Interpretation and Management of Pancreatic cancer
INTERPRETATION AND MANAGEMENT OF
JAIPUR NATIONAL UNIVERSITY
Project work submitted for partial fulfilment for award of
Bachelor of Pharmacy(B.Pharmacy) degree.
Mr. Ganesh N. Sharma
Asst. Professor (Pharmacology),
School of Pharmaceutical Science,
Jaipur National University (Raj.)
B.Pharm (4th year),
Enrollment No: JNU-jpr2009/01508.
TITLES & SUBTITLES
1.1 Cell Cycle
2.1 Functions of pancreas.
2.2 Epidemiology of pancreatic cancer.
2.3 Types of pancreatic cancer.
INTERPRETATION OF PANCREATIC CANCER
CAUSES OF PANCREATIC CANCER
SIGNS AND SYMPTOMS
6.1 Recent advancement in diagnosis
MANAGEMENT OF PANCREATIC CANCER
7.1 Recent approaches in management of pancreatic cancer
Pancreatic cancer is a malignant neoplasm originating from transformed
cells arising in tissues forming the pancreas. The most common type of
pancreatic cancer, accounting for 95% of these tumors, is adenocarcinoma.
Tumors of Pancreas
Broadly there are three basic types:
Ductal adenocarcinoma is 90% of pancreatic cancers with a 4%
5-year survival (worst of any cancer).
Neuroendocrine tumors ( islet-cell tumors).
Cystic neoplasm account for <1% of pancreatic cancer.
1.1 Cell Cycle
Gap 0 (G0)
Gap 1 (G1)
Cells increase in size, control
mechanism to ensure that everything is
ready for DNA synthesis.
DNA replication occurs during this
ensures that everything is ready to
enter the M (mitosis) phase and divide.
Mitosis (M) Cell growth stops at this stage and
cellular energy is focused on the
orderly division into two daughter
Gap 2 (G2)
2. PANCREATIC CANCER
Usually, cancer is named after the body part in which it originate thus
pancreatic cancer refers to the erratic growth and proliferation of cells that
originate in the pancreatic tissue.
Fig.no.2 Human Pancreas
The pancreas is prismoid in shape and appears triangular with two major regions i.e.
head and tail portion.
The head of the pancreas lays in the duodenal C loop in front of the inferior vena cava
(IVC) and the left renal vein.
The body and tail of the pancreas run obliquely upward to the left in front of the aorta
and left kidney.
The main pancreatic duct (Duct of Wirsung) runs from the tail through the body to the
head of the pancreas where it descends into the lower (inferior) part of the head.
There it joins the duct of the uncinate process coming from left and then the lower part
of the common bile duct to form a common channel (hepatopancreatic ampulla).
This duct runs through the medial duodenal wall and opens on the dome of the major
2.2 Epidemiology of pancreatic cancer
Pancreatic cancer is currently the fourth leading cause of cancer
death in the western countries, claiming 32,000 lives annually.
The rate of incidence is increasing which means that the disease is
becoming more common and it is also extremely difficult to treat.
Signs and symptoms of the disease seldom appear until more
advanced stages of cancer.
By the time symptoms appears, cancer cells are likely to have
metastasized to other parts of the body.
While currently pancreatic cancer can be removed by surgery
followed by chemotherapy.
2.3 Types of Pancreatic Cancer
• Pancreatic cancer has been classified into two classes viz. exocrine and
endocrine pancreatic cancer. The endocrine and exocrine pancreatic
carcinomas are further classified into various subclasses.
Fig.no.3 Passaro’s triangle. Typical location of a Gastrinoma
Subclasses of endocrine pancreatic cancer
Gastrinoma (Zollinger- • Gastrinomas overproduce gastrin. Most
are malignant or have the ability to
Cell Tumor (NICT)
• Glucagonomas overproduce glucagon.
They are usually large, often metastasize
and about 70% are malignant.
• Insulinomas overproduce insulin. They
are the most common pancreatic
• Nonfunctional islet cell tumors are usually
malignant. They are hard to detect.
• Somatostatinomas overproduce
somatostatin. They can occur anywhere in
the pancreas and in the duodenum.
• VIPomas overproduce vasoactive
intestinal peptide (VIP). These tumors are
Peptide-ReleasingTumor usually located in the body and tail of the
Various subclasses of exocrine pancreatic cancer
Acinar Cell Carcinoma
• Rare form of pancreatic cancer that may
cause excessive production of pancreatic
lipase, the enzyme secreted to digest fats.
• Adenocarcinoma accounts for about 90%
of all pancreatic cancers and it begins in
cells lining the pancreatic duct.
• Adenosquamous carcinoma is similar to
adenocarcinoma in that it forms glands
but it flattens as it grows.
Intraductal PapillaryMucinous Neoplasm
• Grows from the main pancreatic duct or
from side branches. The tumor appear as
a finger-like projection into the duct.
• Mucinous cystadenocarcinoma is a rare,
malignant, spongy, cystic tumor. The
cyst is filled with a thick fluid called
• Pancreatoblastoma is a rare form of
pancreatic cancer found in children
under the age of 10. It is often called
“pancreatic cancer of infancy.”
3. INTERPRETATION OF PANCREATIC CANCER
There are several stages involved in pancreatic cancer, and two models for
accurately describing them are TNM and Stage models
1. TNM Model
In the Tumor, Node, Metastasis (TNM) system, tumor size, lymph node
health and metastasis activity are measured separately, each with its own
2. STAGE Model
The second model for pancreatic cancer involves 4 numbered stages, as
• T1 :Tumor is less
than 2cm across in
• T2 :Tumor is larger
than 2cm across.
• T3 : Tumor has
started to grow
into the tissues,
• T4: Tumor has
grown into spleen,
large intestine and
major blood vessel.
• N0 : There are no
• N1 : Lymph nodes
and so the tumor
• M 0 : The tumor
has not spread.
• M1 The tumor has
1 or 2,0,0
There has been not spread and is relatively
small. Tumor has not progressed outside
Tumor has grown into nearby tissues and
perhaps the duodenum. Lymph nodes are not
2 or 3,1,0
Tumor may be quite large and has spread to
the lymph node system.
Tumor has grown into nearby organs
including the spleen and/or stomach, as well
as blood vessels.
1,2,3 or 4,1,1
Tumor has spread to other organs such as the
liver or lungs.
4. CAUSES OF PANCREATIC CANCER
5 Major causes:
5. SIGNS AND SYMPTOMS
Fig. No.4 Upper abdominal pain that may extend to middle or
Fig.No.5 Weight loss due to malignant cancer cells tendency
to deprive healthy cells of nutrients.
Fig.No.6 Jaundice leads to yellowing of skin and eyes.
Fig.No.7 Nausea and vomiting can occur during later stages, if
a pancreatic tumor has grown sufficiently larger
Fig. No. 8 Due to Zollinger Ellison syndrome stomach ulcers
can also happen.
Following methods are used for diagnosis of pancreatic
1.Ultrasound of the abdomen.
2.Endoscopic Ultrasonography (EUS).
3.Endoscopic Retrograde Cholangiopancreatography (ERCP).
4.Computed Tomography (CT).
7. MANAGEMENT OF PANCREATIC CANCER
A number of approaches can be made for the management of pancreatic
cancer which are as follows:
Fig.no.9 Whipple procedure for pancreatic cancer
2. Radiation Therapy
Radiation therapy ( radiotherapy, x-ray therapy, or irradiation) is the use of a
beam of energy (called ionizing radiation) to kill cancer cells and shrink
Radiation therapy injures or destroys cells in the area being treated (the
“target tissue”) by damaging their genetic material (DNA), making it
impossible for these cells to continue to grow and divide.
Major side effect is radiation damages both cancer cells and normal cells,
most normal cells can recover from the effects of radiation and function
The goal of radiation therapy is to damage as many cancer cells as possible,
while limiting harm to nearby healthy tissue.
For exocrine pancreatic cancer
Target therapy in exocrine
For endocrine pancreatic cancer
Target therapy for endocrine
Sunitinib , Everolimus
Other drugs for neuroendocrine
For Zollinger Ellison Syndrome
Proton Pump Inhibitors
For Insulinomas( before surgery)
Gemcitabine: A boon for pancreatic cancer
Fig.no.10 Gemcitabine mechanism
7.1 Recent approaches in management of pancreatic cancer:
• Introduction of functional genetic
material into target cells to replace or
supplement defective genes or modify
• Mutations in KRAS are found in more
than 90% of patient . Its inactivation using
suitable vectors is a novel approach.
• Autologous natural killer (NK) cell and activated
T lymphocyte based immunotherapy termed as
autologous immune enhancement therapy.
• Enzymes which are generally given in this
therapy are lipase, protease and amylase.
Pancreatic cancer i.e. mainly adenocarcinoma is the major cause of death
associated with pancreatic cancer. Apart from familial disorders the minor
risk factors also cannot be ignored as smoking causes 40% of pancreatic
Due to its poor prognosis mortality rate with pancreatic cancer is high so
the newly developed cheaper and sensitive diagnostic could create a
breakthrough in determining pancreatic cancer.
Gemcitabine has proved a boon to pancreatic cancer patient Apart from
chemotherapy, gene therapy, oncogens inactivation and enzyme therapy can
be helpful to patients.
With advances in screening, diagnosis, and treatment, the death rate for
pancreatic cancer has declined. Research is ongoing to develop even more
effective screening and treatment programs.
1. Bertran K, Masters S and Anthony T. “Basic and Clinical Pharmacology”,
Tata McGraw hill education Pvt. ltd, New Delhi, 10th edition, 2009, 72151.
2. Neoptolemos John, et.al, “Pancreatic Cancer”, Springer science, USA, 1st
edition 2010,vol-1, 4-60.
3. Heiken Jay, “Pancreatic Cancer”, Cambridge University press, USA, 1st
edition, 2008, vol-1,60-150.
4. Bennet PN and Brown MJ, “Clinical Pharmacology”, Elseiver India Pvt.
ltd, New Delhi, 9th edition,2005, 659-665.
5. Walker R and Whittlesea C, “Clinical Pharmacy and Therapeutics”,
Churchill Livingstone Elseiver, New Delhi, 4th edition, 2008, 480-85.
6. Collinus K, Jacks T and Pvletich PN, “The Cell Cycle and Cancer”, PNAS,
Springer science, USA, 1997 April 1, vol-94, 2776-2778.
Goyton AC and Hall JE, “Textbook of Medical Physiology”, Reed
Elsevier India Pvt. ltd, New Delhi, 10th edition, 2004, 747-766.
Gelone S, Gennaro, Alfonso R (Editors), “Remington The science and
practice of pharmacy, Lippincott Williams & Wilkins, USA, 21st edition,
9. Satou A, Nakamura, “Pancreas Anatomy, Diseases and Health Implications,
Nova Sciences Publishers, NY, 2012, vol-45, 50-110.
10. Bhattacharya SK, et.al, “Pharmacology”, Elesevier India pvt.ltd, New
Delhi, 6th edition, 2004, 335-340.
11. Bell RH, “Atlas of pancreatic surgery: Digestive tract, Lippincott,
Philadelphia, 2nd edition, 1996,963
12. DeLellis, et.al, (Editors), “WHO classification of Tumors, Pathology and
Genetics of Endocrine Organs”, IARC Press, London, 2004, 175-200.
13. Cancer – Its various types along with causes, symptoms, treatments and
stages, cancer info guide,2009 ( retrieved from http://www.cancer-infoguide.com/18/08/12 at 16:00hrs).
14. Tamm PE, SilverMan MP, et.al, “Diagnosis staging and Survillence of
pancreatic cancer, American Journal Of Pancreatic Cancer”, American
journal of roentgenology, USA, May 2003,vol-180,5.
15. Hidalgo Manual, “Pancreatic cancer” The New England journal of
medicine”, IARC Press, London, 2010, vol-362, 1605-1617.
16. Heiser PW and Hebrok M, “Development and Cancer”, Lessons learned in
pancreatic cancer, Cell cycle, 2004, vol-3, 270-2.
17. Klein MW, Hruban RH, et.al, “Direct correlation between proliferative
activity and dysplasia in Pancreatic Intra Epithelial Neoplasia”, Modern
Pathology, 2002, vol- 15, 441-447.
18. Brunton LL, Lazo SJ, Parker Keith, “Goodman & Gilman’s, The Pharmacological
Basis of Therapeutics”, McGraw Hill medical publishing division, New Delhi, 11th
edition, 2005, 401-20.
19. Khosronia I, “Smoking and pancreatic cancer”, Medical journal of Iranian hospital,
vol-4, January 2002, 50-60.
20. Gukovsky I, Todorin J and Karin M, “Inflammation autophagy and Obesity:
Common features in pathogenesis of pancreatitis and pancreatic cancer”,
Gastroenterology, June2013, vol-144(6), 1999-2000.
21. Rang H.P, Dale M.M, Ritter.J.M, Flower.R.J, “Rang and Dales Pharmacology,
Elsevier publication, New Delhi, 6th edition, 2007, 525-530
22. Casper ES, Green MR, Kelsen DP, et al, “ Phase II trial of gemcitabine in patients
with adenocarcinoma of the pancreas”, Invest New Drugs ,1994,vol-12, 29
23. Loscalzo, Hauser, et.al, “Harrison’s Priciples of Internal Medicine”, Mc Graw Hill
medical publishers, New Delhi, Vol-1, 17th edition, 580-620.
24. Lynch HT, Smyr KT, et.al, “Familial pancreatic cancer: A rievew, Europe Pubmed,
Central, 1996, vol-23(2), 251-275.
25. Valiang WG, Anna G and Stephan JP, “Alcohol and pancreatic cancer”, Alcohol
Journal, Elseiver, USA, April 2005, vol-35,205-211.
26. NCCN Clinical Practise Guidelines in Oncology: Pancreatic Adenocarcinoma,
27. Karlson BM, Ekbom Anders, et.al, “Abdominal US for Diagnosis of Pancreatic
Tumor: Prospective Cohort Analysis”, Radiology, Radiological Society of North
America, October 1999, 213, 107-111.
28. Pellegta NS, Sessa, “K-ras and p-53 gene mutation in pancreatic cancer:
ductal and non ductal tumor progress through different genetic lesions”,
Cancer Research, AARC, Philadelphia, March 15, 1994,Vol-54,1556.
29. Beard J, et.al, “The Enzyme treatment of pancreatic cancer and its
scientific basis”, New Spring Press, NY, 1911, 21-50.
30. Venugopal D, et.al, “Pancreatic enzyme supplementation in pancreatic
cancer”, The journal of supportive oncology, Elseiver, USA, vol-6, 393400.