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
