Pancreatic carcinoma and periampulary tumors

MH Emami MH Emami Poursina Hakim Research Institute Poursina Hakim Research Institute IUMS IUMS Isfahan, Iran Isfahan, Iran

Liver, Biliary System, and Pancreas

Pancreatic masses Pancreatitis/cyst/Pseudocyst Autoimmune pancreatitis(AP) Neuroendocrine Tumors Lymphoma Distal CBD cholangiocarcinoma Pancreatic metastasis Periampulary tumors Exocrine pancreatic neoplasms" includes all tumors that are related to the pancreatic ductal and acinar cells and their stem cells (including pancreatoblastoma)

Epidemiology Cancer of the exocrine pancreas is a highly lethal malignancy. It is the fourth leading cause of cancer-related death in the United States and second only to colorectal cancer as a cause of digestive cancer- related death

Pancreatic CA risk factors Heritage Age Sex Oxidized fats Cigarettes Alcohol opium Low exercise, sedentary life obesity Chronic Inflammation ( pancreatitis) Low intake of vegetable and Fibers DM Immunosuppressants

Surgical resection is the only potentially curative treatment. Unfortunately, because of the late presentation, only 15 to 20 percent of patients are candidates for pancreatectomy. Furthermore, prognosis is poor, even after a complete resection. Five-year survival after pancreaticoduodenectomy is about 25 to 30 percent for node-negative and 10 percent for node-positive disease.

Of the several subtypes of ductal adenocarcinoma, most share a similar poor long-term prognosis, with the exception of colloid carcinomas, which have a somewhat better prognosis.

The most frequent symptoms of pancreatic CA at the time of diagnosis Asthenia – 86 percent Weight loss – 85 percent Anorexia – 83 percent Abdominal pain – 79 percent Epigastric pain – 71 percent Dark urine – 59 percent Jaundice – 56 percent Nausea – 51 percent Back pain – 49 percent Diarrhea- 44 percent Vomiting – 33 percent Steatorrhea – 25 percent Thrombophlebitis – 3 percent

The most frequent signs of pancreatic CA at the time of diagnosis Jaundice – 55 percent Hepatomegaly- 39 percent Right upper quadrant mass – 15 percent Cachexia – 13 percent Courvoisier’s sign (nontender but palpable distended gallbladder at the right costal margin) – 13 percent Epigastric mass – 9 percent Ascites – 5 percent

Signs of advanced, incurable disease include: An abdominal mass or ascites Left supraclavicular lymphadenopathy (Virchow's node) A palpable periumbilical mass (Sister Mary Joseph’s node) or a palpable rectal shelf are present in some patients with widespread disease. Pancreatic cancer is the origin of a cutaneous metastasis to the umbilicus in 7 to 9 percent of cases

Clues suggesting the possibility of a primary pancreatic lymphoma include Lack of jaundice, Constitutional symptoms (weight loss, fever, and night sweats), Elevated serum lactate dehydrogenase (LDH) or beta-2 microglobulin level, Normal serum CA 19–9

An endoscopic ultrasound (EUS)-guided biopsy may be recommended if a diagnosis of chronic or autoimmune pancreatitis is suspected on the basis of history (eg, extreme young age, prolonged ethanol abuse, history of other autoimmune diseases), particularly if further imaging studies (either EUS, endoscopic retrograde cholangiopancreatography, magnetic resonance cholangiopancreatography) reveal multifocal biliary strictures (suggestive of autoimmune pancreatitis) or diffuse pancreatic ductal changes (suggestive of chronic pancreatitis).

The rates of unresectable disease among all patients with a CA 19-9 level ≥130 units/mL versus <130 units/mL were 26 and 11 percent, respectively. Among patients with tumors in the body/tail of the pancreas, more than one- third of those who had a CA 19-9 level ≥130 units/mL had unresectable disease.

The addition of molecular genetic analysis (eg, assay for K-ras or p53 gene mutations by RT- PCR) to cytologic examination may improve sensitivity, especially in patients with small primary tumors.

Screening for Extra-Colonic Cancers in FAP Exira-colonic cancerRisk ScreeningRecommendations Duodenal or peri- ampullary cancer 5%-10% Upper Gl endoscopy (including side-viewing exam) every 1 to 3 years, start at age years Pancreatic cancer About 2% Possibly periodic abdominal ultrasound after age 20 years Thyroid cancer About 2% Annual thyroid examination. start age years Gastric cancer About 0.5% Same as for duodenal CNS cancer, usually cerebellar meduloblastoma (Turcot syndrome) <1% but RR=92 Annual physical examination. possibly periodic head CT in affected families Hepatoblastoma 1.6% of children <5 years of age Possibly liver palpation hepatic ultrasound AFP annually, during first decade of life

Screening for Extra-Colonic Cancers in HNPCC(1) Cancer Cancer Risk Screening Recommendations Endometrial cancer43%-60% Pelvic exam, transvaginal ultrasound, and/or endometrial aspirate every 1-2 years, starting at age years Ovarian cancer9%-12% Gastric cancer13%-19% Upper Gl endoscopy every 1-2 years, starting at age years

Screening for Extra-Colonic Cancers in HNPCC (2) Urinary tract cancer4.0%-10%Ultrasound and urinalysis (urine cytology) every 1-2 years, starting at age years Renal cell adenocarcinoma 3.3% Biliary tract and gallbladder cancer 2.0%-18%Uncertain, possibly LFTs annually after age 30 years Central nervous system (usually glioblastoma) 3.7%Uncertain, possibly annual physical examination and periodic head CT in affected families Small bowel cancer1%-4%Uncertain, at least small bowel x-ray if symptoms occur

Screening for Extra-Colonic Cancers in Peutz-Jeghers Syndrome (1) CancerCancer RiskScreening Recommendations stomach duodenum 2%-13% RR=1 3 (includes colon cancer risk) Upper Gl Endoscopy every 2 years, start at age 10 years Small bowelAnnual hemoglobin, small bowel x-ray every 2 years, both start at age 10 years Breast: RR=8.8Annual breast exam and mammography every 2-3 years, both start at age 25 years PancreaticRR=100Endoscopic or abdominal ultrasound every 1-2 years, start at age 30 years

Screening for Extra-Colonic Cancers in Peutz-Jeghers Syndrome (2) UterineRR=8,0Annual pelvic exam with pap smear; and annual pelvic or vaginal ultrasound and/or uterine washings, both start at age 20 years OvarianRR=13 Adenoma malignum (cervix) Rare Sex cord tumor with annular tubules (SCTAT), in almost all women 20% become malignant Sertoli cell tumor (males), unusual 10%-20% become malignant Annual testicular exam, start at age 10 years; testicular ultrasound if feminizing features occur