Pancreatic Cancer

Pancreatic cancer is the tenth common cancer, and the fourth leading cause of cancer deaths in Hong Kong. The incidence and mortality of pancreatic cancer have both continuously increased over the past decade. In 2021, there were 1,116 new cases of pancreatic cancer that accounted for 2.9% of all new cancer cases in Hong Kong. The number of new cases diagnosed has increased by 18.5% compared to 2020 and was more than double since 2011. Males and females share similar rate of getting it and the median age of diagnosis of pancreatic cancer was 70 years old.

More, there were total 889 people died from this cancer in 2021, accounting for 5.9% of all cancer deaths. From 2011 to 2021, the number of deaths due to pancreatic cancer leaped by 75%.

Pancreatic cancer is an aggressive cancer. Since the pancreas is deep inside the body, early tumors can't be seen or felt by health care professionals during routine check-up. When a patient starts experiencing symptoms, the cancer has become large or has already spread to other organs. Therefore, pancreatic cancer is usually diagnosed at advanced stage and has poor prognosis. Only around 20% of the patients can receive operation but the recurrence rate is high.

What is pancreatic cancer?

The pancreas

• The pancreas is a flat, pear-shaped gland behind the stomach. It is part of both digestive and endocrine systems. 
• The pancreas is made up of exocrine and endocrine cell tissues.
  • Exocrine cells in the pancreas produce and release pancreatic juices. These juices travel through the pancreatic duct into the duodenum. Enzymes in the pancreatic juice help digest fat, carbohydrates and protein in food.
  • Endocrine cells in the pancreas produce and release hormones directly into the blood flow. Hormones made by the pancreatic endocrine cells include insulin (lowers the sugar level in blood), glucagon (increase the amount of sugar in blood when the blood sugar is low), somatostatin, pancreatic polypeptide (PP), and vasoactive intestinal peptide (VIP). Each of these hormones play an important role in regulating the body’s metabolism.

Pancreatic cancer

Pancreatic cancer is a type of cancer that occurs in the pancreas. 

Pancreatic cancer is an aggressive cancer. As the malignant tumour within the pancreas grows slowly and often lies deep, it is difficult to detect at its early stage. Even for a person who has regular checks annually, discovering the cancer through general tests is still difficult. Therefore, pancreatic cancer is usually diagnosed at advanced stages, which delays the necessary treatments hence causes a poor survival rate. 

With an untimely diagnosis, even though the tumour has been removed through surgery, pancreatic cancer patient’s lifespans are still shorter than that of other cancer patients.

Most patients of pancreatic cancer are over the age of 65, and the other risk factors include:

• Gender: Being males
• Race: Black racial groups
• Smoking: Smoker’s risks are 2 to 3 times higher than that of non-smokers.
• Obesity
• Over consumption of animal fat or insufficient consumption of vegetables and fruits
• Abnormal sugar metabolism such as diabetes mellitus
• Prolonged contacts with chemicals such as pesticides, petroleum or dyes
• Infection with Helicobacter pylori: Risks for people infected with the bacteria are 2 times higher than others
• Hereditary chronic pancreatitis: Increases risks of pancreatic cancer, though it seldom occurs
• Chronic pancreatitis: Usually discovered alongside pancreatic cancer, though the former may not be the cause of the latter

Symptom of pancreatic cancer include:

• Sustained pain in the upper abdomen which may extend to the back, that is not related to diets
• Loss of appetite, nausea, vomiting, indigestion, and other problems related to the digestive system
• Jaundice, itching skin and clay-coloured stool
• Drastic loss of weight in a short time
• Fixed, hard lumps in upper abdomen
• Ascites

Blood tests

• Liver function test
  • The liver enzymes (alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), bilirubin) may be increased due to:
    • Blockage in the common bile duct by pancreatic head tumour
    • Inflammation of the pancreas
    • Pancreatic cancer spreading to the liver
• Tumour marker test
  • Ca 19.9
    • CA 19-9 is a tumour marker. It is raised in 70% to 80% of people with pancreatic cancer.
  • CEA
    • CEA is a tumour marker. It is raised in about 50% of people with pancreatic cancer.

Endoscopic retrograde cholangiopancreatography (ERCP)

• It is a procedure done with an endoscope (a thin, tube-like instrument with light and lens at its end) to examine the pancreatic and bile ducts. During the procedure, a dye is injected into the ducts which causes them to appear clearly on an X-ray.  
• Generally, the procedure may last for 15-60 minutes depending on individuals. In complicated cases that require additional therapies, the examination time may be prolonged.
• An ERCP can be used for:
  • Getting a biopsy for histological proof
  • Placing a plastic or metal stent to relieve blockage in the bile duct

Percutaneous transhepatic cholangiography (PTC)

• An X-ray on the bile ducts and liver.
• A thin needle is inserted through the skin and into the area of the bile ducts. Then, a dye is injected through the needle, so the bile ducts appear clearer on X-rays. Any blockage in the bile ducts can be seen.
• A PTC can also be used to locate blockage in the bile duct. It can be used as a guide to the site, in order to put a stent at the blocked duct.

Ultrasound

Ultrasound can be used to locate any tumour obstructing the common bile ducts, or causing dilatation of the bile ducts in the liver, as well as guide a biopsy.

• Transabdominal ultrasound
  • It is one of the first tests on abdominal discomfort or deranged liver function.
• Endoscopic ultrasound (EUS) 
  • It is a procedure that involves an endoscope (a thin, lighted tube that is passed through the patient's mouth, stomach and into the small intestine).
  • The doctor then uses the probe pointing towards the pancreas.
  • A biopsy may also be conducted during EUS.

CT (computed tomography) scan 

• A CT scan makes detailed cross-sectional images showing the tumour and the adjacent structures. It can also show if cancer has spread to organs near the pancreas, as well as to lymph nodes and distant organs. 
• Together with injection of intravenous contrast medium, the CT scan can find out exactly where the tumour is related to the nearby organs and blood vessels. This can help surgeon to evaluate whether the pancreatic cancer can be operable or not. 

PET-CT (positron emission tomography) scan 

• PET-CT is a nuclear medicine imaging scan and uses radioactive isotopes to look for changes in the metabolic activity of body tissues.  
• It is used to find out if the cancer has spread to other organs or tissues 

• Ductal adenocarcinoma
  • Most common type of pancreatic cancer, accounting for 95% of pancreatic cancers.
  • More common in men than women (1.5-2: 1)
  • Usually develops between ages of 60 and 80.
  • Many ductal adenocarcinomas occur in the head of the pancreas. They can also occur in the body or tail of the pancreas.
• Adenosquamous carcinoma
  • More common in men than women
  • Can develop at any age
• Pancreatic neuroendocrine tumours (pNET)
  • Can occur in any parts of the pancreas
  • Usually occurs in patients aged 60 years or above
• Others: Acinar cell carcinoma, pleomorphic adenocarcinomas, lymphoma, sarcoma

• Treatment options and recommendations depend on several factors, including the type and stage of cancer, possible side effects, the patient’s preferences and overall health. 
• It is important to clarify matters that are unclear. 
• Discussing the goals and expectations of each treatment in the process with the doctor, known as “shared decision-making”, is a most preferred approach during cancer treatment.

Surgery

• Resection is the only curative treatment
• Indicated in patients who are fit, with no metastatic disease, and without (or limited) invasion into adjacent blood vessels.  

Whipple’s operation 

• The most common operation for pancreatic cancer 
• It is for patients whose tumour is at the pancreatic head or uncinate process
• It involves removal of the pancreatic head, duodenum, the first 15cm of the jejunum, common bile duct, gallbladder, part of the stomach, and adjacent lymph nodes. 
• Usually performed as an open surgery 

Distal pancreatectomy 

• For patients with pancreatic body or tail tumour 
• The procedure is usually combined with splenectomy
• Technically feasible to perform laparoscopically 
• Occasionally, total pancreatectomy (removal of entire pancreas) is needed to clear the cancer completely.

Adjuvant and other treatment types

Adjuvant chemotherapy

• Adjuvant chemotherapy typically lasts for 6 months
• Chemotherapy is a form of systemic therapy, in which drugs travel through the bloodstream to reach and destroy cancer cells all over the body.
• The aim of adjuvant therapy after resection is to prevent or delay recurrence
• Indicated in all pancreatic cancer patients after resection 

Choices of Regime

Modified FOLFIRINOX 

• Three-drug combination involves 5-FU (Fluorouracil), Oxaliplatin, and Irinotecan given every 2 weeks
• Preferred regimen in patients with excellent physical condition, given that it offers the best survival rate (median survival improves by ~40%) compared to older regimens. 
• Common side effects include suppression of bone marrow function, hair loss, numbness in limbs and fingers, tiredness, diarrhoea, nausea and vomiting

For patients who inapplicable: 

• Gemcitabine – Capecitabine: A two-drug combination with more tolerable side effects
• Single drug regime: Gemcitabine or TS-1
• Common side effects: suppression of bone marrow function, tiredness, diarrhoea, nausea and vomiting, as well as hand-foot syndrome 

Adjuvant chemo-radiotherapy 

• The role of radiotherapy in preventing recurrence is less certain.
• Some expert groups suggest that adjuvant chemo-radiotherapy should be considered in patients with node positive or margin positive disease.
• The rationale of using radiotherapy is to sterilise the residual microscopic disease at the post-operative field and adjacent high-risk lymph node area, in order to reduce the local recurrence rate.
• Radiotherapy treatment are typically performed five days a week over 5-6 weeks, and is usually given concurrent with chemotherapy. 

Surveillance after surgery and adjuvant treatment

• To monitor the recovery from treatment-related toxicities and recurrence.
• Clinical examination, tumour marker (CA 19-9) and CT scan every 3-6 months in the first 2 years, and then every 6-12 years afterwards.

Locally advanced cancer means that there is no distant spread of the tumour, while invasion into nearby structures (blood vessels) exists, which renders surgical resection not feasible.

For most of the patients, the treatment goal is to manage the tumour. However, for selected patients, potential curative surgical resection may be possible after initial treatment.

Chemotherapy

• FOLFIRINOX: A three-drug combination that involves 5-FU (Fluorouracil), Oxaliplatin, and Irinotecan given every 2 weeks. Common side effects include deterioration of bone marrow function, hair loss, numbness in limbs and fingers, tiredness, diarrhoea, nausea and vomiting.
• Gemcitabine-Abraxane: A two-drug combination. Common side effects include deterioration of bone marrow function, hair loss, neuropathy, tiredness, nausea and vomiting.
• Other regimes: Gemcitabine-Xeloda, Gemcitabine alone 

Radiotherapy 

• The role of external beam radiation therapy is controversial. It may be offered in patients whose conditions are stable in chemotherapy.  
• Duration: 5 times a week over 5 to 6 weeks
• May improve the local control of the disease.
• Common side effects include a loss of appetite, nausea and vomiting, diarrhoea, and fatigue. Most of these side effects disappear after treatment.

For patients whose diseases have already spread to distant organs (such as the liver, lung and peritoneum), the treatment goal is to prolong life and palliate symptoms. 

Chemotherapy  

• The mainstay of treatments. It is a form of systemic therapy where drugs travel through the bloodstream to reach and disintegrate cancer cells across body. Drugs are given either intra-venously or orally.
• The choice of first line regimen depends on the patient’s overall health and organ function
• For patients who are fit, chemotherapies consisting of two or three drugs are usually preferred, given their superior efficacies. Commonly used regimens are
  • FOLFIRINOX (Oxaliplatin, Irinotecan, and 5FU) 
  • Gemcitabine + Nab-Paclitaxel  
• For patients who are inapplicable, single agent chemotherapy regime is preferred. Commonly used regimens are
  • Gemcitabine
  • TS-1 (oral chemotherapy)  
• For patients who failed in the first line regimen but still has a fit general condition, second line chemotherapy can be considered. Its choice depends on types of medication used in the first line regimen and the patient’s health condition. Commonly used regimens include
  • Oxaliplatin + Capecitabine
  • Gemcitabine + Nab-Paclitaxel
  • Liposomal-Irinotecan + 5FU/LV or 
  • Gemcitabine. 
• Common side effects of chemotherapy includes deterioration of bone marrow function, hair loss, numbness in limbs and fingers, tiredness, diarrhoea, nausea and vomiting.

Targeted therapy 

• For patients with advanced pancreas cancer whose disease is stable after at least 4 months of platinum-based chemotherapy, and harbors DNA-repair gene defects such as BRCA1 and BRCA2, a PARP inhibitor (For example: Olaparib) may be considered.
• Common side effects include fatigue, nausea and vomiting, headaches, diarrhoea, decreased appetite, hair loss and lower levels of certain blood cells. 

Radiotherapy 

• Can be used for relieving pain in cancer that spreads to the bones, lymph nodes, or liver. 
• Usually given in one to ten fractions

Although pancreatic cancer cannot be completely prevented, gradual changes in lifestyle can greatly reduce chances of occurrence.

• Quitting smoking
  • Cigarettes contain many carcinogens capable of damaging DNA sequences severely
    • In particular, the DNA sequences responsible for controlling cell growth and suppressing tumour proliferation will no longer be effective.
• Maintaining a healthy body weight
  • Excessive body weight directly increases risks of pancreatic cancer
  • Body weight reduction should be gradual by healthy methods
    • Instead of starving diets or fasting, a gradual decrease in food portions is much more appropriate.
• Fostering a habit of regular exercise
  • Suitable amounts of exercise may reduce said risks
• Switching to a healthy and balanced diet
  • Consuming more vegetables, fruits and foods with low animal fat, such as fish and chicken.
• Occupational safety
  • If avoiding contact with industrial chemicals like benzene or petroleum products is not an option, adopt suitable safety measures such as using respirators and protective clothing such as suits, goggles, and gloves.

Smart patient (by Hospital Authority): Pancreatic cancer

American Society of Clinical Oncology (ASCO): Pancreatic caner

Canadian Cancer Society: Pancreatic caner

Special thanks to Mr. Joshua Tang, Ms. Maggie Wai-Yin Fung (Class M24), medical student of Li Ka Shing Faculty of Medicine, the University of Hong Kong, and Dr. Chi-Leung Chiang, Department of Clinical Oncology, the University of Hong Kong for authoring and editing this article.

Last updated on 18th Dec, 2023.