Pancreatic tumors

1. Pancreatic tumors Department of General and Transplant Surgery Medical University of Lódź P. HOGENDORF

2. BENIGN EXOCRINE TUMORS • Serous Cystadenoma • Mucinous Tumors • Intraductal Papillary Mucinous Tumor (IPMT) • Solid-Pseudopapillary Tumor of the Pancreas

3. usually asymptomatic but, when symptoms develop, they are usually related to pressure or obstruction of an adjacent organ. BENIGN EXOCRINE TUMORS • Most benign pancreatic exocrine tumors are cystic, but not all cystic tumors are benign • Benign cystic tumors 10% - 15% of pancreatic tumors

4. Rare cases of malignant serous cystic lesions have been reported Resection is indicated when the diagnosis is in doubt or when they become symptomatic. Serous Cystadenoma • 20% to 40% of cystic pancreatic neoplasms • lined by a flattened epithelium • most are benign and have no malignant potential • large, spherical masses that contain a watery fluid and have a central, calcified stellate scar

5. The cysts are lined by a columnar, mucin-producing, and sometimes papillary epithelium Prolonged survival (i.e., >5 years) can be anticipated in more than 50% of patients if these tumors are resected prior to the development of invasive malignancy, but even after the development of malignant changes and invasion, long-term survival is still better than for ductal adenocarcinoma. Mucinous Tumors • 20% to 40% of cystic tumors • could have malignant potential • two types: • 1) contains areas of ovarian-like stroma, almost always in women and in the pancreatic tail. • 2) lacks ovarian stroma, found anywhere in pancreas, male-to-female ratio 1:1 Note multiple large cystic spaces. Microscopic examination revealed multiple areas of ovarian-like stroma.

6. patients can experience pancreatitis when mucus, secreted by the tumor, transiently obstructs the orifice of the pancreatic duct IPMT is believed to follow an adenoma-carcinoma sequence Pan-IN classification: minimal or no dysplasia (PanIN-1), moderate dysplasia (PanIN-2), severe dysplasia/carcinoma in situ (PanIN-3) Resection with, at worst, PanIN-1 changes at the margin, prior to development of invasive malignancy, is usually curative. This may mandate total pancreatectomy. When resection is performed after development of invasive malignancy, cure rates are relatively low. Intraductal Papillary Mucinous Tumor • First described in Japan in the 1980s • male-to-female ratio 1:1 • can be located in any or all parts of the pancreas, although involvement of the head appears to be its most common form • can involve the major ducts (“main duct variety”), the smaller ducts (“branch duct variety”) or both types of ducts

7. The finding of mucin in the cyst, mucin-secreting cells on biopsy, a high cyst fluid viscosity, or a high cyst fluid carcinoembryonic antigen (CEA) is suggestive, but not diagnostic, of a potentially malignant tumor Management of Cystic Pancreatic Neoplasms • The major challenge is distinguishing pseudocysts and serous cystadenomas from the other, malignant or potentially malignant, types of cystic pancreatic tumors. Because of these uncertainties, all neoplastic cysts should be resected unless the diagnosis of a serous cystadenoma can be made with certainty

8. usually large, round, and well-demarcated masses that can occur in any part of the pancreas histologically, the tumor is mostly solid and consists of monomorphous eosinophilic or clear cells that demonstrate a pseudopapillary architecture. In suitable operative candidates, solid-pseudopapillary tumors of the pancreas should be resected. Solid-Pseudopapillary Tumor of the Pancreas • uncommon tumor • occurs in young women • benign course but malignant varieties have been described. • local resection is usually curative

9. 80% of cases occur between 60 and 80 years of age, Only 2 % in patients <40 years of age risk factors: - a history of hereditary or chronic pancreatitis, - cigarette smoking - occupational exposure to carcinogens MALIGNANT PANCREATIC TUMORS • Pancreatic cancer affects 25,000 to 30,000 people in the United States • 4th or 5th leading cause of cancer-related death • ductal adenocarcinoma and its variants account for 80% to 90%

10. codon 12 mutations of the K-ras oncogene (95%) mutation of the p53 tumor suppressor gene (75%) mutations of the tumor suppressor genes, including p16, SMAD-4, DPC, and DCC EGF receptor abnormalities HER2, HER3, and HER4 receptors abnormalities TGF-beta Genetic abnormalities in pancreatic cancer • activation of growth-promoting oncogenes, • mutations that result in the inactivation of tumor suppressor genes, • excessive expression of growth factors and/or their receptors pancreas cancer evolves in a progressive, step-wise fashion, much like that observed for colon cancer

11. Even in the absence of one of these familial cancer syndromes or hereditary pancreatitis,individuals with a family history of pancreatic cancer, especially those with two or more pancreatic cancer–affected first-degree relatives, have an increased risk of developing pancreatic cancer Hereditary Pancreatic Cancer Syndromes • hereditary nonpolyposis colon cancer (HNPCC) • familial breast cancer (associatedwith the BRCA2 mutation) • Peutz-Jeghers syndrome • those with ataxia-telangiectasia • familial atypical multiple mole melanoma (FAMMM)syndrome • patients with hereditary pancreatitis are also at increased risk of developing pancreatic cancer. This is particularly true in those with a paternal pattern of inheritance who may have a 75% risk of developing pancreatic cancer

12. Symptoms and Signs

13. Symptoms and Signs

14. elevation of bilirubin level elevation of alkaline phosphatase level Blood Tests • CA 19–9 > 37 U/mL sensitivity of 86% and a specificity of 87% • CEA

15. Imaging Studies • US scan • helical contrast-enhanced CT • MRI • Positron emission tomography (PET) • ERCP • EUS

16. helical contrast-enhanced CT • hypodense mass with poorly demarcated edges. • It may have a more hypodense center, indicating either central necrosis or cystic change, and the pancreatic duct to the left of the lesion may be dilated

17. (A) Slight enlargement of pancreatic head and without circumscribed tumor on helical CT in arterial phase; suspicion of liver lesions. (B) Marked tracer uptake on 18F-FDG PET in middle abdomen without definite anatomic identification; SUV > 3.5 leads to diagnosis of malignant lesion; additional liver metastases. (C) On image fusion, tracer accumulations are projected on pancreatic body and right liver lobe, proving the presence of hepatic metastases of pancreatic carcinoma.

18. (A) Clear enlargement of pancreatic head on arterial helical CT. (B) Increased tracer uptake on 18F-FDG PET located on retroperitoneal space; SUV of 2.4 leads to diagnosis of inflammatory process (arrow). (C) Image fusion enables definite localization of focal uptake onto pancreatic head.

19. (A) Helical CT demonstrates circumscribed thickening of pancreatic body and atrophy of pancreatic tail commonly seen as indirect sign for malignancy of pancreas. (B) 18F-FDG PET verifies pancreatic carcinoma with SUV of 5.8 and demonstrates additional lesion posterior to first lesion. (C) Image fusion allocates second tumor to unsuspected lymph node on CT representing lymph node metastases.

20. (A) Detection of large pancreatic head carcinoma on retrospective image fusion of helical CT and 18F-FDG PET. (B) Detection of additional pancreatic lesion not evident before image fusion.

21. Glucose uptake was quantified by the standard uptake value (SUV), with an SUV of >3.5 considered as indicative of malignancy

22. American Joint Committee on Cancer: TNM System for Staging of Pancreatic Cancer

23. High-resolution helical CT, with phased imaging for visualization of the pancreas and major peripancreatic vessels, is the most widely used method of evaluating tumor resectability. Circumferential encasement, invasion, or occlusion of the portal vein/superior mesenteric vein and/or the superior mesenteric artery is generally considered to be a sign of unresectability

24. Adenocarcinoma of the pancreatic head in a 71-year-old woman who did not undergo surgery. (a) Transverse CT image shows tumor (straight arrows) abutting the portal vein (curved arrow) near confluence. (b) Thin-slab MIP image shows contour irregularity (arrow) of the inferior surface of the portal confluence.

26. (a) Transverse CT image obtained at the level of the superior mesenteric vein just caudal to the confluence, in which vascular invasion by tumor (arrow) is difficult to appreciate. (b) Shaded surface display of the portal phase shows indentation (arrows) at the confluence of the superior mesenteric and portal veins. Surgical finding confirmed tumor invasion.

30. Palliative double bypass for unresectable pancreatic cancer. An end-to-side hepaticojejunostomy is performed, followed by a side-to side jejunojejunostomy between the afferent loop leading to the biliary anastomosis and the efferent loop leading from it. An opening is made in the lesser omentum, and a chemical splanchnicectomy is performed by injecting alcohol into the celiac plexus.