Pamela Vasikha

CA PANCREAS 112016358
Coass bedah
Pembimbing: dr. Aplin Ismunanto, SpB
ANATOMI
FISIOLOGI
Pancreas is a gland that is located behind and under the gastric, above the first
arch of duodenum
Pancreas are contain the exocrine and endocrine tissues
Exocrine tissues are contain the secretoric cells (looks like grapes) that forming a sac
called asinus, which related to the duct that ended in duodenum.
The endocrine parts contain of Langerhans islands. It produces insulin and glucagon.
Both exocrine and endocrine has a different function under the control of a different
regulatoric mechanism
The exocrine produce 2 components which are (1) pancreatic enzyme
which actively being produce by asinus cells and (2) liquid base which
actively being produced by ductus cell which overlay the pancreatic
duct.
Alkaline liquids contain much of sodium bicarbonate (NaHCO3). It has
an important role of neutralizing the acidic enzyme as it enters the
duodenum from the stomach so it doesnt damaged the duodenum
mucose.
Pancreatic enzymes are important because it digest foods perfectly
Asinus cells secretes 3 pancreatic enzyme, (1) proteolytic enzyme to
digest the protein, (2) amylase for carbs and (3) Lipase for lipid.
For endocrine parts, the hormone is secreted by the Langerhans island.
Each island has a diameter of 75-150 m consist of cell beta () 75%,
cell alfa () 20%, cell delta () 5% dan some cell C.
Alpha cells produce glucagon, Beta cells are the source of insulin,
whereas delta cells secrete somatostatin, gastrin and pancreatic
polypeptides.
The function of insulin is mainly to move glucose and other sugars
through cell membranes to the tissues, especially muscle cells,
fibroblast, and fatty tissues. When there isnt any glucose, fat will be
used for metabolism so that will arise ketosis and acidosis.
DEFINITION
Ca Pancreas consist of 2 types, adenokarsinoma which is from
eksokrin gland and neuroendocrine from endocrine gland.

Adenokarsinoma is the most common type of pancreatic cancer.

 ETIOLOGI
The exact caused of pancreatic cancer is still unknown, but there are some risk
factors that could cause the pancreatic cancer:

Lifestyle Factors : Smoking, alcoholism, consumption of coffee and tea, drugs

(NSAID, aspirin)
Environment Factors : Passive smokers, infection, radiation, peptiside, cadmium
Patient Medical Record : DM, Chronic pancreatitis, cholesistitis, cholesistectomi,
allergic, peptic ulcer
Endogen Factors : Obesity, hormone factor, oksidatif stress
Genetic Factors : Cancer hereditary syndrome, familial pancreatic cancer,
polimorfism
EPIDEMIOLOGI
Pancreatic cancer is the fourth leading cause of death in the world, with an average of
28.000 new cases per year, mostly found in advanced stages, while in developing
countries, it ranked fifth after lung cancer, gastric cancer, colon cancer and breast
cancer. More incidence rates in the decade of 50s with more male than women. Age
between 60-80 years are the most widely found around 80% while the age < 40 years
rarely found. Colored skin is more common than white skin. The mortality rate in
developing countries in male is 7-9 per 100.000 population whereas in women is 4,5-6
per 100.000 population.
Incidence in developing countries is lower than developed countries due to the limited
diagnostic capabilities. Among the developed countries, South America and Central
America are the one that has a high number of pancreatic cancer incidence. The location
of pancreatic cancer is mostly found in the head 65%, body 15% and tail 10%.
PATOFISIOLOGI
Genetic factors play an important roles for the occurance of pancreatic
cancer
There are 4 genes that plays a role and being mutated, such as KRAS,
p161 / CDKN2A, TP53, dan SMDA4 while the other abnormal genes are
rarely such as BRCA2, FANCC, FANCG, FBXW7, BAX, RB1. More than
85% patients experience KRAS mutase and always occur on codon 12,
sometimes codon 13 or 61.
RAS protein plays a central role in regulating cell growth, cell signal
interaction and cell proliferation, so that when a mutation occurs in KRAS,
it will produce abnormal cells.
ANAMNESIS
oAbdominal pain, Jaundice, Anorexia, Weight loss, Diarrhea and the feces is pale are the
most common complaints.
oThe pain is depends on the location of the lesion
oIf theres bloody stools it means that theres a tumor erotion to the duodenum.
oThe history of risk factors such as DM, obesity, alcoholism, smoking, and genetic.
oAbdominal pain + DM + anorexia + weight loss -> 70% chances of pancreatic cancer
PHYSICAL EXAMINATION
The clinical manifestation of pancreatic cancer isnt specific on the early
stage, but if therere signs of obstruction especially the lesion is located
on the head of pancreas, from the physical examination therere
jaundice / icteric, pruritus, sometimes therere courvosier sign
(enlargement of gall bladder) in 20% cases. The present of ascites,
hepatomegaly, Virchows node (left supraventricular adenopathy), sister
mary josephs node (periumbilical adenopathy) means that metastasis
already happened. While if theres an obstruction on the gastric means
that the cancer has been on the late stage and has a bad prognosis.
SUPPORTING EXAMINATION
- Non invasive imaging diagnostic
USG
used to detect tumor with size > 2cm, if theres jaundice and enlargement of pancreatic duct.
Sensitivity 92,3% and specificity 89,1%
CT Scan Abdomen
The most accurate examination because it able to detect tumor with size around 2-3 mm but
unable to detect the involvement of blood vessels and hepar.
MRI
Used if the patient unable to use contrast on CT Scan or allergic to contrast
PET (Positron Emission Tomography)
PET able to detect the metastatic which CT Scan couldnt but it doesnt mean that PET is more
accurate than CT. Sensitivity 71-87% and specificity 87%. PET Scan is used to see the respons from
neoadjuvant theraphy.
- Invasive imaging Diagnostic
EUS (Endoluminar Ultrasonography)
as accurate as CT and able to detect the distant metastatic and nodule involvement. If the EUS showed theres a
lession of pancreas, do the EUS-FNA but if the EUS shows negative then we could deny the pancreatic disease.
FNA (Fine Needle Aspiration)
used to identify the malignancy lesion accurately which CT unable to do. Sensitivity >90% and spesifisity
almost 100%. The risk from this test are pancreatitis, fistule, abcess, perforation
ERCP (Endoscopic Retrograde Cholangiopancreatography)
used if theres a suspicion of a lesion on pancreas head and to insert the stent to minimize the jaundice because
of obstruction. ERCP unable to determine the stadium of cancer but able to evaluate whether the jaundice is
caused by a mass or because of theres another obstruction such as choledocholithiasis or benign stricture.
PTHC (Percutaneus Transhepatic Cholangiography)
used to insert the stent to minimize the jaundice because of obstruction
Percutaneus FNA Sitology
used to diagnose the biopsy of tissues but might caused injury to the peritoneum. Sensitivity 69% and
Spesificity 100%.
Laparascopy and Laparascoy Ultrasound
able to detect the tumor size < 1cm on the surface to hepar.
- Laboratorium
Mild or moderate hiperglicemic
Hiperbilirubinemia
Hiperlipasemia
Mild hypoalbuminemia
Elongated prothrombine time
Normochrome anemia

- Tumor Marker
used to detect the cancer. CA 19-9 is one of the tumor marker which recommended by
NACB (National Academy of Chemical Biochemistry), EGTM (European Group on Tumor and
American Gastroenterological Association) to eliminate the diagnosis of pancreatic cancer. CA
19-9 also used to evaluate the prognosis and to monitor the responds to the theraphy.
Sensitivity 70-90% and spesifisity 90%. Another tumor marker used to detect pancreatic
cancer are: Ca 5, 50, 242, DUPA n1, DUPAN 2, CEA, CA72-4, HCGB, IAPP, POA, YKLas40,
TUM2-PK but none of it able to give the conclusion as the tumor marker for pancreatic cancer.
 CLINICAL MANIFESTATION
- obstructive type
The pancreatic head cancer doesnt usually showed any sign until theres icterus
obstruction. Another signs are weight loss, epigastrium pain, and theres a mass in
epigastrium. The body weight might loss until around 10kg, severe pain on the back is
occurring on 25% patient. The gall bladder is palpable but not painful and obstructive
icterus is often found due to the blockage of choledochus duct, as a sign of a carcinoma
of the pancreas head knows as the law of Courvoisier. If theres icterus, it is almost
always followed by pruritus and 5-10% with cholangitis.

- non obstructive type

whereas in non-obstructive type, pancreatic carcinoma in corpus and pancreas tail is
rarely followed by icterus. Prominent symptoms are weight loss, epigastric and hip pain,
and hepatomegaly when theres metastasis to the hepar.
DIAGNOSIS
To diagnose the pancreatic cancer, clinical symptoms, laboratory results
such as the increasing of bilirubin serum and transaminase, also with
diagnostic support such as CEA tumor marker and Ca 19-9,
gastroduodenography, USG, CT Scan, pancreatic scintigraphy, MRI and
ERCP, endoscopic ultrasound, angiography, PET, surgery and biopsy
should be used.

Pancreatic cancer staging is also an important factor for choosing the

type of therapy and assessing the prognosis of the disease.
- Stage 0 (Tis, N0, M0) = tumors are present only on the top of pancreatic cells
and doesnt invade the deeper tissues.
- Stage 1A (T1, N0, M0) = tumor are < 2cm and there isnt any spread to the
lymph glands and other organs
- Stage 1B (T2, N0, M0) = tumors are > 2cm, there isnt any spread to the lymph
glands and other organs
- Stage 2A (T3, N0, M0) = tumors has spread and expanded to the outside of the
pancreas. No regional lymph node enlargement was observed
- Stage 2B (T1-3, N1, M0) = the tumor has spread and progressed to the outside of the
pancreas but not to the major blood vessels or nearby nerves.
Can be found an enlarged regional lymph nodes
- Stage 3 (T4, Any N, M0) = tumor has spread and progresses the major blood vessels or
nearby nerves. Can be found enlarged regional lymph nodes.
- Stage 4 (Any T, Any N, M1) = tumor has spread to various places
Stage 1 Stage 2 Stage 3 Stage 4
TREATMENT
The aim of pancreatic cancer treatment is to eliminate the cancer as much as possible by using
3 main modalities which are resection, radiotherapy, chemotherapy, and combination therapy
in the hope of improving the quality of life. Based on the staging of pancreatic cancer, the
therapy is divided into:
- Local (resectable)
used if rhe cancer is still in the pancreas. The most widely used techniques are
pancreaticoduodenektomi, while the other techniques are distal pancreatectomy and total
pancreatectomy. The appointments include duodenum, lien, and bile duct, and at least 15
lymph nodes. For pancreatic cancer patients with lessions still localized and has been resected,
the 5 years survival rate may increase up to 25%.
 - Locally Advance
pancreatic cancer have been locally advance when the cancer has
invaded the surrounding blood vessels. Optimal therapy in patients who
are already at this stage is still controversial because it can no longer
able to be done by resection so that it has a limited therapy. Progressive,
systemic and local treatment is needed in these patients. In such patients,
radiotherapy, radiosensitizer, systemic therapy or combination therapy are
usually performed to improve the survival rate. Radiation is intended to
shrink the tumor size. Chemoradiation in pancreatic cancer can improve the
response rate of therapy compared to only radiation or chemotherapy
alone.
 - Metastatic to the organs
when pancreatic cancer has been spread to the other organs, the
management is chemotherapy. The development of a regimen containing
5FU has been widely studied and gives a good result. The combination of
5FU with doxorubicin, mitomycin, methotrexate and some other cytotoxic
also gave hopes to the patients as the response rate was higher in the
combination (17,6%) compared with 5FU alone (8,4%). In 1997, the Food
and Drug Administration recommend the using of regimen containing
gemcitabine in patients with advanced stage of adenocarcinoma
pancreatic cancer. Gemcitabine may also be combined with other
cytotoxic agents such as oxaliplatin, docetaxel, cisplatin, irinotecan.
Combination therapy may increase the response rate, but before the
combination chemotherapy is given, the status of patients percormance
should be considered.
COMPLICATION
Complications that can arise from pancreatic cancer depends
on the size of the tumor, the stadium of cancer, and its
metastatic. Apart from the pancreatic cancer, complications
can also be generated from surgical outcomes and the effects
of chemotheraphy and radiotheraphy that can be different in
each patient.
PROGNOSIS
The prognosis in pancreatic cancer is determined by the stadium of
pancreatic cancer. Pancreatic cancer is often diagnosed too late so
that at the time of diagnosis of pancreatic cancer has been
established in the late stages so that the prognosis becomes very bad
where the life expectancy in 5 years is only less than 15%.
 DIFFERENTIAL DIAGNOSIS
A) pancreatic cyst
It can be neoplastic or not. In cyst less than < 2cm in size, it often doesnt showed any symptoms but if
it size is large, it will provide symptoms of abdominal pain that can penetrate to the back. Large cyst
in the head of pancreas also showed symptoms of obstructive jaundice due to the emphasis on the bile
duct. In addition, large cyst can also suppress other abdominal organs that can cause full sensation to
vomiting. Pancreatic cyst is usually caused by acute pancreatitis. Pancreatic cyst can be distinguished
from pancreatic cancer through EUS examination, histopathologic excision and cystic fluid analysis.
B) choledocholithiasis
It gives symptoms if the stone has been in the common bile duct. The symptoms can be caused by colic
pain and obstructive jaundice due to the stagnation of bile flow. Choledocholithiasis that stayed for
too long can trigger the occurrence of pancreatitis which is one of a risk factor for pancreatic cance.
Choledocholithiasis can be distinguished from pancreatic cancer through anamnesis, physical
examination, USG, CT Scan and EUP.
C) Liver cancer
Liver cancer often gives no specific symptoms. Symptoms that often appear are weakness, fatigue,
abdominal pain, weight loss and the decreasing of appetite. Liver cancer can also provides symptoms
of jaundice, signs of bleeding, hypoalbuminemia, and the others. In addition, the increasing of AFP
and CA 19-9 are also present in liver cancer. Liver cancer can be distinguished from pancreatic cancer
by physical examination, USG Abdomen, abdominal CT Scan and so on.