What are the other Names for this Condition? (Also known as/Synonyms)

• IPMN of Pancreas with Associated Invasive Carcinoma
• Pancreatic Intraductal Papillary Mucinous Neoplasm with Associated Invasive Carcinoma
• Pancreatic IPMN with Associated Invasive Carcinoma

What is Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma? (Definition/Background Information)

• Intraductal Papillary Mucinous Neoplasm (IPMN) of Pancreas is an exocrine, cystic tumor that grows within the pancreatic duct. IPMN cells are characterized by the secretion of mucus, and are typically located in the head region of the pancreas
• Although IPMN is benign, a percentage of tumors in this category can become cancerous. Based on the absence or presence of transition from a benign to malignant state, IPMN can be classified as:
  • Not associated with invasive carcinoma
  • With associated invasive carcinoma
• The exact cause of transition of tumor cells to Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma is unclear at the present time. In majority of cases, the transition to malignancy results in pancreatic ductal adenocarcinoma (or PDAC)
• The most common cancer arising from IPMN is the pancreatic ductal adenocarcinoma, which is the most common type of pancreatic cancer, constituting about 75% of all cancers of the pancreas
• IPMN tumors with a subsequent transition to invasive carcinoma, are more prevalent in elderly adults, typically over the age of 60 years. Although both genders may be affected, these tumor types are more frequently diagnosed in men
• A history of diabetes with insulin use, a family history of pancreatic duct adenocarcinoma, and Peutz-Jeghers syndrome, are some known risk factors for developing IPMN with Associated Invasive Carcinoma
• Based on the location of Intraductal Papillary Mucinous Neoplasm of Pancreas, the lesions can be classified as the following:
  • Main duct IPMN, which originates in the main pancreatic duct
  • Branch duct IPMN, originating from the branches of the main duct
• Individuals with Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma may be asymptomatic, or present with symptoms such as abdominal pain, back pain, jaundice, diabetes, and weight loss, among others
• Several imaging techniques, such as endoscopic ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) scans may be employed to diagnose IPMN of Pancreas, in combination with tissue biopsy
• The classification and diagnosis by the pathologist determines the course of treatment for Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma, which may include surgery, chemotherapy and radiation therapy, or a combination of the methods
• The prognosis for Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma is determined by the extent of cancer, as well as the overall health of the affected individual, and his/her response to treatment

The pancreas is an important organ of the digestive system.

• Functionally, the pancreas can be divided into 2 parts, namely:
  • Exocrine pancreas, which produces digestive enzymes, and constitute about 95% of this important organ
  • Endocrine pancreas, which secretes hormones such as insulin, glucagon, gastrin, and somatostatin. Insulin and glucagon regulate sugar levels in blood

Pancreatic tumors (benign and malignant) can arise from both the exocrine and the endocrine components of the organ. Most endocrine tumors are benign and develop at a slower rate than exocrine tumors.

• Based on the anatomy of the pancreas, it can be divided into 3 main parts, namely the:
  • Head,
  • Body, and
  • Tail

Pancreatic tumors can affect the head, body, and tail region of the pancreas. Some tumors can affect one region of the pancreas more than the other.

Who gets Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma? (Age and Sex Distribution)

• Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma occurs worldwide, in all populations (races and ethnic groups)
• IPMN affects older adults of both male and female genders. However, the condition is more prevalent in men than women

What are the Risk Factors for Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma? (Predisposing Factors)

The risk factors for developing Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma include: 

• Age 60 years or older
• Male gender
• Smoking
• Exposure to toxic chemicals
• Family history: Individuals, with one or more (immediate) family members or relatives with a history of pancreatic ductal adenocarcinoma, may have an increased risk of the condition
• The presence of certain genetic syndromes, such as Peutz-Jeghers syndrome, caused by defects in the STK11 gene

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma? (Etiology)

The exact cause of Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma is not known. The following may contribute to the development of this cancer type:

• Being diagnosed with Pancreatic Intraductal Papillary Mucinous Neoplasm
• A family history of pancreatic ductal adenocarcinoma, particularly if an individual has one or more first degree relatives who are affected
• Mutations in the STK11 gene (also known as LKB1 gene): STK11 gene codes for an enzyme, serine/threonine kinase 11. This enzyme regulates the pace of cell growth, as well as promotes cell death when needed. Mutation(s) in this gene are known to cause Peutz-Jeghers syndrome
• Mutations in the KRAS family of oncogenes, which code for proteins that play a role in regulating cell division
• p53 gene mutations - the gene plays a role in tumor suppression
• SMAD4 gene mutations - SMAD4 codes for a protein signaling molecule
• Genetic changes brought about by certain infections, or exposure to toxic chemicals via smoking and/or one’s occupation

What are the Signs and Symptoms of Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma?

The signs and symptoms of Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma may depend on the site and size of lesions. The following are some symptoms associated with IPMN of Pancreas with Associated Invasive Carcinoma:

• Anorexia (loss of appetite)
• Jaundice, manifested as yellowing of the skin and white part of the eyes
• Dark urine, also a sign of jaundice
• Pain in the upper part of the abdomen or middle of the back
• Fluid accumulation in the abdomen (ascites), abdominal swelling
• Persistent feeling of abdominal bloating with nausea or vomiting
• Feeling full soon after eating less (having a feeling of satiety after eating less)
• Changes in bowel movements, such as constipation
• Fatty stools
• The formation of blood clots in veins, swelling of legs
• Frequent urination (polyuria), excessive thirst, and blurred vision - all signs of elevated blood sugar levels in the body
• Fatigue, feeling tired easily
• Unintended weight loss
• Depression

Some other features of Pancreatic Intraductal Papillary Mucinous Neoplasm with Associated Invasive Carcinoma:

• The tumor may present as a single mass or multiple nodules within the organ
• If there is cyst formation, it may occasionally rupture, spilling its contents into the belly
• These tumors can be locally aggressive, meaning that the tumor may spread to local areas

How is Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma Diagnosed?

The diagnosis of asymptomatic Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma is often incidental. When individuals present with symptoms, the following methods may be employed to diagnose IPMN of Pancreas and to detect an invasive carcinoma:

• Physical examination and medical history evaluation: Diagnosing IPMN with Associated Invasive Carcinoma usually starts with a thorough physical examination and evaluation of complete medical history. During a physical exam, the overall health status and symptoms (such as pain, loss of appetite, and weight loss) of the affected individual are checked
• Computerized tomography (CT) scan of the pancreas: With this radiological procedure, detailed three-dimensional images of structures inside the body are created. CT scans may be also helpful in detecting recurrences, or if pancreatic cancer has metastasized to other organs
• Magnetic resonance imaging (MRI) scan of the pancreas: An MRI scan uses magnetic fields that create high-quality pictures of certain body parts, such as tissues, muscles, nerves, and bones. These high-quality images may indicate to a physician if any pancreatic ductal adenocarcinoma is present
• In addition, there are certain specific types of MRI scans that can be used in an individual who may have pancreatic cancer. Such radiological procedures include:
  • MR cholangiopancreatography (MRCP): It is a noninvasive test that uses a powerful magnetic field to produce images of soft tissues, bones, organs, and all other internal body structures
  • MR angiography (MRA): It is a noninvasive test that uses a powerful magnetic field to evaluate the blood vessels
• Endoscopic ultrasound (EUS): This is a minimally invasive procedure recommended for individuals who are suspected to have IPMN of Pancreas. An ultrasound device is inserted through a thin tube (called endoscope) down the stomach and into a part of the small intestine. It uses high-frequency sound waves to generate detailed images of the pancreas
• Endoscopic retrograde cholangiopancreatography (ERCP): A procedure used when an individual has developed symptoms of IPMN of Pancreas. An ultrasound device is inserted through a thin tube (called endoscope) down the stomach and into the first part of the small intestine. A dye is injected into the pancreas and bile ducts. The movement of the dye is followed through a series of images. A small tissue sample (biopsy) can be collected during this procedure
• Tissue biopsy: A tissue biopsy of the cyst or mass is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies, to assist in the diagnosis
  • In case of IPMN of Pancreas, the fluid inside the cysts is generally analyzed as well
• The tissue for diagnosis can be procured in multiple different ways, and they include:
  • Fine needle aspiration (FNA) biopsy of the pancreatic tumor: A FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor. Hence, a FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
  • Core biopsy of the pancreatic tumor
  • Open biopsy of the pancreatic tumor
  • Endoscopic retrograde cholangiopancreatography
• Positron emission tomography (PET): A PET scan is a nuclear medicine imaging technique that generates three-dimensional images to show how tissue and organs are functioning. A small amount of radioactive material may be injected into a vein, inhaled or swallowed. A PET scan is also helpful in detecting recurrences, or if any metastasis (to the surrounding lymph nodes of the pancreas) has occurred

A number of blood tests can also be helpful in the diagnosis pancreatic cancer or to help determine the treatment options. These may include:

• Liver function blood tests
• Blood tests that may involve tumor markers, such as carcinoembryonic antigen (CEA) and CA 19.9
• Insulin

The diagnostic tests aid in determining the extent of cancer, based on a system of classification, such as the “AJCC system for staging of pancreatic cancer”.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

Determination of type and extent of cancer:

Once a diagnosis of pancreatic cancer has been made, the extent to which the tumor has spread is assessed, known as staging. The system used most often to stage pancreatic cancer is the American Joint Committee on Cancer (AJCC) TNM system, which is based on 3 key pieces of information.

The TNM classification for different types of pancreatic cancer is given below:

Tumor extent (T):

• TX: The main tumor cannot be assessed
• T0: No evidence of a primary tumor
• Tis: Carcinoma in situ (the tumor is confined to the top layers of pancreatic duct cells). (Very few pancreatic tumors are found at this stage.)
• T1: The cancer has not grown outside the pancreas and is 2 centimeters (cm) (about ¾ inch) or less across.
• T2: The cancer has not grown outside the pancreas but is larger than 2 cm across
• T3: The cancer has grown outside the pancreas into nearby surrounding structures but not into major blood vessels or nerves
• T4: The cancer has grown beyond the pancreas into nearby large blood vessels or nerves

Lymph node spread of cancer (N):

• NX: Nearby (regional) lymph nodes cannot be assessed
• N0: The cancer has not spread to nearby lymph nodes
• N1: The cancer has spread to nearby lymph nodes

Distant spread of cancer (M):

• M0: The cancer has not spread to distant lymph nodes (other than those near the pancreas) or to distant organs such as the liver, lungs, brain, etc.
• M1: The cancer has spread to distant lymph nodes or to distant organs

Stage grouping: Once the T, N, and M categories have been assigned, this information is combined to assign an overall stage in a process called stage grouping. The stages identify tumors that have a similar outlook and are treated in a similar way.

Stage 0 (Tis, N0, M0):

• The tumor is confined to the top layers of pancreatic duct cells and has not invaded deeper tissues. It has not spread outside of the pancreas
• These tumors are sometimes referred to as pancreatic carcinoma in situ or pancreatic intraepithelial neoplasia III (PanIN III)

Stage IA (T1, N0, M0):

• The tumor is confined to the pancreas and is 2 cm across or smaller (T1)
• The cancer has not spread to nearby lymph nodes (N0) or distant sites (M0)

Stage IB (T2, N0, M0):

• The tumor is confined to the pancreas and is larger than 2 cm across (T2)
• The cancer has not spread to nearby lymph nodes (N0) or distant sites (M0)

Stage IIA (T3, N0, M0):

• The tumor is growing outside the pancreas but not into major blood vessels or nerves (T3)
• The cancer has not spread to nearby lymph nodes (N0) or distant sites (M0)

Stage IIB (T1-T3, N1, M0):

• The tumor is either confined to the pancreas or growing outside the pancreas but not into major blood vessels or nerves (T1-T3)
• The cancer has spread to nearby lymph nodes (N1) but not to distant sites (M0)

Stage III (T4, Any, N, M0):

• The tumor is growing outside the pancreas and into nearby major blood vessels or nerves (T4)
• The cancer may or may not have spread to nearby lymph nodes (Any N). It has not spread to distant sites (M0)

Stage IV (Any T, Any N, M1): The cancer has spread to distant sites (M1).

(Source: “The AJCC system for staging pancreatic cancer”; information provided by the American Cancer Society, May 2016)

What are the possible Complications of Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma?

Complications of Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma may occur with the progression of pancreatic ductal adenocarcinoma, and may include:

• Jaundice owing to biliary tract obstruction
• Abdominal pain due to tumor growth pressing on the nerves in the abdomen
• Gastrointestinal obstruction
• Diabetes, if the tumor destroys enough islet cells of the pancreas
• Weight loss
• Metastases to the liver and lymph nodes
• Abnormal fistula formation between pancreas and other abdominal organs
• Recurrence of cancer following treatment
• Side effects from the chemotherapy (such as toxicity) and radiation therapy

How is Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma Treated?

The treatment options for Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma may include the following:

• A debulking surgery to reduce the tumor mass (followed by a combination of chemotherapy and radiation therapy may be employed in some instances)
• The debulking procedure helps the chemotherapy treatment in being more effective, since there is lesser tumor mass left for the drugs to act on

Surgery for tumors located in the pancreatic head: Pancreatoduodenectomy

• A surgical procedure that involves the removal of part of the pancreas, part of the small intestine, and the gallbladder
• This procedure is typically used when the tumor is confined to the head of the pancreas
• The technique is also known as a Whipple procedure

Surgery for tumors in the pancreatic tail and body of the pancreas: Distal pancreatectomy

• A surgical procedure that involves the removal of the lower half or tail end of the pancreas
• Post-operative care is important: A minimal physical activity is advised, until the surgical wound heals

After surgical treatment and post-operative care, the attending healthcare professional/specialist may discuss the details of the cancer with the individual. Based on this, further treatment measures may be required that include:

Chemotherapy: It may be administered before or after the debulking procedure, depending on the individual’s specific circumstances.

• Chemotherapy is a treatment that uses drugs to kill cancer cells. In this treatment, a combination of two or more chemotherapy drugs is generally used
• These drugs may be administered orally (by mouth), or intravenously (through a vein in the arm)
• Chemotherapy may be used in addition to radiation therapy (chemoradiation). Chemoradiation is usually used to treat pancreatic cancers that have spread to surrounding organs, but not to distant body regions
• This combination may also be used after surgery to decrease the risk of cancer recurrence

Radiation therapy:

• Radiation therapy attempts to destroy cancer cells by aiming high-energy beams at the cancer cells
• Radiation therapy can be administered either by a machine placed outside the body (external beam radiation), or internally, by a device positioned directly at, or close to the malignant tumor
• This technique may be used before surgery, to decrease the size of a tumor, thus allowing for its easy removal; or after surgery, to kill the remaining cancer cells
• Radiation therapy and chemotherapy are sometimes used as a combination tool

Biological or targeted drug therapy:

• Targeting tumor cells while leaving healthy cells relatively unharmed is the goal of many cancer treatments
• Ongoing scientific research has yielded targeted drug therapy, wherein the unique traits of cancer cells are taken advantage of to destroy those cells

Targeted drug therapy can be effective in many ways, such as:

• Deliver toxic drugs to abnormal cells
• Block pathways that cancer cells use to proliferate without control
• Stop blood supply to actively dividing cancer cells
• Activate the immune system to fight and destroy cancer cells: Living organisms or products from living organisms may be suitably modified and used to initiate an immune response to specifically attack and destroy cancer cells
• Alter the cancer cells to trigger their cell death mechanism

The advantages of targeted therapy over conventional chemotherapy are:

• Increased concentration of medication delivered to specific target cells
• Prolonged interaction of medication with abnormal cells for effective destruction of such cells
• Decreased effect on healthy cells
• Possibly fewer side effects

One type of targeted drug therapy approved for treatment of pancreatic cancer is Erlotinib. Erlotinib is designed to disrupt the epidermal growth factor receptor (EGFR) protein on cancerous cells (located on the exterior of a cell), to arrest cell division. The drug is orally (in pill-form) administered to individuals and usually taken in combination with chemotherapy.

Follow-up care with regular screening and check-ups are important, to monitor the status of the tumor.

How can Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma be Prevented?

• At the present time, no specific methods or guidelines exist for the prevention of Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma
• If an individual is diagnosed with IPMN, and if there exists a family history of pancreatic ductal adenocarcinoma, or if an individual has Peutz-Jeghers syndrome, genetic testing to check for pertinent gene mutations may help detect malignancies early
• Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, particularly for those who have a family history of pancreatic cancer, may be helpful in diagnosing pancreatic cancer in the early stages

What is the Prognosis of Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma? (Outcomes/Resolutions)

• Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma generally results in pancreatic ductal adenocarcinoma. The prognosis of this type of pancreatic cancer is determined by:
  • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • The surgical resectability of the tumor (meaning, if the tumor can be removed completely)
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis 
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
• Typically, the overall 5-year survival rate of individuals with exocrine pancreatic cancer, such as Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma, is poor, even during the early stages of cancer development. In the majority of cases, surgery to remove the tumor is not an option due to the cancer spreading to other parts of the body

Additional and Relevant Useful Information for Intraductal Papillary Mucinous Neoplasm of Pancreas with Associated Invasive Carcinoma:

• It is estimated that the average lifetime risk of developing pancreatic cancer is about 1 in 67 (1.5%)
• Individuals can reduce their risk of developing pancreatic cancer through lifestyle or behavioral changes 
• Several clinical trials are ongoing or scheduled for targeted drug therapy. Information may be found on www.clinicaltrials.gov