1. Periampullary and Pancreatic Tumors
Rod L. Flynn, M.D.
Surgical Oncologist
Mary Washington Hospital
Fredericksburg, VA

2. Periampullary Tumors
Defined as those that arise within 2 cm of the major papilla in the duodenum
Classified on the basis of their tissue of origin
Often difficult or impossible to differentiate from pancreatic head adenocarcinoma before performing a resection

3. Periampullary Tumors Encompass tumors of the: ampulla of Vater
distal common bile duct (intrapancreatic distal common bile duct),
duodenal tumors (usually the second part) involving the papilla
tumors of the pancreatic head involving in close proximity to the ampulla
Pancreatic head adenocarcinoma accounts for most (approximately 80%) tumors in the periampullary region

4. Periampullary Anatomy

5. Periampullary Tumors
In general, the more distal the tumor is along the pancreatobiliary tree, the better the prognosis
Hilar Cholangiocarcinomas (Klatskin Tumors) 15-20% 5-year survival
Distal bile duct cancers 20-30% 5-year survival
Ampullary carcinomas 40-60% 5-year survival
Duodenal carcinomas 60% -70% 5-year survival
Pancreatic head adenocarcinoma 15-20% 5-year survival
Non-pancreatic periampullary cancers tend to have a better prognosis than does pancreatic adenocarcinoma because they are often more resectable
i.e. 90% of ampullary cancers vs 15-20% of pancreatic head cancers

6. Pancreatic Head Adenocarcinoma

7. Pancreatic Head Adenocarcinoma Demographics
Treatment poses diagnostic and therapeutic challenge
Second most common GI malignancy in U.S. (colorectal is the most common)
In 2006, 33,730 new cases were diagnosed in U.S.
Accounted for about 32,300 deaths
Fourth leading cause of cancer-related deaths (following lung, colon, breast/prostate)

8. Pancreatic Head Adenocarcinoma Demographics
Responsible for 5% of all cancer-related deaths
Surgical resection provides the only chance for cure
80% of patients present with advanced disease not amenable to resection

9. Pancreatic Cancer Risk Factors Exact cause is unknown
Environmental exposure
Smoking (main risk factor)
Risk increases with dose and exposure
Other tobacco carcinogens likely involved
Organic and nickel-containing solvents
Chlorinated compounds
High BMI
Diet -- low in vegetables and fruits, high in animal fats and meat products Risk higher in obese individuals
Risk higher in obese individuals
Decreases with weight loss and exercise

10. Pancreatic Cancer Risk Factors (cont’d) Comorbid conditions
Chronic pancreatitis
Diabetes mellitus, type II
Risk doubles with > 5-year history of diabetes mellitus, type II
Genetic factors
Account for 15% to 20% of cases
1 family member affected: 18 times risk
3 family members affected: 57 times risk
Familial syndromes

11. Molecular/Genetic Defect
Familial Syndromes
Syndrome
Molecular/Genetic Defect
Hereditary pancreatitis
7q35
Hereditary nonpolyposis colorectal cancer (Lynch syndrome II)
hMSH2, hMLH1
Hereditary breast and ovarian cancer
BRCA2
Familial atypical multiple mole melanoma (FAMM)
p16 (9p21)
Peutz-Jeghers syndrome
STK11/LKB1 (19p13)
Ataxia-telangiectasia (ATM) syndrome
11q22-23

12. Pancreatic Head Adenocarcinoma Clinical Presentation
Most patients with periampullary cancer present with at least one of the following symptoms:
Weight loss
Jaundice (75% of patients)
Vague epigastric/ back pain (retroperitoneal plexus invasion)
Fatigue
Intestinal malabsorption
New onset diabetes (15%)
Symptom complex is vague, which often delays presentation and diagnosis
As a result about 80% of all patients present with unresectable disease

13. Pancreatic Head Adenocarcinoma Clinical Signs
The presence of clinical signs usually means advanced disease
Courvoisier’s sign
Painless jaundice
Palpable abdominal mass
Large tumor or omental cake
Ascites
Umbillical nodule (Sister Mary Joseph’s node)
Blumer’s shelf (rectovaginal/vescicle mass)
Virchow’s node (left supraclavicular)

14. Pancreatic Cancer Clinical Presentation
Component
Symptom
Local
Epigastric/back pain
Constitutional
Fatigue Anorexia Weight loss
Biliary obstruction
Jaundice Pruritus Pale stools
Malabsorption of fat-soluble vitamins
Pancreatic insufficiency
Malabsorption

15. AJCC STAGING Pancreatic Cancer
TUMOR
Tis: in situ carcinoma
T1: < 2 cm
T2: > 2 cm
T3: beyond pancreas
T4: involves celiac axis or superior mesenteric artery (unresectable)
NODE
N0: no lymph node metastases
N1: regional lymph node metastases
METASTASES
M0: no distant metastases
M1: distant metastases present
Stage 0
Tis, N0, M0
Stage IA
T1, N0, M0
Stage IB
T2, N0, M0
Stage IIA
T3, N0, M0
Stage IIB
T1-3, N1, M0
Stage III
T4, any N, M0
Stage IV
Any T, any N, M1

16. Pancreatic Cancer Diagnosis
The goals of evaluating patients with periampullary cancers is to obtain diagnosis and clinical stage
Based on these determinations the patient can be triaged into a treatment category
(operative or non-operative)
At time of initial diagnosis, approx 50% of patients will have metastatic disease
30% will have locally-advanced disease not amenable to surgical resection
The superior mesenteric vein is involved with the large pancreatic head tumor

17. Pancreatic Cancer Diagnostic Tests
Blood tests including CBC, LFTs, amylase/lipase, CEA, CA 19-9
Abdominal ultrasound
A common initial test to evaluate jaundice
Abdominal CT scan
Gives better anatomical information on the source of the biliary obstruction
Can give information about extrapancreatic sites of spread (liver, peritoneal/omental surfaces, ascites, extensive nodal involvement, adjacent organ involvement)
Can assess involvent of major blood vessels (SMA/portal vein)
Angiography
? PET scan

18. Pancreatic Cancer Diagnostic Tests
ERCP
Brush cytology
Stenting if necessary
Look for dilated pancreatic duct
Look for filling defect within bile duct

19. Pancreatic Cancer Diagnostic Tests
Endoscopic ultrasound
Can detect very small tumors (<2cm)
Can assist in staging by assessing mesenteric vascular involvement
FNA biopsies are relatively easy to do
Operator dependant

20. Laparoscopy for staging
Looking for
Local involvement of adjacent organs
Loco-regional extension (lymph nodes, soft tissue)
Small liver metastases
Peritoneal nodules
Peritoneal Nodule

21. Treatment Available Chemotherapy Radiation therapy
Chemoradiation followed by resection
Resection
Resection + Adjuvant Therapy
Palliation
Stents
Bypass
Feeding tubes

22. Treatment Available Only 10-20% of patients are eligible for surgery
Most have advanced disease at time of diagnosis
Most common chemo 5-FU & Gemcitabine

23. Pancreaticoduodenectomy
Whipple Procedure
Pancreaticoduodenectomy
The Whipple operation was first described in the 1930’s by Allan Whipple
In the 1960’s and 1970’s the mortality rate for the Whipple operation was very high (Up to 25% of patients died from the surgery)
This experience of the 1970’s is still remembered by some physicians who are reluctant to recommend the Whipple operation
Today the Whipple operation has become an extremely safe operation in the USA - At tertiary care centers where large numbers of these procedures are performed by selected surgeons, the mortality rate is less than 4%.

24. Most common Diagnosis of patients undergoing Whipple
Peripancreatic Cancer (jaundice)
Pancreatic head
Ampulla
Bile duct
Duodenal wall
Pancreatitis
Cystic neoplasm
Carcinoid
Islet cell tumors

25. Surgery Incisions Omentum Resectability (Portal Vein/SMA)
Gall Bladder and Porta Hepatis
Gastrectomy
Pancreas Transection
Reconstruction

26. Surgery Incisions Omentum Resectability (Portal Vein/SMA)
Gall Bladder and Porta Hepatis
Gastrectomy
Pancreas Transection
Reconstruction

27. Surgery (cont.) Pylorus Preserving Extended Nodal Dissection
Gastric Inversion

28. Surgery (cont.)
Exposure of SMV

29. Surgery (cont.) Portal Triad Hepatic artery Portal vein
Common bile duct

30. Surgery (cont.)
Division of pancreas

31. Surgery (cont.)
Resected specimen

32. Surgery (cont.)
Plumbing restored

33. Outcomes
Possible complications 44% in modern series out of Johns Hopkins; <5% 30-day mortality; 17day LOS v. 28 for complicated
Pancreatic fistula (Leak-8%)
Gastro paresis
Nutritional deficiencies
Malabsorption
Early satiety
Weight loss
Diabetes

34. Outcomes
(Johns Hopkins study, con’t)
N= 201 patients
The mean age of the patients was 63 years, with a slight male predominance (108 men and 93 women).
There were no differences in survival based on age, gender, or race.
The actuarial one, three and five-year survival rates for all 201 patients were 57%, 26%, and 21% respectively, with a median survival of 15.5 months.
11 five-year survivors,
7 six-year survivors
one fifteen-year survivor.

35. Summary
Periampullary cancers include bile duct, ampulla of vater, duodenal, pancreatic head
Prognoses depend on relative location
Pancreatic head adenocarcinoma carries worst prognosis
Surgery is the only chance of cure, although a majority of patients are unresectable at the time of diagnosis
Better preoperative evaluation can reduce the number of unnecessary operations
Preoperative diagnosis is often very difficult if not impossible to make despite a myriad of diagnostic modalities at our disposal
In this group of patients we surgeons sometime have to tell the patient after a lengthy Whipple operation: “…I have good news, you don’t have cancer…”

36. Bye-bye