INTERPRETATION AND MANAGEMENT OF PANCREATIC CANCER

JAIPUR NATIONAL UNIVERSITY

Project work submitted for partial fulfilment for award of Bachelor of Pharmacy(B.Pharmacy) degree.

Supervised by:Mr. Ganesh N. SharmaAsst. Professor (Pharmacology),School of Pharmaceutical Science,Jaipur National University (Raj.)

Submitted by:Bibin MathewB.Pharm (4th year),Enrollment No: JNU-jpr-2009/01508.

S.No. TITLES & SUBTITLES1. INTRODUCTION

1.1 Cell Cycle

2. PANCREATIC CANCER2.1 Functions of pancreas.2.2 Epidemiology of pancreatic cancer.2.3 Types of pancreatic cancer.

3. INTERPRETATION OF PANCREATIC CANCER

4. CAUSES OF PANCREATIC CANCER

5. SIGNS AND SYMPTOMS

6. DIAGNOSIS6.1 Recent advancement in diagnosis

7. MANAGEMENT OF PANCREATIC CANCER7.1 Recent approaches in management of pancreatic cancer

8. CONCLUSION

9. REFERENCES

1. INTRODUCTION

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

Phases Events

Gap 0 (G0) Resting phase

Gap 1 (G1)Cells increase in size, control mechanism to ensure that everything is ready for DNA synthesis.

Synthesis

(S)

DNA replication occurs during this phase.

Gap 2 (G2)Checkpoint control mechanism 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 cells.

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 duodenal papilla.

2.1 Functions of pancreas

Exocrine Enzyme

Substrate Product

Amylase (active)

Starch, glycogen

Glucose, maltose.

Trypsinogen, Trypsin (active)Chymotrypsin(active).

Cleave peptide bonds in amino acids

Free amino acids and dipeptides.

Pancreatic lipase (active)

Triglyceride Mono glycerides fatty acids.

Endocrine

Beta cells(Insulin)

Alpha Cells(Glucagon)

D-Cells (Somato statin)

Inhibition

Stimulation

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-Ellison Syndrome)

• Gastrinomas overproduce gastrin. Most are malignant or have the ability to become malignant.

Glucagonoma• Glucagonomas overproduce glucagon.

They are usually large, often metastasize and about 70% are malignant.

Insulinoma• Insulinomas overproduce insulin. They

are the most common pancreatic neuroendocrine tumors.

Nonfunctional Islet Cell Tumor (NICT)

• Nonfunctional islet cell tumors are usually malignant. They are hard to detect.

Somatostatinoma• Somatostatinomas overproduce

somatostatin. They can occur anywhere in the pancreas and in the duodenum.

Vasoactive Intestinal Peptide-ReleasingTumor

• VIPomas overproduce vasoactive intestinal peptide (VIP). These tumors are usually located in the body and tail of the pancreas.

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 •Adenocarcinoma accounts for about 90% of all pancreatic cancers and it begins in cells lining the pancreatic duct.

Adenosquamous Carcinoma

• Adenosquamous carcinoma is similar to adenocarcinoma in that it forms glands but it flattens as it grows.

Intraductal Papillary-Mucinous Neoplasm

• Grows from the main pancreatic duct or from side branches. The tumor appear as a finger-like projection into the duct.

Mucinous Cystadenocarcinoma

• Mucinous cystadenocarcinoma is a rare, malignant, spongy, cystic tumor. The cyst is filled with a thick fluid called mucin.

Pancreatoblastoma• 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 number scale.

2. STAGE Model The second model for pancreatic cancer involves 4 numbered stages, as

follows: Stage1 Stage2 Stage3 Stage 4

TUMOR• T1 :Tumor is less

than 2cm across in any direction.

• T2 :Tumor is larger than 2cm across.

• T3 : Tumor has started to grow into the tissues, duodenum and bile duct.

• T4: Tumor has grown into spleen, large intestine and major blood vessel.

NODE

• N0 : There are no lymph nodes containing cancer.

• N1 : Lymph nodes containing cancer and so the tumor has likely metastasized beyond the pancreas.

METASTASIS

• M 0 : The tumor has not spread.

• M1 The tumor has spread.

TNM MODEL

STAGE MODEL

Stages TNM Equivalent

Description

Stage 1 1 or 2,0,0 There has been not spread and is relatively small. Tumor has not progressed outside pancreas.

Stage 2 3,0,0 Tumor has grown into nearby tissues and perhaps the duodenum.  Lymph nodes are not affected. 

Stage 3 2 or 3,1,0 Tumor may be quite large and has spread to the lymph node system.

Stage 44 A 4,2,0 Tumor has grown into nearby organs

including the spleen and/or stomach, as well as blood vessels. 

4 B 1,2,3 or 4,1,1 Tumor has spread to other organs such as the liver or lungs.

4. CAUSES OF PANCREATIC CANCER

Genetics

AgeCigarette smoking Diabetes Chronic pancreatis

Pancreatic cancer

5 Major causes:

5. SIGNS AND SYMPTOMS

Fig. No.4 Upper abdominal pain that may extend to middle or upper back.

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.

6. DIAGNOSIS

1.Ultrasound of the abdomen.

2.Endoscopic Ultrasonography (EUS).

3.Endoscopic Retrograde Cholangiopancreatography (ERCP).

4.Computed Tomography (CT).

5.Carbon nanotubes.

Following methods are used for diagnosis of pancreatic cancer:

7. MANAGEMENT OF PANCREATIC CANCER

A number of approaches can be made for the management of pancreatic cancer which are as follows:

1.Surgery

Fig.no.9 Whipple procedure for pancreatic cancer surgery.

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 tumors.

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 properly.

The goal of radiation therapy is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissue.

3. ChemotherapyS.no Chemotherapy Drugs 1. For exocrine pancreatic cancer Gemcitabine, 5Floro

uracil.2. Target therapy in exocrine Erlotinib,

Erlotinib+Gem.3. For endocrine pancreatic cancer Doxorubicin,

Streptozocin4. Target therapy for endocrine Sunitinib , Everolimus5. Other drugs for neuroendocrine Octreotide,Paseriotide6. For Zollinger Ellison Syndrome Proton Pump Inhibitors7. For Insulinomas( before surgery) Diazoxide

Gemcitabine: A boon for pancreatic cancer

Fig.no.10 Gemcitabine mechanism

7.1 Recent approaches in management of pancreatic cancer:

Gene Therapy• Introduction of functional genetic

material into target cells to replace or supplement defective genes or modify target cells.

Oncogenes Inactivation

• Mutations in KRAS are found in more than 90% of patient . Its inactivation using suitable vectors is a novel approach.

Immune enhancement

• Autologous natural killer (NK) cell and activated T lymphocyte based immunotherapy termed as autologous immune enhancement therapy.

Enzyme therapy• Enzymes which are generally given

in this therapy are lipase, protease and amylase.

8. CONCLUSION

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 cancer.

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.

 

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