1 Pankrease vähk - see lootusetuMari-Liis Riibak Tallinn 2008

2 Juttu tuleb: Erinevatest pankrease tuumoritest, etioloogiast, kliinilisest pildist Modaliteetidest – milline ja milleks? Ja kuidas kõige paremini TNM klassifikatsioonist Diferentsiaaldiagnostilistest raskuspunktidest. Skriining?

3 Juttu tuleb: Erinevatest pankrease tuumoritest, etioloogiast, kliinilisest pildist Modaliteetidest – milline ja milleks? Ja kuidas kõige paremini TNM klassifikatsioonist Diferentsiaaldiagnostilistest raskuspunktidest. Skriining?!

4 Pankrease adenokartsinoom, probleemistikM>N, 60-80a, harvem <50e.a, v harva<40e.a. Kesise elulemusega – 5a / 4% Läänemaailmas tõusva tendentsiga “salakaval mõrtsuk” Seerumi marker CA-19-9 on sensitiivne, kuid mittespetsiifiline. TA90-IC ? Tants “operaabelne / mitteoperaabelne” ümber Operaabelsed 10-20% -> 5 a elulemus kuni 35% Statistika erinev. Pancreatic adenocarcinoma is known to be one of the leading causes of cancer death in the West, with a poor overall 5-year survival rate of only 4%.[1] US data showed that in 2005 there were cases of diagnosed pancreatic cancer and patients died from the disease.[2] The incidence of pancreatic adenocarcinoma is still increasing; because of its silent course, late clinical symptoms, and rapid growth patterns, it has been named the "silent killer".[3] Late clinical presentation with an advanced disease resulting in a low rate of surgical intervention (10-20%) of the tumor is the cause of this high mortality.[4] In a study conducted by Tsuchiya et al.,[5] patients with resectable pancreatic cancer (i.e. patients who presented early) had a 5-year survival rate of 35%. This provides an impetus to detect pancreatic cancer early and to stage it accurately on imaging for preoperative planning to enable curative resection. The ideal imaging test for pancreatic malignancy should both detect and stage pancreatic tumor so that a pancreatic surgeon can make an informed preoperative decision on the treatment. However, a single ideal imaging test for the pancreas remains elusive. Although a pancreatic tumor may be detected on one particular diagnostic imaging study, staging frequently involves additional studies, sometimes with a different modality.[6] Furthermore, small tumors are notoriously difficult to detect.[5,7] Another clinical problem lies in the difficulty in the reliable differentiation between pancreatic malignancy and focal chronic pancreatitis. Tumor serum marker CA 19-9 is readily available and sensitive, although not a specific marker for the diagnosis of adenocarcinomas of the pancreas.[8] Another serum marker TA90-IC is being investigated for pancreatic cancer detection. It is believed that when used in combination with CA 19-9, the latter can significantly improve the diagnostic rate for tumor detection.[9]

5 Pankrease tuumorid, eksokriinsedMaliigsed Duktaalrakuline adenoca! (90% kõikidest juhtudest). Atsinaarrakuline ca!, Papillaarne mutsinoosne ca! Sõrmusrakuline ca! Adenoskvamoosne ca! Diferentseerimata ca! Mutsinoosne ca! Giantrakuline ca! Segatüüpi (duktaal-endokriinne või atsinaar-endokriinne). Väikeserakuline Tsüstadenoca! (seroosne ja mutsinoosne tüüp). Klassifitseerimata Pankreatoblastoom Papillaarne – tsüstiline tuumor (Frantz tumor) – madala maliigsuspotensiaaliga, võib olla ravitav üksnes kirurgiliselt. Invasiivne adenoca, mis on seotud tsüstilise mutsinoosse või intraduktaalse papillaarse mutsinoosse kasvajaga. Piiripealsed maliigsused Düsplaasiaga mutsinoosne tsüstiline tuumor Düsplaasiaga intraduktaalne papillaarne mutsinoosne tuumor. Pseudopapillaarne soliidne tuumor. Tumors may arise from pancreatic ducts (99%) or from acinar cells (1%). More than 90% of pancreatic cancers appear in the late stage of disease; Of all the GI malignancies, pancreatic adenocarcinoma is the second most common cause of death from cancer. In clinical practice, pancreatic cancer is synonymous with pancreatic ductal adenocarcinoma, which constitutes 90% of all primary malignant tumors arising from the pancreatic gland. Tumors may arise from pancreatic ducts (99%) or from acinar cells (1%). More than 90% of pancreatic cancers appear in the late stage of disease; this observation emphasizes the role of radiology in early detection and determination of resectability of the tumor. The role of diagnostic imaging is to demonstrate the tumor and its relationship to surrounding vasculature, and the results determine the possibility of curative resection.

6 Pankrease adenokartsinoomKliiniline leid Enamasti valu (34%), tugeva valu võib näidata perineuraalsete lümfiteede haaratust Valu ja ikterus (46%) Ikterus ilma valuta (13%) Harva hematemesis ja meleena. Paleeritav sapipõis (Courvoisier smp) Pankrease keha ja saba tuumorid avastatakse hilja Hepatomegaalia - võib viidata maksa MTS-le, Astsiit, äkki tekkinud diabeet, tromboflebiit, väsimus Positiivne kliiniline leid viitab ravimatule haigusele Clinical symptoms and signs develop late and depend on the site of the tumor. Tumors in the body and tail produce late symptoms. Pain is the most consistent symptom. Painless jaundice alone is uncommon and is seen in 13% of patients. Approximately 34% present with pain alone, and about 46% with pain and jaundice. Severe pain invariably indicates spread of tumor to perineural lymphatics. Weight loss and anorexia are observed in 7% of patients. Hematemesis and melena occasionally occur in late cases, and these may be caused by direct invasion of the adjacent duodenum or stomach or as a result of portal hypertension from splenic and portal vein obstruction. Physical examination A palpable gall bladder (Courvoisier sign) is observed in approximately 25% of patients with operable tumors. Tumors in the body and tail appear late, as they do not cause any immediate pressure effects on ducts. They present with pain when large. Hepatomegaly is seen in 65% of patients and may indicate liver metastasis, although the sign is nonspecific. Positive clinical signs indicate incurable disease, and a palpable abdominal mass is observed in 10% and ascites in 5%, which suggests advanced disease. Obstructive jaundice is seen in 75% of patients. Other signs include new onset of diabetes in 25-50% of patients, thrombophlebitis, and fatigue. More than 90% of patients present at a late stage in the disease process. Laboratory tests reveal elevated bilirubin concentrations. The total bilirubin level tends to be greater with malignant obstruction, as compared with the increase in bilirubin levels due to ductal obstruction caused by choledocholithiasis (mean levels of 15 vs 5 mg/dL). Conjugated bilirubin and alkaline phosphatase levels are higher in patients with obstructive jaundice than in those with liver parenchymal disease. Elevation of serum amylase values is less common and seen in about 5% of patients with pancreatic cancer.

7 Pankrease adenokartsinoom, etioloogiaRasva ja valgurikas toit Suitsetamine, risk 2x Diabeet 2 x Kokkupuude tööstuslike kartsinogeenidega Pärilik pankreatiit (40% dgn vähijuhtudest) Alkoholi liigtarvitamine The definitive causative factors that indicate an increased incidence of pancreatic cancer are unknown. High-protein and high-fat diets, cigarette smoking, and exposure to industrial carcinogens are implicated as causative factors. An increased incidence has been reported in chemists, workers in metal industries, and coke- and gas-plant employees. Hereditary pancreatitis is present in 40% of patients with pancreatic carcinoma. Cigarette smoking increases the risk by 2 times and diabetes by 2 times more than the general population. Alcohol abuse is seen in 4% of patients. Asbestos exposure is not associated with pancreatic carcinoma. Undoubtedly, an association exists between pancreatic cancer and diabetes mellitus. Association of alcohol and pancreatic cancer is indirectly related to the development of alcohol-induced pancreatitis. The acquired variety of chronic pancreatitis does not seem to be strongly related to pancreatic cancer. Individuals with the hereditary type of chronic pancreatitis seem to have a predisposition for pancreatic cancer stronger than that of the general population.

8 Pankrease tuumorid, tsüstilisedSuur grupp harvaesinevaid lesioone 10% tsüstilistest pankrease lesioonidest 1% pankrease tuumoritest MCN (mutsinoosne tsüstiline neoplasma), IPMT (intraduktaalne papillaarne mutsinoosne tuumor) ja serosne adenoom moodustavad 90% mutsinoossetest tuumoritest Elulemus oluliselt parem 5a ~95% - beniigsed piiripealsed tuumorid 50-75% - maliigsed tsüstilised tuumorid. N:M, 4:1; 55-65e.a. Erinevaid pankrease tsüstilisi lesioone on raske diferentsida beniigne seroosne tsüstadenoom? Põletikuline pseudotsüst? Maliigne tsüstiline tuumor? IPMT

9 Pankrease tuumorid, tsüstilisedSeroosne beniigne tsüstadenoom 1-25cm, ühekambriline, beniigne Põletikuline pankrease pseudotsüst Põletikuline, võib olla verd ja nekroosi Mutsinoossed pankrease tuumorid (eelistatult pankrease keha ja sabaosas) Perifeersed (mutsiini prod tsüstadenoom, tsüstadenokartsinoom) Duktaalsed (intraduktaalne papillaarne mutsinoosne tuumor IPMT) Muud tsüstilised lesioonid Mucinous cystic tumors of the pancreas, so-called macrocystic cystadenomas or cystadenocarcinomas, which predominate in the body and tail of the pancreas, have a strong female predilection. MCNs are the most common of cystic pancreatic tumors, accounting for 45-50% of tumors. They are multiloculated tumors with a characteristic smooth glistening surface. They arise from oversecretion of the mucus by the hyperplastic columnar lining of the ducts. The cysts contain thickened viscous material, which can also be hemorrhagic. The differential diagnosis includes the following: pancreatic pseudocyst or pancreatic fluid collections, serous cystadenomas, pancreatic abscess, benign pancreatic cysts, retention pancreatic cysts, parasitic cysts, lymphoepithelial cysts (LECs), pancreatic dermoid cysts, pancreatic hematoma and traumatic pancreatitis, von Hippel-Lindau (VHL) syndrome, papillary pancreatic tumors, dysontogenic cysts, pseudoaneurysms, retroperitoneal neurofibroma or schwannoma, obstructed roux loop, duodenal diverticula, gastric/duodenal leiomyosarcoma or leiomyoma, pancreatic sarcoma, pancreatic lymphoma, pancreatic metastases, and pancreatic tuberculosis. Imaging findings that suggest a diagnosis of pseudocyst rather than cystic neoplasms include the following: lack of septae, loculations, solid components, or cyst-wall calcifications on CT; hypovascularity on angiograms; and communication between the cyst and pancreatic ducts on endoscopic retrograde cholangiopancreatography (ERCP). Most pseudocysts are extrapancreatic, whereas pancreatic cystic neoplasms are intrapancreatic Fine-needle aspiration (FNA) of pseudocyst contents reveals high levels of amylase. When in doubt, it is better to resect a pseudocyst than to observe or drain a pancreatic cystic neoplasm, which allows tumor progression to unresectability, metastasis, and death. Tsüstiline Mutsinoosne tuumor

10 Pankrease tuumorid, endokriinsedSaarerakk tuumorid (islet cell, APUD cell tumors - APUDoma) ~2% pankrease tu-st Haruldased, sporaadilised või mõne sündroomiga seoses multiple endocrine neoplasia 1tüüp (MEN 1) ja von Hippel–Lindau (VHL) haigus Funktsionaalsed / mittefunktsionaalsed Võivad produtseerida rohkem kui ühte tüüpi hormooni Insulinoom (5-9 90% pt-dest, üksik 90%, healoom 90%, < 5 cm 90% ja 95% pankreasesisene)>> gastrinoom> mittefn saarerakk tuumor> glükagonoom> vipoma> somatostatinoma jne Väikerakk tuumorid Pancreatic islet cells are part of the diffuse neuroendocrine system of the gut and pancreatic endocrine system. Islet cells commonly are referred to as APUD cells, a name derived from their high amine content and capacity for amine precursor uptake with decarboxylation. Tumors of pancreatic islet cells are uncommon. They may manifest as sporadic tumors or as part of certain syndromes, including multiple endocrine neoplasia type 1(MEN 1) and von Hippel–Lindau (VHL) disease. Islet cell tumors may be functional or nonfunctional; although nonfunctional islet cell tumors are not uncommon at autopsy, most islet cell tumors with clinical manifestations are functional Functioning tumors produce a clinical syndrome as a result of excessive hormone production. Clinical features of the syndrome depend on tumor cell type. Pancreatic islet cell tumors may secrete 2 or more polypeptide hormones. Functioning tumors usually are small at presentation, and localizing these tumors can be challenging to the radiologist. Hormonal and biochemical parameters are invaluable for skillful interpretation of the imaging and clinical features and to arrive at a specific diagnosis. Nonfunctioning tumors usually are larger and present because of their size or metastatic spread. The rule of nines can be applied to insulinomas in that they are sporadic in 90% of patients, solitary in 90%, benign in 90%, less than 5 cm in 90%, and 95% intrapancreatic. No predilection exists for a specific site within the pancreas No universally agreed-upon algorithm exists in the radiologic investigation of islet cell tumors of the pancreas. The diagnosis usually is made by the clinician, and the role of the radiologist is to localize, demonstrate the extent, and stage the lesion, thereby allowing correct management. The best modality for diagnosis is debatable and depends on the expertise of the radiologist at each institution. Larger lesions are easily identifiable by modern cross-sectional imaging techniques. Smaller lesions are difficult to demonstrate, requiring more sophisticated imaging and meticulous technique. Endoscopic ultrasonography (EUS) is performed by using a 10-MHz transducer incorporated into an endoscope. Lesions are seen as well-rounded, oval echogenic, or hypoechoic areas in the gland parenchyma. A retrospective study by Boukhman et al (1999) evaluated the sensitivities of different techniques to localize insulinomas as follows: Arteriography - 47% CT - 24% Preoperative ultrasound (US) - 50% MRI - 30% Gadolinium-enhanced MRI - 40% Transhepatic venous sampling - 55% Intraoperative palpation - 76% Intraoperative ultrasonography - 91%

11 Pankrease tuumorid, muuSekundaarsed RCC, melanoom, kopsuvähk, rinnavähk... Mitte-epiteliaalsed Pehmekoelised tuumorid Lümfoom Tuumorisarnased lesioonid Pankreatiit Lümfoepiteliaalne tsüst Pseudotsüst Mts-nud Rinna ca Fokaalne pankreatiit

12 Juttu tuleb: Erinevatest pankrease tuumoritest, etioloogiast, kliinilisest pildist Modaliteetidest – milline ja milleks? Ja kuidas kõige paremini TNM klassifikatsioonist Diferentsiaaldiagnostilistest raskuspunktidest.

13 Pankrease adenokartsinoomSuurus vs elulemus Zosia Chustecka, January 31, “Smaller Pancreatic Tumors Have Dramatically Better Prognosis “ Relationship Between Pancreatic Tumor Size on Diagnosis and Survival Tumor Size at Diagnosis (mm) Median Survival (mo) ≤20 17.2 21 – 25 12.3 26 – 30 8.5 ≥30 7.6

14 Pankrease adenokartsinoomOperaabelne vs mitteoperaabelne Opereeritavatele tuumoritele pakub kirurgia parimat elulemustulemust Piiratud levik SMV-sse on veel operaabelne J Gastroenterol Hepatol.  2008;23(1):23-33 Mitteoperaabelne Invasioon ekstrapankreaatilistesse suurtesse veresoontesse (truncus coeliacus, a hepatica, v porta, SMA või SMV või massiivne venoosne invasioon koos tromboosiga); kontakt veresoonega >50% Kaugmetastaasid maksas, regionaalsetes l/-s, rasvikus Venoosne invasioon ilma tromboosi või ahenemiseta – võib siiski pidada resetseeritavaks adenoca-ks. Typically, the treatment approach is based on whether the tumor is resectable or non-resectable at presentation. For resectable tumors, surgery offers the best survival benefit.[10] For locally advanced pancreatic cancer, chemotherapy or radiotherapy alone or in conjunction are considered as alternatives to surgery. Patients with distant metastases are deemed ineligible for radiation treatment, as no additional survival benefit has been shown with adjuvant radiation.[6] Also, clinical trials with recent treatment methods, such as anti-angiogenic drugs, mandate the absence of metastatic disease as an eligibility criterion for enrollment in the trial.[11] With recent surgical advances, limited invasion into the superior mesenteric vein (SMV) can be classified as resectable tumor as opposed to the previous tumor nodes metastasis (TNM) classification where these tumors were considered unresectable.[12] The criteria of the unresectability of pancreatic adenocarcinoma now includes extrapancreatic invasion of major vessels (defined as tumor-to-vessel contiguity >50%), such as celiac artery, hepatic artery, portal vein, superior mesenteric artery (SMA) or SMV, or massive venous invasion with thrombosis (Figs 1a,b,2). Likewise, the presence of distant metastasis to the liver, regional lymph nodes, or omentum is a contraindication for surgical resection. However, venous invasion without thrombosis or obliteration of the vessel lumen can still be classified as resectable adenocarcinoma.[13,14]

15 Pankrease adenokartsinoomFigure 1.  (click image to zoom) (a) Axial pancreatic-phase multidetector computed tomography shows a low attenuation mass (arrow) located at the head of pancreas and extending superiorly and encasing the superior mesenteric artery. A biliary stent is in place (*). (b) Coronal reformatted image better defines the cranio-caudal extent of the tumor (arrow) and its relationship to the adjacent vasculature. This was categorized as unresectable pancreatic adenocarcinoma due to encasement of superior mesenteric artery (SMA) and celiac artery (CHA). A biliary stent is in place (*). Figure 2.  (click image to zoom) Coronal maximal intensity projection image from multidetector computed tomography of a patient with adenocarcinoma of the head of the pancreas. Low attenuating adenocarcinoma (M; arrowheads) reduces the caliber and infiltrates the superior mesenteric vein, the spleno-mesenteric confluence and the portal vein (short arrows). In addition, direct invasion into the duodenum is also obvious. D, duodenum; M, mass; PV, portal vein; SMV, superior mesenteric vein.

16 Pankrease adenokartsinoomPatsiendi käsitlus radioloogias: Patsient, kes vajab diagnoosi Patsient, kellel vaja määrata pankrease vähi staadium Kõrge riskiga patsient –skriining?

17 Pankrease adenokartsinoomRadioloogiline leid - UH: Transabd. sonograafia – hea “ilma” korral hea meetod. EUS – väga hea väikeste lesioonide avastamiseks / välistamiseks, lokaalse staadiumi määramiseks; FNB Mass pankreases; hüpo-, iso-, hüperehhogeenne, pankrease juha laienemine.

18 Pankrease adenokartsinoomRadioloogiline leid - KT: Bifaasiline uuring (PP 35-45s, PVP 65-70s) PO rö+ / rö – kontrastaine Buscopani Absoluutne vastunäidustus glaukoom Suhteline vn – prostata hüperplaasia, arütmia Fokaalne mass (suhteline atroofia foonil), peripankreaatilise rasvkoe infiltratsioon, selgete piirjoonte kadu, ebatavaline pankrease kuju, pankrease atroofia ja juha ning CBD laienemine distaalsemal. A change in size is usually focal, and focal enlargement is seen in about 96% of patients with pancreatic adenocarcinoma. The size is an unreliable indicator of tumor, as a normally sized pancreatic head is consistent with a carcinoma of pancreas when atrophy of the body and tail is observed. This feature may be seen in pancreatic carcinoma in as many as 20% of patients. Focal enlargement also can occur in benign disease; thus, it is a nonspecific finding. Diffuse enlargement is less common and usually suggests pancreatitis.

19 Pankrease adenokartsinoomRadioloogiline leid - KT: Hägusad piirkooned, fibrootilne vähekontrasteeruv tsentraalosa (83%), nekroos Juha laienemine (58%) Vaskulaarne haaratus – mitteoperaabelne Operaabelsuse korral märkida ära vaskulaarsete struktuuride kulgemine, normi teisendid Kollateraalne venoosne võrgustik veeni obstrukts korral Ulatus porta hepatisse 68%, region. l/s – 38-65%, maksa mts – 17-55%, astsiit 13%, Sissekav naaberorganitesse low-attenuating mass in the head of the pancreas, adjacent to the superior mesenteric vein (SMV)

20 Pankrease adenokartsinoomRadioloogiline leid - mri: Teise rea “probleemi lahendav” modaliteet MDCT leid ebamäärane, joodi allergia, NP T1 madala, T2 keskmise signaaliga muutus; ilma kontrastita tuleb väike lesioon harva nähtavale. Hüpointensiivne, eristatavaim 10s peale k/a. FLASH+Gd ; MRA MRCP (fMRCP + serotoniin) Maliigne obstruktsioon – järsk katkemine, obstruktsiooni ja papilla Vateri vaheline ala tavaline ; double duct sign Beniigne pankreatiidist tingitud – kogu ulatuses ebaühtlane Tsüstiliste lesioonide eristamine Maksa ja peritoneumi kolded Nefrogeenne fibroseeruv dermopaatia n patients with a high clinical suspicion of a tumor or those with suspected pancreatic mass not satisfactorily identified on a high-quality MDCT exam, MR imaging or EUS may be considered as second-line imaging modalities urrently, MR is used as a "problem-solving" tool in patients with an inconclusive CT diagnosis or in suspected masses without contour deformity of the pancreas. MR can also be considered an alternative preoperative staging exam in patients with allergies to iodinated contrast agents and in patients with renal insufficiency

21 Pankrease adenokartsinoomRadioloogiline leid - invasiivsed ERCP PTBD – perkutaanne transhepaatiline biliaarne drenaazh Kui seespidi ei saa, komplikatsioonide risk suurem (hemobiilia, hematoom, kolangiit, hemoperitoneum, biliaarne peritoniit, pleuriit. Terapeutiline biliaarne stentimine Pankrease biopsia (FNA, TruCut) For a final diagnosis, histologic or cytologic confirmation is needed. The reported sensitivity and diagnostic accuracy are high for both histologic and cytologic examinations. Specificity is near to 100% in most published series. These studies are from centers of excellence. However, in practice, obtaining a diagnosis by means of percutaneous biopsy can be problematic, and in some patients malignancy is confirmed on follow-up images, which demonstrate an increase in the size of a lesion or by hepatic metastases. Percutaneous FNA biopsy does pose a small but real risk of tumor implantation along the biopsy track of the needle. It has a clear advantage in patients with advanced disease in whom the diagnosis is to be established without subjecting the patient to surgery. A Tru-cut biopsy using 18-gauge needle can be safely and effectively performed under guidance. Microscopic confirmation is required in all patients in whom chemotherapy, radiation therapy, or both are planned. For attempted radical surgery, biopsy is not mandatory if the clinical suspicion of cancer is high and the surgical team has documented low postoperative morbidity and mortality rates. FNAC does not allow sufficient yield to characterize the subtype of the pancreatic carcinoma. The morbidity of pancreatic fistula from FNAC can be reduced by using a transduodenal approach. The sensitivity of EUS-guided FNA is 75-97%, similar to that of CT-guided FNA. Pancreatic mass FNA is highly sensitive and specific (94-100%) for lesions smaller than 3 cm in diameter. Similar high specificity is found with EUS-guided FNA of lymph nodes. An FNA specimen is almost always adequate.

22 Pankrease adenokartsinoomNM SPECT Endokriinsed pankrease tuumorid, somatostatiini retseptorid, 111 In Octreaotide 18 FDG PET CT Tuumori levik, retsidiiv Dif dgn? Krooniline pankreatiit / tuumor Dünaamiline ja hilisskaneerimine. Uueteks lootusandvateks märkaineteks σ-receptor ligand ja 18Ffluorothymidine (FLT)

23 Pankrease tuumorid, endokriinsedDif dgn MTS Hästipiirdunud, hüpervaskulaarne Võivad näida KT natiivis iso/hüperdensetena T1 hüpo-, T2, STIR hüperintensiivne Harva ikterus ja pankrease juha obstruktsion EUS!!! – parim preop lokaliseerimiseks NM – somatostatiini retseptorid! (60-70% insulinoomidest) Dif dgn Hüpervaskulaarsed mts-d pankreases Renal cell carcinoma, Leiomyosarcoma, Melanoma, Carcinoid, Adrenal carcinoma, Thyroid carcinoma, Angiosarcoma jne RCC Ca ja hüpervaskulaarne mts pankreases.

24 Juttu tuleb: Erinevatest pankrease tuumoritest, etioloogiast, kliinilisest pildist Modaliteetidest – milline ja milleks? Ja kuidas kõige paremini TNM klassifikatsioonist Diferentsiaaldiagnostilistest raskuspunktidest. Skriining?

25 TNM klassifikatsioon Eksokriinse pankrease vähi kohtaPrimaarne tuumor T Tx – primaarne tuumor pole hinnatav T0 – primaarset tuumorit ei ole Tis – carcinoma in situ T1 – tuumor piirdub pankrease koega ja <=2cm suurimas Dm-s. T2 – tuumor piirdub pankreasega ,>2cm T3 – tuumor ulatub pankrease kontuurist välja, kuid ei haara truncus coeliacust ega SMA-d T4 – tuumor haarab truncus coeliacuse või SMA Ei sisalda ampulla Vateri, sapiteede ega endokriinsete tuumorite klassifikatsiooni.

26 TNM klassifikatsioon Regionaalsed lümfisõlmed- N Kaugmetastaastd – MNx – regionaalsed lümfisõlmed pole hinnatavad N0 – regionaalsetes l/s-s ei ole MTS-e N1 – MTS-d regionaalsetes l/s-s Kaugmetastaastd – M Mx – kaugmetastaasid pole hinnatvad M0 – kaugmetastaasid puuduvad M1 – kaugmetastaasid olemas

27 Pankrease anatoomia Pankrease pea tuumorid tekivad smv ja portaali konfluensist paremal, keha tuumorid veenide konfluentsi ja aordi vahelisel alal ja saba tuumorid aordi ja põrna vahelisel alal.

28 Regionaalsed lümfisõlmedant pancreaticoduodenal nodes (sup, inf) Post pancreaticoduodenal nodes (sup, inf) Pyloric nodes Gastroduodenal nodes Hepatic nodes Cystic node Sup mesenteric nodes Celiac nodes Supra-, infrapancreatic nodes Mesocolic nodes Splenic nodes Gastrosplenic nodes Renal nodes Pankreasel kaks suurt gruppi sõlmi – need, mis ümbritsevad pankreast ja need, mis asuvad lähedlasetsevate suurte veresoonte ümber – kõhuaort ja selle harud. Distaalsed mts-d tavaliselt maksa, peritoneaalõõnde ja kopsu

29 Regionaalsed lümfisõlmedEestvaade, pankrease keha taga

30 T1 / T2 T1 – tuumor pankreases < 2cmT2 – tuumor piirdub pankreasega > 2cm

31 T3 Tuumor ulatub pankrease kontuurilt välja, kuid ei haara truncus coeliacut ega SMA-d Tuumor iniltreerib ühissapijuha, kuid mitte SMA-d Tuumor haarab peripankreaatilisi kudesi, kuid mitte truncus coeliacust

32 T3 T3 – tuumor infiltreerib duodeenumi, ei haara SMA-dT3 – tuumor tungib põrna, ei haara SMA-d ega truncus coeliacust.

33 T4 Tuumor haarab kas SMA või truncus coeliacuse

34 N1 N1 – regionaalsed l/s metastaasidPrimaarne tuumor ja regionaalne metastaseerunud l/s pankrease peas

35 N1 Primaarne tuumor ja mitmesed l/s metastaasid pankrease pea ümberPrimaarne tuumor keaosas ja mitmesed mts l/-d pea ja keha osas

36 N1 Primaarne tuumor sabaosas ja mitmesed mts-d l/s-d pankrease sabaosas ja põrna hiiluses

37 TNM klassifikatsioon, staadiumidTis N0 M0 IA T1 IB T2 IIA T3 IIB N1 III T4 Any N IV Any T M1

38 Juttu tuleb: Erinevatest pankrease tuumoritest, etioloogiast, kliinilisest pildist Modaliteetidest – milline ja milleks? Ja kuidas kõige paremini TNM klassifikatsioonist Diferentsiaaldiagnostilistest raskuspunktidest. Skriining?

39 Primaarset pankrease tuumorit simuleerivad muutusedHead and neck Unenhanced bowel Groove, focal, or autoimmune pancreatitis Pancreas divisum Annular pancreas Tuberculosis Duodenal diverticula Duodenal duplication Gastrointestinal stromal tumors (GISTs) Postsurgical distortion Choledochal cysts Mesenteric masses Right adrenal masses Pancreatic body Parasitic cysts GISTs Pseudocysts Tumors of the posterior gastric wall Duodenal tumors and lesions Pancreatic tail Accessory spleen Small bowel lesions Pseudocysts Tumors of the gastric fundus Colonic lesions Left renal masses Left adrenal masses Miscellaneous locations Vascular lesions Lymphadenopathy Castleman disease Retroperitoneal masses Duodenal diverticula Metastatic lesions Fatty replacement

40 Kontrasteerimata duodeenum / kontrasteeritudNormal unenhanced duodenum mimicking a pancreatic mass. (a) CT scan shows findings that suggest enlargement of the head of the pancreas (). (b) Repeat CT scan obtained with additional oral contrast material shows a normal pancreatic head, with contrast material in the duodenum (arrow) and gallbladder

41 Annullaarne pankreas Annular pancreas. (a) CT scan shows pancreatic tissue encircling the duodenum (*). (b) ERCP image shows the main pancreatic duct wrapped around the endoscope (arrows). In addition, the annular pancreas causes stenosis of the common bile duct, which is distended proximally (arrowhead).

42 Duodeenumi duplikatsioonDuodenal duplication. (a) CT scan shows a fluid-filled, circumferential duodenal duplication, which may be mistaken for a pancreatic mass on axial sections. (b) Coronal multiplanar reformatted image demonstrates the full extent of the duodenal duplication (*) adjacent to the pancreas

43 Pankreasesisene lisapõrnIntrapancreatic splenic rest. (a) Axial contrast-enhanced spoiled gradient-echo T1-weighted MR image shows a lesion (*) that is isointense relative to the spleen (S). P pancreatic tail. (b) Coronal T1-weighted MR image demonstrates the pancreas wrapped around the lesion (*). P pancreatic tail, S spleen

44 Ühissapijuha tsüst Choledochal cyst. (a) CT scan demonstrates a dilated, redundant common bile duct simulating a cystic lesion within the pancreatic head (*). (b) ERCP image shows contrast material filling a choledochal cyst

45 Komplitseerunud pankreatiit vs tuumorComplications of pancreatitis mimicking a pancreatic tumor. (a) CT scan demonstrates hemorrhagic pancreatitis as a heterogeneous mass in the area of the pancreatic bed (*). Arrow indicates active extravasation (hemorrhage). (b) Pancreatic phase helical CT scan obtained in a 70-year-old woman with a history of pancreatitis who presented with abdominal pain shows numerous thick-walled cystic lesions throughout the pancreas (*). The patient’s condition was initially diagnosed as an intraductal papillary mucinous neoplasm but later proved to be a complex pseudocyst at surgery

46 Autoimmuunne pankreatiitAutoimmune pancreatitis. (a) CT scan demonstrates an enlarged, heterogeneous pancreatic head (*) with perivascular inflammation simulating neoplastic vascular involvement (arrow). (b) Coronal half-Fourier RARE T2-weighted MR image obtained in a different patient with abdominal pain demonstrates narrowing of the intrapancreatic common bile duct (arrow) by a diffusely enlarged pancreatic head without evidence of a specific mass.

47 Muud kasvajad Duodeenumisse Mts-nud Bronhogeenne ca Duodeenumi adenocaMao GIST

48 Juttu tuleb: Erinevatest pankrease tuumoritest, etioloogiast, kliinilisest pildist Modaliteetidest – milline ja milleks? Ja kuidas kõige paremini TNM klassifikatsioonist Diferentsiaaldiagnostilistest raskuspunktidest. Skriining?

49 Skriining Kas pikendab elulemust?5-10% pankrease vähkidest päriliku algega Pärilikud riskifaktorid Pärilik mittepolüpoosne jämesoole vähk (HNPCC) Perekonlik rinnavähk (BRCA2) Perekondlik adenomatoosne polüpoos Peutz-Jeghers Ataksia telangiektaasia Perekondlik atüüpiline mitmesed sünnimärk-melanoomid Perekondlik pankreatiit. Arvamused vastandlikud Evidence is inconclusive that early detection in subgroups at risk for pancreatic cancer would improve survival. No reliable screening tests are available for detecting early pancreatic cancer in asymptomatic patients. Imaging techniques are not suitable as screening tests because of many factors, including cost and/or their invasive nature. Tumor markers are nonspecific. Screening for pancreatic cancer is not recommended at this time. Canto et al.[66] studied the effectiveness of screening using EUS in relatives of patients with pancreatic cancer and patients with Peutz-Jeghers syndrome. The diagnostic yield for detecting clinically significant pancreatic neoplasms was 5.3% (two of 38). They concluded that the screening of asymptomatic high-risk individuals offers the ability to detect resectable pancreatic neoplasia. Asymptomatic patients with a family history of genetically-acquired pancreatic cancer or patients exposed to exogenous risk factors may therefore benefit from CT screening to enable the early detection of cancerous or precancerous lesions.[7] With pancreatic-phase CT imaging techniques and near isotropic resolution of the available MDCT scanners, MDCT is positioned to become the modality of choice for screening patients with high risk of pancreatic cancers. Findings of altered pancreatic attenuation or a focal mass with or without pancreatic duct dilatation or an isolated pancreatic duct dilatation with an abrupt transition should be considered suspicious for pancreatic cancer on CT. However, the frequency of screening CT exams and the duration of follow up has not been defined. In patients less than 40 years of age, the risk of excessive radiation exposure due to repeat screening CT studies remains a valid concern. Therefore, non-ionizing radiation benefits and superior contrast resolution of MR imaging can also be utilized for screening high-risk individuals.

50 Kasutatud materjal eMedicine - Pancreas, Adenocarcinoma Article by Mahesh Kumar Neelala Anand 04/2007 eMedicine - Pancreas, Islet Cell Tumors Article by Mahesh Kumar Neelala Anand 01/2007 “Smaller Pancreatic Tumors Have Dramatically Better Prognosis “Zosia Chustecka, January 31, Medscape Medical news RadioGraphics 2005; 25:949–965 Pancreatic and Peripancreatic Diseases Mimicking Primary Pancreatic Neoplasia Ajcc cancer staging atlas, 2006, lk eMedicine - Pancreas, Mucinous Cystic Neoplasm Article by Ali Nawaz Khan 02/2007

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