Management of pancreatic cancer: a case report

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Management of pancreatic cancer a case report

• Giovanni Brandi

Institute of Hematology end Medical Oncology L e
A Seràgnoli Bologna University
2
The patient

• Male, 68 year-old
• Presentation with epigastric pain by 2 months
• Negative the abdominal and thoraco-pulmonary
  objectivity
• X-ray of the abdomen negative
• X-ray of the chest negative

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Abdomen computed tomography
Nonhomogeneus pancreatic nodular area
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Serum markers level

• CEA 3.4
• Ca 19.9 0

Within the normal range
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Carbohydrate antigen 19.9

• Recognized by a monoclonal antibody targeting a
  sialylated Lewis A blood group antigen epitope
• 5-10 of people lack fucosyltransferase and do
  not synthesize the antigen

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PANCREATIC CARCINOMA
Low Sensitivity
SMALL CANCER
CA 19.9
VIRAGGIO P. C. IN CA
CEA
gt
CA 19.9
Small Cancer Only in the 50 of cases
Lewis Blood Group Antigen
CA 19.9
Negative (4-15 of population)
MASAFUMI IKEDA, AMERICAN CANCER SOCIETY 2001
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CA19-9
CA19-9 determined 72/78 (92.3) CA19-9 37
U/µL 26/72 (36.1) CA19-9 gt 37 U/ µ L 46/72
(63.9) In 50 patients with histology/cytology S
ensitivity 27/47 (57.4) Specificity 0/3 (0)VP
27/30 (90.0)VP - 0/20 (0)
42 patients with pancreatic cancer and 5 with
biliary tract cancer
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CA19-9 and operability
Resected CA19-9 determined 31/34
(91.2) CA19-9 gt37 U/ µ L 18/31 (58.1) Non
resected CA19-9 determined 41/44 (93.2) CA19-9
gt37 U/ µ L 13/41 (31.7)
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Carbohydrate antigen 19.9
ASCO Guidelines 2006
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Pancreatic Masses

• Abscess
• Acute autoimmune pancreatitis
• Pseudocyst
• Cyst
• Tumor

• Adenocarcinoma
• Cystic tumor
• Neuroendocrine tumor
• Soft tissue sarcoma
• Metastases

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15 1 MILLION 14 500.000 13 250.000 12
100.000 11 50.000 10 25.000 9 16.000 8
8.000 7 4.000 6 2.000 5 1.000 4
500 3 300 2 200 1 100
What is the next step?
Select between
Biopsy
MRI
FDG-PET
CEUS
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Biopsy of pancreatic nodule
Adenocarcinoma
Surgical intervention ?
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Radiological staging
Vascular involvement

• Portal vein
• Superior mesenteric vein
• Superior mesenteric artery
• Celiac tripode

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GRADE O no vascular involvement
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GRADE 1 disappear of adipous resection plane
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GRADE 2 circumferential infiltration lt 2/3 of
the vessel lumen
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GRADE 3 2/3 circumferential infiltration
Dong IL Park, J. Kyun Lee J CLIN GASTROENT. 2001
TEARDROP
T.Hough,V. Raptopoulos AJR 1999
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GRADE 4 neoplastic thrombosis
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Criterion for surgical intervention
Pancreatic cancer
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No arterial (hepatic or superior
mesenteric) infiltration
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No distant metastases
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Filmsy peri-hepatic ascites suspicion of
peritoneal involvement
No peritoneal involvement
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Should we perform extended pancreatic resection ?
Total pancreatectomy
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Extended lymph node dissection
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Venous resection
Rationales for vein resection (VnR) tumor
invasion of vessels or infiammatory adhesions
that preclude adequate separation from tumor to
veins gain benefits for extended pancreasectomy

• No prospective randomized trials comparing
  pancreatectomy with and without VnR.
• Morbidity and mortality with and without VnR are
  similar.
• No study dimostrated that Vnr increase R0
  resection rate.
• Despite great diversity in OS, pooling results of
  23 studies showed that addition of VnR did not
  provide longer 5-years OS, with 3 studies noting
  shorter survival after VnR.

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Arterial resection

• Mesenteric, celiac and hepatic arteries resection
  are more rarely performed compared with VnR
• Long term survival is lower with combined VnR and
  arterial resection compared with VnR alone (2y OS
  0 vs 17 plt0,02. Nakao WJS 2006)
• Long term survival is similar between patients
  treated with arterial resection and patients
  completly unresected. (Nakao WJS 2006)

SRINEVAS K. Extended Resection for Pancreatic
Adenocarcinoma. Oncologist 2007
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Ductal adenocarcinoma
Resecability index
AMERICANS/EUROPEANS 10-30
JAPANASE 45-60
5-years SURVIVAL 10 -15
Saffire S.K.S-J of Surg Onc 2005
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Surgical intervention
Resection of tail and body of pancreas with
splenectomy and lymphadenectomy
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Pathologist response

• Moderately differentiated adenocarcinoma
  associated with a neuroendocrine neoplastic
  component immunoreactive for insuline, glucagon
  and somatostatin.

Resection border infiltrated by the neoplasm
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Post-operative analysis

• CEA 2.9
• Ca 19.9 0

For error we measured the ?-fetoprotein level
2259 ng/mL (normal value lt 10 ng/mL)
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?-fetoprotein

• Glycoprotein of 65 kd molecular weight
• Serum marker of hepatocellular carcinoma
• Serum marker of germ line tumors
• Rarely described in pancreatic cancer

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Pancreatic cancer with high level of
?-fetoprotein
N of cases Age ?FP (ng/mL) Range Liver mets Histology
29 28-78 42 65000 22 Yes 13 adenocarcinoma
29 28-78 42 65000 22 Yes 6 insular carcinoma
29 28-78 42 65000 22 Yes 3 acinar carcinoma
29 28-78 42 65000 7 No 2 ductal carcinoma
29 28-78 42 65000 7 No 2 undifferentiated
29 28-78 42 65000 7 No 1 unknown
Kawamoto 92 McIntire 75 Lokich 87
Scheithauer 89 Kubo 74 Tomada 74 Ikida 77
Nagamine 78 Nagata 80 Katoh 81 Inui 83
Ono 84 Harnazoe 87
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15 1 MILLION 14 500.000 13 250.000 12
100.000 11 50.000 10 25.000 9 16.000 8
8.000 7 4.000 6 2.000 5 1.000 4
500 3 300 2 200 1 100
Pancreatic cancer esocrine/endocrine with
hepatoid behaviour? Hypotesis
Select between
Occult HCC
Hard discount ELISA kit
Common neoplastic precursor with
transdifferentiation ability
Drunk laboratorist
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Hypotesis

• HCC escluded by hepatic US and CT

Hepatic nodules was signaled 7 months after
surgery reasonably indicating their secondary
nature
The patient did not have any risk factors
for hepatocellular carcinoma
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Hypotesis

• Supported by
• _Peters J. Ontogeny, differentiation and
  Growth of the endocrine pancreas. Wirchows Arch.
  2000.
• _Yang YH. The relation of pancreatic ducts
  to the islets of Langerhans study of three
  cases. AMA Arch Pathol. 1959

_Pour PM. What is the origin of pancreatic
adenocarcinoma ? Mol Cancer. 2003
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An islet in thevicinity of a well-differentiated
adenocarcinoma containing large atypical cells
intermingled with intact islet cells.
Pour PM.Mol Cancer. 2003
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Pathologist analysis
Strong and diffuse immunoreactivity for
?-fetoprotein.
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Pathologist response
Focal reactivity for albumin mRNA on
in-situ hybridization
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15 1 MILLION 14 500.000 13 250.000 12
100.000 11 50.000 10 25.000 9 16.000 8
8.000 7 4.000 6 2.000 5 1.000 4
500 3 300 2 200 1 100
Anything else to improve the patients outcome?
Select between
Observation
Chemotherapy
Chemoradiation
Radiotherapy
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Adjuvant treatment ?
Wolff et all. JAMA 2008
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Neoptolemos et al. NEJM 2004
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Oettle H. JAMA 2007
Adjuvant treatment the CONKO-001
DFS
OS
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Adjuvant treatment

• External radiotherapy on pancreatic region
• (total dose of 4140 cGy)
• Followed by

10 infusion of gemcitabine (1000 mg/m² weekly)
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Revaluation

• 1 lesion of 3 cm of diameter in the gastric
  curves
• 1 lesion of 1 cm of diameter in the fourth
  hepatic segment
• 1 lesion of 1 cm of diameter in the caudal lobe

Abdomen CT
Pet

• Confirm of the CTs findings

Markers

• CEA and Ca 19.9 within the normal range
• ?FP gt 7000 ng/ml

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What about the neuroendocrine component ?
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Somatostatins receptors

• Octreoscan was performed to evaluate the
  possibility of treatment with somatostatines
  analogues

No expression of somatostatins receptors
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• 10 further infusion of gemcitabine due to a
  clinical benefit

But..
3 months after a CT found progression of the
disease
Meanwhile, clinical condition gradually
worsened with signs and symptoms of hepatic
failure
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• Treatment was modified
• Gemcitabine 1500 mg/m²
• 5-fluorouracil 600mg/m² on day 1, 8 and 15

(repeated every 28 days)
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In the end

• Chemotherapy was interrupted 6 months later due
  to a clinical progression of the disease

• Support therapy was performed at home because of
  worsening clinical condition

• The patient died 1 month later,
• 1 year after the surgery

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Brandi G. Pancreas 2008 Exocrine/endocrine
pancreatic cancer and ?-fetoprotein.