Karsinoma Pankreas

I MADE ADI SUNANTARA

PENDAHULUAN

Tumor ganas eksokrin pankreas

Di USA kurang lebih 30.300 (2002) Ca pankreas

Mortality rates yang hampir 100 %

Sering pada usia tua > 60 th

Pankreas
Embriologi
Merupakan jaringan retroperitonial
Dua tunas lapisan endoderm duodenum
tunas dorsal
tunas ventral
Anatomi
Pankreas terletak melintang di bagian atas abdomen dibelakang
gaster, di antara duodenum pada bagian kanan (kaput), lien di
bagian kiri (ekor)
Panjang pankreas 15-20 cm
Berat 75-100 gr
Duktus pankreas : duktus wirsungi dan duktus santorini
Pankreas mendapat pasokan darah dari
cabang arteri gastroduodenalis
cabang arteri mesenterika superior
cabang dari arteri lienalis
Anatomi pankreas. Disadur dari Clinically oriented anatomy. 4th Ed. Philadelphia : Baltimore Williams & Wilkins, 1999, p 258 - 262 5
Fisiologi pankreas
Terdiri dari 2 bagian kelenjar yaitu
Kelenjar eksokrin
mengsekresikan cairan, elektrolit dan enzim pencernaan
Kelenjar endokrin
Sekresi hormon pankreas 20% sel alfa (A), 75% sel beta
(B), 5 % sel delta (D) dan beberapa sel C
 Etiologi karsinoma pankreas belum begitu jelas
Risk faktor
faktor eksogen : merokok, diit tinggi lemak dan kalori,
konsumsi kopi, alkohol dan zat karsinogen industri
faktor endogen : faktor genetik, usia, adanya penyakit dasar
seperti diabetes melitus, pankreatitis kronis, ulkus peptikum
Faktor genetik merupakan faktor endogen yang sangat
penting
Adanya mutasi genetik
K- ras
Tumor supresor genes : p53, p16, SMAD4, dan pada BRCA 2
Over ekspresi dari reseptor faktor pertumbuhan
DIAGNOSTIK
Gejala klinis Gejala awalnya tidak
spesifik
sakit perut, penurunan berat badan, Ikterus
teraba suatu massa yaitu tumor padat di
epigastrium , hepatomegali dan splenomegali
Couversier sign
perdarahan gastrointestinal,edema tungkai.
Pemeriksaan penunjang
Penanda tumor yaitu
Carcinoembryonikantigen (CEA)
Carbohidrate Antigenic Determinant 19-9 (Ca 19-9).
 Pemeriksaan radiologis
Ultrasonografi (USG)
CT Scan abdomen sensitivitas 83-98 %
Magnetic Resonance Imaging (MRI)
Endoscopic Retrograde Cholangio-pancreaticography (ERCP)
sensitivitas 92 % , spesifisitas 96 %.
kaput pankreas double ducktus sign
badan dan ekor pankreas struktur yang terlokalisir
mengetahui atau menyingkirkan kelainan gastroduodenum
dan ampula vateri
mengambil sample pemeriksaan histopatologi dan sitologi
ERCP pemasangan stent
Endoscopic Ultrasonografi (EUS)
sensitivitas dan spesifisitasnya tinggi
Deteksi invasi lokal dan metastasis dalam limponodi
Penggunaan EUS sebagai penuntun transluminasi biopsi
Staging
Primary tumor (T) TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor limited to pancreas, 2 cm in
greatest dimension
T2 Tumor limited to pancreas, > 2 cm in
greatest dimension
T3 Tumor extends beyond pancreas but
without involvement
of celiac axis or SMA
T4 Tumor involves celiac axis or SMA

Regional lymphnodes (N) NX Regional lymph nodes cannot be

assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis

Distant metastasis (M) MX Distant metastasis cannot be assessed

M0 No distant metastasis
M1 Distant metastasis
 Stage 0 Tis,N0,M0
Stage IA T1,N0,M0
Stage IB T2,N0,M0
Stage IIA T3,N0,M0
Stage IIB T1, T2, T3N1M0
Stage III T4, Any N,M0
Stage IV Any T,Any N,M1
Deteksi dini karsinoma pankreas
Belum ada satu pedoman baku
Pendapat ahli :
Pelebaran duktus pankreatikus USG
Lesi precursor mutasi genetika
Tahap pertama mutasi pada tumor supresor gen (BRCA 2):
Jika tidak diketemukannya mutasi pada BRCA 2 saat dilakukan
skrining maka skrining ini tidak dilanjutkan lagi.
Jika positif tahap kedua lesi precursor sample sitologi
dan histopatologis
Jika tes positif karsinoma pankreas
PENATALAKSANAAN
Pembedahan terapi utama dari karsinoma pankreas
Pembedahan
Kuratif
Paliatif
Pembedahan kuratif Hanya 10-15 %
Kriteria pembedahan kuratif :
Tidak adanya metastase maupun ekstra pankreas tumor.
tidak adanya bendungan pada sistem portal maupun vena
mesenterika superior
tidak adanya perluasan lesi sampai ke arteri mesenterika
superior.
Keberhasilan dari bedah kuratif : besarnya tumor, tehnik operasi,
prosedur yang dipilih, pengalaman operator, serta tersedianya peralatan
yang memadai
Pembedahan

Pankreatikoduodenektomi Ca kaput pankreas

Subtotal Pankreatikoduodenektomi (Whipple operation)
Pylorus preserving pancreaticoduodenectomy

Whipple operation :
kolesistektomi,
diseksi ligamentum hepatoduodenum,
reseksi duktus kholedokus distal
reseksi duodenum
reseksi bagian distal gaster serta bagian kanan dari omentum mayus
reseksi dari kaput, leher dan limponodus dari pankreas
rekontruksi dari saluran pencernaan
pankreatikojejunostomi
hepatikojejunostomi
gastroenterostomi
 Pylorus preserving pancreaticoduodenectomy
1-2 cm dari distal dari pilorus
end to side duodenojejunostomi
tujuan mempertahankan fungsi gaster
Total pankreatikojejunostomi
menjamin radikalitas
diabetes militus dan malabsorbsi dengan steatorhoe

Pembedahan pada badan dan ekor pankreas

Pankreotektomi distal
Pankreotektomi total
Bedah paliatif
Non resectable
Harapan hidup lebih dari 6 bulan
Bedah terbuka billiary by pass dan gastrojejunostomi
kolesistojejunostomi
koledokojunostomi
Pemasangan stent
Kemoterapi dan radioterapi
ADJUVANT
5-fluorouracil (500mg/m2 IV)
radioterapi (40 Gy)
Paliatif kemoterapi GEMCITABINE
Molekular target terapi
Syntetic Matrixs Metalloproteinase Inhibitor (MMPIs)
Farnesyltranferase Inhibitor (FTI)
Epidermal Growth Factor Reseptors
Vaskular endotelial Growth Factor Reseptors
Kesimpulan
Karsinoma pankreas penyebab kematian nomor empat
Patofisiologi belum jelas
Faktor genetik peranan terpenting
CT Scan px penunjang
EUS, analisa genetik dengan komfirmasi histopatologis
deteksi dini
 Algoritme Diagnosis dan Penatalaksanaan

CT Scan
Spiral
3mm Cuts

Unresectable Mass Resectable Mass No Mass but

Suspicion Remains

Diagnostic EUS
Whipple
Laparoscopy Diagnostic
Prosedure
selektive Laparoscopy
CT or
EUS Guide Biopsy
ERCP with Brushings
EUS
Observe/Repeat CT

Neoadjuvant
CLINICAL TRIAL
Clinical Trial Clinical Trial

Gambar 7. Algoritme Diagnosis dan Penatalaksanaan karsinoma pancreas.

Disadur dari Schwartzs Principles of Surgery .8th Ed. New York : Mc Graw Hill. 2005, p 1221-1290 1
SUKSME BLI
Pancreatic Resectin
in
Pancreatic Cncer

Benny Philippi, MD
Toar JM Lalisang, MD. PhD.

Digestive Surgery Division

Cipto Mangunkusumo Hospital
Faculty of Medicine, Universitas Indonesia
 History of Pancreatic
Surgery
In 1898, Halsted was the first to successfully remove the
head of the pancreas and a portion of the duodenum for
ampullary cancer

Several surgeons in the United States and abroad

subsequently developed two-stage operations for
removal of the head of the pancreas

These efforts culminated in 1940 with Whipple's one-

stage operation
 Hallmark of
Pancreaticoduodenectomy
Anatomy
Anatomy
 Lets start with some numbers

Pancreatic cancer is the 3rd

most common malignancy of the
GI tract
10 cases every 100,000 people
per year (2 cases per 100,000
people in Africa and Asia)
 With the diagnosis of pancreatic
cancer, the majority of patients are
faced with an unexpected tragedy

low rate of curability, high rate of

case fatality
H. Riess, A Goerke, H Oettle
Pancreatic Cancer. Springer 2008
Eternal Dilemma

PD/PPPD
 RSUPN-CM
Digestive Surgery
 Digestive Cancer Cases
RSUPN-CM, 2012
28.9% 28%
Outpatients Operative
 Total Number of Outpatients at Digestive
Surgery Division RSUPN-CM
Based on Gender Based on Age

T=4.967
 Digestive Mortality Cases
RSUPN-CM, 2012
Total Mortality Digestive
surgery Cases 91 (8.7%) Digestive Cancer 22

24.2%
Operative Digestive Cancer
Cases
HPB Cases
Diagnostic
Algorithm

/resectable

Curative/Palliative
Peri Ampullary Tumor Management :
Removable Unremovable Metastatic

PD/PPPD Double Stent

Surgery bypass/Stent
TP + D

Radiotherapy -- -- --

Chemotherapy adjuvant better QL --

 Management of Pancreatic Cancer

Radical resection offers the only chance for cure

in the management of pancreatic cancer

Adjuvant therapy remains of marginal benefit

Centralization of pancreatic surgery to high-

volume centers has been widely recommended
 TNM Staging of
Pancreatic Adenocarcinoma

TNM Atlas 5th Ed. UICC 2004

 Histopathology
Usually arises from the ductal epithelial cells of the
exocrine part of the gland
Pancreatic endocrine neoplasms, are not uncommon,
while acinar cell carcinomas, arising from the enzyme-
producing pancreatic cells, are rare
Histologically the vast majority of malignant pancreatic
cancers are adenocarcinoma
 Resectability
CT criteria for a resectable tumor

A patent SMV-PV confluence

No direct tumor extension to the Celiac axis, CHA, SMA

The absence of extrapancreatic disease (M0)

Stage I, II (T1-3, Nx, Mo)

Resectable adenocarcinoma
Resectable of the pancreatic
adenocarcinoma of the head
pancreatic head

SMV
SMA

Kitts 527268
 Locally Advanced and Borderline

Locally Advanced

Celiac, SMA encasemet (>180)

Stage III (T4, Nx, Mo)

Borderline
Arterial abutment ( 180)

Stage III (minimal T4)

Locally advanced adenocarcinoma of the
pancreatic head
 Ideal Objective

Oncological the disappearance of the tumor

and absence of recurrence and / or metastasis
after 5 years of treatment with radical intent;
Functional dealing with complications caused
by the expansive tumor: biliary retention,
pancreatic retention, possible duodenal stenosis
Standard Resection

Pancreaticoduodenectomy
pancreatic head
duodenum
gallbladder
bile duct
+/- gastric antrum
 Vascular Resection
Survival of patients with pancreatic cancer who undergo
an R0 resection with venous reconstruction is
comparable to those who have a standard pan-
creaticoduodenectomy with no added mortality or
morbidity
Conversely, arterial resection is associated with a higher
morbidity, mortality and overall poorer survival, perhaps
reflecting more advanced disease

Marangoni et al. the surgeon 2012;10: 102-106

Clinical Features
 Pitts score

Malignancy, Age > 60, Bilirubin > 10, WBC > 10000, Ht < 30,
ALP > 200, Albumin < 3, Creatinin > 1.3

Am J Surg 1980;141
Periampullary Tumor Malignancy
1998- 2012
2012
 Digestive Surgery Division
Cipto Mangunkusumo Hospital - FMUI

2000 - 2012
65 Pancreaticoduodenectomies
Median Age 50 (17 73) yo
Male Predominance (60%)
PV

Pancreas

IVC
MV
Types of Procedure

Cipto Mangunkusumo Hospital 2000 - 2012

 Perioperative Outcome
Median Range
Operating Time (min) 450 300 - 570
Blood Loss (ml) 800 300 2,200
Length of Stay (days) 17 7 - 47

Perioperative Mortalty 21.5%

Mortality less than 5 % in the last 4 years

Anastomosis PJ leaks all heal spontaneously

Survival of Resected Pancretic Cancer

Median survival 20 months

 PROGNOSIS

Buchler et al. Disease of The Pancreas. Karger 2004

PD Procedure
 DISTAL PANCREATECTOMY

(DP) usually consists of the resection of pancreatic

parenchyma left to the portal vein and can be
performed with or without splenectomy.
 Current indications

Benign pancreatic tumors

Malignant pancreatic
tumors
Chronic pancreatitis
Trauma
Distal pancreatectomy (DP)

Performed for tumors in the body and tail

Distal Pancreatectomy
 Total Pancreatectomy
TP + Duodenectomy 3 cases before 2000
on tumor pancreas in head and corpus
In Severe pancreatic jejonostomy leaks
completion or near total Pancreatectomy
was done ( preserve hormonal function)
Longer operative time
Recovery faster
Problem in A pancreatic management at
home

Near Total
 SUMMARY
Surgery for pancreatic cancer involves the establishment
of a solid multidisciplinary team where perioperative
assessment took place.
With the continuous effort to improve, a zero
perioperative mortality and a better overall survival will
not be just a dream.