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PANCREATIC CANCER

PANCREATIC CANCER. Aswad H. Al.Obeidy FICMS, FICMS GE&Hep Kirkuk General Hospital. PANCREATIC CANCER. Second most common gastrointestinal malignancy It is a disease with an extremely poor prognosis Fewer than 20% of affected patients survive the first year

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PANCREATIC CANCER

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  1. PANCREATIC CANCER Aswad H. Al.Obeidy FICMS, FICMS GE&Hep Kirkuk General Hospital

  2. PANCREATIC CANCER • Second most common gastrointestinal malignancy • It is a disease with an extremely poor prognosis • Fewer than 20% of affected patients survive the first year • Only 4% are alive 5 years after diagnosis • Pancreatic cancer is the fourth leading cause of cancer death in both men and women • Pancreatic cancer is very rare before the age of 45 years • It affects males more than females • more common in black persons. The incidence in black men is 14.8 per 100,000, compared with 8.8 in the general population • The etiology of pancreatic cancer remains unknown

  3. Risk factors • Hereditary pancreatitis 10%, abnormal trypsin gene that is transmitted as an autosomal dominant trait,risk for pancreatic cancer by age 70 years is estimated at 40% • Nonhereditary forms of chronic pancreatitis also have a higher likelihood of pancreatic cancer. A multinational study found this risk to be 2% per decade, independent of the type of pancreatitis • Genetic factors predispose to pancreatic cancer in some families. In several population studies, 7% to 8% of patients with pancreatic cancer have a first-degree relative with the disease • Diabetes mellitus is very common in pancreatic cancer, recent onset of diabetes without family history may help identify patients with pancreatic cancer, particularly in individuals older than 50 years, higher production of islet amyloid polypeptide (amylin) by the tumor is responsible for the diabetogenic state • Cigarette smoking. Multiple cohort and case-control studies have found that the relative risk for smokers of developing pancreatic cancer is at least 1.5 • A high intake of fat and/or meat has been linked to the development of this neoplasm • Women taking 14 tablets or more of aspirin per week for 4 years or more increased their risk of pancreatic cancer by 86% • An association between Helicobacter pylori infection and pancreatic cancer has also been reported

  4. Pathology • Three different epithelial cell types can be found in the normal pancreas: • (1) Acinar cells, which account for about 80% of the gland volume • (2) Ductal cells, composing 10% to 15% • (3) Endocrine (islet) cells, making up about 1% to 2% • More than 95% of the malignant neoplasms of the pancreas arise from the exocrine elements of the gland (ductal and acinar cells) and demonstrate features consistent with adenocarcinoma. • Endocrine neoplasms account for only 1% to 2% of pancreatic tumors • Nonepithelial malignancies are exceedingly rare

  5. Genetic Mutations in Pancreatic Cancer • Gene Pancreatic Cancer (%) Colorec.Ca (%) • P1695 0 • K-ras 90 50 • P53 75 60 • DPC4 55 15 • BRCA2 7 ?

  6. CLINICAL FEATURES • Most patients with pancreatic cancer experience symptoms late in the course of disease • less than 20% of patients present with resectable disease • Tumors of the head of the pancreas produce symptoms earlier in the course of disease • Jaundice is often the first sign in more than 50% of patients • In less than one third of patients, a palpable nontender gallbladder, referred to as Courvoisier's sign • Pancreatic exocrine insufficiency in the form of steatorrhea and malabsorption • Pain in pancreatic cancer is primarily due to invasion of the celiac and superior mesenteric arterial plexus • Other common symptoms are fatigue, anorexia, and weight loss • New-onset diabetes mellitus may also herald pancreatic cancerandcan be observed in 6% to 68% of patients • Acute pancreatitis is occasionally the first manifestation of pancreatic cancer

  7. DIAGNOSIS • The method of choice for diagnosis and staging of pancreatic cancer is CT. The pancreas is ideally imaged by means of the thin-section, pancreatic protocol, helical CT. In large series, a correct diagnosis of pancreatic cancer can be made in up to 97% of patients • ERCP has become a mainstay in the differential diagnosis of various tumors of the pancreatobiliary junction. Of these, 85% are pancreatic, 6% originate in the distal common bile duct, and 4% each are ampullary or duodenal carcinomas • EUS may be the most accurate test for the diagnosis of pancreatic cancer • Magnetic resonance imaging (MRI) has been increasingly used in the evaluation of pancreatic tumors, In one study, pancreatic tumor detection was reported in 90% of patients for MRI versus 76% for helical CT • FDG-PET can be helpful in differentiating benign from malignant pancreatic masses when morphologic data are equivocal • Serum Marker CA 19-9,in one study, in which a cutoff of 37 U/mL was used, sensitivity and specificity were 86% and 87%, respectively

  8. STAGING • TNM System • Tumor • Tis Carcinoma in situ • T1 Tumor limited to the pancreas, 2cm or less in greatest dimension • T2 Tumor limited to the pancreas, >2cm in greatest dimension • T3 Tumor extends directly into any of the following: duodenum, bile duct, peripancreatic tissues • T4 Tumor extends directly into any of the following: stomach, spleen, colon, adjacent large vessels • Lymph Node Metastases • N0 No regional lymph node metastases • N1 Regional lymph node metastases • Distant Metastases • M0 No distant metastases • M1 Distant metastases

  9. AJCC Staging • Stage I T1-T2 N0 M0 • Stage II T3 N0 M0 • Stage III T1-T3 N1 M0 • Stage IVA T4 Any N M0 • Stage IVB Any T Any N M1

  10. TREATMENT • Surgical resection is the only potentially curative treatment for pancreatic cancer • Only about 15% of patients are candidates for pancreatectomy • Absolute contraindications for resection include presence of metastases in the liver, peritoneum, omentum, or any extra-abdominal site • More relative contraindications include involvement of the bowel mesentery, portomesenteric vasculature, and celiac axis and its tributaries • The most common operation for pancreatic cancer is the Whipple pancreaticoduodenectomy • In the classic Whipple operation, the gastric antrum is resected en bloc with the pancreas and duodenum primarily to secure a “negative” resection margin • A popular modification of the Whipple procedure is the pylorus-preserving pancreaticoduodenectomy (PPPD) • Overall, no survival benefit was observed with the radical lymphadenectomy • Many recent large series show mortality rates of less than 3%

  11. Palliative Procedures • Biliary bypass operations are quite effective and have the advantage of offering a preventive or therapeutic concomitant gastrojejunostomy as well as a celiac plexus block for pain control • One large series reported a postoperative mortality of 3.1% and a complication rate of 22%, with a median survival of 6.5 months • Relief of jaundice can also be achieved by stents placed percutaneously or endoscopically, In experienced hands, endoscopic stent placement has a success rate of more than 85%, with a 1% to 2% procedure-related mortality rate • Several randomized trials have found no difference in survival between endoscopic stent placement and surgical bypass for malignant obstructive jaundice, but patients with stents do have more frequent readmissions for stent occlusion, recurrent jaundice, and cholangitis • Duodenal obstruction traditionally has been treated with surgery, Reports of the use of expandable metallic stents to relieve duodenal malignant obstruction have shown success, and this modality may be used increasingly in the future • Randomized trials have shown that surgical and percutaneous chemical neurolysis of the celiac ganglion can offer relief to many patients. Radiation therapy may also significantly alleviatepain

  12. Chemotherapy and Radiation Therapy • The best available data today are equivocal regarding the use of chemoradiation in adjuvant fashion outside clinical trials • Conventional EBRT combined with 5-FU as a radiosensitizer has been shown to yield better survival than either EBRT alone or chemotherapy alone • Intraoperative radiation therapy offers the possibility of delivering a higher dose to the cancer without increasing the injury to neighboring tissues • Patients presenting with stage IV disease as well as those in whom distant metastasis develops after attempted curative resection are candidates for chemotherapy • Only two chemotherapy agents have been associated with survivals longer than 5 months in pancreatic cancer, 5-FU and gemcitabine • Assessment of tumor response to chemotherapy is based primarily on serial imaging studies, serum marker (CA 19-9) trends, and changes in tumor-related symptoms

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