diagnosis, prognosis and detection of recurrence in patients with gastric cancer. appeared to be a useful marker for managing gastric cancer.  highly specific to gastric cancer and may be more reliable as a tumour marker than CEA for gastric cancer.  a reliable tumour marker of disease stage and activity in gastric cancer.

51 CEA (carcinoembryonic antigen) *  RT-PCR analysis of CEA mRNA in the peripheral blood seems to be a promising tool for the early detection of micrometastatic circulating tumor cells in gastric carcinoma patients and that it can be useful used to identify patients at risk for recurring. CD44V6  could now be used as an indicator of tumor progression in biopsies of patients with gastric carcinoma. CDw75  in tumor tissue may be a new marker of the biological behavior of gastric carcinoma.  a significant histopathological marker for more advanced stage of gastric carcinoma and indicates a poor prognosis for the patients.

52 Cobalamin-binding protein (binder)  Detection of the binder may be clinically valuable as a possible marker in the diagnosis of gastric cancer. CPS1 (Carbamyl phosphate synthetase I)  can be used as a novel marker for gastric carcinoma originating from complete type intestinal metaplasia.

53 DR-70  is a simple blood test that screens for 13 different cancers at the same time. It is highly specific and catches cancer long before you would suspect anything was amiss.  Cancers that can be detected by the test are of the lung, colon, breast, stomach, liver, rectum, ovary, cervix, esophagus, thyroid, and pancreas, and trophoblast and malignant lymphoma.  AMDL has also received clearance from the FDA to market the PyloriProbe™ test, which can detect the presence of Helicobacter Pylori in the stomach, the primary cause of ulcers and a potential cause of stomach cancer.

54 CA PANCREAS

55 Pancreatic Cancer Symptoms: Location Matters  Initially, pancreatic cancer tends to be silent and painless as it grows.cancer  By the time it's large enough to cause symptoms, pancreatic cancerhas generally grown outside the pancreas. At this point, symptoms depend on the cancer's location within the pancreas:cancerpancreascancerpancreas  Pancreatic cancer in the head of the pancreas tends to cause symptoms such as weight loss, jaundice (yellow skin), dark urine, light stool color, itching, nausea, vomiting, abdominal pain, back pain, and enlarged lymph nodes in the neck.weight lossjaundiceskinitchingnauseavomitingabdominal painback painenlarged lymph nodes  Pancreatic cancer in the body or tail of the pancreas usually causes belly and/or back pain and weight loss.back pain

56 Gastrointestinal Symptoms  Abdominal pain. More than 80% of people with pancreatic cancer eventually experience some abdominal pain as the tumor grows. Pancreatic cancer can cause a dull ache in the upper abdomenradiating to the back. The pain may come and go.abdomen  Bloating. Some people with pancreatic cancer have a sense of early fullness with meals (satiety) or an uncomfortable swelling in the abdomen. Bloating  Nausea  Diarrhea Diarrhea  Pale-colored stools. If the duct draining bile into the intestine is blocked by pancreatic cancer, the stools may lose their brown color and become pale or clay-colored. Urine may become darker.

57 Whole-Body Symptoms  Weight loss  Malaise  Loss of appetite  Elevated blood sugars. Some people with pancreatic cancer develop diabetes as the cancer impairs the pancreas' ability to produce insulin. blooddiabetesinsulin

58 Risk factors for pancreatic cancer  Environmental and familial risk factors for the disease  Male gender, aging, obesity, diabetes (type 2 or hyperglycemia occurring as a paraneoplastic phenomenon), tobacco smoking, high consumption of fried/grilled/processed meats, and chronic pancreatitis.  Risk factors are common to the etiology of cardiovascular disease and other frequently occurring malignancies.  Genetic risk factors are believed responsible for 5–10% of pancreatic cancer cases [Table 2]. They include both genetic disorders where pancreatic involvement is not the usual target organ and also pancreas-specific genetic mutations causing cancer

59 Hypothesis Driven Research  Pathways important to the development of pancreas cancer including stimulation of proto-oncogenes, inactivation of tumor suppressor gene, dysregulation mechanisms including aberrant methylation and telomerase activity, and the role of proteins known to be important in gastrointestinal cancers including the mucin family.  Proto-oncogenes that promote abnormal proliferation are thought to be important in pancreas cancer.  K-ras, which encodes a signal transduction protein, has been found to have a mutation in codon 12 in greater than 90% of pancreas cancer cases [72]. However, it is frequently detected in the serum and pancreatic juice only in those with advanced disease

60  There are no population wide screening tests for pancreas cancer. The best established marker is CA which is a sialylated Lewis antigen of the MUC1 protein with an overall sensitivity of 80% and specificity of 90%.  Unfortunately, CA 19-9 may be positive in patients with non malignant diseases including cirrhosis, chronic pancreatitis, cholangitis, as well as other gastrointestinal cancers. Patients with certain blood types are incapable of expressing the antigen recognized by CA Furthermore, only 65% of those with resectable pancreas cancer have elevated CA 19-9 levels [5].  Additionally, CA 19-9 is a poor screening test.

61  Precursor lesions of pancreas cancer include intraductal papillary mucinous neoplasms (IPMN), mucinous cysts, and pancreatic intraepithelial neoplasia (PanIN).  Brugge et al.demonstrated that carcinoembryonic antigen (CEA) at a level greater than 192 ng/mL optimally predicted that a cyst was mucinous  The pancreatic cyst fluid DNA analysis (PANDA) investigators reported that a DNA quality and mutational analysis can improve the differentiation of malignant from benign mucinous cysts  Analysis of EUS-FNA tissue for K-ras point mutations can also help differentiate pseudo-tumoral chronic pancreatitis from pancreas cancer thus improving the accuracy of cytopathology from 86% to 90%

62

63 Starts with an initiatingi nsult followed by changes in the cellular environment and premature digestive enzyme activation. Mutations of genes associated with trypsinogen activation/inactivation predispose the pancreas to development of disease. As disease progresses defective autophagy, increased inflammation, pancreatic stellate cell activation, and fibrosis occur. Advancement toward pancreatic cancer and metastasis is also associated with defective autophagy, as well as extracellular matrix degradation, cell proliferation, expression of oncogenic Kras and loss of tumor suppressors (e.g.,P16 and P53).

64

65 CA Marker ut karsinoma colorectal dan pankreas - Disintesis : 1. Pankreas 2. Sel duktus biliaris 3. Gaster, kolon, endometrium dan epitel saliva

66 Peningkatan CA 19-9 (> 37 kU/L) terdapat: 1. Kanker Pankreas (80%) 2. Kanker Hepatobilier (67 %) 3. Kanker Gaster (40-50%) 4. Kanker Hepatoselluler (30-50%) 5. Kanker Payudara 15% Kadar CA 19-9 berkorelasi dgn stadium Ca pankreas

67 CA 19-9 * - Berhub erat dgn ukuran tumor - Bukan utk skrining - Jika kadar >1000 U/ml berhub dgn unresectable surgically - Cut off 37 bisa membedakan Ca pankreas dgn yg jinak dgn sensi 77% dan spesi 87%

68 Negatif palsu : - Pada std awal Positif palsu Pasien jaundice meskipun ca pankreas (-) CA 19-9 berguna - Diukur pd waktu awal diagnosis - Sesudah terapi utk evaluasi respons terapi tiap 3 bln - Follow up (relaps atau tdk)

69

70

71 Pathology of pancreatic adenocarcinoma and its precursor lesions. (a Gross photograph of an infiltrating adenocarcinoma. Note the dramatic narrowing of the pancreatic duct associated with the poorly defined white neoplasm.

72 Carcino Embryonic Antigen (CEA) * Sel epitel pankreas tda 3 yaitu: 1.Asiner ± 80% 2.Duktus ± 10-15% 3.Islet ± 1-2% Sekitar 95% bagian eksokrin pankreas (duktus dan asiner) dan bagian endokrin hanya 1-2%

73 Greenbaum Cancer Center defines the stages of pancreatic Stage I: Cancer is found only in the pancreas itself and not in other organs. Stage II: Cancer has spread to nearby organs, such as the duodenum or bile duct,but has not entered the lymph nodes. Stage III: Cancer has spread to lymph nodes near the pancreas. The cancer may or may not have spread to nearby organs. Stage IVA: Cancer has spread to organs, such as the stomach, spleen, and colon,which are near the pancreas, but it has not spread to distant organs, such as the liver or lungs. Stage IVB: Cancer has spread to organs, such as the stomach, spleen, or colon,that are near the pancreas or to places far away from the pancreas, such as the liver or lungs

74

75 PENDAHULUAN CA COLON  Penyakit keganasan  penyebab kematian ke-2 (22%) stlh kardiovaskular.  Kanker kolon dan rektum  kanker kolorektal.  Insidensi tertinggi  Eropa barat dan Amerika utara, Eropa timur  Insidensi rendah  Asia, Afrika & Amerika Sltn. 75

76  thn 2002 di Amerika : insidensi kanker kolon / thn, mortalitas  / thn. insidensi kanker rektum / thn, mortalitas 8.500/ thn Di Indonesia belum diperoleh data pasti 76

77 PENDAHULUAN  laporan dari India  30%-50% pndrt dtg dg penyakit ↓ sudah lanjut Sos-ek = Ind. Gejala stadium awal sgt minimal  Perbed pendapat petunjuk umum skrining : Tanpa faktor risiko dg risiko atau dg gjl:perdarahan 77

78 PENDAHULUAN  30%-40% org dewasa > 50 th (sosioekonomi atas):  mlkkn px skrining teratur  dapat m’deteksi awal  tx kuratif  Mcm px laboratorium  dx / monitoring / prognosis penderita kanker kolorektal ? 78

79 I. Kanker Kolon dan Rektum.  Lebih dari 80% tumor kolorektal berkembang dari polip adenoma A. Penyebab:  Sebagian besar tidak diketahui. Defek dalam ge n lingk./ lain2? diturunkan spontan riw.kel (+) 79

80 Penyebab: A. Faktor genetik (6%) 1. Gen APC  FAP:  Dalam kead normal  supresor  Dalam kead tergg  m’aselerasi pertumb.sel mjd polip. Familial adenomatous polyposis (FAP)  diturunkan. Mutasi gen tdk diturunkan (>>> tjd pd kanker kolon spontan).  2- Hereditary Nonpolyposis Colorectal Cancer (HNPCC):  < 3% mrp penyebab kslrhn kanker kolon.  50% - 80% org dgn keturunan kelainan gen  kanker (+).  2 gen yg m’pengaruhi HNPCC  MSH-2 dan MLH-1. 80

81 Penyebab: B. Faktor-faktor biokimia  Cyclooxygenase (COX-2):  meningkatkan kadar prostaglandin E2 (PGE2)  akibat proses inflamasi, vasodilatasi, vasokonstrk, mengatur kontraksi otot.  m’hambat hormon-hormon yang meregulasi metabolisme lemak.  m’stimulasi faktor penghambat apoptosis pd semua sel, termasuk sel-sel kanker  m’aktivasi interleukin-6 (IL-6)  berhub. dgn invasi sel kanker. 81

82 Penyebab: C.Inflamatory bowel disease (IBD)  termasuk Crohn’s disease dan Colitis ulcerative.  disebabkan oleh tjdnya luka yg menetap di dlm sal.gastro intestinal.  Pd bbrp kasus m’hslkan perub. kanker. 82

83 Gejala Klinis.  Perub.pola BAB: ( menetap lebih dari 6 bulan)  nyeri perut kolik/ menetap.  BAB padat/ cair.  BAB tdk tuntas.  muntah-muntah, perut distensi/ kembung (krn sumbatan usus). BB  Perub.pola BAB: ( menetap lebih dari 6 bulan)  nyeri perut kolik/ menetap.  BAB padat/ cair.  BAB tdk tuntas.  muntah-muntah, perut distensi/ kembung (krn sumbatan usus). BB  Perdarahan rektal :  Hematochezia  awal peny  prog. Baik.  melena  letak lbh atas. anemia def. Fe.  Perdarahan rektal :  Hematochezia  awal peny  prog. Baik.  melena  letak lbh atas. anemia def. Fe. 83

84 Gejala berdasarkan letak kanker Letak pada rektum & rektosigmoid:  Melena  Konstipasi  Pencil- shape stools  Tenesmus  Diare  Nyeri abdomen Letak pada kolon kiri:  Nyeri abdomen  Melena  Konstipasi  Mual,muntah 84

85 Gejala berdasarkan letak kanker Letak pada kolon kanan:  Nyeri abdomen  Lemah  Terdapat gejala anemia (defisiensi besi)  Melena intermitten atau kronik  Mual  Massa abdomen Letak pada kolon melintang:  Konstipasi  Melena  Nyeri abdomen-kejang  Obstruksi parsial atau total / perforasi usus.  Gejala anemia 85

86 Faktor-faktor Risiko Jenis kelamin: - wanita dan laki-laki  risiko sama. - Laki-laki  kanker rektal - Wanita  kanker kolon. Umur: - > 90% tjd pada usia > 50 thn. (sekitar 1/ 2000 / th) - stlh usia 65 thn  3/ 1000 / th - < 20 thn  kurang dari 1/ per th. Jenis kelamin: - wanita dan laki-laki  risiko sama. - Laki-laki  kanker rektal - Wanita  kanker kolon. Umur: - > 90% tjd pada usia > 50 thn. (sekitar 1/ 2000 / th) - stlh usia 65 thn  3/ 1000 / th - < 20 thn  kurang dari 1/ per th. Riwayat keluarga (+): - 15% dari 25% riw. Kel.(+)  < 45 th berkembang mjd kanker. Faktor gaya hidup : - Negara industri > neg. berkmbg.  Orang dengan penyakit infeksi usus besar. 86

87 Petunjuk-petunjuk skrining umum:  Klmp risiko ringan (> 50 th): - FOBT(fecal occult blood test) tiap th - Sigmoidoskopi fleksibel tiap 5 th - Kolonoskopi tiap 10 th.  Klmp risiko sedang : - mempunyai riwayat keluarga polip  dianjurkan untuk kolonoskopi tiap 3 tahun  Kelompok risiko tinggi meliputi: -1 memp. keturunan gen mutasi HNPCC (sebagai contoh: gen MSH- 2 atau MLH-1)  Kolonoskopi tiap 1 th/ 2 th mulai usia 20 th. -2 mempunyai gen mutasi (APC)  sigmoidoskopi atau kolonoskopi dimulai pada awal pubertas. -3 predisp. kolitis (Chron,s desease)  skrining tahunan dengan kolonoskopi,  biopsi pada daerah yang dicurigai. 87

88 Petunjuk monitoring stlh deteksi polip pre kanker  kolonoskopi berulang 1-3 kali setelah terdeksi, tgt perub.ukuran, jmlh, dan tipe polip.  digital rectal examination (DRE)  FOBT.  kolonoskopi berulang 1-3 kali setelah terdeksi, tgt perub.ukuran, jmlh, dan tipe polip.  digital rectal examination (DRE)  FOBT. 88

89 Pemeriksaan laboratorium pada kanker kolorektal Px untuk skrining umum:  a. FOBT (Fecal Occult Blood Test): * - darah tersamar  untuk m’deteksi adanya darah yang tersembunyi (tu. pd usus) X prinsip (metode)  1. guaiac based (tradisional) 2. immunoassay  1. guaiac based:  3 sampel feses  restriksi mkn tertentu 2 hr sbl px.  me(-) mortalitas sebesar 15%-35%  Sensitivitas rendah 20%-30%.  Spesifisitas rendah.  akurasi dipengaruhi ol: mknn yg mgndg Fe, zat kimia peroksidase, obat-obatan misalnya Aspirin, anti radang non steroid, vitamin C.  sekitar 5%-10% kasus betul-betul terdeteksi sebagai kanker  tdk cocok utk skrining. 89

90 Px skrining umum 2. Immunoassay: rapid test  kualitatif, prinsip ELISA  sampel tunggal, tanpa restriksi mknn  m’deteksi kadar darah tersamar hingga 50 ng/ mL Hb atau 6 ug Hb/ gr feses, atau 0,3 ml darah feses   sensi, spesi > guaiac based b. Px Faecal Calprotectin:  kuantitatif, prinsip ELISA  sampel tunggal, tanpa restriksi mknn  protein sitosolik pd netrofil & makrofag  proses inflamasi.  normal dlm feses adlh 0,5-10,5 mg/L.  pd kanker kolorektal ˜ 101 mg/L  sensitivitas 90%, spesifisitas 72%. b. Px Faecal Calprotectin:  kuantitatif, prinsip ELISA  sampel tunggal, tanpa restriksi mknn  protein sitosolik pd netrofil & makrofag  proses inflamasi.  normal dlm feses adlh 0,5-10,5 mg/L.  pd kanker kolorektal ˜ 101 mg/L  sensitivitas 90%, spesifisitas 72%. 90

91 Px skrining genetika. a.Skrining FAP & HNPCC:  m’deteksi mutasi gen pd APC (cacat pd kromosom 5q lengan pendek).  m’deteksi mutasi gen pd HNPCC (kromosom p 53)  b.Skrining IGF-2:  peptida asam amino 67, 7,5 kDa, m’mediasi bbrp aksi hormon pertumb., berfungsi slm perkemb. fetal.  pd kanker kolorektal: m’alami perub. Epigenetik.  Px metode ELISA  hanya utk penelitian. 91

92 Px skrining genetika  c.Tes DNA feses:  deteksi terhdp perub. DNA (kesalahan replikasi) pd sel-sel kanker yg tlh dilepaskan dari kolon dan diekskresikan ke dlm feses.  petanda yg baik krn stabil.  metode PCR.  sensi 57%, spesi 97%.  Hasil feses pasien kanker kolorektal  fragmen DNA dg berat molekul > pasien kolonoskopi negatif. 92

93 Px monitoring dan prognosis (petanda tumor) : a.Carcinoembryonic Antigen (CEA):  Ditemukan pertama kali oleh Gold dan Freedman pada tahun  glikoprotein terdiri atas 60% karbohidrat dengan berat molekul kDa.  sebagai indikator prognosis. Px metode ELISA.  Kadar pd org normal tdk > 2,5 ng/ml.  ke ↑ kadar 5-10 X normal  kanker (+) 93

94 a.Carcinoembryonic Antigen (CEA): *  CEA ↑ pd kead.: perokok (meningkat sekitar 10%), kanker (paru, pankreas, payudara), beberapa kondisi (hepatitis, emfisema, sirosis, kolitis ulseratif, infeksi paru, gastritis, pankreatitis, polip, penyakit ginjal dan hipertrofi prostat)  Proporsi pasien dengan peningkatan kadar CEA (>2,5 ug/L):  Dukes A (tumor terbatas di dalam usus) adl 28%  Dukes B (tumor keluar dinding usus tp blm sampai lnn) adl 45%  Dukes C (tumor metastase lnn) adl 75%  Dukes D (tumor metastase luar organ) 48%. 94

95 CEA  Skrining kanker :utk m’deteksi pd Dukes A /B. dg cutoff 2,5 ug/L sensitivitas 36% dan spesifisitas 87%  tdk utk skrining populasi tanpa gjl.  Sbg indikator prognosis: - CEA tinggi pd pre op  prognosis buruk - 5-year rates CEA > 5 ng/L  55%. - 5-year rates CEA < 5 ng/L  85%. - CEA tinggi post op  rekurensi (post op CEA ↓ dlm 4-6 mgg) - deteksi rekurensi  sensi 66%, spesi 94%. - deteksi metastase hepar  sensi 94%, spesi 96%.  Sbg faktor prediktor: - pe ↓ CEA slm kemotx  harapan hidup baik - pe ↑ CEA slm kemotx  kanker progresif. - monitoring pd awal kemotx, tiap 2-3 bl slm kemotx. 95

96 Px Petanda tumor lain :  b.Gen p 53.:  Pd kead. normal gen ini ptg utk regulasi pertumb.sel.  petanda prognosis buruk.  pd kead.tdk normal  blm jelas.  C.petanda tumor msh dlm penelitian: - GLUT-1 - CA MMP-9 - CD 44.  C.petanda tumor msh dlm penelitian: - GLUT-1 - CA MMP-9 - CD

97 KESIMPULAN.  Aspek laboratorium m’punyai kepentingan thdp kanker GI Tract:  m’bantu dx  populasi risiko tinggi  monitoring tx  petunjuk prognostik.  Pem. utk m’bantu dx kanker GITract: - px darah tersamar (metode guaiac based, rapid test immunoassay kualitatif) - px kadar Calprotectin feses. - skrining genetika (DNA feses).  Px utk monitoring tx / prognostik : - petanda tumor: dan petanda tumor lain dlm taraf penelitian. 97

98 CLINICAL APPLICATIONS OF SECRETED TUMOR MARKERS  Never use for screening except for certain conditions / high risk  Complementary to diagnosis, staging, prognosis  Confirmation and information on extend of disease  Most useful in supporting disease management, therapeutic response and follow up

99 APPLICATIONS AND INTERPRETATIONS IN GENERAL  None of the tumor markers known today meets the requirements of an ideal marker (none has 100% sensitivity & 100% specificity)  Most of the tumor markers are not disease specific  Not every tumor of the same organ express the  same tumor marker  Marker’s level should increase with progression  and decrease with regression  A decrease of 50% = partial remission  An increase of 25% from last level = progression  Needs reference values and decision values

100 100


Download ppt "LABORATORY EXAMINATION OF ABDOMINAL MALIGNANCY Dr.. dr.Siti Muchayat, MS, Sp PK (K)"

Presentasi serupa


Iklan oleh Google