Pancreatic Cancer: Case and Discussion

1. Pancreatic Cancer: Case and Discussion Andrew D. Rhim, MD University of Michigan Medical School

2. Clinical Case • 72yo man presents to General GI clinic for abdominal discomfort after eating • Developed over the past 8-9 months • Vague, dull discomfort/pressure starting 10-20 minutes after eating and lasting for 30min to a few hours • Does not interfere with daily activities (2-3/10) • Located in the epigastrum, MAYBE radiating to his back • Not eating helps, though he has been careful to maintain caloric intake

3. HPI • 72yo man presents to General GI clinic for abdominal discomfort after eating • No associated nausea, vomiting, diarrhea or constipation • Has noted 20lb weight loss in the past 2-3 months, though he denies anorexia • Denies new-onset depression, jaundice, malaise • Has noted increased urination and thirst (maybe)

4. Review of Systems • Constitutional: Positive for unexpected weight change. Negative for fever, chills, diaphoresis, activity change, appetite change and fatigue. • HENT: Negative. • Eyes: Negative. • Respiratory: Positive for apnea and cough. Negative for choking, chest tightness, shortness of breath, wheezing and stridor. • Cardiovascular: Negative. • Gastrointestinal: Positive for abdominal pain. Negative for nausea, vomiting, diarrhea, constipation, blood in stool, abdominal distention, anal bleeding and rectal pain. • Endocrine: Negative. • Genitourinary: Negative. • Musculoskeletal: Negative. • Skin: Negative. • Allergic/Immunologic: Negative. • Neurological: Negative. • Hematological: Negative. • Psychiatric/Behavioral: Negative. (No depression)

5. Past Medical History • History of colon cancer 10 years ago, in remission after colectomy. • GERD • HTN • COPD (previous smoker) • Cataracts • Diabetes mellitus II • Diagnosed 6 months ago • Recent requirement of insulin 2 weeks ago

6. Social History • Previous smoker—quit 2011 • EtOH—4 cans a week, denies history of binging • No IVDA • Married with 3 grown children • Retired school teacher

7. Family history • Colon cancer in father (60) • Unknown cancer in mother, sister, maternal aunt, maternal uncle.

8. Physical Exam • Constitutional: He is oriented to person, place, and time. He appears well-developed and well-nourished. No distress. • HENT: Normal • Head: Normocephalic and atraumatic. • Nose: Nose normal. • Mouth/Throat: No oropharyngeal exudate. • Eyes: Conjunctivae are normal. Pupils are equal, round, and reactive to light. Right eye exhibits no discharge. Left eye exhibits no discharge. No scleral icterus. • Neck: Neck supple. No tracheal deviation present. • Cardiovascular: Intact distal pulses. • Pulmonary/Chest: Effort normal and breath sounds normal. No stridor. No respiratory distress. He has no wheezes. • Abdominal: Soft. Nl bowel sounds. He exhibits no distention. There is no guarding. • Musculoskeletal: Normal range of motion. He exhibits no edema. • Neurological: He is alert and oriented to person, place, and time. No cranial nerve deficit. Coordination normal. • Skin: Skin is warm and dry. No rash noted. He is not diaphoretic. No erythema. No pallor or jaundice • Psychiatric: He has a normal mood and affect. His behavior is normal. Judgment and thought content normal.

9. 31.5 1.0 144 98 10 241 4.3 30 0.98 Labs 14.8 4.4 365 ALT = 37 AST = 36 TBili = 1.6 AlkPhos = 99 Alb = 4.1

10. CT abdomen/pelvis • Pancreas: • Atrophy of body and tail of pancreas • Dilated main pancreatic duct with transition point, with no obvious mass lesion • Remainder of the pancreas appears normal • No lymph node enlargement or other masses. • Exam otherwise normal

12. Next steps? • Repeat cross sectional imaging (MRCP) • Endoscopic ultrasound +/- FNA • EGD + colonoscopy • Treat patient for IBS • Pancreatic enzyme supplementation

13. Next steps? • Repeat cross sectional imaging (MRCP) • Endoscopic ultrasound +/- FNA • EGD + colonoscopy • Treat patient for IBS • Pancreatic enzyme supplementation

14. Why? High suspicion for neoplasm • HPI: • Vague, dull discomfort/pressure starting 10-20 minutes after eating and lasting for 30min to a few hours • Located in the epigastrum, MAYBE radiating to his back • Has noted 20lb weight loss in the past 2-3 months, though he denies anorexia • Denies new-onset depression, jaundice, malaise • Has noted increased urination and thirst

15. Why? High suspicion for neoplasm • PMH • Diabetes mellitus II • Diagnosed 6 months ago • Recent requirement of insulin 2 weeks ago • Labs: • Fasting glucose elevated • CT pancreas: • Abrupt cut-off of pancreatic duct • Atrophy of distal pancreas

16. Mass in body of pancreas Diagnosis: Pancreatic ductal adenocarcinoma, Stage 1 Treatment: Surgical resection + Adjuvant chemo

17. Pancreatic Cancer Epidemiology • Incidence: 11.7 per 100,000 • Rising incidence • 6.7% increase 19952005 • Lifetime risk: 1.41% • 1 in 71 Americans will be diagnosed w/ PC • Median age of diagnosis: 72 • Median age of death: 73 SEER, 2009

18. Pancreatic Cancer: An Imminent Threat Matrisian, Cancer Res 2014

19. Pancreatic Cancer: Poor survival due to metastatic disease • 5 year survival from diagnosis: <5% (all-comers) • 80% will present with invasive and metastatic disease at diagnosis • Even with chemotherapy, median survival is ~6mo • 20% will present with limited primary tumors with no metastatic disease • Most of these patients will undergo surgical resection

20. Surgical Treatment • Only chance at cure • Only indicated for patients with: • Limited tumor burden • No evidence of mets • Satisfactory surgical risk • Whipple procedure v. distal • Relatively high morbidity • Post-op infection, leaks, bleeding • Brittle diabetes • Malnutrition and weight loss • Adjuvant chemtherapy recommended

21. Poor survival even after surgery • Even without clinical evidence of metastasis, 5y survival after resection is poor (~20%) • Even with small tumors • Mostly due to metastatic disease Agarwal et al., Pancreas 2008

22. Early warning signs of PDAC • Abrupt onset of diabetes in non-obese individuals over the age of 60 • OR sudden insulin requirements or erratic blood sugar control • Depression • Evidence of pancreatic exocrine insufficiency • Foul smelling, floating stools • Malabsorption • Weight loss despite sufficient caloric intake • Non-specific symptoms: • Malaise, weight loss, anorexia, dull abdominal discomfort • Diagnostic test: pancreas protocol CT scan + IV contrast (though MR may be better)

23. High risk groups • Chronic pancreatitis • Especially hereditary pancreatitis • Familial pancreatic cancer • ≥2 first degree relatives with PDAC • Other genetic syndromes • Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM; 38-fold increased risk) • Peutz-Jeghers Syndrome (36% lifetime risk) • BRCA 2 mutation • Cystic fibrosis? • Screening: alternating annual EUS + MRI/CT

24. Conclusions • Pancreatic cancer is a horrible disease • Median survival of 6-8mo • Will soon be the second leading cause of cancer-related deaths in the US • While not perfect, there are “early” warning signs • Abrupt onset diabetes, weight loss, depression • Surgery is the only treatment that may lead to durable cure at this point in time (~20% live to 5y)