Management of Management of pancreatic cancer: a case pancreatic cancer: a case

reportreport

Giovanni BrandiGiovanni Brandi

Institute of Hematology end Medical Oncology “L e A Seràgnoli”

Bologna University

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

Nonhomogeneus pancreatic nodular Nonhomogeneus pancreatic nodular areaarea

Abdomen computed tomographyAbdomen computed tomography

Serum markers Serum markers levellevel

CEA = 3.4

Ca 19.9 = 0

Within the normal rangeWithin the normal range

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

CEACEA

SMALL CANCERSMALL CANCER

VIRAGGIO P. C. IN CA

VIRAGGIO P. C. IN CA

Low SensitivityLow Sensitivity

MASAFUMI IKEDA, AMERICAN CANCER SOCIETY 2001MASAFUMI IKEDA, AMERICAN CANCER SOCIETY 2001

CA 19.9CA 19.9

PANCREATIC CARCINOMAPANCREATIC CARCINOMAPANCREATIC CARCINOMAPANCREATIC CARCINOMA

Negative (4-15 % of population)

Negative (4-15 % of population)

>CA 19.9

CA 19.9

Small Cancer

Only in the 50% of cases

Small Cancer

Only in the 50% of cases

Lewis Blood Group Antigen

CA19-9CA19-9 determined 72/78 (92.3%)

CA19-9 ≤ 37 U/μL 26/72 (36.1%)CA19-9 > 37 U/ μ L 46/72 (63.9%)

In 50 patients with histology/cytology:Sensitivity* 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

Carbohydrate antigen Carbohydrate antigen 19.919.9

ASCO Guidelines 2006

Pancreatic Masses

Abscess

Acute autoimmune pancreatitis

Pseudocyst

Cyst

Tumor

…

AdenocarcinomaCystic tumorNeuroendocrine tumorSoft tissue sarcomaMetastases

Select between

Biopsy MRI

FDG-PET CEUS

What is the next step?15 $1 MILLION14 $500.00013 $250.00012 $100.00011 $50.00010 $25.0009 $16.0008 $8.0007 $4.0006 $2.0005 $1.0005 $1.0004 $5003 $3002 $2001 $100

Biopsy of pancreatic noduleBiopsy of pancreatic nodule

Adenocarcinoma

Surgical intervention ?

Vascular involvementVascular involvement

Radiological stagingRadiological stagingRadiological stagingRadiological staging

Portal vein

Superior mesenteric vein

Superior mesenteric artery

Celiac tripode

GRADE O: no vascular involvement

GRADE O: no vascular involvement

GRADE 1: disappear of

adipous resection plane

GRADE 1: disappear of

adipous resection plane

GRADE 2: circumferential infiltration < 2/3 of the vessel

lumen

GRADE 2: circumferential infiltration < 2/3 of the vessel

lumen

GRADE 3:≥ 2/3

circumferential infiltration

GRADE 3:≥ 2/3

circumferential infiltrationDong IL Park, J. Kyun LeeJ CLIN GASTROENT. 2001Dong IL Park, J. Kyun LeeJ CLIN GASTROENT. 2001

T.Hough,V. Raptopoulos AJR 1999

T.Hough,V. Raptopoulos AJR 1999

TEARDROPTEARDROP

GRADE 4: neoplastic thrombosis

GRADE 4: neoplastic thrombosis

Criterion for surgical

intervention

Criterion for surgical

intervention

Pancreatic cancer

No arterial (hepatic or superior mesenteric)

infiltration

No arterial (hepatic or superior mesenteric)

infiltration

Nodistant metastases

No peritoneal involvementNo peritoneal involvement

Filmsy peri-hepatic ascites: suspicion of peritoneal involvement

Should we perform extended Should we perform extended pancreatic resection ?pancreatic resection ?

Total pancreatectomy

Extended lymph node dissection

Venous resectionVenous resection

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.

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

Arterial resectionArterial resectionMesenteric, 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%; p<0,02. 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

Resecability index Resecability index

AMERICANS/EUROPEANS 10-30% AMERICANS/EUROPEANS 10-30%

JAPANASE 45-60% JAPANASE 45-60%

5-years SURVIVAL 10 -15%

5-years SURVIVAL 10 -15%

Ductal Ductal adenocarcinomaadenocarcinoma

Ductal Ductal adenocarcinomaadenocarcinoma

Saffire S.K.S-J of Surg Onc 2005 Saffire S.K.S-J of Surg Onc 2005

Surgical intervention

Resection of tail and body of pancreas with Resection of tail and body of pancreas with splenectomy and lymphadenectomysplenectomy and lymphadenectomy

Pathologist response

Moderately differentiated

adenocarcinoma associated with a neuroendocrine

neoplastic component

immunoreactive for insuline, glucagon and somatostatin.

Resection border infiltrated by the neoplasm

Post-operative analysis

CEA = 2.9Ca 19.9 = 0

For error we measured the -fetoprotein level

2259 ng/mL (normal value < 10 ng/mL)

-fetoprotein

Glycoprotein of 65 kd molecular

weight

Serum marker of hepatocellular

carcinoma

Serum marker of germ line

tumors

Rarely described in pancreatic

cancer

Pancreatic cancer with high level of

-fetoprotein

Kawamoto ‘92; McIntire ’75; Lokich ’87; Scheithauer ’89; Kubo ’74; Tomada ’74Ikida ’77; Nagamine ’78; Nagata ’80; Katoh ’81; Inui ’83; Ono ’84; Harnazoe ‘87

N of cases

AgeFP

(ng/mL)Range

Liver mets

Histology

29 28-78

42

65000

22 Yes

13 adenocarcinoma

6 insular carcinoma

3 acinar carcinoma

7 No

2 ductal carcinoma

2 undifferentiated

1 unknown

Select between

Occult HCC Hard discount ELISA kit

Common neoplastic precursor with

transdifferentiation ability

Drunk laboratorist

Pancreatic cancer esocrine/endocrine with

hepatoid behaviour?Hypotesis:

15 $1 MILLION14 $500.00013 $250.00012 $100.00012 $100.00011 $50.00010 $25.0009 $16.0008 $8.0007 $4.0006 $2.0005 $1.0004 $5003 $3002 $2001 $100

HypotesisA. HCC escluded by hepatic US and CT

Hepatic nodules was signaled 7 months after surgeryreasonably indicating their secondary nature

The patient did not have any risk factors forhepatocellular carcinoma

Hypotesis

C. 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

An islet in theAn islet in thevicinity of a well-differentiated vicinity of a well-differentiated

adenocarcinoma containing large atypical adenocarcinoma containing large atypical cells intermingled with intact islet cells.cells intermingled with intact islet cells.

Pour PM.Mol Cancer. 2003

Pathologist analysis

Strong and diffuse

immunoreactivity for

-fetoprotein.

Pathologist response

Focal reactivity for albumin mRNA on

in-situhybridization

Select between

Observation Chemotherapy

Chemoradiation Radiotherapy

Anything else to improve the patient’s

outcome?

15 $1 MILLION14 $500.00013 $250.00013 $250.00012 $100.00011 $50.00010 $25.0009 $16.0008 $8.0007 $4.0006 $2.0005 $1.0004 $5003 $3002 $2001 $100

Adjuvant treatment ?

Wolff et all. JAMA 2008

Neoptolemos et al. NEJM 2004

Oettle H. JAMA 2007

Adjuvant treatment: the CONKO-001

DFS OS

Adjuvant treatment

External radiotherapy on pancreatic region

(total dose of 4140 cGy)

Followed by

10 infusion of gemcitabine (1000 mg/m² weekly)

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 CTAbdomen CT

PetPet Confirm of the CT’s findings

Markers CEA and Ca 19.9 within the normal rangeFP > 7000 ng/ml

What about the What about the neuroendocrineneuroendocrine component ? component ?

Octreoscan® was performed to evaluate the possibility of treatment with somatostatine’s analogues

No expression of somatostatin’s receptors

Somatostatin’s receptors

10 further infusion of gemcitabine due 10 further infusion of gemcitabine due to a clinical benefitto a clinical benefit

But..But..

3 months after a CT found progression of the disease

Meanwhile, clinical condition gradually worsenedwith signs and symptoms of hepatic failure

Treatment was modified:Gemcitabine 1500 mg/m²

+5-fluorouracil 600mg/m² on day 1, 8

and 15

(repeated every 28 days)

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

conditionThe patient died 1 month later, 1 year after the surgery

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