Duodenal and Periampullary Neoplasms

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Duodenal and Periampullary Neoplasms

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

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Duodenal and Periampullary Neoplasms
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Benign Tumors of Small Bowel
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 gt3cm adenoma has foci of adenocarcinoma

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Malignant Tumors of Small Bowel
Devita, Hellman and Rosenberg, eds. Cancer
Principles and Practice of Oncology, 5th ed.
Philadelphia Lippincott-Raven, 1997

• 40 of adenocarcinoma occurs in Duodenum
• 2/3 of duodenal adenoCA are periampullary
• Most of these sarcomas are malignant GIST

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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

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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

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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 2.41
• No proven survival advantage with current
  chemotherapy
• Radiation therapy may be beneficial

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Duodenal Lymphoma

• Small bowel lymphomas
• Only 5 of all lymphomas
• 15-20 of all small bowel neoplasm
• gt 25 presents with Complications
• Bleeding
• Perforation
• Obstruction
• Best managed with surgery

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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

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Duodenal GIST

• 30 in Small bowel
• IHC positive for protooncogene CD117 and CD34
• Malignant potential determined by
• Mitotic frequency (gt2 mitoses/HPF)
• Nuclear atypia
• Cellularity
• Size of tumor
• Central necrosis
• Metastases in 30
• Gleevec tyrosine kinase inhibitor

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Periampullary Neoplasm

• Carcinomas of ampulla or distal common bile duct
• Exocrine Pancreatic Cancers
• Ductal Adenocarcinoma (90)
• Acinar cell carcinoma (lt5)
• Endocrine Pancreatic Cancers
• Islet cell tumors
• Insulinoma, Glucagonoma, VIPoma etc.

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Survival Data Localized Pancreatic
Adenocarcinoma after surgical resection
NA, Not available
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Survival Data Localized Periampullary
(nonpancreatic) adenocarcinoma after surgical
resection
NA, Not available
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Survival Data Localized, NODE POSITIVE
Periampullary (nonpancreatic) adenocarcinoma
after surgical resection
NA, Not available
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Median Survival (months)
5-year Survival ()
11-18
20.3
6-12
8
5-7
1.7
Evans DB, et al. Ca of Pancreas in DeVita,
Cancer Principles Practice in Oncology 2001
Source American Cancer Society, 2008
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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 (10th 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

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Trends in Five-year Relative Survival Rates
(), 1975-2003
1984-1986
1996-2003
     
Site
1975-1977

• All sites 50 54 66
• Breast (female) 75 79 89
• Colon 51 59 65
• Lung and bronchus 13 13 16
• Melanoma 82 87 92
• Ovary 37 40 45
• Pancreas 2 3 5
• Prostate 69 76 99
• Rectum 49 57 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.
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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

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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 gt40 years warrants an evaluation

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Clinical Presentation (contd)

• Several large reviews of pancreatic cancer note
  delay in diagnosis of gt 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

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Risk Factors

• Cigarette smoking (2X)
• most strongly (evidence) linked
• Chronic Pancreatitis (2X)
• 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

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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

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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

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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

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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.

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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

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Tumor Marker CA 19-9

• gt 90 U/mL 85 Accuracy
• gt 200 U/mL 95 Accuracy
• gt 750 U/mL associated with Advanced Disease
• Combination of CT and CA 19-9 (gt100 U/mL) has PPV
  of 99-100

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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

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Pancreaticoduodenectomy
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Earlier Surgical Results Pancreaticoduodenectomy

• Historically (1960s) Poor Surgical Outcome
• Morbidity gt 50
• Mortality 20
• Lieberman et al., Ann Surg 1995 (New York State,
  1984-1991)
• 75 at hospitals with lt 7cases/year
• Mean hospital stay gt 1 month
• Risk-adjusted perioperative mortality 12-19

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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)

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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 gt70 vs. lt50 9.5 vs. 2.6
• Low/Medium volume vs. High volume center
  (gt18/year)
• 11.1 vs. 2.7

McPhee et al, Ann Surg August 2007
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Pancreatectomy Mortality

• Distal Pancreatectomy (21) - 3.5
• Men vs. women 4.9 vs. 2.8
• Age gt70 vs. lt50 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 August 2007
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5-year survival, Morbidity and Mortality after
Whipple
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Advance in SurvivalGemcitabine (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
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Surgical Oncology Sinai Hospital (2005-2007)

• Total number of Pancreatectomies - 65
• PD or Whipple - 49
• Distal Pancreatectomy - 16
• Mortality - 0
• Morbidity - 15

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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

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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 August 2007
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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 August 2007
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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

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Cyberknife
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Stereotactic Radiosurgery (STRS) or Cyberknife
(CK) in Surgical OncologySinai Experience Feb 3,
2004 Oct 7, 2006
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CK Contouring Pancreas
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Sinai CyberKnife Experience Pancreatic
CancerPatient 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)

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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)

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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)

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Survival Time from CyberKnife Treatment Local
Response
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Toxicity
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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 gt70cc
• 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

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Post-Operative Complications
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Survival Time from Diagnosis - All Patients
Median 18.4 mos Mean 20.4 mos
Estimated Survival Function
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Survival Time from CK Treatment - All Patients
Median 8.3 mos Mean 11.3 mos
Estimated Survival Function
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Correlation of Survival After CK Treatment
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Survival Time from CK Treatment - Prior RT
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Survival Time from CK Treatment Distant
Progression
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Acute Duodenitis
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Late Duodenal Ulcer
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CyberKnife Treatment for Pancreatic Cancer
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Duodenal and Periampullary Neoplasms