Duodenal and

Periampullary
Neoplasms
Kyo U. Chu, MD, FACS
Surgical Oncology, Sinai Hospital of
Baltimore

Duodenal and
Periampullary
Neoplasms

Benign Tumors of Small

Bowel
Tumor Type

Duodenum

Jejunum

Ileum

Total (%)

Leiomyoma

24

64

47

135 (37)

Adenoma

34

17

17

68 (19)

Lipoma

11

13

30

54 (15)

Hemangioma

10

26

37 (10)

Fibroma

12

23 (6)

Other

27

13

48 (13)

Total (%)

101 (27)

119 (33)

145 (40)

365 (100)

Devita, Hellman and Rosenberg, eds. Cancer: Principles and

Practice of Oncology,
5th ed. Philadelphia: Lippincott-Raven, 1997

Most of leiomyoma is now better

defined as GIST
10-30% are malignant
1/3 of >3cm adenoma has foci of

Malignant Tumors of Small

Bowel
Tumor Type

Duodenum

Jejunum

Ileum

Total (%)

Adenocarcinoma

634

454

301

1389 (44)

Carcinoid

60

92

781

933 (29)

Lymphoma

34

183

276

493 (15)

Sarcoma

61

159

148

368 (12)

Total (%)

789 (25)

888 (28)

1506 (47)

3183 (100)

Devita, Hellman and Rosenberg, eds. Cancer: Principles and Practi

5th ed. Philadelphia: Lippincott-Raven, 1997

40% of adenocarcinoma occurs in

Duodenum
2/3 of duodenal adenoCA are
periampullary

Surgical Treatment:
Duodenal Tumors

Depends on
Benign or Malignant
Size
Location
Local extension to adjacent structures
Lymph node involvement
Distant metastasis

Known natural history of tumor

Types of Surgical
treatment

Simple excision: small benign, less than

half the circumference of duodenum
Pancreaticoduodenectomy: Malignant
lesion located at 2nd and 3rd portion of
duodenum
Antrectomy and/or duodenectomy: Small
malignant tumor located at 1st portion of
duodenum or 4th portion of duodenum

Adenocarcinoma of Duodenum

K-ras & p53 gene similar as in CRC, but much

less APC mutation
Risk factors

Crohns disease
Villous adenomas
Polyposis syndromes, FHx of hereditary nonpolyposis
colorectal cancer (HNPCC)

Mean age: 60, male predominance 2.4:1

No proven survival advantage with current
chemotherapy
Radiation therapy may be beneficial

Duodenal Lymphoma

Small bowel lymphomas

> 25% presents with Complications

Only 5% of all lymphomas

15-20% of all small bowel neoplasm
Bleeding
Perforation
Obstruction

Best managed with surgery

Duodenal Carcinoid

Rare, only 2% of all SB carcinoid

85% of all carcinoid occur at Appendix

15% in small bowel (90% in ileum)

30% of SB carcinoid have multiple synchronous

lesions at jejunum and ileum
Managed similarly to adenocarcinomas
Chemotherapy 20-30% RR
Radiation therapy not useful
Overall 5-year survival 60%

Resected nodal disease 15 years Median survival vs.

5 years unresected

Duodenal GIST

30% in Small bowel

IHC positive for protooncogene CD117 and CD34
Malignant potential determined by

Mitotic frequency (>2 mitoses/HPF)

Nuclear atypia
Cellularity
Size of tumor
Central necrosis

Metastases in 30%
Gleevec tyrosine kinase inhibitor

Periampullary
Neoplasm
Carcinomas of ampulla or distal common

bile duct
Exocrine Pancreatic Cancers
Ductal Adenocarcinoma (90%)
Acinar cell carcinoma (<5%)
Endocrine Pancreatic Cancers
Islet cell tumors
Insulinoma, Glucagonoma, VIPoma etc.

Survival Data: Localized

Pancreatic
Adenocarcinoma after surgical
resection

Author (Year)

No. of
Patients

Median Survival
(Months)

Estimated 4- or 5year survival (%)

Spitz (1997)

60

20.2

NA

Yeo (1997)

282

18

NA

Nitecki (1995)

174

17.5

6.8

Tsao (1994)

27

18

6.6

Geer (1993)

146

18

24

Bakkevold (1993)

83

11.4

NA

Roder (1992)

53

12

6
NA, Not available

Survival Data: Localized

Periampullary
(nonpancreatic)
adenocarcinoma
after surgical resection
Author (Year)

No. of Patients

Median Survival
(Years)

Estimated 5-year
Survival (%)

Roberts (1999)

32

NA

46

Howe (1998)

101

4.9

46

Talamini (1997)

106

3.8

38

Harada (1997)

63

NA

46

Allema (1995)

67

NA

50

Monson (1991)

104

2.8

34
NA, Not available

Survival Data: Localized, NODE

POSITIVE
Periampullary (nonpancreatic)
adenocarcinoma after surgical
resection
Author (Year)

No. of
Patients

Median Survival Estimated 5-year

(Years)
Survival (%)

Howe (1998)

46

2.0

NA

Harada (1997)

28

NA

35

Kayahara (1997)

15

NA

31

Talamini (1997)

40

2.0

31

Allema (1995)

35

NA

41

Monson (1991)

31

1.4

16
NA, Not available

*Median **5-year
Survival Survival
(months) (%)
11-18

20.3

6-12

5-7

1.7

*Evans DB, et al. Ca of Pancreas in DeVita, Cancer Principles &

Practice in Oncology 2001 ** Source: American Cancer
Society, 2008

Exocrine Pancreatic
Cancer

Almost all eventually die of disease,

thus incidence rates and mortality rates
were nearly identical in the past but
separating more over last few decades.

American Cancer Society:

Estimates for 2008 in United States
New cases: 37,680 (10 th most common)

Incidence rates stable over last 20-30 years

Deaths: 34,290 (4th leading cause)

Declining in men since 1970s

Leveled off in women since 1980s

Trends in Five-year Relative Survival

Rates (%)*, 1975-2003
Site

1975-1977 1984-1986 1996-2003

All sites

5054

66

Breast (female)

7579

89

Colon

5159

65

Lung and bronchus

1313

16

Melanoma

8287

92

Ovary

3740

45

Pancreas

23

Prostate

6976

99

Rectum

4957

66

*5-year relative survival rates based on follow up of patients through 2004.

Source: Surveillance, Epidemiology, and End Results Program, 1975-2004, Division of Cancer Control and
Population Sciences, National Cancer Institute, 2007.

Exocrine Pancreatic
Cancer

Although these survival statistics are

sobering,
certain groups of patients do
better.
Clear surgical margins and no lymph node
metastases:
5-year survival is as high as
25%
Well-differentiated tumors:
5-year survival is 50%

Unfortunately, only a minority of patients

fall
into these categories.

Yeo et al. Ann Surg

1995

Clinical Presentation

Most common: Weight loss, pain, and

malnutrition
Painless jaundice
Abdominal Pain

Low intensity, visceral in origin and poorly

localized to upper abdomen
Severe upper back pain is more characteristic of
advanced disease

Sudden onset of diabetes mellitus in

nonobese adults >40 years warrants an
evaluation

Clinical Presentation
(contd)

Several large reviews of pancreatic cancer

note delay in diagnosis of > 2 months from
the onset of symptoms in the majority of
patients.
Although many are asymptomatic at early
stage, subtle signs and symptoms should
alert possible diagnosis of Pancreatic cancer
Vague abdominal pain or discomfort
New onset of diabetes

Risk Factors

Cigarette smoking (2X)

Chronic Pancreatitis (2X)

most strongly (evidence) linked

1.8% of patients with chronic pancreatitis
developed
pancreatic cancer during a
mean follow-up of 7.4 years.
(Fernandez et al . Pancreas 1995; Lowenfels
et al. NEJM 1993)

Obesity
Family History (18-57X) only ~5% of
patients

Diagnostic Studies

Thin-section helical CT with IV and oral

contrast
CT Resectability (accuracy 80%)

1. Absence of extra pancreatic disease

2. Absence of direct tumor extension to the superior
mesenteric artery (SMA) and celiac axis
3. Patent superior mesenteric-portal vein confluence

Endoscopic retrograde
cholangiopancreatography (ERCP)
Endoscopic Ultrasound (EUS)
Percutaneous CT-guided needle biopsy

May be useful if initial non-surgical treatments

are considered

Tumor Marker: CA19-9

Diagnostic Studies

Thin-section helical CT with IV and oral contrast

CT Resectability (accuracy 80%)
1. Absence of extra pancreatic disease
2. Absence of direct tumor extension to the
superior mesenteric artery (SMA) and celiac axis
3. Patent superior mesenteric-portal vein
confluence

Endoscopic retrograde
cholangiopancreatography (ERCP)
Endoscopic Ultrasound (EUS)
Percutaneous CT-guided needle biopsy

May be useful if initial non-surgical treatments are

considered

Tumor Marker: CA19-9

Diagnostic Studies

Thin-section helical CT with IV and oral

contrast
CT Resectability (accuracy 80%)

1. Absence of extra pancreatic disease

2. Absence of direct tumor extension to the superior
mesenteric artery (SMA) and celiac axis
3. Patent superior mesenteric-portal vein confluence

Endoscopic retrograde
cholangiopancreatography (ERCP)
Endoscopic Ultrasound (EUS)
Percutaneous CT-guided needle biopsy

May be useful if initial non-surgical treatments

are considered

Tumor Marker: CA19-9

ERCP and Pre-operative biliary

tract drainage

Historically was done to lower the bilirubin

Thought to provide benefit by improving

immunologic, hepatic and renal function

Randomized prospective trials have failed

to demonstrate a reduction in operative
morbidity or mortality following routine
preoperative biliary drainage.
Decompression is recommended only

For patients with symptomatic jaundice who

are to be treated with pre-operative radiation
or chemotherapy.

Diagnostic Studies

Thin-section helical CT with IV and oral

contrast
CT Resectability (accuracy 80%)

1. Absence of extra pancreatic disease

2. Absence of direct tumor extension to the superior
mesenteric artery (SMA) and celiac axis
3. Patent superior mesenteric-portal vein confluence

Endoscopic retrograde
cholangiopancreatography (ERCP)
Endoscopic Ultrasound (EUS)
Percutaneous CT-guided needle biopsy

May be useful if initial non-surgical treatments

are considered

Tumor Marker: CA19-9

Tumor Marker: CA 199

> 90 U/mL 85% Accuracy

> 200 U/mL 95% Accuracy

> 750 U/mL associated with

Advanced Disease

Combination of CT and CA 19-9

(>100 U/mL) has PPV of 99-100%

Surgical Treatment

Still remains as only potentially curative

modality
No role in the presence of metastatic
disease
Intraoperative Evaluation for resectability
Liver
Peritoneum
Para-aortic lymphatic/root of mesentery
Primary tumor

Pancreaticoduodenectom
y

Earlier Surgical Results:

Pancreaticoduodenectomy

Historically (1960s) Poor Surgical

Outcome
Morbidity > 50%
Mortality ~20%

Lieberman et al., Ann Surg 1995 (New York

State, 1984-1991)
75% at hospitals with < 7cases/year
Mean hospital stay > 1 month
Risk-adjusted perioperative mortality: 1219%

Recent Surgical Result:

McPhee et al, Ann Surg August
2007

Examined in-hospital mortality after

pancreatectomy
Based on large national database, National
Inpatient
Sample (NIS), from 1998-2003
~7 million nonfederal hospital
discharges/year
279,445 patients with pancreatic cancer
39,463 patients underwent resection (14%)

Pancreatectomy:
Mortality

PD or Whipple (72%) - 6.6%

Decrease Trend:
8.2% in 1998 to 5.5% in 2003
Men vs. Women: 8.2% vs. 4.8%
Age >70 vs. <50: 9.5% vs. 2.6%
Low/Medium volume vs. High
volume center (>18/year)
11.1% vs. 2.7%

McPhee et al, Ann Surg Augu

Pancreatectomy:
Mortality

Distal Pancreatectomy (21%) - 3.5%

Men vs. women: 4.9% vs. 2.8%
Age >70 vs. <50: 6.5% vs. 0.3%
Low/medium volume vs. High volume
Center
5.1% vs. 0.43%

Total Pancreatectomy (3.7%) 8.3%

Hospital volume, age, and sex did not
influence
mortality rate

McPhee et al, Ann Surg Augu

5-year survival, Morbidity

and Mortality after Whipple
Authors

Morbidit
y (%)
18

Trede
(Mannheim,
Germany)
Cameron (JHH) 36
Grace (UCLA)
26
Geer (MSK)
27

Mortali
ty (%)
0

Survival
(%)
24

2
2
3

19
13
24

Advance in Survival:
Gemcitabine (Gemzar) after Whipple

Phase III Randomized prospective multicenter

trial
6 months of Gemcitabine after surgical resection
Disease-Free Survival
13.4 months vs. 6.9 months
Overall Survival
22.8 months vs. 20.2 months
Neuhaus et al., ASCO meeting May-June 2008

Surgical Oncology
Sinai Hospital (20052007)
Total number of
Pancreatectomies - 65
PD or Whipple - 49
Distal Pancreatectomy - 16
Mortality - 0 %
Morbidity - 15 %

Improved Surgical
Outcome

Better patient selection for Surgery

Advances in CT or imaging for accurate
staging
Laparoscopy
Improved Surgical Procedure
Regionalization of high risk cases
Experience of Surgeons
Advance in operative instruments and
equipments
Improved Peri-operative Management
Anesthesia
Critical Care

American College of Surgeons

National Cancer Data Base
(NCDB): 1995-2004

Total patients with pancreatic cancer:

192,565
9559 (5%) clinically stage I and
potentially
resectable
Only 29% had SURGERY

96% success; 4% unresectable

Median Survival
Resected 19months
No Surgery 8 months

5-year survival for resected 19%

Bilimoria et al, Ann Surg Augu

American College of Surgeons

National Cancer Data Base
(NCDB): 1995-2004

Of 9559 clinically stage I and potentially

resectable, 71% had NO
SURGERY
19% clear reason given
9% Age, 4% refused, 6% comorbidities
52% no clear reason given
nihilistic attitudes toward the disease
among patients, referring physicians
and some surgeons

Bilimoria et al, Ann Surg Augu

Summary

Early detection
Clinical diagnosis: early signs or symptoms
and risk factors
Improved Imaging and Diagnostic studies

All Resectable pancreatic cancer should

be offered surgical resection
Improved surgical Outcome
Restrain Fatalistic attitude

Cyberknife

Stereotactic Radiosurgery (STRS) or

Cyberknife (CK) in Surgical Oncology
Sinai Experience Feb 3, 2004 Oct 7, 2006
Pancreas

45

Liver

25

Rectum

16

Retroperitoneum&
Sarcomas

Head & Neck

Adrenal Meta

CK Contouring: Pancreas

Sinai CyberKnife Experience:

Pancreatic Cancer
Patient Characteristics

Total number = 45
Age range = 43 84 years, median 64
Location of tumor:
head = 31 (69%), body = 14 (31%)
Stage T3 T4 = 45, N1/NX = 45, M1 = 8 (18%)
Prior RT = 20 (45%)
Prior surgical resection = 9 (20%)
Prior chemo = 15 (33%)

CK Treatment

GTV (gross tumor volume): median 65 cc

(11 - 189 cc)
CK dose median 25.2 Gy
Number of fractions mean 3 (range 1-4)
% Isodose median 0.8 (0.7 0.88)

Results

Pain relief 24/28 (86%)

CA 19-9 response 15/35 (43%)
Local tumor control: 91%
Complete Response 4 (9%)
Partial Response 19 (42%)
Stable Disease 18 (40%)
Progressive Disease 4 (9%)

Distant progression 30 (67%)

Survival Time from CyberKnife Treatment:

Local Response
Local Response = Complete or Partial

1.0

Local Response = Static

0.8

0.6

0.4

Estimated Survivor Function

0.2

0.0

200

400
Time (days)

600

800

Toxicity
TOXICITY Grade III - IV
Duodenitis
Gastritis
Diarrhea
Hepatic
Hematologic, Renal, CNS

#
8
5
3
1
0

%
18%
11%
7%
2%
0

No statistical correlation of GI toxicity to prior RT or Tumor Volume

CK: CONCLUSIONS

CyberKnife is alternative treatment modality for

Unresectable pancreatic cancer

Poor surgical candidate

Acute toxicity was minimal

GI toxicity (Duodenitis or gastritis) is a major side
effect

mainly in patients with tumors >70cc

Convenience: Delivered in 2-3 sessions without

hospitalization
Local tumor control and improves the pain in most
Shows a trend towards improvement in survival,
compared to
historical controls
No impact on development of distant metastases

Post-Operative
Complications
Sepsis
Renal Failure
Gastrointestinal Hemorrhage
Pancreatic Fistula
Biliary fistula
Pulmonary
Cardiac
Pancreatitis

13%
13%
10%
10%
5%
7%
5%
2%

Survival Time from Diagnosis - All Patients

1.0

Estimated Survival
Function

Median 18.4 mos

Mean 20.4 mos

0.8

0.6

0.4

0.2

0.0
0

500

1000

Time (days)

1500

Survival Time from CK Treatment

- All Patients
1.0

Estimated Survival
Function

Median 8.3 mos

0.8

Mean 11.3 mos

0.6

0.4

0.2

0.0

200

400

Time (days)

600

800

Correlation of Survival After CK Treatment

FACTORS
Prior RT
Local response
Distant progression
Prior surgical resection
Tumor location
Stage at diagnosis M1 vs M0

P Value
P = 0.04
P = 0.05
P = 0.01
NS
NS
NS

Survival Time from CK Treatment - Prior RT

Prior RT = No

1.0

Prior RT = Yes

0.8

0.6

0.4

Estimated Survivor Function

0.2

0.0

200

400
Time (days)

600

800

Survival Time from CK Treatment:

Distant Progression
Distant Progression = Yes
Distant Progression = No

1.0

0.8

0.6

0.4

Estimated Survivor Function

0.2

0.0

200

400
Time (days)

600

800

Acute Duodenitis

Late Duodenal Ulcer

CyberKnife Treatment for

Pancreatic Cancer
Phase I
A Koong (2003)

Phase II
A Koong (2005)

Phase II
M Didolkar (2006)

Number

15

16

45

CK Dose

15-25 Gy

25 Gy

24 Gy

Prior RT

No

No

Yes

IMRT & CK

No

45 Gy

No

Volume in cc

29 cc

57 cc

65 cc

Response Local

100%

93%

91%

Survival Overall

47.6 wks

33 wks

79 wks

Toxicity II IV

37.5%

33.3%

Duodenal and
Periampullary
Neoplasms