Tobacco/Cigarette Smoking

Chronic tobacco chewing or cigarette smoking exposes the body to various carcinogens that increase the risk of pancreatic cancer. This has been identified as one of the major pancreatic cancer risk factors, but the risk reduces significantly after cessation of smoking.

Obesity

Obesity increases the risk of pancreatic cancer, which was linked to the increased level of insulin and insulin growth factors, lower level of anti-inflammatory cytokines, and increased carcinogen exposure related to food consumption. Regular physical activity may help in reducing the risk of pancreatic cancer.

Industrial/Occupational exposure

Chronic exposure to chemicals like benzidine, pesticides, asbestos, and chlorinated hydrocarbons that are generally encountered in dry cleaning and metal industry, has been found to increase the pancreatic cancer risk factors.

Family history

Risk of developing pancreatic cancer increases threefold in individuals with a family history of pancreatic cancer in first-degree relatives, especially with the number of first-degree relatives diagnosed.

Chronic pancreatitis

The long-term inflammation of the pancreas, which may arise due to heavy alcohol consumption, biliary duct blockage, or hereditary genetic mutation, have been reported to increase the risk of developing pancreatic cancer.

Diet

A diet rich in animal protein, low intake of fruits and vegetables, and improperly prepared/stored food are considered to elevate the pancreatic cancer risk factors. High fat and high cholesterol diet may also be a risk factor for the disease.

Genetic Cancer Predisposition Syndromes

Some inherited cancer predisposition syndromes have been reported to be associated with  pancreatic cancer:

• Hereditary breast and ovarian cancer syndrome (caused by mutation in the BRCA1 or BRCA2 genes);
• Lynch syndrome or hereditary non-polyposis colorectal cancer (HNPCC)
• Familial pancreatitis (caused by mutations in the PRSS1 gene);
• Familial atypical multiple mole melanoma (caused by mutation in the p16/CDKN2A gene),
• Peutz-Jeghers syndrome (caused by mutation in the STK11 gene),
• Von Hippel-Lindau syndrome (caused by mutations in the VHL gene), etc.

Other Factors

Older age individuals are at a significantly higher chance of developing pancreatic cancer.

Presence of diabetes or cirrhosis of the liver may also predispose a person to develop pancreatic cancer.

Consumption of coffee/tea, infection with Helicobacter pylori, and liver cirrhosis, and diabetes are other reported for pancreatic cancer risk factors.

Symptoms and Signs of Pancreatic Cancer

The most common site for pancreatic cancer is the head and uncinate process of the pancreas.

Jaundice and biliary colic are the most common symptoms produced by tumors in this location, due to the obstruction of the bile duct which passes through the head of the pancreas.

Due to the close proximity to the duodenum, head of pancreas tumors may lead to duodenal obstruction leading to GI distress.

Obstruction of the pancreatic ducts may occur due to the tumors present in the head of the pancreas. Also by tumors present in other parts, such as the tail of the pancreas.

Obstruction of the pancreas duct may led to the development of acute pancreatitis, which presents as pain in the abdomen.

It also prevents the release of pancreas enzymes into the intestine, which presented as steatorrhea, or fatty stools.

Except these, other symptoms of pancreas cancer are, abdominal pain, aching/pressure/burring sensation in abdomen, loss of weight or appetite, and very rarely, venous thrombosis.

Localised/Locally Advanced Disease

• Pain in the upper abdomen or back
• Newly diagnosed diabetes
• Jaundice or yellowish discoloration of eye and/or urine
• Loss of appetite, early satiety, vomiting

Metastatic Disease

• Cough, breathlessness, chest pain
• Jaundice, right upper abdominal discomfort
• Abdominal distension, bloating

Most common sites of spread of pancreatic cancer are liver, lung and peritoneum.

Pancreatic Cancer Staging Investigations

Endoscopic retrograde cholangiopancreatography (ERCP)

This is a diagnostic technique which utilizes an endoscope – a long, flexible, slender tube usually equipped with a camera, a light source, and some special instruments for biopsy or surgery. The endoscope is passed down to duodenum to locate the ampulla of Vater (an opening of the common bile duct in the duodenum).

A dye is then injected into the common bile duct via a catheter and several x-ray images are taken to detect any abnormality in the pancreatic duct or bile duct. If required, a stent can be placed in the bile duct or pancreatic duct. Also, biopsy samples can be collected from abnormal areas diagnosed during the examination.

Endoscopic Ultrasound

In this technique, an ultrasound device is used along with an endoscope, to determine the location and the size of a tumor in the pancreas and to detect any involvement of nearby lymph nodes/blood vessels. This technique is sensitive enough to find small lesions (<2 cm) in the pancreas and can accurately predict the size of the tumor.

It can distinguish between solid and cystic lesions in the pancreas, and also enables the collection of biopsy samples from the affected area via a special biopsy instrument in conjunction with the endoscope.

Laboratory Tests for Biopsy Samples

Biopsy from pancreatic mass helps in confirmation of diagnosis and also helps in detecting genetic/molecular abnormalities that may guide in treatment with targeted therapy or immunotherapy.

Tumor marker

An elevated level of carbohydrate antigen (CA) 19-9 is generally associated with pancreatic cancer, but it is of little value in detecting early-stage disease. However, it is helpful to assess the effectiveness of the treatment/surgery and the progression/recurrence of the disease.

Imaging Tests

These help in locoregional and distant staging of the tumor. One or more of the following may be required.

• Computed tomography (CT) scan
• Magnetic resonance imaging (MRI) scan
• Positron emission tomography (PET) scan

Laparoscopy

In this technique, camera is introduced into the peritoneal cavity to look for radiologically occult disease and also take biopsies from the suspected areas.

Stages of Pancreatic Cancer

To understand the staging better, lets have a look at the normal anatomy of the pancreas.

This is the head of the pancreas, present in the right side of the abdomen, and is largest part of pancreas.

Neck is the narrow portion of pancreas that connects the head with body.

This prismatic shaped main structure of pancreas is called as body.

This narrow down terminal portion of pancreas, present in the left side of the abdomen, is called as tail.

This look like projection from the lower part of head of pancreas is called as uncinate process.

This figure shows the location of pancreas in the abdomen.

First part of the small intestine, called as duodenum curves along the head of pancreas.

The spleen is located on the left side of abdomen, close to the tail of pancreas.

And here lies the left kidney, above which lies the suprarenal gland.

Superior mensentric artery is a branch of aorta, that crosses the uncinate process of the pancreas.

Bile duct passes through the head of the pancreas to join the duodenum.

Main pancreatic duct passes from the tail to the head of the pancreas, and ultimately joins the duodenum.

This structure present above the pancreas is called as coeliac artery.

It gives a branch on the right side, which is called as common hepatic artery.

And on the left is called as splenic artery.

Behind the neck of the pancreas, the mesenteric vein and splenic vein join to form portal vein.

Very rarely, it may also spread to brain or bones.

Survival Rate/ Life Expectancy according to Stage

It is calculated based on whether the disease is Localised, Regional or Distant.

Localised

• Cancer is limited to the pancreas.
• 5 year survival 37%.

Regional

• Cancer has spread to nearby structures or lymph nodes
• 5 year survival 12%.

Distant

• Cancer has spread to distant body parts.
• 5 year survival 3%.

Stage IV

Any T Any N M1 Chemotherapy or immunotherapy is the mainstay of treatment in case the disease has spread to distant body parts. Along with the chemotherapy, palliative therapy to relieve pain or stent placement may be employed as and when required.

Treatment of Localised and Locally Advanced Pancreatic Cancer

Treatment of pancreatic cancer depends on the stage, resectability, performance status of the patient, along with other factors. But the final treatment decision is taken by the oncologist after clinical evaluation of the patient. We will first discuss the resectability of the pancreatic tumor, depending upon the extent of tumor.

Also read-

• Symptoms and Signs of Pancreatic Cancer
• Stages of Pancreatic Cancer
• Risk Factors for Pancreatic Cancer

Resectability of Pancreatic Tumor

Tumor located within the pancreas, without extension to adjacent structutes, is considered to be resectable. This figure shows a resectable tumor located in the head of pancreas. Similarly, this is a resectable tumor located in the tail of pancreas. A tumor located in the head of the pancreas, that extends to involve the duodenum, is also considered to be resectable. Similarly, tumors arising from the tail of pancreas, that involve the spleen, left kidney, or left suprarenal gland, may also be resected. Superior mesenteric vein involvement maybe considered resectable, boderline resectable or unresectable, depending upon the extent of arterial involvement. Similarly, involvement of portal vein maybe considered resectable, borderline resectable or unresectable, depending upon the extent of arterial involvement. Infiltration of tumor into common hepatic artery only, is borderline resectable in most of the cases. Infiltration of tumor into the superior mesentric artery maybe considered borderline resectable or unresectable, depending upon the extent of arterial involvement. Celiac artery involvement may also be borderline resectable or unresectable, depending upon the extent of arterial involvement.

Treatment of Pancreatic Cancer based on Resectability

Now we will discuss the treatment for all the three, that is resectable, borderline resectable, and unresectable disease.

Resectable

It includes the cases that are localised to pancreas, or infiltrate into duodenum, spleen or left kidney or suprarenal gland. Superior mesenteric vein or portal vein involvement may be resectable only in selected cases.

Surgical Resection is the treatment of choice for resectable disease, with addition of chemotherapy in high-risk cases.

Borderline Resectable

Common hepatic artery involvement by tumor is included in this. Depending on the extent of involvement, invasion of superior mesenteric artery, celiac artery, superior mesenteric vein or portal vein may be considered borderline resectable.

In such cases, chemotherapy with/without radiotherapy is given and then decision for surgery is taken depending on response to treatment.

Unresectable

Depending on the extent of involvement, invasion of superior mesenteric artery, celiac artery, superior mesenteric vein or portal vein may be considered unresectable.

Chemotherapy with/without radiotherapy is the preferred treatment in such cases.

The final decision is taken by the oncologist, on an individual patient basis, depending upon the performance status of the patient and exact stage of the disease.

Role of Surgery

Surgery provides significantly longer survival and is considered as the treatment of choice for resectable pancreatic cancers.

Radical pancreatic resection such as Whipple procedure (resection of pancreas and duodenum), partial, or complete pancreatic resection are some common surgical procedures employed with a curative intent for resectable and borderline resectable pancreatic cancers.

For unresectable pancreatic cancers, surgery is employed for palliation of symptoms, which may include biliary/gastric bypass surgery and biliary stent placement to relieve bile duct blockage.

Chemotherapy for Pancreatic Cancer

Chemotherapy may be used for pancreatic cancer in neoadjuvant setting (before surgery to downsize the tumor and make it resectable), concurrent chemoradiation (used along with radiation therapy), adjuvant treatment (after surgical resection of tumor) or palliative treatment (in case of unresectable or metastatic disease).

Chemotherapeutic agents used for pancreatic cancer treatment are-

• 5-fluorouracil
• Gemcitabine
• Capecitabine
• Cisplatin, Oxaliplatin
• Nab-Paclitaxel
• Irinotecan

Role of Immunotherapy

Pembrolizumab had been granted US FDA approval for the treatment of MSI-H or dMMR positive unresectable/metastatic pancreatic cancers that have progressed on prior treatment and for which no satisfactory alternative treatment option is available.

Role of Targeted Therapy

Targeted drugs target a specific gene or protein characteristic of the pancreatic cancer cells, for example, erlotinib targets epidermal growth factor receptor (EGFR). They are generally used alone or in combination with chemotherapy for the treatment of advanced disease.