Familial pancreatic cancer

Familial pancreatic cancer is a term to describe families with a high rate of pancreatic cancer or families with a clustering of pancreatic cancer diagnoses. Families are considered to have familial pancreatic cancer if there are at least 2 members of the family with pancreatic cancer who are first-degree relatives, such as a parent, child, or siblings of one another, or if there are at least 3 members of the family who have pancreatic cancer. Healthy individuals who come from a family with familial pancreatic cancer are likely to have an increased risk of developing pancreatic cancer in their lifetime.

At this time, there is no specific test for familial pancreatic cancer. Families are considered to have familial pancreatic cancer if there are:

• 2 or more members of a family who are first-degree relatives, such as parents, children, or siblings, who have been diagnosed with pancreatic cancer, or
• 3 or more close relatives from the same side of the family who have been diagnosed with pancreatic cancer.

If you have symptoms of pancreatic cancer, talk with your doctor. They will perform a physical exam and ask you about your medical history. Your doctor will also recommend specific tests to help find pancreatic cancer.

An estimated 57,600 adults (30,400 men and 27,200 women) in the United States will be diagnosed with pancreatic cancer. About 10% of those cases are thought to be caused by familial pancreatic cancer.

Figure 1. Pancreas anatomy

Figure 2. Pancreas location

Figure 3. Pancreas cell types

Familial pancreatic cancer causes

Individuals from familial pancreatic cancer families should consider genetic testing to see if there is a specific germline genetic mutation that may have caused the pancreatic cancers in their family. A germline mutation is a genetic mutation found in every cell of a person’s body from birth. Some genes linked to familial pancreatic cancer families include BRCA1, BRCA2, PALB2, CDKN2A, and ATM, and the genes linked to Lynch syndrome (MLH1, MSH2, MSH6, PMS2, and EPCAM). Germline mutations in genes that cause other rare inherited cancer syndromes (TP53 mutations in Li-Fraumeni syndrome and STK11 mutations for Peutz-Jeghers syndrome) can also increase the risk of pancreatic cancer. Individuals who carry germline genetic mutations in these genes are at an increased risk of pancreatic cancer as well as other types of cancers. Genetic testing for these genes is available, but your decision to have genetic testing should be discussed carefully with a medical professional with expertise in this area.

It is important to note that genetic testing is still evolving, and only 10% to 20% of families with familial pancreatic cancer will have a mutation identified by genetic testing. Currently, most families with familial pancreatic cancer will have normal genetic testing results, suggesting that the genes responsible for most familial pancreatic cancer families have not yet been discovered. Researchers continue to search for other specific genes that may be linked to familial pancreatic cancer. Since most familial pancreatic cancer families will have normal genetic testing results, it is important to realize that individuals from familial pancreatic cancer families are still at an increased risk of pancreatic cancer, even when genetic testing results are normal. Talk with a genetic counselor before you have any genetic testing.

Familial pancreatic cancer inheritance pattern

Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. Researchers think that familial pancreatic cancer typically follows an autosomal dominant inheritance pattern, even though the specific genes that cause familial pancreatic cancer are mostly unknown. In autosomal dominant inheritance, a mutation happens in only 1 copy of the gene. This means that a parent with a gene mutation may pass along a copy of their normal gene. Or, that parent may pass along a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation. However, if the parents test negative for the mutation (meaning each person’s test results found no mutation), the risk to the siblings significantly decreases but their risk may still be higher than an average risk.

Options exist for people interested in having a child when a prospective parent carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to reduce the likelihood that their children will inherit the condition. A woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos which do not have the mutation. Preimplantation genetic diagnosis has been in use for over 2 decades and has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.

Figure 4. Familial pancreatic cancer autosomal dominant inheritance pattern

Genetic counseling and testing

If you’ve been diagnosed with pancreatic cancer, your doctor might suggest speaking with a genetic counselor to determine if you could benefit from genetic testing.

Some people with pancreatic cancer have gene mutations (such as BRCA mutations) in all the cells of their body, which put them at increased risk for pancreatic cancer (and possibly other cancers). Testing for these gene mutations can sometimes affect which treatments might be helpful. It might also affect whether other family members should consider genetic counseling and testing as well.

People with specific questions about genetic risks or genetic testing for themselves or family members should speak with a genetics professional.

Resources for locating a genetics professional in your community are available online:

• The National Society of Genetic Counselors (https://www.findageneticcounselor.com/) offers a searchable directory of genetic counselors in the United States and Canada. You can search by location, name, area of practice/specialization, and/or ZIP Code.
• The American Board of Genetic Counseling (https://www.abgc.net/about-genetic-counseling/find-a-certified-counselor/) provides a searchable directory of certified genetic counselors worldwide. You can search by practice area, name, organization, or location.
• The Canadian Association of Genetic Counselors (https://www.cagc-accg.ca/index.php?page=225) has a searchable directory of genetic counselors in Canada. You can search by name, distance from an address, province, or services.
• The American College of Medical Genetics and Genomics (http://www.acmg.net/ACMG/Genetic_Services_Directory_Search.aspx) has a searchable database of medical genetics clinic services in the United States.

What are the estimated cancer risks associated with familial pancreatic cancer?

The lifetime risk of pancreatic cancer for the average individual without a family history of pancreatic cancer is approximately 1%. Individuals with a family history of pancreatic cancer are at an increased lifetime risk for developing pancreatic cancer. This risk is likely higher for individuals from a family with familial pancreatic cancer. The following cancer risk estimates are generalized and should be interpreted with caution since the actual risk for each individual may be different:

• Individuals from familial pancreatic cancer families who have 1 first-degree relative, meaning a parent, sibling, or child, with pancreatic cancer are estimated to have an increased lifetime risk of pancreatic cancer that is 3 to 5 times higher than the general population.
• Individuals from familial pancreatic cancer families who have 2 first-degree relatives with pancreatic cancer are estimated to have an increased lifetime risk of pancreatic cancer that is 5 to 7 times higher than the general population.
• Individuals from familial pancreatic cancer families who have 3 or more first-degree relatives with pancreatic cancer are estimated to have an increased lifetime risk of pancreatic cancer that may be up to 30 times higher than the general population.

Individuals who carry germline mutations in known genes linked to pancreatic cancer risk (BRCA1, BRCA2, PALB2, CDKN2A, ATM, TP53, STK11, MLH1, MSH2, MSH6, PMS2, and EPCAM) are also at an increased risk of various cancers, including pancreatic cancer. For individuals with a mutation in 1 of these genes, the risk of pancreatic cancer may be particularly higher if there is also a history of pancreatic cancer in the family. Recent studies have found that 4% to 10% of individuals with pancreatic cancer will have a mutation in 1 of these genes. Individuals with pancreatic cancer who are of Ashkenazi Jewish ancestry are even more likely to carry 1 of these genetic mutations. Some national guidelines now recommend genetic testing for any person diagnosed with pancreatic cancer, regardless of their family history of cancer or age at diagnosis.

Tobacco use increases an individual’s lifetime risk of pancreatic cancer, regardless of their family history. Tobacco use may significantly increase the risk of pancreatic cancer for individuals from familial pancreatic cancer families.

Familial pancreatic cancer signs and symptoms

Early pancreatic cancers often do not cause any signs or symptoms. By the time they do cause symptoms, they have often grown very large or already spread outside the pancreas.

Having one or more of the symptoms below does not mean you have pancreatic cancer. In fact, many of these symptoms are more likely to be caused by other conditions. Still, if you have any of these symptoms, it’s important to have them checked by a doctor so that the cause can be found and treated, if needed.

Jaundice and related symptoms

Jaundice is yellowing of the eyes and skin. Most people with pancreatic cancer and nearly all people with ampullary cancer will have jaundice as one of their first symptoms.

Jaundice is caused by the buildup of bilirubin, a dark yellow-brown substance made in the liver. Normally, the liver releases a liquid called bile that contains bilirubin. Bile goes through the common bile duct into the intestines, where it helps break down fats. It eventually leaves the body in the stool. When the common bile duct becomes blocked, bile can’t reach the intestines, and the amount of bilirubin in the body builds up.

Cancers that start in the head of the pancreas are near the common bile duct. These cancers can press on the duct and cause jaundice while they are still fairly small, which can sometimes lead to these tumors being found at an early stage. But cancers that start in the body or tail of the pancreas don’t press on the duct until they have spread through the pancreas. By this time, the cancer has often spread beyond the pancreas.

When pancreatic cancer spreads, it often goes to the liver. This can also cause jaundice.

There are other signs of jaundice as well as the yellowing of the eyes and skin:

• Dark urine: Sometimes, the first sign of jaundice is darker urine. As bilirubin levels in the blood increase, the urine becomes brown in color.
• Light-colored or greasy stools: Bilirubin normally helps give stools their brown color. If the bile duct is blocked, stools might be light-colored or gray. Also, if bile and pancreatic enzymes can’t get through to the intestines to help break down fats, the stools can become greasy and might float in the toilet.
• Itchy skin: When bilirubin builds up in the skin, it can start to itch as well as turn yellow.

Pancreatic cancer is not the most common cause of jaundice. Other causes, such as gallstones, hepatitis, and other liver and bile duct diseases, are much more common.

Belly or back pain

Pain in the abdomen (belly) or back is common in pancreatic cancer. Cancers that start in the body or tail of the pancreas can grow fairly large and start to press on other nearby organs, causing pain. The cancer may also spread to the nerves surrounding the pancreas, which often causes back pain. Pain in the abdomen or back is fairly common and is most often caused by something other than pancreatic cancer.

Weight loss and poor appetite

Unintended weight loss is very common in people with pancreatic cancer. These people often have little or no appetite.

Nausea and vomiting

If the cancer presses on the far end of the stomach it can partly block it, making it hard for food to get through. This can cause nausea, vomiting, and pain that tend to be worse after eating.

Gallbladder or liver enlargement

If the cancer blocks the bile duct, bile can build up in the gallbladder, making it larger. Sometimes a doctor can feel this (as a large lump under the right side of the ribcage) during a physical exam. It can also be seen on imaging tests.

Pancreatic cancer can also sometimes enlarge the liver, especially if the cancer has spread there. The doctor might be able to feel the edge of the liver below the right ribcage on an exam, or the large liver might be seen on imaging tests.

Blood clots

Sometimes, the first clue that someone has pancreatic cancer is a blood clot in a large vein, often in the leg. This is called a deep vein thrombosis or DVT. Symptoms can include pain, swelling, redness, and warmth in the affected leg. Sometimes a piece of the clot can break off and travel to the lungs, which might make it hard to breathe or cause chest pain. A blood clot in the lungs is called a pulmonary embolism or PE.

Still, having a blood clot does not usually mean that you have cancer. Most blood clots are caused by other things.

Diabetes

Rarely, pancreatic cancers cause diabetes (high blood sugar) because they destroy the insulin-making cells. Symptoms can include feeling thirsty and hungry, and having to urinate often. More often, cancer can lead to small changes in blood sugar levels that don’t cause symptoms of diabetes but can still be detected with blood tests.

Pancreatic cancer complications

As pancreatic cancer progresses, it can cause complications such as:

• Weight loss. A number of factors may cause weight loss in people with pancreatic cancer. The cancer itself may cause weight loss. Nausea and vomiting caused by cancer treatments or a tumor pressing on your stomach may make it difficult to eat. Or your body may have difficulty processing nutrients from food because your pancreas isn’t making enough digestive juices. Your doctor may recommend pancreatic enzyme supplements to aid in digestion. Try to maintain your weight by adding extra calories where you can and making mealtime as pleasant and relaxed as possible.
• Jaundice. Pancreatic cancer that blocks the liver’s bile duct can cause jaundice. Signs include yellow skin and eyes, dark-colored urine, and pale-colored stools. Jaundice usually occurs without abdominal pain. Your doctor may recommend that a plastic or metal tube (stent) be placed inside the bile duct to hold it open. This is done with the help of a procedure called endoscopic retrograde cholangiopancreatography (ERCP) (see Figure 5). During ERCP an endoscope is passed down your throat, through your stomach and into the upper part of your small intestine. A dye is then injected into the pancreatic and bile ducts through a small hollow tube (catheter) that’s passed through the endoscope. Finally, images are taken of the ducts.
• Pain. A growing tumor may press on nerves in your abdomen, causing pain that can become severe. Pain medications can help you feel more comfortable. Radiation therapy might help stop tumor growth temporarily to give you some relief. In severe cases, your doctor might recommend a procedure to inject alcohol into the nerves that control pain in your abdomen (celiac plexus block). This procedure stops the nerves from sending pain signals to your brain.
• Bowel obstruction. Pancreatic cancer that grows into or presses on the first part of the small intestine (duodenum) can block the flow of digested food from your stomach into your intestines. Your doctor may recommend a tube (stent) be placed in your small intestine to hold it open. Or surgery may be necessary to attach your stomach to a lower point in your intestines that isn’t blocked by cancer.

Figure 5. Endoscopic retrograde cholangiopancreatography (ERCP)

Footnote: Endoscopic retrograde cholangiopancreatography (ERCP) uses a dye to highlight the bile ducts on X-ray images. A thin, flexible tube (endoscope) with a camera on the end is passed down your throat and into your small intestine. The dye enters the ducts through a small hollow tube (catheter) passed through the endoscope.

Familial pancreatic cancer diagnosis

If a person has signs and symptoms that might be caused by pancreatic cancer, certain exams and tests will be done to find the cause. If cancer is found, more tests will be done to help determine the extent (stage) of the cancer.

Medical history and physical exam

Your doctor will ask about your medical history to learn more about your symptoms. The doctor might also ask about possible risk factors, including smoking and your family history.

Your doctor will also examine you to look for signs of pancreatic cancer or other health problems. Pancreatic cancers can sometimes cause the liver or gallbladder to swell, which the doctor might be able to feel during the exam. Your skin and the whites of your eyes will also be checked for jaundice (yellowing).

If the results of the exam are abnormal, your doctor will probably order tests to help find the problem. You might also be referred to a gastroenterologist (a doctor who treats digestive system diseases) for further tests and treatment.

Imaging tests

Imaging tests use x-rays, magnetic fields, sound waves, or radioactive substances to create pictures of the inside of your body. Imaging tests might be done for a number of reasons both before and after a diagnosis of pancreatic cancer, including:

• To look for suspicious areas that might be cancer
• To learn how far cancer may have spread
• To help determine if treatment is working
• To look for signs of cancer coming back after treatment

Computed tomography (CT) scan

The CT scan makes detailed cross-sectional images of your body. CT scans are often used to diagnose pancreatic cancer because they can show the pancreas fairly clearly. They can also help show if cancer has spread to organs near the pancreas, as well as to lymph nodes and distant organs. A CT scan can help determine if surgery might be a good treatment option.

If your doctor thinks you might have pancreatic cancer, you might get a special type of CT known as a multiphase CT scan or a pancreatic protocol CT scan. During this test, different sets of CT scans are taken over several minutes after you get an injection of an intravenous (IV) contrast.

CT-guided needle biopsy: CT scans can also be used to guide a biopsy needle into a suspected pancreatic tumor. But if a needle biopsy is needed, most doctors prefer to use endoscopic ultrasound (described below) to guide the needle into place.

Magnetic resonance imaging (MRI)

MRI scans use radio waves and strong magnets instead of x-rays to make detailed images of parts of your body. Most doctors prefer to look at the pancreas with CT scans, but an MRI might also be done.

Special types of MRI scans can also be used in people who might have pancreatic cancer or are at high risk:

• MR cholangiopancreatography (MRCP), which can be used to look at the pancreatic and bile ducts, is described below in the section on cholangiopancreatography.
• MR angiography (MRA), which looks at blood vessels, is mentioned below in the section on angiography.

Ultrasound

Ultrasound (US) tests use sound waves to create images of organs such as the pancreas. The two most commonly used types for pancreatic cancer are:

• Abdominal ultrasound: If it’s not clear what might be causing a person’s abdominal symptoms, this might be the first test done because it is easy to do and it doesn’t expose a person to radiation. But if signs and symptoms are more likely to be caused by pancreatic cancer, a CT scan is often more useful.
• Endoscopic ultrasound (EUS): This test is more accurate than abdominal US and can be very helpful in diagnosing pancreatic cancer. This test is done with a small US probe on the tip of an endoscope, which is a thin, flexible tube that doctors use to look inside the digestive tract and to get biopsy samples of a tumor.

Cholangiopancreatography

This is an imaging test that looks at the pancreatic ducts and bile ducts to see if they are blocked, narrowed, or dilated. These tests can help show if someone might have a pancreatic tumor that is blocking a duct. They can also be used to help plan surgery. The test can be done in different ways, each of which has pros and cons.

Endoscopic retrograde cholangiopancreatography (ERCP): For this test, an endoscope (a thin, flexible tube with a tiny video camera on the end) is passed down the throat, through the esophagus and stomach, and into the first part of the small intestine. The doctor can see through the endoscope to find the ampulla of Vater (where the common bile duct empties into the small intestine).

X-rays taken at this time can show narrowing or blockage in these ducts that might be due to pancreatic cancer. The doctor doing this test can put a small brush through the tube to remove cells for a biopsy or place a stent (small tube) into a bile or pancreatic duct to keep it open if a nearby tumor is pressing on it.

Magnetic resonance cholangiopancreatography (MRCP): This is a non-invasive way to look at the pancreatic and bile ducts using the same type of machine used for standard MRI scans. Unlike ERCP, it does not require an infusion of a contrast dye. Because this test is non-invasive, doctors often use MRCP if the purpose is just to look at the pancreatic and bile ducts. But this test can’t be used to get biopsy samples of tumors or to place stents in ducts.

Percutaneous transhepatic cholangiography (PTC): In this procedure, the doctor puts a thin, hollow needle through the skin of the belly and into a bile duct within the liver. A contrast dye is then injected through the needle, and x-rays are taken as it passes through the bile and pancreatic ducts. As with ERCP, this approach can also be used to take fluid or tissue samples or to place a stent into a duct to help keep it open. Because it is more invasive (and might cause more pain), PTC is not usually used unless ERCP has already been tried or can’t be done for some reason.

Positron emission tomography (PET) scan

For a PET scan, you are injected with a slightly radioactive form of sugar, which collects mainly in cancer cells. A special camera is then used to create a picture of areas of radioactivity in the body.

This test is sometimes used to look for spread from exocrine pancreatic cancers.

PET/CT scan: Special machines can do both a PET and CT scan at the same time. This lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT scan. This test can help determine the stage (extent) of the cancer. It might be especially useful for spotting cancer that has spread beyond the pancreas and wouldn’t be treatable by surgery.

Angiography

This is an x-ray test that looks at blood vessels. A small amount of contrast dye is injected into an artery to outline the blood vessels, and then x-rays are taken.

An angiogram can show if blood flow in a particular area is blocked by a tumor. It can also show abnormal blood vessels (feeding the cancer) in the area. This test can be useful in finding out if a pancreatic cancer has grown through the walls of certain blood vessels. Mainly, it helps surgeons decide if the cancer can be removed completely without damaging vital blood vessels, and it can also help them plan the operation.

X-ray angiography can be uncomfortable because the doctor has to put a small catheter into the artery leading to the pancreas. Usually the catheter is put into an artery in your inner thigh and threaded up to the pancreas. A local anesthetic is often used to numb the area before inserting the catheter. Once the catheter is in place, the dye is injected to outline all the vessels while the x-rays are being taken.

Angiography can also be done with a CT scanner (CT angiography) or an MRI scanner (MR angiography). These techniques are now used more often because they can give the same information without the need for a catheter in the artery. You might still need an IV line so that a contrast dye can be injected into the bloodstream during the imaging.

Blood tests

Several types of blood tests can be used to help diagnose pancreatic cancer or to help determine treatment options if it is found.

Liver function tests: Jaundice (yellowing of the skin and eyes) is often one of the first signs of pancreatic cancer. Doctors often get blood tests to assess liver function in people with jaundice to help determine its cause. Certain blood tests can look at levels of different kinds of bilirubin (a chemical made by the liver) and can help tell whether a patient’s jaundice is caused by disease in the liver itself or by a blockage of bile flow (from a gallstone, a tumor, or other disease).

Tumor markers: Tumor markers are substances that can sometimes be found in the blood when a person has cancer. Tumor markers that may be helpful in pancreatic cancer are:

• CA 19-9. CA 19-9 is a tumor marker that may be helpful in pancreatic cancer. A drop in the CA 19-9 level after surgery (compared to the level before surgery) and low levels of CA 19-9 after pancreas surgery tend to predict a better prognosis (outlook).
• Carcinoembryonic antigen (CEA), which is not used as often as CA 19-9

Neither of these tumor marker tests is accurate enough to tell for sure if someone has pancreatic cancer. Levels of these tumor markers are not high in all people with pancreatic cancer, and some people who don’t have pancreatic cancer might have high levels of these markers for other reasons. Still, these tests can sometimes be helpful, along with other tests, in figuring out if someone has cancer.

In people already known to have pancreatic cancer and who have high CA19-9 or CEA levels, these levels can be measured over time to help tell how well treatment is working. If all of the cancer has been removed, these tests can also be done to look for signs the cancer may be coming back.

Other blood tests: Other tests, like a complete blood count (CBC) or chemistry panel, can help evaluate a person’s general health (such as kidney and bone marrow function). These tests can help determine if they’ll be able to withstand the stress of a major operation.

Biopsy

A person’s medical history, physical exam, and imaging test results may strongly suggest pancreatic cancer, but usually the only way to be sure is to remove a small sample of tumor and look at it under the microscope. This procedure is called a biopsy. Biopsies can be done in different ways.

Percutaneous (through the skin) biopsy: For this test, a doctor inserts a thin, hollow needle through the skin over the abdomen and into the pancreas to remove a small piece of a tumor. This is known as a fine needle aspiration (FNA). The doctor guides the needle into place using images from ultrasound or CT scans.

Endoscopic biopsy: Doctors can also biopsy a tumor during an endoscopy. The doctor passes an endoscope (a thin, flexible, tube with a small video camera on the end) down the throat and into the small intestine near the pancreas. At this point, the doctor can either use endoscopic ultrasound (EUS) to pass a needle into the tumor or endoscopic retrograde cholangiopancreatography (ERCP) to place a brush to remove cells from the bile or pancreatic ducts.

Surgical biopsy: Surgical biopsies are now done less often than in the past. They can be useful if the surgeon is concerned the cancer has spread beyond the pancreas and wants to look at (and possibly biopsy) other organs in the abdomen. The most common way to do a surgical biopsy is to use laparoscopy (sometimes called keyhole surgery). The surgeon can look at the pancreas and other organs for tumors and take biopsy samples of abnormal areas.

Some people might not need a biopsy

Rarely, the doctor might not do a biopsy on someone who has a tumor in the pancreas if imaging tests show the tumor is very likely to be cancer and if it looks like surgery can remove all of it. Instead, the doctor will proceed with surgery, at which time the tumor cells can be looked at in the lab to confirm the diagnosis. During surgery, if the doctor finds that the cancer has spread too far to be removed completely, only a sample of the cancer may be removed to confirm the diagnosis, and the rest of the planned operation will be stopped.

If treatment (such as chemotherapy or radiation) is planned before surgery, a biopsy is needed first to be sure of the diagnosis.

Lab tests of biopsy samples

The samples obtained during a biopsy (or during surgery) are sent to a lab, where they are looked at under a microscope to see if they contain cancer cells.

If cancer is found, other tests might be done as well. For example, tests might be done to see if the cancer cells have mutations (changes) in certain genes, such as the BRCA genes (BRCA1 or BRCA2) or NTRK genes. This might affect whether certain targeted therapy drugs might be helpful as part of treatment.

Genetic testing for pancreatic cancer risk

It is unknown if screening for pancreatic cancer is effective, and there is no routine screening for pancreatic cancer that is currently recommended for the general population. The medical community continues to research who to screen, which tests to use, and how often to use them.

Given that individuals from familial pancreatic cancer families, or individuals with germline genetic mutations in BRCA1, BRCA2, PALB2, CDKN2A, ATM, MLH1, MSH2, MSH6, PMS2, STK11, and EPCAM, are at increased risk for pancreatic cancer, there is special interest in researching pancreatic cancer screening for these high-risk individuals. It’s important to talk with your doctor about the screening options below, as each person is different.

Current guidelines recommend that healthy individuals from familial pancreatic cancer families should consider pancreatic cancer screening beginning at age 50, or 10 years younger than the earliest pancreatic cancer diagnosis in the family, if at least 1 of the pancreatic cancers in their family was in a first-degree relative. Guidelines also recommend that individuals with germline mutations in the genes listed above should consider screening beginning at age 50, or 10 years younger than the earliest pancreatic cancer diagnosis in the family, if they have a family history of pancreatic cancer. Some experts have recommended that all individuals with germline mutations in STK11 (which causes Peutz-Jeghers syndrome) or CDKN2A (which causes familial atypical multiple mole melanoma [FAMMM] syndrome), have screening regardless of their family history, with Peutz-Jeghers syndrome patients being recommended to begin screening at age 30 to 35 and FAMMM syndrome patients being recommended to begin by age 40. The screening tests that are most commonly used include:

• Magnetic resonance imaging (MRI) – An MRI uses magnetic fields to produce detailed images of the pancreas.
• Endoscopic ultrasound (EUS) – A thin, lighted tube is passed through the patient’s mouth and stomach. The tube goes down into the small intestine to take a picture of the pancreas.

Screening options are likely to change over time as new technologies are developed and more is learned about familial pancreatic cancer. It’s important to talk with your doctor about screening tests that are right for you.

Pancreatic cancer staging

After someone is diagnosed with pancreatic cancer, doctors will try to figure out if it has spread, and if so, how far. This process is called staging. The stage of a cancer describes how much cancer is in the body. It helps determine how serious the cancer is and how best to treat it. Doctors also use a cancer’s stage when talking about survival statistics and to help them decide on treatment.

The earliest stage pancreas cancers are stage 0 (carcinoma in situ), and then range from stages I (1) through IV (4). As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage IV, means a more advanced cancer. Cancers with similar stages tend to have a similar outlook and are often treated in much the same way.

The staging system used most often for pancreatic cancer is the American Joint Committee on Cancer (AJCC) TNM system, which is based on 3 key pieces of information:

• The extent of the tumor (T): How large is the tumor and has it grown outside the pancreas into nearby blood vessels?
• The spread to nearby lymph nodes (N): Has the cancer spread to nearby lymph nodes? If so, how many of the lymph nodes have cancer?
• The spread (metastasized) to distant sites (M): Has the cancer spread to distant lymph nodes or distant organs such as the liver, peritoneum (the lining of the abdominal cavity), lungs or bones?

The system described below is the most recent American Joint Committee on Cancer TNM system, effective January 2018. It is used to stage most pancreatic cancers except for well-differentiated pancreatic neuroendocrine tumors (NETs), which have their own staging system.

The staging system in the table uses the pathologic stage. It is determined by examining tissue removed during an operation. This is also known as the surgical stage. Sometimes, if the doctor’s physical exam, imaging, or other tests show the tumor is too large or has spread to nearby organs and cannot be removed by surgery right away or at all, radiation or chemotherapy might be given first. In this case, the cancer will have a clinical stage. It is based on the results of physical exam, biopsy, and imaging tests. The clinical stage can be used to help plan treatment. Sometimes, though, the cancer has spread further than the clinical stage estimates, and may not predict the patient’s outlook as accurately as a pathologic stage. For more information, see Cancer Staging.

Numbers or letters after T, N, and M provide more details about each of these factors. Higher numbers mean the cancer is more advanced. Once a person’s T, N, and M categories have been determined, this information is combined in a process called stage grouping to assign an overall stage.

Cancer staging can be complex. If you have any questions about your stage, please ask your doctor to explain it to you in a way you understand. (Additional information of the TNM system also follows the stage table below.)

Table 1. Stages of pancreatic cancer

Footnotes: * The following additional categories are not listed on the table above:

• TX: Main tumor cannot be assessed due to lack of information.
• T0: No evidence of a primary tumor.
• NX: Regional lymph nodes cannot be assessed due to lack of information.

Stage 0 pancreatic cancer

Stage 0 pancreatic cancer is also called carcinoma in situ, this means the cancer is confined to the top layers of pancreatic duct cells and has not invaded deeper tissues. The cancer has not spread outside of the pancreas to nearby lymph nodes (N0) or to distant sites (M0).

Stage 1 pancreatic cancer

Stage 1 pancreatic cancer means the cancer is not more than 4cm in size and it hasn’t spread outside the pancreas. Stage 1 pancreatic cancer is divided into 1A and 1B.

• Stage 1A pancreatic cancer means the cancer is completely inside the pancreas and is 2cm or less. There is no cancer in the lymph nodes Open a glossary item or other areas of the body. In TNM staging, this is the same as T1, N0, M0.
• Stage 1B pancreatic cancer means the cancer is completely inside the pancreas and is larger than 2cm but no bigger than 4cm. There is no cancer in the lymph nodes or other areas of the body. In TNM staging, this is the same as T2, N0, M0.

Stage 2 pancreatic cancer

Stage 2 pancreatic cancer is divided into into 2A and 2B:

• Stage 2A pancreatic cancer means the cancer is bigger than 4 cm but is still within the pancreas. It has not spread to the lymph nodes Open a glossary item or other areas of the body. In TNM staging, this is the same as T3, N0, M0.
• Stage 2B pancreatic cancer means the cancer is any size within the pancreas and has spread to no more than 3 nearby lymph nodes. It has not spread anywhere else in the body. In TNM staging, this is the same as T1, 2 or 3, N1, M0.

Stage 3 pancreatic cancer

Stage 3 pancreatic cancer is also called locally advanced cancer.

• Stage 3 pancreatic cancer can mean that the cancer is any size within the pancreas and has spread to 4 or more nearby lymph nodes. In TNM staging, this is the same as T1, 2 or 3, N2, M0.
• OR
• Stage 3 pancreatic cancer can also mean the cancer has started to grow outside the pancreas into the major blood vessels nearby. It may or may not have spread into the lymph nodes. It hasn’t spread to any other areas of the body. In TNM staging, this is the same as T4, Any N, M0.

Stage 4 pancreatic cancer

Stage 4 pancreatic cancer is also called advanced (metastatic) cancer, this means that the cancer has spread to other areas of the body, such as the liver or lungs. In TNM staging, this is the same as Any T, Any N, M1.

Other prognostic factors

Although not formally part of the TNM system, other factors are also important in determining a person’s prognosis (outlook).

Tumor grade

The grade describes how closely the cancer looks like normal tissue under a microscope.

• Grade 1 (G1) means the cancer looks much like normal pancreas tissue.
• Grade 3 (G3) means the cancer looks very abnormal.
• Grade 2 (G2) falls somewhere in between.

Low-grade cancers (G1) tend to grow and spread more slowly than high-grade (G3) cancers. Most of the time, Grade 3 pancreas cancers tend to have a poor prognosis (outlook) compared to Grade 1 or 2 cancers.

Extent of resection

For patients who have surgery, another important factor is the extent of the resection — whether or not all of the tumor is removed:

• R0: All of the cancer is thought to have been removed. (There are no visible or microscopic signs suggesting that cancer was left behind.)
• R1: All visible tumor was removed, but lab tests of the removed tissue show that some small areas of cancer were probably left behind.
• R2: Some visible tumor could not be removed.

Resectable versus unresectable pancreatic cancer

The AJCC staging system gives a detailed summary of how far the cancer has spread. But for treatment purposes, doctors use a simpler staging system, which divides cancers into groups based on whether or not they can be removed (resected) with surgery:

• Resectable
• Borderline resectable
• Unresectable (either locally advanced or metastatic)

Resectable

If the cancer is only in the pancreas (or has spread just beyond it) and the surgeon believes the entire tumor can be removed, it is called resectable. In general, this would include most stage IA, IB, and IIA cancers in the TNM system.

It’s important to note that some cancers might appear to be resectable based on imaging tests, but once surgery is started it might become clear that not all of the cancer can be removed. If this happens, only some of the cancer may be removed to confirm the diagnosis (if a biopsy hasn’t been done already), and the rest of the planned operation will be stopped to help avoid the risk of major side effects.

Borderline resectable

This term is used to describe some cancers that might have just reached nearby blood vessels, but which the doctors feel might still be removed completely with surgery.

Unresectable

These cancers can’t be removed entirely by surgery.

Locally advanced: If the cancer has not yet spread to distant organs but it still can’t be removed completely with surgery, it is called locally advanced. Often the reason the cancer can’t be removed is because it has grown into or surrounded nearby major blood vessels. (This would include some stage III cancers in the TNM system.)

Surgery to try to remove these tumors would be very unlikely to be helpful and could still have major side effects. Some type of surgery might still be done, but it would be a less extensive operation with the goal of preventing or relieving symptoms or problems like a blocked bile duct or intestinal tract, instead of trying to cure the cancer.

Metastatic: If the cancer has spread to distant organs, it is called metastatic (Stage IV). These cancers can’t be removed completely. Surgery might still be done, but the goal would be to prevent or relieve symptoms, not to try to cure the cancer.

Familial pancreatic cancer treatment

Treatment for pancreatic cancer depends on the stage and location of the cancer as well as on your overall health and personal preferences. For most people, the first goal of pancreatic cancer treatment is to eliminate the cancer, when possible. When that isn’t an option, the focus may be on improving your quality of life and preventing the cancer from growing or causing more harm.

Depending on the type and stage of the cancer and other factors, treatment options for people with pancreatic cancer can include:

• Surgery
• Ablation or Embolization
• Radiation Therapy
• Chemotherapy
• Targeted Therapy
• Immunotherapy
• Palliative care

Treatment may include surgery, radiation, chemotherapy or a combination of these. When pancreatic cancer is advanced and these treatments aren’t likely to offer a benefit, your doctor will offer symptom relief (palliative care) that makes you as comfortable as possible.

Deciding which treatment you need

To decide about what treatment you need, your healthcare team looks at your test and scan results to see if they can remove (resect) the cancer. Your cancer may be:

• Resectable, which means pancreatic cancer can be removed with surgery. Generally, stage 1 and 2 pancreatic cancers are resectable.
• Borderline resectable, which means the cancer is right next to a main blood vessel and so it is less clear if surgery is possible. You may have chemotherapy first to shrink the cancer.
• Unresectable, which means that surgery to remove the cancer is not possible. The cancer may have grown into nearby organs (locally advanced cancer) or to more distant areas of the body (metastatic cancer).

Pancreatic cancer surgery

The type of surgery you need depends on where the cancer is in your pancreas.

To find out if it might be possible to remove the cancer, your surgeon will look at:

• the size of the tumor
• where it is in the pancreas
• whether the cancer has grown into the tissues around the pancreas
• whether the cancer is in any of the lymph nodes around the pancreas
• whether the cancer has grown into the major blood vessels in or around the pancreas
• whether the cancer has spread to any other parts of the body

To determine which type of surgery might be best, it’s important to know the stage (extent) of the cancer. But it can be hard to stage pancreatic cancer accurately just using imaging tests. Sometimes laparoscopy is done first to help determine the extent of the cancer and if it can be resected.

For this procedure, the surgeon makes a few small incisions (cuts) in the abdomen (belly) and inserts long, thin instruments. One of these has a small video camera on the end so the surgeon can see inside the abdomen and look at the pancreas and other organs. Biopsy samples of tumors and other abnormal areas can show how far the cancer has spread.

Two general types of surgery can be used for pancreatic cancer:

1. Potentially curative surgery is used when the results of exams and tests suggest that it’s possible to remove (resect) all the cancer.
2. Palliative surgery may be done if tests show that the cancer is too widespread to be removed completely. This surgery is done to relieve symptoms or to prevent certain complications like a blocked bile duct or intestine, but the goal is not to cure the cancer.

If it is possible to remove your cancer your surgeon might suggest a:

• Total pancreatectomy. Your surgeon removes all your pancreas. You can live relatively normally without a pancreas but do need lifelong insulin and enzyme replacement.
• Distal pancreatectomy. Your surgeon removes the body and tail of your pancreas. Your surgeon may also remove your spleen.
• Pylorus preserving pancreaticduodenectomy (PPPD). A PPPD operation means removing:
  • the head of your pancreas
  • the duodenum – the first part of the small bowel (intestine)
  • gallbladder
  • part of the bile duct
• Kausch Whipple operation also called Whipple procedure is the same as a pylorus preserving pancreaticduodenectomy (PPPD) operation but you also have part of your stomach removed.
• Surgery for tumors affecting nearby blood vessels. Many people with advanced pancreatic cancer are not considered eligible for the Whipple procedure or other pancreatic surgeries if their tumors involve nearby blood vessels. At a very few medical centers in the United States, highly specialized and experienced surgeons will safely perform these operations with removal and reconstruction of parts of blood vessels in select patients.

Each of these surgeries carries the risk of bleeding and infection. After surgery some people experience nausea and vomiting if the stomach has difficulty emptying (delayed gastric emptying). Expect a long recovery after any of these procedures. You’ll spend several days in the hospital and then recover for several weeks at home.

Extensive research shows pancreatic cancer surgery tends to cause fewer complications when done by highly experienced surgeons at centers that do many of these operations. Don’t hesitate to ask about your surgeon’s and hospital’s experience with pancreatic cancer surgery. If you have any doubts, get a second opinion.

Whipple procedure (pancreaticoduodenectomy)

Whipple procedure (pancreaticoduodenectomy) is the most common operation to remove a cancer in the head of the pancreas.

During this operation, the surgeon removes the head of the pancreas and sometimes the body of the pancreas as well. Nearby structures such as part of the small intestine, part of the bile duct, the gallbladder, lymph nodes near the pancreas, and sometimes part of the stomach are also removed. The remaining bile duct and pancreas are then attached to the small intestine so that bile and digestive enzymes can still go into the small intestine. The end pieces of the small intestine (or the stomach and small intestine) are then reattached so that food can pass through the digestive tract (gut).

Most often, this operation is done through a large incision (cut) down the middle of the belly. Some doctors at major cancer centers also do the operation laparoscopically, which is sometimes known as keyhole surgery.

A Whipple procedure is a very complex operation that requires a surgeon with a lot of skill and experience. It carries a relatively high risk of complications that can be life threatening. When the operation is done in small hospitals or by doctors with less experience, as many as 15% of patients may die as a result of surgical complications. In contrast, when the operation is done in cancer centers by surgeons experienced in the procedure, fewer than 5% of patients die as a direct result of surgery.

To have the best outcome, it’s important to be treated by a surgeon who does many of these operations and to have the surgery at a hospital where many of them are done. In general, people having this type of surgery do better when it’s done at a hospital that does at least 15 to 20 Whipple procedures per year.

Still, even under the best circumstances, many patients have complications from the surgery. These can include:

• Leaking from the various connections between organs that the surgeon has to join
• Infections
• Bleeding
• Trouble with the stomach emptying after eating
• Trouble digesting some foods (which might require taking some pills to help with digestion)
• Weight loss
• Changes in bowel habits
• Diabetes

Distal pancreatectomy

In this operation, the surgeon removes only the tail of the pancreas or the tail and a portion of the body of the pancreas. The spleen is usually removed as well. The spleen helps the body fight infections, so if it’s removed you’ll be at increased risk of infection with certain bacteria. To help with this, doctors recommend that patients get certain vaccines before this surgery.

This surgery is used to treat cancers found in the tail and body of the pancreas. Unfortunately, many of these tumors have usually already spread by the time they are found and surgery is not always an option.

Total pancreatectomy

This operation removes the entire pancreas, as well as the gallbladder, part of the stomach and small intestine, and the spleen. This surgery might be an option if the cancer has spread throughout the pancreas but can still be removed. But this type of surgery is used less often than the other operations because there doesn’t seem to be a major advantage in removing the whole pancreas, and it can have major side effects.

It’s possible to live without a pancreas. But when the entire pancreas is removed, people are left without the cells that make insulin and other hormones that help maintain safe blood sugar levels. These people develop diabetes, which can be hard to manage because they are totally dependent on insulin shots. People who have had this surgery also need to take pancreatic enzyme pills to help them digest certain foods.

Before you have this operation, your doctor will recommend that you get certain vaccines because the spleen will be removed.

Potentially curative surgery

Studies have shown that removing only part of a pancreatic cancer doesn’t help patients live longer, so potentially curative surgery is only done if the surgeon thinks all of the cancer can be removed.

This is a very complex surgery and it can be very hard for patients. It can cause complications and might take weeks or months to recover from fully. If you’re thinking about having this type of surgery, it’s important to weigh the potential benefits and risks carefully.

Fewer than 1 in 5 pancreatic cancers appear to be confined to the pancreas at the time they are found. Even then, not all of these cancers turn out to be truly resectable (able to be completely removed). Sometimes after the surgeon starts the operation it becomes clear that the cancer has grown too far to be completely taken out. If this happens, the operation may be stopped, or the surgeon might continue with a smaller operation with a goal of relieving or preventing symptoms. This is because the planned operation would be very unlikely to cure the cancer and could still lead to major side effects. It would also lengthen the recovery time, which could delay other treatments.

Surgery offers the only realistic chance to cure pancreatic cancer, but it doesn’t always lead to a cure. Even if all visible cancer is removed, often some cancer cells have already spread to other parts of the body. These cells can grow into new tumors over time, which can be hard to treat.

Curative surgery is done mainly to treat cancers in the head of the pancreas. Because these cancers are near the bile duct, they often cause jaundice, which sometimes allows them to be found early enough to be removed completely. Surgeries for other parts of the pancreas are described below, and are done if it’s possible to remove all of the cancer.

Palliative surgery

If the cancer has spread too far to be removed completely, any surgery being considered would be palliative (intended to relieve symptoms). Because pancreatic cancer can spread quickly, most doctors don’t advise major surgery for palliation, especially for people who are in poor health.

Sometimes surgery might be started with the hope it will cure the patient, but once it begins the surgeon discovers this is not possible. In this case, the surgeon might do a less extensive, palliative operation known as bypass surgery to help relieve symptoms.

Cancers growing in the head of the pancreas can block the common bile duct as it passes through this part of the pancreas. This can cause pain and digestive problems because bile can’t get into the intestine. The bile chemicals will also build up in the body, which can cause jaundice, nausea, vomiting, and other problems. There are two main options to relieve bile duct blockage in this situation:

• Stent placement. The most common approach to relieving a blocked bile duct does not involve actual surgery. Instead, a stent (small tube, usually made of metal) is put inside the duct to keep it open. This is usually done through an endoscope (a long, flexible tube) while you are sedated. Often this is part of an endoscopic retrograde cholangiopancreatography (ERCP). The doctor passes the endoscope down the throat and all the way into the small intestine. Through the endoscope, the doctor can then put the stent into the bile duct. The stent can also be put in place through the skin during a percutaneous transhepatic cholangiography (PTC). The stent helps keep the bile duct open even if the surrounding cancer presses on it. But after several months, the stent may become clogged and may need to be cleared or replaced. Larger stents can also be used to keep parts of the small intestine open if they are in danger of being blocked by the cancer. A bile duct stent can also be put in to help relieve jaundice before curative surgery is done (which would typically be a couple of weeks later). This can help lower the risk of complications from surgery.
• Bypass surgery. In people who are healthy enough, another option for relieving a blocked bile duct is surgery to reroute the flow of bile from the common bile duct directly into the small intestine, bypassing the pancreas. This typically requires a large incision (cut) in the abdomen, and it can take weeks to recover from this. Sometimes surgery can be done through several small cuts in the abdomen using special long surgical tools. This is known as laparoscopic or keyhole surgery. Having a stent placed is often easier and the recovery is much shorter, which is why this is done more often than bypass surgery. But surgery can have some advantages, such as:
  • It can often give longer-lasting relief than a stent, which might need to be cleaned out or replaced.
  • It might be an option if a stent can’t be placed for some reason.
  • During surgery, the surgeon may be able to cut some of the nerves around the pancreas or inject them with alcohol. Because pancreatic cancer often causes pain if it reaches these nerves, this procedure may reduce or get rid of any pain caused by the cancer.
  • Sometimes, the end of the stomach is disconnected from the duodenum (the first part of the small intestine) and attached farther down the small intestine during this surgery as well. This is known as a gastric bypass. This is done because over time the cancer might grow large enough to block the duodenum, which can cause pain and vomiting and often requires urgent surgery. Bypassing the duodenum before this happens can sometimes help avoid this.
  • Bypass surgery can still be a major operation, so it’s important that you are healthy enough to tolerate it and that you talk with your doctor about the possible benefits and risks before you have the surgery.

Ablation or embolization treatments for pancreatic cancer

Ablation and embolization treatments are different ways of destroying tumors, rather than removing them with surgery. They are used much less often for pancreatic cancers but can sometimes be used to help treat pancreatic cancer that has spread to other organs, especially the liver.

These treatments are very unlikely to cure cancers on their own. They are more likely to be used to help prevent or relieve symptoms, when there are only a few areas of spread, and are often used along with other types of treatment.

Ablative treatments

Ablation refers to treatments that destroy tumors, usually with extreme heat or cold. They are generally best for tumors no more than about 2 cm (a little less than an inch) across. Typically, with this type of treatment you will not need to stay in the hospital. There are different kinds of ablative treatments:

• Radiofrequency ablation (RFA) uses high-energy radio waves for treatment. A thin, needle-like probe is put through the skin and into the tumor. Placement of the probe is guided by ultrasound or CT scans. The tip of the probe releases a high-frequency electric current which heats the tumor and destroys the cancer cells.
• Microwave thermotherapy is similar to RFA, except it uses microwaves to heat and destroy the cancer cells.
• Ethanol (alcohol) ablation also known as percutaneous ethanol injection kills the cancer cells by injecting concentrated alcohol directly into the tumor. This is usually done through the skin using a needle guided by ultrasound or CT scans.
• Cryosurgery also known as cryotherapy or cryoablation destroys a tumor by freezing it with a thin metal probe. The probe is guided through the skin and into the tumor, using ultrasound. Then very cold gasses are passed through the probe to freeze the tumor, killing the cancer cells. This method may be used to treat larger tumors than the other ablation techniques, but it sometimes requires general anesthesia (where you are put into a deep sleep).
  Side effects of ablation treatments

Possible side effects after ablation therapy include abdominal pain, infection, and bleeding inside the body. Serious complications are uncommon, but they are possible.

Embolization treatments

During embolization, substances are injected into an artery to try to block the blood flow to cancer cells, causing them to die. This may be used for larger tumors (up to about 5 cm or 2 inches across) in the liver.

There are 3 main types of embolization:

1. Arterial embolization also known as trans-arterial embolization (TAE) involves putting a catheter (a thin, flexible tube) into an artery through a small cut in the inner thigh and threaded up into the hepatic artery feeding the tumor. Blood flow is blocked (or reduced) by injecting materials that plug up that artery. Most of the healthy liver cells will not be affected because they get their blood supply from a different blood vessel, the portal vein.
2. Chemoembolization also known as trans-arterial chemoembolization (TACE) combines embolization with chemotherapy. Most often, this is done by using tiny beads that give off a chemotherapy drug during the embolization. Trans-arterial chemoembolization (TACE) can also be done by giving chemotherapy through the catheter directly into the artery, then plugging up the artery.
3. Radioembolization combines embolization with radiation therapy. In the United States, this is done by injecting small radioactive beads (called microspheres) into the hepatic artery. The beads lodge in the blood vessels near the tumor, where they give off small amounts of radiation to the tumor site. Since the radiation travels a very short distance, its effects are limited mainly to the tumor.

Possible side effects after embolization include abdominal pain, fever, nausea, infection, and blood clots in nearby blood vessels. Serious complications are not common, but they can happen.

Chemotherapy for pancreatic cancer

Chemotherapy uses drugs to help kill cancer cells. These drugs can be injected into a vein or taken orally. You may receive one chemotherapy drug or a combination of them. Chemo drugs enter the bloodstream and reach almost all areas of the body, making this treatment potentially useful for cancers whether or not they have spread.

Chemo is often part of the treatment for pancreatic cancer and may be used at any stage:

• Before surgery (neoadjuvant chemotherapy): Chemo can be given before surgery (sometimes along with radiation) to try to shrink the tumor so it can be removed with less extensive surgery. Neoadjuvant chemo is often used to treat cancers that are too big to be removed by surgery at the time of diagnosis (called locally advanced cancers).
• After surgery (adjuvant chemotherapy): Chemo can be used after surgery (sometimes along with radiation) to try to kill any cancer cells that have been left behind or have spread but can’t be seen, even on imaging tests. If these cells were allowed to grow, they could form new tumors in other places in the body. This type of treatment might lower the chance that the cancer will come back later.
• For advanced pancreatic cancer: Chemo can be used when the cancer is advanced and can’t be removed completely with surgery, or if surgery isn’t an option, or if the cancer has spread to other organs.

When chemo is given along with radiation, it is known as chemoradiation. It helps the radiation work better, but can also have more side effects.

In most cases (especially as adjuvant or neoadjuvant treatment), chemo is most effective when combinations of drugs are used. For people who are healthy enough, 2 or more drugs are usually given together. For people who are not healthy enough for combined treatments, a single drug (usually gemcitabine, 5-FU, or capecitabine) can be used.

The most common drugs used for both adjuvant and neoadjuvant chemo include:

• Gemcitabine (Gemzar)
• 5-fluorouracil (5-FU)
• Oxaliplatin (Eloxatin)
• Albumin-bound paclitaxel (Abraxane)
• Capecitabine (Xeloda)
• Cisplatin
• Irinotecan (Camptosar)

Chemotherapy for advanced pancreatic cancer:

• Gemcitabine (Gemzar)
• 5-fluorouracil (5-FU) or Capecitabine (Xeloda) (an oral 5FU drug)
• Irinotecan (Camptosar) or Liposomal Irinotecan (Onivyde)
• Platinum agents : Cisplatin and Oxaliplatin (Eloxatin)
• Taxanes: Paclitaxel (Taxol), Docetaxel (Taxotere), and Albumin-bound paclitaxel (Abraxane)

Chemo drugs for pancreatic cancer can be given into a vein (IV) or by mouth as a pill. The infusion can be done in a doctor’s office, chemotherapy clinic, or in a hospital setting.

Often, a slightly larger and sturdier IV is required in the vein system to give chemo. They are known as central venous catheters (CVCs), central venous access devices (CVADs), or central lines. They are used to put medicines, blood products, nutrients, or fluids right into your blood. They can also be used to take out blood for testing.

Doctors give chemo in cycles, with each period of treatment followed by a rest period to give you time to recover from the effects of the drugs. Cycles are most often 2 or 3 weeks long. The schedule varies depending on the drugs used. For example, with some drugs, the chemo is given only on the first day of the cycle. With others, it is given for a few days in a row, or once a week. Then, at the end of the cycle, the chemo schedule repeats to start the next cycle.

Adjuvant and neoadjuvant chemo is often given for a total of 3 to 6 months, depending on the drugs used. The length of treatment for advanced pancreatic cancer is based on how well it is working and what side effects you may have.

Chemo drugs can cause side effects. These depend on the type and dose of drugs given and how long treatment lasts. Common possible side effects include:

• Nausea and vomiting
• Loss of appetite
• Hair loss
• Mouth sores
• Diarrhea or constipation

Chemo can also affect the blood-forming cells of the bone marrow, which can lead to:

• Increased chance of infection (from low white blood cells)
• Bleeding or bruising (from low platelet counts)
• Fatigue or shortness of breath (from low red blood cells)

These side effects usually go away after treatment is finished. There are often ways to lessen these side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting.

Some chemo drugs can cause other side effects. For example:

• Drugs such as cisplatin, oxaliplatin, and paclitaxel can damage nerves, which can lead to symptoms of numbness, tingling, or even pain in the hands and feet (called peripheral neuropathy). For a day or so after treatment, oxaliplatin can cause nerve pain that gets worse with exposure to cold, including when swallowing cold foods or liquids.
• Cisplatin can damage the kidneys. Doctors try to prevent this by giving the patient lots of intravenous (IV) fluid before and after the drug is given.
• Cisplatin can affect hearing. Your doctor may ask if you have any ringing in the ears or hearing loss during treatment.

Targeted therapy for pancreatic cancer

As researchers have learned more about the changes in pancreatic cancer cells that help them grow, they have developed newer drugs to specifically target these changes. These targeted drugs work differently from standard chemo drugs. Sometimes they work when standard chemo drugs don’t, and they often have different (and less severe) side effects.

EGFR inhibitor

Erlotinib (Tarceva) is a drug that targets a protein on cancer cells called EGFR, which normally helps the cells grow. In people with advanced pancreatic cancer, this drug can be given along with the chemo drug gemcitabine. Some people may benefit more from this combination than others.

Erlotinib (Tarceva) is taken as a pill, once a day.

Common side effects of erlotinib include an acne-like rash on the face and neck, diarrhea, loss of appetite, and feeling tired. Less common but more serious side effects can include serious lung, liver, or kidney damage; holes (perforations) forming in the stomach or intestines; serious skin conditions; and bleeding or blood clotting problems.

PARP inhibitor

In a small number of pancreatic cancers, the cells have changes in one of the BRCA genes (BRCA1 or BRCA2). Changes in one of these genes can sometimes lead to cancer.

Olaparib (Lynparza) is a type of drug known as a PARP inhibitor. PARP enzymes are normally involved in a pathway that helps repair damaged DNA inside cells. The BRCA genes are normally involved in a different pathway of DNA repair, and mutations in one of these genes can block that pathway. By blocking the PARP pathway as well, this drug makes it very hard for tumor cells with a mutated BRCA gene to repair damaged DNA, which often leads to their death.

Olaparib can be used to treat advanced pancreatic cancer in people with a known or suspected BRCA gene mutation, whose cancer has not gotten worse after at least 4 months of chemo that included a platinum drug (such as oxaliplatin or cisplatin).

This drug has been shown to help shrink or slow the growth of some advanced pancreatic cancers, although so far it’s not clear if it can help people live longer.

Olaparib (Lynparza) is taken by mouth as pills, typically twice a day.

Side effects of this drug can include nausea, vomiting, diarrhea or constipation, fatigue, feeling dizzy, loss of appetite, taste changes, low red blood cell counts (anemia), low white blood cell counts (with an increased risk of infection), belly pain, and muscle and joint pain. Less common but more serious side effects can include inflammation in the lungs and the development of certain blood cancers, such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

NTRK inhibitors

A small number of pancreatic cancers have changes in one of the NTRK genes. These gene changes can sometimes lead to abnormal cell growth and cancer.

Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) target the proteins made by the NTRK genes. These drugs can be used in people with advanced pancreatic cancer that has been found to have an NTRK gene change, typically when the cancer is still growing despite other treatments.

These drugs are taken as pills, once or twice daily.

Common side effects of these drugs can include dizziness, fatigue, nausea, vomiting, constipation, weight gain, and diarrhea. Less common but more serious side effects can include abnormal liver tests, heart problems, and confusion.

Immunotherapy for pancreatic cancer

Immunotherapy is the use of medicines to stimulate a person’s own immune system to recognize and destroy cancer cells more effectively. Certain types of immunotherapy can be used to treat pancreatic cancer.

Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking the body’s normal cells. To do this, it uses “checkpoint” proteins on immune cells, which act like switches that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to keep the immune system from attacking them. But drugs that target these checkpoints hold a lot of promise as cancer treatments.

Drugs called checkpoint inhibitors can be used for people whose pancreatic cancer cells have tested positive for specific gene changes, such as a high level of microsatellite instability (MSI-H), or changes in one of the mismatch repair (MMR) genes. Changes in MSI or in MMR genes (or both) are often seen in people with Lynch syndrome.

The drugs are used for people whose cancer starts growing again after chemotherapy. They might also be used to treat people whose cancer can’t be removed with surgery, has come back (recurred) after treatment, or has spread to other parts of the body (metastasized).

PD-1 inhibitor

Pembrolizumab (Keytruda) is a drug that targets PD-1, a checkpoint protein on immune system cells called T cells, that normally helps keep these cells from attacking normal cells in the body. By blocking PD-1, this drug boosts the immune response against pancreatic cancer cells and can often shrink tumors.

This drug is given as an intravenous (IV) infusion every 2 or 3 weeks.

Side effects can include fatigue, cough, nausea, itching, skin rash, decreased appetite, constipation, joint pain, and diarrhea.

Other, more serious side effects occur less often. This drug works by basically removing the brakes from the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, or other organs.

It’s very important to report any new side effects to your health care team promptly. If serious side effects do occur, treatment may need to be stopped and you may get high doses of corticosteroids to suppress your immune system.

Radiation therapy for pancreatic cancer

Radiation therapy uses high-energy beams, such as those made from X-rays and protons, to destroy cancer cells. You may receive radiation treatments before or after cancer surgery, often in combination with chemotherapy. Or your doctor may recommend a combination of radiation and chemotherapy treatments when your cancer can’t be treated surgically.

Radiation therapy usually comes from a machine that moves around you, directing radiation to specific points on your body (external beam radiation). In specialized medical centers, radiation therapy may be delivered during surgery (intraoperative radiation).

Radiation therapy traditionally uses X-rays to treat cancer. Some medical centers offer proton beam radiation therapy, which may be a treatment option for some people with advanced pancreatic cancer.

The type of radiation most often used to treat pancreatic cancer is known as external beam radiation therapy, which focuses radiation from a source outside of the body on the cancer.

Getting radiation therapy is much like getting an x-ray, but the radiation is stronger. The procedure itself is painless. Each treatment lasts only a few minutes, although the setup time – getting you into place for treatment – usually takes longer. Most often, radiation treatments are given 5 days a week for several weeks.

When might radiation therapy be used?

• Radiation might be given after surgery (known as adjuvant treatment) to try to lower the chance of the cancer coming back. The radiation is typically given along with chemotherapy, which is together known as chemoradiation or chemoradiotherapy.
• For borderline resectable tumors, radiation might be given along with chemotherapy before surgery (neoadjuvant treatment) to try to shrink the tumor and make it easier to remove completely.
• Radiation therapy combined with chemotherapy may be used as part of the main treatment in people whose cancers have grown beyond the pancreas and can’t be removed by surgery (locally advanced/unresectable cancers).
• Radiation is sometimes used to help relieve symptoms (such as pain) in people with advanced cancers or in people who aren’t healthy enough for other treatments like surgery.

Some of the more common side effects of radiation therapy include:

• Skin changes in areas getting radiation, ranging from redness to blistering and peeling
• Nausea and vomiting
• Diarrhea
• Fatigue
• Loss of appetite
• Weight loss

Radiation can also lower blood counts, which can increase the risk of serious infection.

Usually these effects go away within a few weeks after the treatment is complete. Ask your doctor what side effects to expect and how to prevent or relieve them.

Resectable pancreatic cancer treatment

Surgeons usually consider pancreatic cancer to be resectable if it looks like it is still just in the pancreas or doesn’t extend far beyond the pancreas, and has not grown into nearby large blood vessels. A person must also be healthy enough to withstand surgery to remove the cancer, which is a major operation.

If imaging tests show a reasonable chance of removing the cancer completely, surgery is the preferred treatment if possible, as it offers the only realistic chance for cure. Based on where the cancer started, usually either a Whipple procedure (pancreaticoduodenectomy) or a distal pancreatectomy is used.

Sometimes even when a cancer is thought to be resectable, it becomes clear during the surgery that not all of it can be removed. If this happens, continuing the operation might do more harm than good. The surgery might be stopped, or the surgeon might continue with a smaller operation with a goal of relieving or preventing problems such as bile duct blockage.

• Neoadjuvant treatment (treatment before surgery). Sometimes, if the tumor is thought to be resectable but is very large, has many nearby large lymph nodes, or is causing significant pain, chemotherapy or chemoradiation may be given before surgery to shrink the tumor (known as neoadjuvant treatment). This may make it easier to remove all the cancer at the time of surgery. Additional chemo may still be recommended after surgery.
• Adjuvant treatment (treatment after surgery). Even when the surgeon thinks all of the cancer has been removed, the cancer might still come back. Giving chemotherapy (chemo), either alone or with radiation therapy (chemoradiation), after surgery (known as adjuvant treatment) might help some patients live longer. The chemo drugs most often used are gemcitabine (Gemzar) or 5-FU.

Borderline resectable pancreatic cancer treatment

A small number of pancreatic cancers have reached nearby blood vessels but have not grown deeply into them or surrounded them. These cancers might still be removable by surgery, but the odds of removing all of the cancer are lower, so they are considered borderline resectable.

These cancers are often treated first with neoadjuvant chemotherapy (sometimes along with radiation therapy) to try to shrink the cancer and make it easier to remove. Imaging tests (and sometimes laparoscopy) are then done to make sure the cancer hasn’t grown too much to be removed. As long as it hasn’t, surgery is then done to remove it. This might be followed by more chemotherapy.

Another option might be to have surgery first, followed by adjuvant chemotherapy (and possibly radiation). If, during the surgery, it becomes clear that not all of the cancer can be removed, continuing the operation might do more harm than good. The surgery might be stopped, or the surgeon might continue with a smaller operation with a goal of relieving or preventing problems such as bile duct blockage.

Locally advanced pancreatic cancer treatment

Locally advanced cancers have grown too far into nearby blood vessels or other tissues to be removed completely by surgery, but have not spread to the liver or distant organs and tissues. Surgery to try to remove these cancers does not help people live longer. Therefore, if surgery is done, it is to relieve bile duct blockage or to bypass a blocked intestine caused by the cancer pressing on other organs.

Chemotherapy, sometimes followed by chemoradiation, is the standard treatment option for locally advanced cancers. This may help some people live longer even if the cancer doesn’t shrink. Giving chemo and radiation therapy together may work better to shrink the cancer, but this combination has more side effects and can be harder on patients than either treatment alone. Sometimes, targeted therapy may be added to chemotherapy before chemoradiation is given.

Other times, immunotherapy given alone may also be an option.

Surgery might be done after chemo or chemoradiation, if imaging shows the cancer has become smaller and can be removed completely by surgery.

Stage 4 pancreatic cancer treatment

Stage 4 pancreatic cancer also called advanced (metastatic) pancreatic cancer, means that the cancer has spread to other areas of the body, such as the liver or lungs. Stage 4 pancreatic cancers have spread too much to be removed by surgery. Even when imaging tests show that the spread is only to one other part of the body, it is often assumed that small groups of cancer cells (too small to be seen on imaging tests) have already reached other organs of the body.

Chemotherapy is typically the main treatment for these cancers. It can sometimes shrink or slow the growth of these cancers for a time and might help people live longer, but it is not expected to cure the cancer.

Gemcitabine is one of the drugs used most often. It can be used alone (especially for people in poor health), or it can be combined with other drugs like albumin-bound paclitaxel (Abraxane), capecitabine (Xeloda), or the targeted drug erlotinib (Tarceva).

Another option, especially for people who are otherwise in good health, is a combination of chemo drugs called FOLFIRINOX. This consists of 4 drugs: 5-FU, leucovorin, irinotecan (Camptosar), and oxaliplatin (Eloxatin). This treatment might help people live longer than getting gemcitabine alone, but it can also have more severe side effects.

In certain cases, immunotherapy or targeted therapy may be options for people whose cancer cells have certain gene changes.

Other treatments might also be used to help prevent or relieve symptoms from these cancers. For example, radiation therapy or some type of nerve block might be used to help relieve cancer pain, or a stent might be placed during an endoscopy to help keep the bile duct open.

Because the treatments now available don’t work well for many people, you may want to think about taking part in a clinical trial of new drugs or combinations of drugs.

Pancreatic cancer that progresses or recurs treatment

If cancer continues to grow during treatment (progresses) or comes back (recurs), your treatment options will depend on:

• Where and how much the cancer has spread
• What treatments you have already had
• Your health and desire for more treatment

It’s important that you understand the goal of any further treatment, as well as the likelihood of benefits and risks.

When pancreatic cancer recurs, it most often shows up first in the liver, but it may also spread to the lungs, bone, or other organs. This is usually treated with chemotherapy if you are healthy enough to get it. If you have had chemo before and it kept the cancer away for some time, the same chemo might be helpful again. Otherwise, different chemo drugs might be tried, sometimes along with targeted therapy. Immunotherapy may also be helpful in some cases of recurrent pancreatic cancer. Other treatments such as radiation therapy or stent placement might be used to help prevent or relieve symptoms from the cancer.

If the cancer progresses while you are getting chemotherapy, another type of chemotherapy might be tried if you are healthy enough.

At some point, it might become clear that standard treatments are no longer controlling the cancer. If you want to continue getting treatment, you might think about taking part in a clinical trial of a newer pancreatic cancer treatment. While these are not always the best option for every person, they may benefit you, as well as future patients.

Ampulla of Vater cancer treatment

The ampulla of Vater is the area where the pancreatic duct and the common bile duct empty into the duodenum (the first part of the small intestine). Cancer at this site (known as ampullary cancer) can start in the pancreatic duct, the duodenum, or the common bile duct. In many patients, ampullary cancer can’t be distinguished from pancreatic cancer until surgery has been done.

These cancers often cause early symptoms such as jaundice, so they are often found while they are still resectable. Surgery with the Whipple procedure is often successful in treating these early stage cancers. Adjuvant chemoradiotherapy is often recommended after surgery.

More advanced ampullary cancers are treated like pancreatic cancer.

Clinical trials

Clinical trials are studies to test new treatments, such as systemic therapy, and new approaches to surgery or radiation therapy. If the treatment being studied proves to be safer and more effective than are current treatments, it can become the new standard of care.

Clinical trials for pancreatic cancer might give you a chance to try new targeted therapy, chemotherapy drugs, immunotherapy treatments or vaccines.

Clinical trials can’t guarantee a cure, and they might have serious or unexpected side effects. On the other hand, cancer clinical trials are closely monitored to ensure they’re conducted as safely as possible. And they offer access to treatments that wouldn’t otherwise be available to you.

Talk to your doctor about what clinical trials might be appropriate for you.

Pancreatic cancer diet

Having cancer of the pancreas will affect your eating and drinking habits, whatever your stage of cancer or treatment. Many people with pancreatic cancer lose weight. The pancreas is not only close to the stomach and bowel, it produces insulin and enzymes which help to digest food.

If you’ve had all or part of your pancreas removed, you may need to take insulin or tablets to regulate your blood sugar. You may also need to take enzyme supplements when you eat to help your digestion.

Blood sugar

If you are on insulin or tablets to regulate your blood sugar, your doctor will ask you to check your urine for sugar. Too much sugar in the urine indicates that the sugar balance of your body is not yet right.

If you are on insulin, you will probably also have to test your blood sugar levels. You will have to prick your finger and squeeze a drop of blood onto a test strip. This will show how much sugar is in your blood. You will then know how much insulin to take.

It takes time to get used to doing these tests. You will be shown how to do it before you leave hospital.

You may also have a nurse to visit you at home to help you and answer your questions.

Enzyme supplements

Digestive enzymes help your body to break down and absorb fats and proteins. Without enough enzymes, you may have diarrhoea or your poo (stools) may float, look pale and smell offensive. This is due to the undigested fat in the stool.

It might be difficult to put on weight as you are unable to absorb the nutrients from your food. If your pancreas is not working properly due to the cancer or you’ve had all or part of your pancreas removed, you may need to take enzyme supplements to reduce these effects.

Types of enzyme supplements

There are several different types of enzyme supplement. Creon is the most commonly used. The dose depends on:

• how well the remaining part of your pancreas is working
• your diet

You might need to take more enzymes if you are about to eat a large or fatty meal.

How to take them

You swallow the enzyme capsules whole, immediately before your meal. If you find it difficult to swallow capsules, you can open them and mix the granules in soft acidic foods that are at room temperature and easy to swallow. This can include apple sauce or mashed banana.

You must not chew or crush the granules. Have a drink of water afterwards to make sure none of the granules stay in your mouth as they can irritate the lining and cause mouth ulcers.

Your dietician will give you a diet plan to suit you and advise you on taking the supplements. It can take a bit of time to get the right dose of enzymes for you.

Snacks and small meals

You may find it easier to have lots of small meals through the day, rather than sticking to the traditional three meals a day.

It is a good idea to have plenty of nutritious snacks to hand that you can have whenever you feel like eating. If you can manage it, it’s best to choose full fat versions of yoghurts and puddings, so that you get the most calories.

You could try:

• yoghurts or fromage frais
• other soft puddings such as trifle or chocolate mousse
• dried fruit
• stewed or fresh fruit (bananas are high in calories)
• nuts
• cheese
• instant soups (make up with milk to boost calories)
• cereal
• milky drinks
• flapjacks

Some of these ideas may not suit your digestion but they might be worth a try. If in doubt, check with your dietitian.

Try to think of quick ways of having the things you like to eat. If possible, get someone to prepare your favourite foods in advance and freeze them in small portions. A microwave makes defrosting and heating easier and quicker.

Managing diarrhea

If you have diarrhea after pancreatic surgery, it is probably related to difficulty digesting fat. Avoid very high fibre foods (such as cereal and dried fruit) for a time as these may make things worse. Tell your doctor, nurse or dietitian.

You may need some medicines to control your symptoms. If you’re taking enzyme supplements, your dietitian may need to alter the dose. They can also suggest some changes to your diet that may help.

Nutritional supplements

If you are finding it hard to eat, there are plenty of nutritional supplements available on prescription. Some are powders you sprinkle on your food and some are drinks that are complete meals in themselves.

Sipping a supplement between meals throughout the day can really boost your calorie intake. Again, ask your doctor or dietitian.

Supportive (palliative) care

Advanced pancreatic cancer means that a cancer that began in the pancreas has spread to another part of the body or has come back after previous treatment. Advanced cancer can cause symptoms. Tell your doctor or nurse about any symptoms that you have so they can help you.

Palliative care is specialized medical care that focuses on providing relief from pain and other symptoms of a serious illness. Palliative care specialists work with you, your family and your other doctors to provide an extra layer of support that complements your ongoing care. Palliative care can be used while undergoing aggressive treatments, such as surgery, chemotherapy and radiation therapy.

When palliative care is used along with other appropriate treatments — even soon after the diagnosis — people with cancer may feel better and live longer.

Palliative care is provided by teams of doctors, nurses and other specially trained professionals. These teams aim to improve the quality of life for people with cancer and their families. Palliative care is not the same as hospice care or end-of-life care.

Treatments such as chemotherapy or radiotherapy can sometimes help to shrink the cancer, reduce symptoms and help you feel better. Other treatments such as stents can treat specific symptoms such as a blockage in the stomach.

Tiredness and feeling unwell

Tiredness is a common symptom of advanced cancer. It can feel a bit overwhelming and as though you don’t have any energy.

Let your doctor or nurse know if you’re very tired as they might be able to prescribe medicine to help or other treatments. For example, a blood transfusion can give you more energy if you’re tired due to anaemia (low red blood cell levels).

• Resting. It’s important to rest a few times throughout the day. Resting regularly can help you feel less tired and more able to cope. You don’t have to sleep during these times. Just sitting or lying down will help.
• Exercise. Exercising can be hard when you feel very tired. Research has shown that daily light to moderate exercise can give you more energy. Going for a gentle walk is enough. Gentle exercises in bed or standing up can help if you can’t move around easily. Your hospital physiotherapist or community palliative care team might be able to help you plan an exercise programme that suits your needs.
• Sleeping. You might feel more tired if you have trouble sleeping at night. It can help to change a few things about when and where you sleep.

A blockage in the stomach

The cancer might block the entrance to the stomach or the entrance to the bowel. Then food can’t pass through. This causes pain, sickness and makes you feel very unwell. You may need to go to the hospital if this happens. They might put a tube called a stent into your stomach to allow food to pass through. Surgery to bypass or remove part of your stomach can help if you’re well enough to cope with it.

Loss of appetite

You might not feel like eating and may lose weight. It is important to eat as much as you can. Most hospital pancreatic cancer specialist teams include a dietitian. Talk to the dietitian about help with eating and getting high calorie drinks to boost your calorie intake if you need them.

Tips:

• Eating several small meals and snacks throughout the day can be easier to manage.
• Ask your doctor or dietitian to recommend high calorie drinks to sip if you are worried about losing weight.
• Eat whatever you feel like eating rather than what you think you should eat.
• Eat plenty of calories when you can to make up for times when you don’t feel like eating.
• Drink plenty of fluids even if you can’t eat.
• Don’t fill your stomach with a large amount of liquid before eating.
• Try to eat high calorie foods to keep your weight up.

A swollen abdomen (ascites)

You might have a swollen tummy (abdomen) if your cancer has spread to the liver. The swelling is due to a build up of fluid called ascites. It can make your clothes feel tighter. Your tummy might feel bloated. You might also find it difficult to sit comfortably or to move around.

Your doctor might drain off the fluid by putting a small flexible tube into the tummy (abdomen). They might use an ultrasound scan to make sure the tube is in the right place. Draining off the fluid helps you to feel more comfortable.

Sometimes the fluid builds up again over a few weeks. If this happens, you might have another tube into your abdomen called an indwelling peritoneal catheter (IPC). This means you can drain the fluid off when you need to at home. This means you won’t need to go to hospital each time.

Bowel problems

You might pass pale, offensive smelling stools (poo) that float. This is called steatorrhea (fatty poop).

Bowel problems such as diarrhea or constipation can be caused by the cancer. They can also be caused by cancer treatments or medicines. For example, painkillers commonly cause constipation.

Talk to your doctor or nurse if you have bowel problems. They can help by giving you medicine. And they can refer you to a dietitian for advice on what to eat or drink.

Pain control for pancreatic cancer

Pain can be a major problem for people with pancreatic cancer. These cancers can invade and press on nerves near the pancreas, which can cause pain in the abdomen or back. Treatment is available to help relieve this pain. If you are having any pain, please be sure to tell your doctor or nurse. Pain is easier to control if the treatment is started when you first have it. You and your doctor or nurse can talk about the best ways to treat your pain. A pain specialist can also help develop a treatment plan.

Some proven ways to relieve pain from pancreatic cancer include:

• Pain medicines. For most patients, morphine or similar drugs (opioids) can help control the pain. Many people are worried about these drugs because they fear becoming addicted, but studies have shown that the risk of this is low if the patient takes the drug for pain as directed by the doctor. Pain medicines work best when they are taken on a regular schedule. They do not work as well if they are only used when the pain becomes severe. Several long-acting forms of morphine and other opioids are in pill form and only need be taken once or twice a day. There is even a long-acting form of the drug fentanyl that is applied as a patch every 3 days. Common side effects of these drugs are nausea and feeling sleepy, which often get better over time. Constipation is a common side effect that does not get better on its own, so it needs to be treated. Most people need to take stool softeners and/or laxatives daily.
• Other treatments for pain. Sometimes certain procedures might be needed to treat pain. For example, cutting or injecting alcohol into some of the nerves (that carry pain sensations) near the pancreas can often improve pain and may allow you to use lower doses of pain medicines. If you are having surgery for some reason (such as to remove the cancer or relieve bile duct blockage), this can usually be done as part of the same operation. This can also be done as a separate procedure. The doctor might do a nerve block by injecting the nerves near the pancreas with either an anesthetic or a medicine that destroys the nerves. This can be done with the help of an ultrasound or CT scan either by:
  • passing a needle through the skin or
  • by using an endoscope (a long, flexible tube that is passed down the throat and past the stomach) that guides a needle to the nerves.

Treating the cancer with chemotherapy and/or radiation therapy can also sometimes relieve pain by shrinking the size of the cancer.

Treatments to help you cope with distress

People with cancer frequently experience distress. Some research suggests distress is more common in people with pancreatic cancer than it is in people with other types of cancer.

If you’re distressed, you may have difficulty sleeping and find yourself constantly thinking about your cancer. You may feel angry or sad.

Discuss your feelings with your doctor. Specialists can help you sort through your feelings and help you devise strategies for coping. In some cases, medications may help.

Integrative medicine and alternative therapies may also help you cope with distress. Examples include:

• Art therapy
• Exercise
• Meditation
• Music therapy
• Relaxation exercises
• Spirituality

Talk with your doctor if you’re interested in these treatment options.

Coping and support

Learning you have a life-threatening illness can be devastating. Some of the following suggestions may help:

• Learn what you need to know about your cancer. Learn enough about your cancer to help you make decisions about your care. Ask your doctor about the details of your cancer and your treatment options. Ask about trusted sources of further information. If you’re doing your own research, good places to start include the National Cancer Institute and the Pancreatic Cancer Action Network.
• Assemble a support system. Ask your friends and family to form a support network for you. They may feel helpless and uncertain after your diagnosis. Helping you with simple tasks might give them comfort. And you might find relief in not having to worry about certain tasks. Think of things you want help with, such as meal preparation or getting to appointments.
• Find someone to talk with. Although friends and family can be your best allies, in some cases they have difficulty coping with the shock of your diagnosis. In these cases, talking with a counselor, medical social worker, or a pastoral or religious counselor can be helpful. Ask your doctor for a referral.
• Connect with other cancer survivors. You may find comfort in talking with other cancer survivors. Contact your local chapter of the American Cancer Society to find cancer support groups in your area. The Pancreatic Cancer Action Network can connect you with a pancreatic cancer survivor who can provide support by phone or email.
• Consider hospice. Hospice care provides comfort and support to terminally ill people and their loved ones. It allows family and friends — with the aid of nurses, social workers and trained volunteers — to care for and comfort a loved one at home or in a hospice residence. Hospice care also provides emotional, social and spiritual support for people who are ill and those closest to them.

Pancreatic neuroendocrine tumor treatment

For pancreatic neuroendocrine tumors (PNETs), treatment options might include surgery, ablation or embolization treatments, radiation therapy, or different types of medicines.

Treatment of pancreatic neuroendocrine tumors (PNETs) depends to a large extent on whether they can be resected (removed) completely or not. But other factors, such as your overall health, can also affect treatment options. Talk to your doctor if you have any questions about the treatment plan they recommend.

Pancreatic NETs are more likely to be resectable than exocrine pancreas cancers (the most common type of pancreatic cancer). Most NETs that have not spread to distant parts of the body are resectable. Even some NETs that have spread might be resectable if they have not spread too far (such as only to a few spots in the liver).

Treating resectable tumors

Pancreatic NETs that have not spread outside the pancreas should be completely removed, if possible, because these tumors are more likely to be cured with surgery. The procedure used depends on the type of tumor, its size, and its location in the pancreas. Types of potentially curative surgery include enucleation (removing only the tumor), central pancreatectomy, distal pancreatectomy, the Whipple procedure (pancreaticoduodenectomy), and total pancreatectomy. The type of surgery needed depends on several factors, including the location, size, and specific kind of pancreatic NET (functioning or nonfunctioning). Lymph nodes are often removed to check for tumor spread.

Before any surgery, medicines are often given to control any symptoms caused by the tumor. For example, drugs to block stomach acid (like proton pump inhibitors) are used for gastrinomas. Often, people with insulinomas are treated with diazoxide to keep blood sugar from getting too low. If the tumor was visible on somatostatin receptor scintigraphy, a somatostatin analog such as octreotide may be used to control any symptoms.

Surgery alone is all that is needed for many pancreatic NETs, but after surgery, close monitoring is important to look for signs that the cancer may have come back or spread.

Enucleation (removing just the tumor)

Sometimes if a pancreatic NET is small, just the tumor itself is removed. This is called enucleation. This operation may be done using a laparoscope, so that only a few small cuts on the belly are needed. This operation may be all that is needed to treat an insulinoma. Small gastrinomas and some other pancreatic NETs may also be treated with enucleation, but sometimes the duodenum (the first part of the small intestine) is removed as well. The lymph nodes around the pancreas might also be removed so that they can be checked for cancer cells.

Central pancreatectomy

A central pancreatectomy is used to treat small, low grade tumors. For this operation, the surgeon removes only the neck and part of the body of the pancreas keeping the head and tail intact. This helps maintain most of the function of the pancreas.

Distal pancreatectomy

A distal pancreatectomy is used to treat pancreatic NETs found in the tail and body of the pancreas. In this operation, the surgeon removes only the tail of the pancreas or the tail and a portion of the body of the pancreas. The spleen is usually removed as well. The spleen helps the body fight infections, so if it’s removed you’ll be at increased risk of infection with certain bacteria. To help with this, doctors recommend that patients get certain vaccines before this surgery.

Whipple procedure (pancreaticoduodenectomy)

A Whipple procedure is used to treat pancreatic NETs found in the head of the pancreas. During this operation, the surgeon removes the head of the pancreas and sometimes the body of the pancreas as well. Nearby structures such as part of the small intestine, part of the bile duct, the gallbladder, lymph nodes near the pancreas, and sometimes part of the stomach are also removed. The remaining bile duct and pancreas are then attached to the small intestine so that bile and digestive enzymes can still go into the small intestine. The pieces of the small intestine (or the stomach and small intestine) are then reattached so that food can pass through the digestive tract.

Most often, this operation is done through a large incision (cut) down the middle of the belly. Some doctors at major cancer centers also do the operation laparoscopically, which is sometimes known as keyhole surgery.

This is a very complex operation that requires a surgeon with a lot of skill and experience. It carries a relatively high risk of complications that can be life threatening. When the operation is done in small hospitals or by doctors with less experience, as many as 15% of patients may die as a result of surgical complications. In contrast, when the operation is done in cancer centers by surgeons experienced in the procedure, less than 5% of patients die as a direct result of surgery.

To have the best outcome, it’s important to be treated by a surgeon who does many of these operations and to have the surgery at a hospital where many of them are done. In general, people having this type of surgery do better when it’s done at a hospital where at least 15 to 20 Whipple procedures are done per year.

Still, even under the best circumstances, many patients have complications from the surgery. These can include:

• Leaking from the various connections between organs that the surgeon has joined
• Infections
• Bleeding
• Trouble with the stomach emptying after eating
• Trouble digesting some foods (which might require taking pancreatic enzymes in pill form to help with digestion)
• Weight loss
• Changes in bowel habits
• Diabetes

Total pancreatectomy

Total pancreatectomy might be an option if the cancer has spread throughout the pancreas but can still be removed. This operation removes the entire pancreas, as well as the gallbladder, part of the stomach and small intestine, and the spleen. But this type of surgery is used less often than the other operations because there doesn’t seem to be a major advantage in removing the whole pancreas, and it can have major side effects.

It’s possible to live without a pancreas. But when the entire pancreas is removed, people are left without the cells that make insulin and other hormones that help maintain safe blood sugar levels. These people develop diabetes, which can be hard to manage because they are totally dependent on insulin shots. People who have had this surgery also need to take pancreatic enzyme pills to help them digest certain foods.

Before you have this operation, your doctor will recommend that you get certain vaccines because the spleen will be removed.

Palliative surgery

If the cancer has spread too far to be removed completely, any surgery being considered would be palliative (intended to relieve symptoms). This type of surgery may be considered in some people with pancreatic NETs whose tumor has recurred and is causing local problems or is making too many hormones that are causing symptoms.

Sometimes surgery might be started with the hope it will cure the patient, but once it begins the surgeon discovers this is not possible. In this case, the surgeon might do a less extensive, palliative operation known as bypass surgery instead to help prevent or relieve symptoms.

Cancers growing in the head of the pancreas can block the common bile duct as it passes through this part of the pancreas. This can cause pain and digestive problems because bile can’t get into the intestine. The bile chemicals will also build up in the body, which can cause jaundice, nausea, vomiting, and other problems.

There are 2 main options for relieving bile duct blockage: stent placement, and bypass surgery.

• Stent placement. The most common approach to relieving a blocked bile duct does not involve actual surgery. Instead, a stent (small tube, usually made of metal) is put inside the duct to keep it open. This is usually done through an endoscope (a long, flexible tube) while you are sedated. Often this is part of an endoscopic retrograde cholangiopancreatography (ERCP). The doctor passes the endoscope down the throat and all the way into the small intestine. The doctor can then insert the stent into the bile duct through the endoscope. The stent can also be put in place through the skin during a percutaneous transhepatic cholangiography (PTC). The stent helps keep the bile duct open even if the surrounding cancer presses on it. But after several months, the stent may become clogged and may need to be cleared or replaced. Larger stents can also be used to keep parts of the small intestine open if they are in danger of being blocked by the cancer. A bile duct stent can also be put in to help relieve jaundice before curative surgery is done (which would typically be a couple of weeks later). This can help lower the risk of complications from surgery.
• Bypass surgery. In people who are healthy enough, another option for relieving a blocked bile duct is surgery to reroute the flow of bile from the common bile duct directly into the small intestine, bypassing the pancreas. This typically requires a large incision (cut) in the abdomen, and it can take weeks to recover from this. Sometimes surgery can be done through several small cuts in the abdomen using special long surgical tools. This is known as laparoscopic or keyhole surgery. Having a stent placed is often easier and the recovery is much shorter, which is why this is done more often than bypass surgery. But this surgery can have some advantages:
  • It can often give longer-lasting relief than a stent, which might need to be cleaned out or replaced.
  • It might be an option if a stent can’t be placed for some reason.
  • During surgery, the surgeon may be able to cut some of the nerves around the pancreas or inject them with alcohol. This may reduce or get rid of any pain caused by the cancer.
  • Sometimes, the end of the stomach is disconnected from the duodenum (the first part of the small intestine) and attached farther down the small intestine during this surgery as well. This is known as a gastric bypass. This is done because over time the cancer might grow large enough to block the duodenum, which can cause pain and vomiting and often requires urgent surgery. Bypassing the duodenum before this happens can sometimes help avoid this.
  • Bypass surgery can still be a major operation, so it’s important that you are healthy enough to withstand it and that you talk with your doctor about the possible benefits and risks before you have the surgery.

Surgery for cancer that has spread

Surgery may be used to remove metastases if a pancreatic NET has spread to the liver (the most common site of spread) or the lungs. Surgically removing metastases can improve symptoms and help patients with pancreatic NETs live longer. In rare cases, a liver transplant might be used to treat pancreatic NETs that have spread to the liver.

Treating unresectable tumors

Unresectable tumors can’t be removed completely with surgery. Pancreatic NETs are often slow growing, so lab and imaging tests are used to monitor the tumor(s) and look for signs of growth.

People with NETs that have spread outside the pancreas often have symptoms like diarrhea or hormone problems. These can often be helped with medicines like octreotide, lanreotide, diazoxide, and proton pump inhibitors. Some of these might also slow the growth of the tumor.

If further treatment is needed, chemotherapy or targeted drugs (such as sunitinib or everolimus) might be used, but this is usually delayed until a person is having symptoms that can’t be controlled with other drugs or has signs of tumor growth on scans. Surgery or ablative techniques might also be used to treat cancer spread to the liver.

For people with poorly differentiated tumors (neuroendocrine carcinomas), chemotherapy is typically the first treatment.

For adults with somatostatin (a type of hormone) receptor-positive pancreatic neuroendocrine tumors, a radiopharmaceutical drug, called Lutathera (lutetium Lu 177 dotatate), is also an option for treatment.

If treatment is no longer working at some point, you might want to think about taking part in a clinical trial testing a newer treatment. While these are not always the best option for every person, they may benefit you as well as future patients.

Ablation or embolization for pancreatic cancer

Ablation and embolization treatments are different ways of destroying tumors, rather than removing them with surgery. Ablation or embolization can sometimes be used to help treat pancreatic neuroendocrine tumor (NET) that has spread to other organs, especially the liver. When pancreatic NETs have spread to other sites, these treatments can often reduce tumor size and improve symptoms. But these treatments are very unlikely to cure cancers on their own. They are more likely to be used to help prevent or relieve symptoms, and are often used along with other types of treatment.

Ablative treatments (ablation)

Ablation refers to treatments that destroy tumors, usually with extreme heat or cold. They are generally best for tumors no more than about 2 cm (a little less than an inch) across. There are different kinds of ablative treatments:

• Radiofrequency ablation (RFA) uses high-energy radio waves. A thin, needle-like probe is put through the skin and into the tumor. Placement of the probe is guided by an ultrasound or CT scan. The tip of the probe releases a high-frequency electric current which heats the tumor and destroys the cancer cells.
• Microwave thermotherapy is similar to RFA, except it uses microwaves to heat and destroy the cancer cells.
• Ethanol (alcohol) ablation also known as percutaneous ethanol injection kills the cancer cells with concentrated alcohol injected directly into the tumor. This is usually done using a needle through the skin, guided by ultrasound or CT scans.
• Cryosurgery also known as cryotherapy or cryoablation destroys a tumor by freezing it with a thin metal probe. The probe is guided through the skin and into the tumor using an ultrasound. Then very cold gasses are passed through the probe to freeze the tumor, killing the cancer cells. This method may be used to treat larger tumors than the other ablation techniques, but it sometimes requires general anesthesia (where you are asleep).

Possible side effects after ablation therapy include abdominal pain, infection, and bleeding inside the body. Serious complications are uncommon, but they are possible.

Embolization

During embolization, substances are injected into an artery to try to block the blood flow to cancer cells, causing them to die. This may be used for larger tumors (up to 5cm or 2 inches across) in the liver.

There are 3 main types of embolization:

1. Arterial embolization also known as trans-arterial embolization (TAE) involves putting a catheter (a thin, flexible tube) into an artery through a small cut in the inner thigh and threading it up into the hepatic artery feeding the tumor. Blood flow is blocked (or reduced) by injecting materials to plug up that artery. Most of the healthy liver cells will not be affected because they get their blood supply from a different blood vessel, the portal vein.
2. Chemoembolization also known as trans-arterial chemoembolization (TACE) combines embolization with chemotherapy. Most often, this is done by using tiny beads that give off a chemotherapy drug during the embolization. TACE can also be done by giving chemotherapy through the catheter directly into the artery, then plugging up the artery.
3. Radioembolization combines embolization with radiation therapy. In the United States, this is done by injecting small radioactive beads (called microspheres) into the hepatic artery. The beads lodge in the blood vessels near the tumor, where they give off small amounts of radiation to the tumor site for several days. Since the radiation travels a very short distance, its effects are limited mainly to the tumor.

Possible complications after embolization include abdominal pain, fever, nausea, infection, and blood clots in nearby blood vessels. Serious complications are not common, but they can happen.

Radiation therapy for pancreatic neuroendocrine tumor

Radiation therapy uses high-energy rays (such as x-rays) or radioactive particles to kill cancer cells. Surgery is the main treatment for most pancreatic neuroendocrine tumors (NETs), but radiation therapy may be an option for those who can’t have surgery for some reason. It may also be given after surgery in some cases if there’s a chance some of the tumor was not removed and is causing problems. Radiation is sometimes used to treat pancreatic NETs that have spread to the bone and are causing pain. It may also be used in the form of radioembolization to treat NETs that have spread to the liver.

External beam radiation therapy

External beam radiation therapy uses a machine that delivers a beam of radiation to a specific part of the body. Before your treatment starts, the radiation team will determine the correct angles for aiming the radiation beams and the proper dose of radiation. The treatment is much like getting an x-ray, but the radiation is stronger. The procedure itself is painless. Each treatment lasts only a few minutes, although the setup time – getting you into place for treatment – usually takes longer. Most often, radiation treatments are given 5 days a week for several weeks, but this can vary based on the reason it’s being given.

Some common side effects of radiation therapy include:

• Skin changes in areas getting radiation, ranging from redness to blistering and peeling
• Nausea and vomiting
• Diarrhea
• Fatigue
• Loss of appetite
• Weight loss
• Low blood counts, which can increase the risk of serious infection.

Usually these side effects go away within a few weeks after the treatment is complete. Ask your doctor what side effects to expect and how to prevent or relieve them.

Radioembolization

Radioembolization combines embolization with radiation therapy and can be used to treat liver metastases. Small beads called microspheres are attached to a radioactive element called yttrium-90 (or 90Y) and then injected into an artery close to the liver. The beads travel in the liver blood vessels until they get stuck in small blood vessels near the tumor. There they give off radioactivity for a short while, killing nearby tumor cells. The radiation travels a very short distance, so its effects are limited mainly to the tumor.

Peptide receptor radionuclide therapy (PRRT)

People with somatostatin receptor-positive neuroendocrine tumors may be candidates for peptide receptor radionuclide therapy (PRRT). In PRRT, a radioactive element is linked to a small part (peptide) of a somatostatin analog, and injected into a vein in the arm. The drug travels throughout the body, attaches to the somatostatin receptor (a protein) on the cancer cell, and gives off radiation to kill it. The radiation is delivered directly to the tumor, so there is less effect on healthy tissue. There are several drugs that might be used:

• The radioactive element Yttrium-90
• The radioactive element Lutathera (lutetium or Lu-177 dotatate)

If you are already taking octreotide or lanreotide, you will most likely need to stop taking these medicines for a certain time before you can be treated with PRRT.

Common side effects of peptide receptor radionuclide therapy (PRRT) include low levels of white blood cells, abnormal liver tests, nausea and vomiting, high levels of blood sugar, and pain.

Serious side effects include low levels of blood cells, development of certain blood or bone marrow cancers, kidney damage, liver damage, abnormal levels of hormones in the body, and infertility. Tell your cancer care team if you are pregnant or might become pregnant, because Lu-177 dotatate can harm the baby. There is not enough information regarding Yttrium-90 in pregnant women so you should discuss this with your doctor.

Since these drugs expose you to radiation, people who might come into contact with you need to follow certain radiation safety practices to limit their exposure.

Chemotherapy for pancreatic neuroendocrine tumor

Chemotherapy (chemo) uses anti-cancer drugs injected into a vein or taken by mouth to kill cancer cells. These drugs enter the bloodstream and reach almost all areas of the body, making this treatment useful for some types of cancers that have spread.

Chemo is most often used to treat pancreatic neuroendocrine tumors (PNETs) if they:

• Have not responded to other medicines (such as somatostatin drugs or targeted therapy),
• Have spread to other organs,
• Are large or growing quickly,
• Are causing severe symptoms, or
• Are high grade (grade 3)

The most commonly used drugs for pancreatic NETs include:

• Doxorubicin (Adriamycin)
• Streptozocin
• Fluorouracil (5-FU)
• Dacarbazine (DTIC)
• Temozolomide (Temodar)
• Capecitabine (Xeloda)
• Oxaliplatin (Eloxatin)

Some tumors might be treated with more than one drug. Possible combinations include:

• Doxorubicin plus streptozocin
• 5-FU plus doxorubicin plus streptozocin
• Temozolomide plus capecitabine
• 5-FU plus streptozocin

Chemo drugs are typically given into a vein (IV), either as an injection over a few minutes or as an infusion over a longer period of time. This can be done in a doctor’s office, chemotherapy clinic, or in a hospital setting.

Doctors give chemo in cycles, with each period of treatment followed by a rest period to give you time to recover from the effects of the drugs. Cycles are most often 2 or 3 weeks long. The schedule varies depending on the drugs used. For example, with some drugs, the chemo is given only on the first day of the cycle. With others, it is given for a few days in a row, or once a week. Then, at the end of the cycle, the chemo schedule repeats to start the next cycle.

The length of treatment for advanced pancreatic NETs is based on how well it is working and what side effects you have.

Chemo drugs attack cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow (where new blood cells are made), the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemo, which can lead to side effects.

The side effects of chemo depend on the type and dose of drugs given and the length of time they are taken. Common side effects can include:

• Nausea and vomiting
• Loss of appetite
• Hair loss
• Mouth sores
• Diarrhea or constipation
• Increased chance of infections (from having too few white blood cells)
• Easy bruising or bleeding (from having too few blood platelets)
• Fatigue (from having too few red blood cells)

Most side effects go away after treatment is finished. Tell your cancer care team about any side effects or changes you notice while getting chemotherapy, so that they can be treated promptly. Often medicines can help prevent or minimize many of the side effects. For example, your doctor can prescribe drugs to help prevent or reduce nausea and vomiting. In some cases, the doses of the chemo drugs might need to be lowered or treatment might need to be delayed or stopped to keep the effects from getting worse.

Targeted drug therapy for pancreatic neuroendocrine tumor

Targeted drugs used to treat pancreatic neuroendocrine tumors (NETs) work by blocking angiogenesis (the growth of new blood vessels that nourish cancers) or important proteins (called tyrosine kinases) in cancer cells that help them grow and survive.

Sunitinib (Sutent)

Sunitinib blocks several tyrosine kinases and attacks new blood vessel growth. It has been shown to help slow tumor growth. This drug is taken as a pill once a day.

The most common side effects are nausea, diarrhea, changes in skin or hair color, mouth sores, weakness, and low blood cell counts. Other possible effects include tiredness, high blood pressure, heart problems, bleeding, hand-foot syndrome (redness, pain, and skin peeling of the palms of the hands and the soles of the feet), and low thyroid hormone levels.

Everolimus (Afinitor)

Everolimus blocks a protein known as mTOR, which normally helps cells grow and divide. It has been shown to help treat advanced pancreatic NETs. Everolimus is a pill taken once a day.

Common side effects of this drug include mouth sores, infections, nausea, loss of appetite, diarrhea, skin rash, feeling tired or weak, fluid buildup (usually in the legs), and increases in blood sugar and cholesterol levels. A less common but serious side effect is damage to the lungs, which can cause shortness of breath or other problems.

Belzutifan (Welireg)

Belzutifan is a type of drug known as a HIF inhibitor. It blocks a protein called hypoxia-inducible factor 2 alpha (HIF-2a), which is involved in both cancer cell growth and the formation of new blood vessels in tumors. This drug is taken as pills, typically once a day.

Belzutifan can be used in people with von Hippel-Lindau (VHL) disease who have a pancreatic NET and don’t need surgery right away.

Common side effects of this drug include low red blood cell counts (anemia), feeling tired and/or dizzy, nausea, headache, increased blood sugar levels, and changes in lab tests showing the drug might be affecting the kidneys. Less common but more serious side effects can include very low red blood cell counts (severe anemia), which might require blood transfusions, and low oxygen levels in the body, for which you might need oxygen therapy or even be admitted to the hospital.

Advanced pancreatic neuroendocrine tumors treatment

For people with advanced pancreatic neuroendocrine tumors (NETs), several medicines can help control symptoms and tumor growth. These drugs are used mainly when the tumor can’t be removed with surgery.

Somatostatin analogs

Somatostatin analogs are related to somatostatin, a natural hormone in the body. They can help slow the growth of neuroendocrine tumor cells. They can be very helpful for some patients with pancreatic NETs because these drugs stop tumors from releasing hormones into the bloodstream, which can often relieve symptoms and help patients feel better. They also seem to help slow the growth of some tumors, but cannot cure them.

These drugs can help reduce diarrhea in patients with VIPomas, glucagonomas, and somatostatinomas, help the rash of glucagonomas, and lower the levels of insulin in insulinomas. They are very useful in people who have carcinoid syndrome (facial flushing, diarrhea, wheezing, rapid heart rate), although this syndrome is not as common with NETs in the pancreas as it is with NETs found in other places. The drugs are also helpful for people whose tumors show up on a somatostatin receptor scintigraphy (SRS) scan or gallium-68 Dotatate scans.

• Octreotide (Sandostatin): One version of octreotide is short-acting and is injected 2 to 4 times a day under the skin. There is also a long-acting form of the drug (called Sandostatin LAR Depot) that only needs to be given once a month, by injection into a muscle. Depending on the severity of symptoms, some people are given injections every day when first starting treatment. Once symptoms are controlled, the longer-acting monthly injection may then be used. Other times, the long acting drug may be started from the beginning.
• Lanreotide (Somatuline Depot): This somatostatin analog is injected under the skin about once a month.

Either drug may be given by your doctor or nurse, or you may learn how to give the injection at home.

The main side effects of these drugs are pain at the site of the injection, and rarely, stomach cramps, nausea, vomiting, headaches, dizziness, and fatigue. These drugs can also cause sludge to build up in the gallbladder, which can lead to gallstones. They can also make the body resistant to the action of insulin, which can raise blood sugar levels and make pre-existing diabetes harder to control. As a result, these drugs are only used to treat insulinomas if the tumor has somatostatin receptors as seen by a positive somatostatin receptor scintigraphy (SRS) or gallium-68 Dotatate scan.

Other drugs used for specific pancreatic neuroendocrine tumors

Gastrinomas make too make gastrin, which increases stomach acid levels, and can lead to stomach ulcers. Proton pump inhibitors, for example omeprazole (Prilosec), esomeprazole (Nexium), or lansoprazole (Prevacid), block stomach acid production and may be given to decrease the chance of ulcers forming.

Insulinomas make too much insulin which causes very low blood glucose (sugar) levels. If the somatostatin receptor scintigraphy (SRS) or gallium-68 Dotatate scans are negative, showing the cancer does not have the somatostatin protein, then other treatments besides somatostatin analogs are considered to even out glucose levels. Diazoxide, a drug that keeps insulin from being released into the bloodstream, or diet changes (higher carbohydrate intake or more frequent meals) may be started to raise glucose levels.

Glucagonomas make too much glucagon, a hormone that increases blood glucose (sugar) levels. It works opposite of insulin. These cancers may be treated with medicines for diabetes if somatostatin analogs alone are not enough to control the high glucose levels.

VIPomas make too much vasoactive intestinal peptide (VIP), a hormone that regulates water and mineral (such as potassium and magnesium) levels in the gut. Treatment may involve giving intravenous (IV) fluids to treat the dehydration from diarrhea as well as certain minerals that are low.

Pancreatic cancer life expectancy and survival

Survival rates tell you what portion of people with the same type and stage of cancer are still alive a certain amount of time (usually 5 years) after they were diagnosed. They can’t tell you how long you will live, but they may help give you a better understanding about how likely it is that your treatment will be successful. Some people will want to know the survival rates for their cancer, and some people won’t. If you don’t want to know, you don’t have to.

Pancreatic cancer survival rate

Statistics on the outlook for a certain type and stage of cancer are often given as 5-year survival rates, but many people live longer – often much longer – than 5 years. The 5-year survival rate is the percentage of people who live at least 5 years after being diagnosed with cancer. For example, a 5-year survival rate of 70% means that an estimated 70 out of 100 people who have that cancer are still alive 5 years after being diagnosed. Keep in mind, however, that many of these people live much longer than 5 years after diagnosis. In general, people who can be treated with surgery tend to live longer than those not treated with surgery.

But remember, the 5-year relative survival rates are estimates – your outlook can vary based on a number of factors specific to you.

Cancer survival rates don’t tell the whole story

Survival rates are often based on previous outcomes of large numbers of people who had the disease, but they can’t predict what will happen in any particular person’s case. There are a number of limitations to remember:

• The numbers below are among the most current available. But to get 5-year survival rates, doctors have to look at people who were treated at least 5 years ago. As treatments are improving over time, people who are now being diagnosed with pancreatic cancer may have a better outlook than these statistics show.
• These statistics are based on the stage of the cancer when it was first diagnosed. They do not apply to cancers that later come back or spread, for example.
• The outlook for people with pancreatic cancer varies by the stage (extent) of the cancer – in general, the survival rates are higher for people with earlier stage cancers. But many other factors can affect a person’s outlook, such as age and overall health, and how well the cancer responds to treatment. The outlook for each person is specific to their circumstances.
• Survival rates tell you what portion of people with the same type and stage of cancer are still alive a certain amount of time (usually 5 years) after they were diagnosed. These numbers can’t tell you how long you will live, but they may help give you a better understanding about how likely it is that your treatment will be successful. Some people will want to know the survival rates for their cancer, and some people won’t.

Your doctor can tell you how these numbers may apply to you, as he or she is familiar with your particular situation.

The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database tracks 5-year relative survival rates for pancreatic cancer in the United States, based on how far the cancer has spread. The SEER database, however, does not group cancers by American Joint Committee on Cancer (AJCC) TNM stages (stage 1, stage 2, stage 3, etc.). Instead, it groups cancers into localized, regional, and distant stages:

• Localized: There is no sign that the cancer has spread outside of the pancreas. This usually includes Stage 0 and 1 cancers.
• Regional: The cancer has spread from the pancreas to nearby structures or lymph nodes. This typically includes Stage 2 and 3 cancers.
• Distant: The cancer has spread to distant parts of the body such as the lungs, liver or bones. This usually includes all stage 4 cancers.

Table 3. 5-year relative survival rates for pancreatic cancer

Footnote: SEER= Surveillance, Epidemiology, and End Results

Understanding the numbers

• Based on people diagnosed with pancreatic cancer between 2011 and 2017.
• These numbers apply only to the stage of the cancer when it is first diagnosed. They do not apply later on if the cancer grows, spreads, or comes back after treatment.
• These numbers don’t take everything into account. Survival rates are grouped based on how far the cancer has spread, but your age, overall health, how well the cancer responds to treatment, tumor grade, extent of resection, level of tumor marker (CA 19-9) and other factors will also affect your outlook.
• People now being diagnosed with pancreatic cancer may have a better outlook than these numbers show. Treatments improve over time, and these numbers are based on people who were diagnosed and treated at least five years earlier.

Survival rates for exocrine pancreatic cancer

The numbers below come from the National Cancer Data Base and are based on people diagnosed with exocrine pancreatic cancer between 1992 and 1998 ³. In general, people who can be treated with surgery tend to live longer than those not treated with surgery.

• The 5-year survival rate for people with stage 1A pancreatic cancer is about 14%. For stage 1B cancer, the 5-year survival rate is about 12%.
• For stage 2A pancreatic cancer, the 5-year survival rate is about 7%. For stage 2B cancer, the 5-year survival rate is about 5%.
• The 5-year survival rate for stage 3 pancreatic cancer is about 3%.
• Stage 4 pancreatic cancer has a 5-year survival rate of about 1%. Still, there are often treatment options available for people with this stage of cancer.

According to Surveillance, Epidemiology, and End Results Program (SEER 18) 2007-2013, All Races, Both Sexes ~ 8.2 Percent Surviving 5 Years ⁴.

Survival by Stage

Cancer stage at diagnosis, which refers to extent of a cancer in the body, determines treatment options and has a strong influence on the length of survival ⁴. In general, if the cancer is found only in the part of the body where it started it is localized (sometimes referred to as stage 1). If it has spread to a different part of the body, the stage is regional or distant. The earlier pancreatic cancer is caught, the better chance a person has of surviving five years after being diagnosed. For pancreatic cancer, 9.7% are diagnosed at the local stage. The 5-year survival for localized pancreatic cancer is 31.5%.

Remember, these survival rates are only estimates – they can’t predict what will happen to any individual person. We understand that these statistics can be confusing and may lead you to have more questions. Talk to your doctor to better understand your specific situation.

Survival rates for neuroendocrine pancreatic tumors (treated with surgery)

For pancreatic neuroendocrine tumors (PNETs), survival statistics by stage are only available for patients treated with surgery. These numbers come from the National Cancer Data Base and are based on patients diagnosed between 1985 and 2004.

• The 5-year survival rate for people with stage 1 pancreatic NETs is about 61%.
• For stage 2 pancreatic NETs, the 5-year survival rate is about 52%.
• The 5-year relative survival rate for stage 3 pancreatic NETs is about 41%.
• Stage 4 pancreatic NETs have a 5-year survival rate of about 16%. Still, there are often treatment options available for people with these cancers.

In this database, the overall 5-year survival rate for people who did not have their tumors removed by surgery was 16%.

The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database tracks 5-year relative survival rates for pancreatic NET in the United States, based on how far the cancer has spread. The SEER database, however, does not group cancers by AJCC TNM stages (stage 1, stage 2, stage 3, etc.). Instead, it groups cancers into localized, regional, and distant stages:

• Localized: There is no sign the cancer has grown outside of the pancreas.
• Regional: The cancer has grown outside the pancreas into nearby tissues or has spread to nearby lymph nodes.
• Distant: The cancer has spread to distant parts of the body such as the lungs, liver or bones.

Table 4. 5-year relative survival rates for pancreatic neuroendocrine tumors (PNETs)

Footnotes:

• These numbers are based on people diagnosed with pancreatic NET between 2011 and 2017.
• These numbers apply only to the stage of the cancer when it is first diagnosed. They do not apply later on if the cancer grows, spreads, or comes back after treatment.
• These numbers don’t take everything into account. Survival rates are grouped based on how far the cancer has spread, but your age, overall health, how well the cancer responds to treatment, tumor grade, tumor function, and other factors can also affect your outlook.
• People now being diagnosed with pancreatic NET may have a better outlook than these numbers show. Treatments improve over time, and these numbers are based on people who were diagnosed and treated at least five years earlier.

1. Pancreatic Cancer Stages. https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/staging.html
2. Survival Rates for Pancreatic Cancer. https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html
3. Pancreatic Cancer Survival Rates, by Stage. https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html
4. Cancer Stat Facts: Pancreatic Cancer. https://seer.cancer.gov/statfacts/html/pancreas.html
5. Survival Rates for Pancreatic Neuroendocrine Tumor. https://www.cancer.org/cancer/pancreatic-neuroendocrine-tumor/detection-diagnosis-staging/survival-rates.html

Cloacal exstrophy

Cloacal exstrophy, also known as OEIS Syndrome, occurs when a portion of the large intestine lies outside of the body and on either side of it and connected to it are the two halves of the bladder. The intestine may be short and the anus may not open. The bony pelvis is also split open like a book. In males, the penis is usually flat and short, with the exposed inner surface of the urethra on top. The penis is sometimes split into a right and left half. In girls, the clitoris is split into a right half and left half and there may be one or two vaginal openings. Cloacal exstrophy (OEIS syndrome) is a very rare birth defect, affecting 1 in every 250,000 births. Although cloacal exstrophy is a serious condition and requires a series of operations, the long-term outcome is good for many children. Patients and families need to be counseled about the complexity of the anomaly, the need for multiple procedures, and long-term expectations for continence, sexual function, and fertility.

Cloacal exstrophy is known as OEIS Syndrome because of the four features that are typically found together ¹:

• Omphalocele: Some of the abdominal organs protrude through an opening in the abdominal muscles in the area of the umbilical cord. The omphalocele may be small, with only a portion of the intestine protruding outside the abdominal cavity, or large, with many of the abdominal organs (including intestine, liver and spleen) protruding outside the abdominal cavity.
• Exstrophy of the bladder and rectum: The bladder is open and separated into two halves. The rectum and colon are similarly open and the segment of the rectum is placed between the bladder halves on the surface of the abdomen.
• Imperforate anus: The anus has not been formed or perforated and the colon connects to the bladder.
• Spinal defects: These defects may either be major or minor. Often children born with cloacal exstrophy are also born with some degree of spina bifida.

With cloacal exstrophy there are often other birth defects, like spina bifida. This occurs in up to 75 percent of cases. Kidney abnormalities and omphalocele are also common. An omphalocele is when an infant’s intestine or other abdominal organs are open to the outside the body. This is from a hole in the belly button (navel) area. The intestines are covered only by a thin layer of tissue and can be easily seen.

Cloacal exstrophy (OEIS Syndrome) is a complex anomaly that often requires several surgical procedures and requires lifelong medical follow-up care.

As soon as possible, surgical reconstruction is done. Surgery is major, and often done in parts. The schedule of surgery depends on the child’s condition and overall health. Surgery can return the bladder and bowel organs back into the body, to a healthy position. It can provide ways for bowel and urinary control, better kidney function, and improve the way the sex organs or genitals look.

Reconstruction surgery often starts within the first few days of life. It is sometimes delayed to allow the baby to grow and develop. Surgical repair is generally divided into steps and include:

• Repair of spinal abnormalities, and if needed, the repair of a large omphalocele.
• Once the child has recovered from spinal surgery, the gastrointestinal tract is treated. Many babies require a stoma because the colon is not normal, and the anus is not formed. The stoma will allow for waste to be released from the intestines to a pouch on the outside of the body.
• Closure of the exposed bladder and bowel and reconstruction of the genitals are next. This may be done in steps if the pelvic bones are widely separated. For a successful closure, a pelvic osteotomy (cutting the bones to allow the pelvis to close more easily) is critical. In some cases, the abdominal wall, the bladder and genitals (genitourinary system) and the bowel may be repaired at the same time. Bladder reconstruction often includes the use of a catheter for some time.

Figure 1. Cloacal exstrophy

Figure 2. Cloacal exstrophy ultrasound

Footnote: Fetal ultrasound at 36 weeks’ gestation demonstrating bowel loops herniating between 2 bladder plates (“elephant trunk”).

Figure 3. Cloacal bladder exstrophy female infant

Figure 4. Cloacal bladder exstrophy male infant

Will my child be able to have children when they reach adulthood?

In many cases, the answer to this question is: yes. But almost always, assisted fertility is necessary for adults.

With regard to sexuality, males are generally potent, but some report inadequate phallus or residual curvature. Females report normal sexual function ⁴.

With respect to fertility and childbearing, retrograde ejaculation or iatrogenic obstruction of the ejaculatory ducts or vas deferens after surgical reconstruction may result in abnormal semen analysis. Antegrade ejaculation is preserved after single-stage repair, but abnormal semen parameters are common. However, fertilization, with viable pregnancy, has been achieved by male patients with cloacal exstrophy ⁵.

Females have had successful pregnancies ⁶. Cesarean delivery is recommended to avoid injury to continence mechanism. Postpartum uterine prolapse is common because of aggravation of preexisting abnormal pelvic support.

Cloacal exstrophy causes

The cause of cloacal exstrophy is currently unknown, so there is also no known way to prevent it. On the basis of the known embryologic principles of cloacal development, any inciting event would have to occur early in pregnancy.

There is a higher incidence of cloacal exstrophy in families in which one member is affected as compared with the general population. Offspring of patients with exstrophy-epispadias complex have a 1 in 70 risk (500 times that of the general population) of being affected. Nevertheless, familial occurrence is uncommon in large series ⁷. The heritability of cloacal exstrophy has not been established, because no offspring have been reported. Moreover, there’s no evidence to suggest that anything done by expectant parents leads to the condition.

At present, 22q11.2 duplication is the genetic variant most commonly associated with bladder exstrophy-epispadias complex ⁸.

Cloacal exstrophy has been reported in twins. Concordance rates show strong evidence of genetic effects ⁹, but less than 100% concordance among identical twins suggests some role for environmental effect on development of exstrophy-epispadias.

A higher incidence of bladder exstrophy is observed in infants of younger mothers and in those with relatively high parity.

Maternal tobacco exposure is associated with more severe defects (cloacal vs classic exstrophy).

Growing evidence suggests an increased incidence of cloacal exstrophy and bladder exstrophy-epispadias with in-vitro fertilization (IVF) pregnancies ¹⁰.

Cloacal exstrophy symptoms

In some cases, cloacal exstrophy is detected from a routine prenatal ultrasound. In other cases, it isn’t diagnosed until birth, when physicians can clearly see the exposed organs.

Antenatal ultrasound findings suggestive of exstrophy-epispadias complex include the following:

• Repeated failure to visualize the bladder on ultrasound
• Lower-abdominal-wall mass
• Low-set umbilical cord
• Abnormal genitalia
• Increased pelvic diameter

Additional antenatal ultrasound findings suggestive of cloacal exstrophy include the following:

• Omphalocele
• Limb abnormalities
• Myelomeningocele
• Trunk sign from prolapsed intestine

Increased use of fetal magnetic resonance imaging (MRI) may further improve the accuracy of antenatal diagnosis, but this test is not necessary if suspicion is high on the basis of ultrasound findings.

Classic bladder exstrophy and cloacal exstrophy are obvious to all in the delivery room. Variants of the exstrophy-epispadias complex exist, including skin-covered bladder exstrophy, duplicate bladders, superior vesical fistula, and epispadias with major bladder prolapse ¹¹. Most exstrophy variants and epispadias are also identifiable at birth. Unrecognized female epispadias may present as persistent childhood incontinence. Unrecognized split-symphysis variants of exstrophy may be identified in childhood only because of persistent incontinence or a waddling gait.

Physical examination

Patients with classic bladder exstrophy or epispadias typically appear as term infants. Patients with cloacal exstrophy, however, are often preterm. They may have respiratory embarrassment requiring mechanical ventilation.

Abdominal findings

In classic cloacal bladder exstrophy (see the images above), the bladder is open on the lower abdomen, with mucosa fully exposed through a triangular fascial defect. The abdominal wall appears long because of a low-set umbilicus on the upper edge of the bladder plate. The distance between the umbilicus and anus is foreshortened. The recti diverge distally, attaching to the widely separated pubic bones. Indirect inguinal hernias are frequent (>80% of males, >10% of females) because of wide inguinal rings and the lack of an oblique inguinal canal.

Nearly all patients with cloacal exstrophy have an associated omphalocele. The bladder is open and separated into two halves, flanking the exposed interior of the cecum. Openings to the remainder of the hindgut and to one or two appendices are evident within the cecal plate. Terminal ileum may prolapse as a “trunk” of bowel onto the cecal plate.

In cloacal exstrophy variants, the pubic symphysis is widely separated, and the recti diverge distally. The umbilicus is low or elongated. A small superior bladder opening or a patch of isolated bladder mucosa may be present. The intact bladder may be externally covered by only a thin membrane. Isolated ectopic bowel segments have been reported.

Genital findings

In describing the anatomy of the penis, the terms dorsal and ventral refer to a normal phallus in the erect state. The dorsal surface is in continuity with the abdominal wall, and the ventral surface is in continuity with the scrotum.

In cloacal exstrophy, the penis is generally quite small and bifid, with a hemiglans located just caudal to each hemibladder. Infrequently, the phallus may be intact in the midline. In females, the clitoris is bifid, and two vaginas are present. The anus is absent.

In exstrophy variants, the genitalia generally are intact (see the image below), though epispadias can occur.

In classic bladder exstrophy in males, the phallus is short and broad with upward curvature (dorsal chordee). The glans lies open and flat like a spade, and the dorsal component of the foreskin is absent. The urethral plate extends the length of the phallus without a roof. The bladder plate and urethral plate are in continuity, with the verumontanum and ejaculatory ducts visible within the prostatic urethral plate. The anus is anteriorly displaced with a normal sphincter mechanism.

In classic bladder exstrophy in females, the clitoris is uniformly bifid with divergent labia superiorly. The open urethral plate is in continuity with the bladder plate. The vagina is anteriorly displaced. The anus is anteriorly displaced with a normal sphincter mechanism.

In male epispadias, the phallus is short and broad with upward curvature (dorsal chordee). The glans lies open and flat like a spade, and the dorsal component of the foreskin is absent. The urethral meatus is located on the dorsal penile shaft, anywhere between the penopubic angle and the proximal margin of the glans.

In female epispadias, the clitoris is most often bifid with divergent labia superiorly. The dorsal aspect of the urethra is open distally. The urethra and bladder neck are patulous and may allow visualization of bladder. Bladder mucosa may prolapse through the bladder neck.

Musculoskeletal findings

In classic bladder exstrophy, the pubic symphysis is widely separated. Divergent rectus muscles remain attached to the pubis. External rotation of the innominate bones results in a waddling gait in ambulatory patients but does not appear to result in orthopedic problems later in life.

In cloacal exstrophy, the examination is the same as for bladder exstrophy. As many as 65% of patients have a clubfoot or major deformity of a lower extremity. As many as 80% of patients have vertebral anomalies.

In split-symphysis variants of exstrophy, the pubic symphysis is widely separated (see the image below), and the rectus muscles are divergent.

Neurologic findings

In cloacal exstrophy, as many as 95% of patients have myelodysplasia, which may include myelomeningocele, lipomeningocele, meningocele, or other forms of occult dysraphism. These patients are at risk for neurologic deterioration, and they should be observed closely. Early neurosurgical consultation is appropriate if a radiographic abnormality of the spinal cord or canal is observed.

Cloacal exstrophy diagnosis

Cloacal exstrophy can usually be diagnosed by fetal ultrasound before an infant is born. Upon birth, a physical exam will confirm the diagnosis.

Laboratory studies

Before complex reconstruction of the urinary tract, it is important to obtain information about the patient’s baseline renal function. In patients with cloacal exstrophy, losses from the terminal ileum short-gut physiology can result in significant electrolyte abnormalities.

Imaging studies

Baseline examination of the kidneys with ultrasonography is recommended for all patients with exstrophy because increased bladder pressure after bladder closure can lead to hydronephrosis and upper urinary tract deterioration. Congenital upper urinary tract anomalies are uncommon with classic exstrophy and epispadias but are present in approximately one third of patients with cloacal exstrophy (eg, ectopic pelvic kidney, renal agenesis, or hydronephrosis).

Spinal ultrasound or radiography may be helpful. Myelodysplasia should be excluded in newborns with cloacal exstrophy. This can be accomplished by means of ultrasound early in life. In cloacal exstrophy, magnetic resonance imaging (MRI) is recommended to help identify occult abnormalities that may predispose to symptomatic spinal cord tethering.

Bilateral vesicoureteral reflux (VUR) is present in nearly all patients with classic bladder exstrophy. Voiding cystourethrography (VCUG) is performed in early childhood to assess bladder capacity in preparation for reconstructive continence surgery. Evaluation of the bladder neck and proximal urethra is recommended in patients with epispadias in order to plan surgical management.

Managing pregnancy after a cloacal exstrophy diagnosis

Because cloacal exstrophy is a high-risk condition, you will need to be monitored throughout your pregnancy. In some cases, pregnancy may be complicated by polyhydramnios (excess amniotic fluid) during the third trimester, which may trigger preterm labor and delivery. Your delivery should also be planned at our state-of-the-art facility. This way, our delivery team can address any complications should they arise and the baby will have immediate access to treatment and the best surgical professionals.

Cloacal exstrophy treatment

Cloacal exstrophy is treated through surgical repair after birth, usually in stages to address each defect. This requires an in-depth treatment plan to be created for your child’s specific needs. The extent of cloacal exstrophy surgery required for your baby depends on the type and severity of his or her abnormalities.

Your child will undergo a series of surgeries over a number of years — referred to as staged reconstruction. The exact timing, nature and outcome of each cloacal exstrophy surgery will depend on your child’s particular situation. Your child’s surgeons will create a treatment plan based on the type and the extent of your child’s condition and discuss the plan with you. Usually surgery begins in the first days of life with the highest-priority procedure. Surgeons usually repair the bladder, create a colostomy (an opening in the colon with an attached “bag” that allows stool to pass) and repair the abdominal wall defect.

Babies with spinal defects usually have them repaired sometime in the first few days of life. Later surgeries include urinary and genital reconstruction, as well as an operation to create a rectum and close the colostomy opening. There are no fetal interventions (surgical procedures while inside the uterus) for cloacal exstrophy.

Treatment may include:

• Abdominal repair: Typically, soon after your child is born, the surgeons will repair the omphalocele by closing the bladder and creating a colostomy so your child can eliminate stool. With a colostomy, the large intestine is separated from the bladder halves and reclosed. The two halves of the bladder are brought together and placed into the abdomen. The end of the large intestine is brought to the surface of the skin through an opening in the abdomen. A plastic bag, called a colostomy pouch, is placed over the opening to collect the stool.
• Other surgery, such as surgery to repair the spine, may be planned around the initial stage of the abdominal repair.

After the initial surgery, your child will remain in the hospital where we will monitor the intestine as it begins to function. Our team will work with you and your family to ensure that the plan for your child is clear and that you have access to the supports you need.

• Osteotomies: Once your child has healed from his first procedure and had some time to grow, we will schedule the second stage of the repair. This primarily involves working on the bladder. The orthopedic surgeon on our team will perform osteotomies to help ensure that your child’s pelvis can best support the bladder over time. During the osteotomy the hip bones are cut and adjusted. Your child will need to be in traction or in a spica cast for several weeks following this surgery.
• Pull-through procedure: If your child was born with a significant amount of colon and is capable of forming solid stool, a surgical procedure, known as a “pull through” may eventually be performed. The purpose of this procedure is to connect the colon to the rectum.

Subsequent surgeries may also involve major urinary reconstructive surgery and further genital reconstruction. These issues will be discussed with you and your family as your child grows up.

Cloacal exstrophy repair

Reconstruction of exstrophy-epispadias complex remains one of the greatest challenges facing the pediatric urologist. Many modifications in surgical procedures have improved outcomes, but the optimal approach remains uncertain. Longitudinal prospective assessment of the two main current surgical approaches (staged procedure and total reconstruction) is critical for optimizing functional and cosmetic outcomes.

Complete primary reconstruction is now more than 20 years old; however, each approach is in a constant state of minor modification. Data on this approach continue to mature and are updated almost yearly ¹². Analysis of each experience focuses on daytime continence with volitional voiding, need for further surgical procedures, and complication rates. In experienced hands, the safety and efficacy of the different approaches are comparable.

Goals of therapy include provision of urinary continence with preservation of renal function and reconstruction of functional and cosmetically acceptable genitalia. Creation of a neoumbilicus is also important to many of these patients.

Surgical techniques used in the treatment of exstrophy-epispadias complex include the following:

• Staged functional closure for classic bladder exstrophy (ie, modern staged repair of exstrophy) ¹³
• Complete primary repair for classic bladder exstrophy
• Urinary diversion for classic bladder exstrophy
• Closure for cloacal exstrophy
• Gender reassignment

Staged functional closure for classic bladder exstrophy

Modern staged repair of exstrophy, which represents the traditional surgical approach, comprises a series of operations. Initial bladder closure is completed within 72 hours of birth. If this is delayed, pelvic osteotomies are required to facilitate successful closure of the abdominal wall and to allow the bladder to lie within a closed and supportive pelvic ring.

Epispadias repair with urethroplasty is performed at age 12-18 months. This allows enough increase in bladder outlet resistance to improve the bladder capacity.

Bladder neck reconstruction (typically a modified Young-Dees-Leadbetter repair) is performed at age 4 years. This allows continence and correction of vesicoureteral reflux (VUR). Multiple modifications have been proposed. The procedure is delayed until bladder capacity is adequate; better results are reported with a capacity greater than 85 mL.

Chua et al retrospectively studied a modification of staged exstrophy repair aimed at incorporating the advantages of complete primary repair for classic bladder exstrophy by avoiding concurrent epispadias repair and adding bilateral ureteral reimplantation and bladder neck tailoring (staged repair of bladder exstrophy with bilateral ureteral reimplantation) at the initial repair ¹⁴. They found staged repair of bladder exstrophy with bilateral ureteral reimplantation to be a safe alternative for exstrophy-epispadias repair, preventing penile tissue loss and yielding long-term outcomes comparable to those of complete primary repair for classic bladder exstrophy.

The radical soft-tissue mobilization (radical soft-tissue mobilization) procedure, also referred to as the Kelly repair, has been suggested as an alternative approach to staged reconstruction of bladder exstrophy ¹⁵. Radical soft-tissue mobilization has been performed not only as the second part of a two-step strategy (after bladder closure) but also as part of a combined procedure that includes delayed bladder closure and radical soft-tissue mobilization in a single stage without pelvic osteotomy ¹⁶.

Complete primary repair for classic bladder exstrophy

Compared with modern staged repair of exstrophy, complete primary repair for classic bladder exstrophy is a newer approach to exstrophy closure. Primary bladder closure, urethroplasty, and genital reconstruction are performed in a single stage in newborns. This procedure involves complete penile disassembly in males and mobilization of the urogenital complex in females. Hypospadias is a common outcome in males and requires subsequent reconstruction.

The goal is early bladder cycling. A subset of patients have achieved continence without bladder neck reconstruction.

In a study of 34 boys treated with a modified penile disassembly technique (15 with bladder exstrophy who underwent complete primary repair for classic bladder exstrophy, 11 with penopupic epispadias after previous closure of bladder exstrophy, and eight with isolated complete epispadias), Anwar et al found the modified technique to yield excellent cosmetic results ¹⁷. Preservation of the distal urethral plate along with both hemiglans avoided shortening and prevented occurrence of hypospadias.

Urinary diversion for classic bladder exstrophy

Urinary diversion was the original surgical treatment of choice. Diversion may be performed in a patient with an extremely small bladder plate not suitable for functional closure ¹⁸. In Europe, early diversion has been widely used, with success for most exstrophy patients.

Closure for cloacal exstrophy

Treatment of myelodysplasia and gastrointestinal anomalies has priority over management of urinary and genital anomalies.

Closure can be either staged or performed in a single stage, depending on the overall condition of the child and the severity of the abdominal wall defect. If a large omphalocele is present, successful closure of the abdomen and the bladder in one stage may be difficult to accomplish.

The first stage involves separation of the gastrointestinal and genitourinary (genitourinary) tracts, closure of the colon, creation of a colostomy, and closure of the omphalocele. The bladder plates are brought together in the midline.

Because virtually all of these patients have some element of short-gut syndrome, the hindgut should be incorporated into the gastrointestinal tract to maximize absorptive surface area. Ileostomy should be avoided because of the high incidence of recurrent hospitalizations for dehydration and severe electrolyte abnormalities. The decision between rectal pull-through and permanent colostomy is based on the surgeon’s preference and the projected potential for social fecal continence ¹⁹.

Subsequent bladder closure is carried out as in surgical management of classic bladder exstrophy. The principles of complete primary repair have been applied at this point as well. Consideration may be given to continent diversion as the second stage, on the basis of poor potential for volitional voiding and continence.

Because of more severe pubic diastasis, pelvic osteotomies are required. Staged pelvic osteotomy (staged pelvic osteotomy) with gradual closure of the pelvis may be needed in severe cases ²⁰. In a study comparing staged pelvic osteotomy before bladder closure with combined pelvic osteotomy (combined pelvic osteotomy) at the time of closure in cloacal exstrophy patients, Inouye et al found that staged pelvic osteotomy reduced preoperative diastasis more than combined pelvic osteotomy did, without appearing to incur increased rates of complication, closure failure, or incontinence ²¹.

Gender reassignment

Historically, all males with cloacal exstrophy underwent early gender conversion because of inadequate male genitalia. Testicular histology is normal despite frequent cryptorchidism.

Evidence suggesting that testosterone in utero has a significant impact on the developing brain has led to a change in surgical philosophy, as has anecdotal evidence suggesting that raising a 46,XY cloacal exstrophy patient as female can result in significant gender dysphoria. Cloacal exstrophy is now included as a subset of disorders of sex development ²². Multidisciplinary evaluation and both early and long-term counseling should be offered.

Intraoperative concerns

Multiple or lengthy surgical procedures with exposure to latex antigens increase the risk of latex sensitization or allergy ²³. Approximately 30% of patients with bladder exstrophy have demonstrated symptoms of latex allergy, and 70% reveal sensitization (elevation of specific immunoglobulin E [IgE] antibody) to latex antigens. For practical purposes, all patients with exstrophy-epispadias complex should be considered to be latex-sensitive.

Full latex precautions are recommended in the operating room, beginning with preparation for the first operative procedure. Potential latex-containing materials in the operating room include gloves, catheters, drains, masks, anesthesia materials, bandages, and thromboembolic stockings. Polyvinyl chloride and silicone are acceptable alternatives. Latex allergy should be considered seriously in the event of intraoperative anaphylaxis. The offending agent should be removed and the surgical procedure aborted if necessary.

Treatment includes cardiopulmonary resuscitation with fluids, epinephrine, steroids, and histamine blockade. In those with a known latex allergy, premedication with steroids and histamine H1 and H2 blockers should be considered.

After cloacal exstrophy repair

The goal of surgeons and doctors is to help improve the child’s quality of life. Better tools for anesthesia and infant nutrition have helped to increase the survival rate for newborns with this condition.

Postoperatively, patients with exstrophy remain in the hospital in modified Bryant traction (legs adducted and pelvis slightly elevated) for 3 weeks after bladder closure. Alternative techniques of immobilization may be used, based on osteotomies or institutional protocol.

Bladder and kidneys are drained fully with multiple catheters during the first few weeks after closure.

Nutritional support is mandatory for patients with cloacal exstrophy. Patients with classic bladder exstrophy may also have early difficulties feeding because of the body position in traction.

It’s important to work closely with your health care team to prevent infection after surgery, and learn about long-term care. After surgery, a child born with cloacal exstrophy can usually grow to manage urine and stool in a socially acceptable way. Further operations may be needed over time to improve the child’s ability to control their bladder and bowel function. More surgery may also be needed to rebuild and/or make better the outer sex organs.

Time and patience will be important for the parents and child. Neurologic issues from spina bifida, if present, can be managed, but requires ongoing medical care.

Complications

In the treatment of complex congenital anomalies, the distinction between technical complications and problems inherent to the anomaly is not always obvious.

Failure of closure may occur. If the bladder plate is adequate, reclosure with pelvic osteotomies is recommended. In this instance, bladder closure and epispadias repair are performed in one stage. Urinary diversion is the alternative therapy.

A vesicocutaneous fistula or urethrocutaneous fistula may form after primary closure or urethral reconstruction. If spontaneous closure does not occur, surgical repair is required.

Loss of the hemiglans or corporal body has been reported as a result of complete primary repair ²⁴.

Minor orthopedic complications may occur after osteotomy or immobilization.

Upper urinary tract deterioration is a potential complication. Causes include excessive outlet resistance and high pressure in a small-capacity reservoir and persistent VUR.

Abnormal bladder function may result in poor emptying. Clinical problems related to poor emptying include recurrent febrile infections, epididymitis, bladder stones, acute urinary retention, and rupture of the native bladder.

Bladder prolapse is a potential complication. Posterior bladder wall may prolapse through the patulous bladder neck after primary closure (see the image below). Recurrent prolapse, congestion, ischemia of bladder mucosa, or failure of ureteral drainage warrants early surgical correction.

Malignancy is a rare late complication of bladder exstrophy and is more common in untreated patients whose bladders are left exstrophic for many years. Adenocarcinoma is the most common of these malignancies, from the precursor cystitis glandularis, which is caused by chronic irritation and inflammation of exposed mucosa of the exstrophic bladder. Squamous cell carcinoma and rhabdomyosarcoma have also been reported.

Adenocarcinoma may develop adjacent to the ureterointestinal anastomosis in patients with urinary diversions that mix the urinary and fecal streams. This malignancy was reported in more than 10% of patients in one series ²⁵. Patients younger than 25 years with ureterosigmoidostomy have a 7000-fold greater risk of adenocarcinoma of the colon than the general population (mean latency, 10 years).

Complications of short-gut syndrome are as follows:

• Paucity of hindgut and, in many cases, limited small intestine can result in electrolyte abnormalities in patients with cloacal exstrophy
• Dehydration is particularly a concern during an acute GI illness with diarrhea
• Nutritional supplementation may be required

Cloacal exstrophy prognosis

Surgical techniques to treat cloacal exstrophy have improved dramatically in recent years, which means 90% to 100% of babies survive after surgery. Their quality of life and degree of need for ongoing care vary from case to case.

Mortality with classic bladder exstrophy or epispadias is rare. Historically, cloacal exstrophy was associated with significant mortality. Reconstruction was not attempted until the 1970s. Advances in the care of critically ill neonates and recognition of the importance of early parenteral nutritional support have allowed successful reconstruction and survival of children with cloacal exstrophy.

Survival rates after surgical treatment are excellent. With respect to bladder function or continence, reports vary according to the type of reconstruction performed ²⁶. Objective and subjective evidence indicates that many exstrophic bladders do not function normally after reconstruction and may deteriorate over time.

Continence rates of 75-90% have been reported after staged reconstruction in classic exstrophy, but more than one continence procedure may be required (eg, bladder neck reconstruction, bladder augmentation, bladder neck sling, or artificial urinary sphincter). Many of these patients require clean intermittent catheterization (CIC) through the urethra or a continent stoma because they are unable to void spontaneously to completion. Less encouraging results also are reported.

Continence results after staged reconstruction are poor (< 25%) in cloacal exstrophy because of abnormal bladder innervation in many patients. Experience with rectal reservoirs (ureterosigmoidostomy and variants) for exstrophy continence demonstrates rates higher than 95%, but they present long-term malignancy risks ²⁷. Continent reconstruction with intestinal bladder augmentation and clean intermittent catheterization has a success rate greater than 90%.

With regard to psychosocial concerns, education, employment, and social relationships generally are not affected substantially in adults with a history of bladder exstrophy and epispadias ²⁸. Age-appropriate adaptive behaviors may be delayed in children with chronic medical conditions ²⁹. One study revealed below-average daily living skills and socialization but above-average self-esteem. Children may need support in disclosing their condition to new peers.

Multiple anomalies associated with cloacal exstrophy can have a significant impact on daily life. Patients are affected by permanent colostomy, the need for clean intermittent catheterization, and impaired ambulation.

Diet

Some young patients with cloacal exstrophy are seriously affected by short-gut syndrome and may depend on long-term supplemental parenteral nutrition for growth and development.

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What is colon cleanse

Colon cleanse also called colonic irrigation is a complementary therapy. It involves flushing waste material out of the bowel (large intestine) using water ¹. The procedure is also known as colonic hydrotherapy. Colon cleanse is carried out by colonic hydrotherapists who may be registered with the Association of Registered Colon Hydrotherapists ².

During the procedure, you will lie on your side while warm water is passed into your bowel through a tube inserted into your rectum (back passage). Warm filtered water is introduced into your colon through a small tube called a speculum that is gently inserted about an inch and a half into your rectum. As the warm water enters, you’ll feel a fullness as your colon fills up, then a relaxing feeling as it empties. The water pressure and temperature are carefully controlled and all waste is drained away discreetly in a closed system with absolutely no mess or odors.

This filling and emptying is repeated several times and massage is applied to your abdomen. Unlike an enema, colonic hydrotherapy reaches the whole length of your large intestine, with the massage from your therapist helping to ensure you benefit from an effective cleanse.

The water circulates through your colon, and waste products are passed out of your body through the tube.

The procedure lasts about 30-45 minutes, during which around 60 liters of water is introduced into the rectum. Herbal infusions are sometimes added to the water.

The concept behind colon cleanse

It is well known that in antiquity medicine often resorted to the use of enemas and rectoclysis to “free” the body of the “humors” and “poisons” believed to originate in the intestine and to cause diseases in many other organs. Indeed, an Egyptian papyrus dating back to the XVI century B.C. provides evidence of the belief that toxic substances produced by poorly digested foods could pass through the intestinal lumen and into the blood stream causing disorders even in distant organs. In the early 1900s a British surgeon, Sir William Arbuthnot Lane, was profoundly convinced of this theory: when the contents of the large intestine stagnate, “toxic substances” are more easily absorbed and lead to chronic disorders. As a result, he performed extensive colon cleanse on patients with a wide range of disorders: from arthritis to hypertension and skin pathologies. In those same years, the British Medical Journal published an article that concluded by saying that fecal stasis altered colon bacterial flora, thus favoring bacteria capable of toxin production (either anaerobes or coliforms) with systemic effects ³.

The concept of “autointoxication” as a cause of disease was later abandoned as modern medical research gained sway and did not produce proof supporting this theory ⁴. Despite harsh criticism from the scientific community, the practice of colon cleanse has remained deeply rooted and the use of various instruments—from simple rectoclysis that operates by force of gravity to complex (and costly) colon hydrotherapy machinery—has continued to be widely accepted. Today’s therapists use hygienic closed systems, with clean, filtered water to cleanse the colon quickly and easily, with no fuss, no mess and no smell, making modern colon hydrotherapy safer and more convenient than ever before.

While the treatment has taken many forms over the centuries, the essence of the therapy has remained the same – a gentle wash out of the colon or large intestine, using warm water to remove waste matter, rehydrate and exercise the bowel.

Moreover, some controlled studies have appeared comparing the effect of irrigation and lavage with conventional treatment approaches, in particular, for constipation and fecal incontinence which reap the greatest benefits both in terms of symptoms and quality of life ⁵, ⁶, ⁷. These studies have used different irrigation methods and do not reflect an “impeccable” experimental design. However, beyond a shadow of a doubt, they do provide enough data to assert, as a recent Dutch study has done, that colonic irrigation is an effective treatment for untreatable defecation disorders ⁸ and for patients with functional bowel disorders, as another paper concludes ⁹. In one study of 57 patients with severe constipation, an immune activation condition was reflected by numerous indicators including elevated counts of CD3, CD4 and CD25, increased spontaneous proliferation of lymphocytes and increased ovoalbumin. Such activation tended to normalize when constipation was relieved with laxatives. The authors concluded that constipation is associated with striking changes in fecal flora, intestinal permeability and systemic immune response ¹⁰.

Why have people have colon cleanse ?

People have colon hydrotherapy for a wide range of reasons. Some are looking for relief from the symptoms of IBS (irritable bowel syndrome) and other gastro-intestinal problems such as bloating, constipation or diarrhea, while others simply want to maintain and improve their digestive health and enjoy the fresh, light feeling and enhanced energy levels that often comes from the treatment.

Unhealthy modern lifestyles

According to the Association of Registered Colon Hydrotherapists (ARCH) ² colon cleanse can help your body, helping to return your digestive system to a more natural, healthy state. The gentle flow of water works in two ways: firstly it cleans out waste matter in the colon, and secondly it stimulates the natural nerve and muscle action of the bowels to encourage proper bowel function.

Unlike an enema, colon hydrotherapy, combined with gentle abdominal massage from your therapist, can reach the full length of the large intestine, ensuring a thorough cleanse and the maximum benefit ¹¹.

According to the Association of Registered Colon Hydrotherapists ¹¹ colon cleanse gives many people a sensation of overall well-being and energy.

What’s more, since your digestive system is closely linked with the rest of your body’s functions, the therapy may also help you with headaches, allergies and acne, and improve mental and physical sluggishness ¹¹.

Does colon cleanse have health benefits ?

Despite many people having colon cleanse, there is no scientific evidence to suggest there are any health benefits associated with the procedure. In 2009, researchers in America analyzed studies about the procedure, but found no strong scientific evidence to support it ¹².

Colonic irrigation can be used effectively to treat defecation disorders when other conservative treatments fail or in addition to unsuccessful or partially successful surgical treatment ¹³. Briel et al. ¹⁴ found a success rate of 38% of retrograde colonic irrigation for fecal incontinence and a significant improvement in quality of life. Recently, another study reported a success rate of 41% in patients with fecal incontinence and 65% in patients with constipation ¹³. The success rate is based on patient satisfaction. Although patient satisfaction is the primary goal of treatment, it is a subjective measure. In future research, this should be combined with objective measures such as validated quality of life questionnaires in a prospective study design.

Antegrade colonic irrigation is especially known for the treatment of evacuation disorders in small children and can be performed through an appendico-cecostomy (MACE) or a cecostomy button ¹⁵. Alternative enteral access is a sigmoid tube or transverse colonic conduit for patients with a left colonic evacuation disorder ¹⁶. The most common problems of MACE are stoma stenosis and leakage ¹⁷. In this study ¹⁸, four patients performed antegrade irrigation via a colostomy or a MACE with good results. O’Bichere et al. ¹⁹ performed an experimental study investigating the effect of retrograde vs antegrade colonic irrigation in pigs. That study demonstrates that colonic emptying is more efficient with antegrade irrigation compared to retrograde irrigation ¹⁹. Although a reasonable success rate can be achieved with antegrade irrigation (64–85%) ²⁰, retrograde colonic irrigation is preferred above antegrade irrigation as initial treatment because of its non-invasive nature and benign complications. Retrograde colonic irrigation is performed through the anorectum or via a colostomy.

In a study ²¹ involving 23 children (2-15 years of age) with the following: spina bifida (n = 11), anorectal anomaly (n = 6), Hirschsprung’s (n = 1), and other complex anomalies (n = 5). Median follow-up is 2 (0.7–3.4) years. Diagnoses include sixteen (70%) patients had associated anomalies (those anomalies were not specified). Twelve (52%) had constipation and overflow soiling, and 11 (48%) had fecal incontinence. Twenty (87%) had associated urinary wetting. Sixteen (70%) children used alternate-day irrigations, 4 (17%) daily irrigations, and 3 (13%) every third-day irrigations. Nine (39%) patients were taking oral laxatives. Sixteen (70%) reported to be clean and 3 (13%) reported a significant improvement, although were having occasional soiling. Four patients (17%) did not tolerate the irrigations and underwent subsequent colostomy formation for intractable soiling. That study ²¹ showed transanal colonic irrigation is an effective method of managing fecal soiling in childhood. Majority (83%) of children achieve social fecal continence or a significant improvement with occasional soiling ²¹. This was accompanied by high parental satisfaction. Transanal colonic irrigation is a valid alternative to invasive surgical procedures and should be considered the first line of treatment for bowel management in children with soiling where simple pharmacological maneuvers failed to be effective.

Another study in a group of patients with “neurogenic bowel” resulting from spinal cord injury ²² where 87 patients with spinal cord injury with neurogenic bowel dysfunction were randomly assigned to either transanal irrigation (42 patients) or conservative bowel management (45 patients) for a 10-week trial period. Compared with conservative bowel management, transanal irrigation improves constipation, fecal incontinence, and symptom-related quality of life ²². These patients have been using this technique for a few years now, some every other day and some every 3 days maximum. It is not unusual to find that, even after a single colon hydrotherapy session, the patient starts to improve, achieving evacuation that is satisfactory both in terms of frequency and completeness. This may be because, following treatment, the patient appears to better handle the administration of fiber, symbiotics and/or macrogol products which previously had caused abdominal discomfort and were thus taken only sporadically.

Is colon cleanse safe ?

The Association of Registered Colon Hydrotherapists recommends that you should not have colon cleanse if you have ²³:

• Pregnancy
• Uncontrolled high blood pressure
• Severe hemorrhoids
• Severe anaemia
• Rectal bleeding
• Heart disease
• Strangulated abdominal or inguinal hernias
• Fissures or fistulas
• Kidney failure / insuffiency
• Bowel or rectal cancer
• Liver disease
• Colitis / Crohns disease
• GI hemorrhage / perforation.

Colon hydrotherapy FAQ

It is perfectly normal to be a little apprehensive about colon hydrotherapy at first, and naturally you’ll have some questions about the treatment. Your ARCH therapist will be happy to talk you through any concerns you have.

Here are some of the more frequently asked questions about colon hydrotherapy ²⁴:

How do I prepare for a colon cleanse ?

You don’t need to do anything special before your treatment, but for your own comfort you should avoid a heavy meal or drinking a lot immediately before your appointment. You should also avoid alcohol.

What if I am constipated ?

If you are particularly constipated, you should ask your therapist for advice on what you can do beforehand to maximize the benefits of your treatment.

What does a colon cleanse feel like ?

Most people find the procedure to be quite relaxing, with no discomfort. The colon fills and empties regularly as part of its normal function, so the treatment is nothing new. You may feel varying sensations of fullness and movement in your abdomen throughout the treatment.

Isn’t it embarrassing ?

Your therapy will take place in a private treatment room by a trained therapist who understands the sensitivity of the procedure. It is perfectly normal to be a little embarrassed, but your therapist will completely understand and will try to put you at your ease. Once the tube has been inserted, you’ll remain covered for the rest of the treatment.

Is there any mess or smell ?

None whatsoever. Modern colon hydrotherapy equipment forms a sealed system that carries away all the waste cleanly and hygienically.

How safe is colon cleanse ?

Your safety is of paramount importance. Modern equipment constantly maintains the water temperature and pressure within safe limits, and ARCH standards insist that a new, single use, disposable speculum is used for each treatment.

Does colon cleanse hurt ?

It may feel a little strange as the small tube is inserted, and you may have a natural urge to squeeze it out again, but this passes quickly. Your therapist will then closely control the filling and emptying to ensure that you remain comfortable at all times. Occasionally the colon may contract during the treatment, giving a cramping sensation but this is easily tolerated and passes as soon as the bowel empties again.

How do I know if a colon cleanse will help me ?

Everyone is different and colonics help some people more than others. ARCH members do not make any promises or wild claims for our treatments. The best way to find out if they will benefit you is to book a treatment and see for yourself.

What can I expect afterwards ?

Generally speaking as soon as your treatment is completed you can carry on with your normal routine. You may experience an increase in bowel movements over the first few hours, to eliminate any remaining water or waste. This is perfectly normal and shouldn’t involve any undue urgency or discomfort. After that you may find that you don’t need to go to the toilet for a while, perhaps as long as a few days, as your bowels have been emptied.

Does a colon cleanse wash away ‘good bacteria’ ?

Most of the important bowel bacteria are present on the bowel wall and are not removed during colon hydrotherapy. Since these good bacteria breed best in a balanced environment, a colonic cleanse may actually improve their environment and increase their numbers. However, if your therapist thinks that your bowel bacteria may be out of balance, they may suggest a pro-biotic after your treatment.

How long does a colon cleanse take ?

The treatment itself takes up to 45 minutes, so with changing time, you’ll need to allow at least an hour. Your first treatment will normally take longer as your therapist will need to review your medical history and assess your current bowel health before proceeding with your therapy.

What kind of water is used for colon cleanse hydrotherapy ?

ARCH use drinking water from the mains supply. This is then thoroughly filtered for your complete safety and warmed to body temperature or just above for your comfort.

Will it be okay to eat after having a colon cleanse ?

After a colonic, you can continue with your normal daily routine, including eating and drinking. However, you should avoid any foods that you know irritate or upset your stomach and avoid alcohol. Your therapist will offer advice on healthy eating options to help you maintain the benefits you have gained from the treatment.

How many treatments will I need ?

This depends on your reason for having a colonic in the first place, as well as how successful the treatment was. Your therapist will advise you on whether you need further treatments, as well as when and how often you need to return. Many therapists offer reduced rates for a course of treatments.

How much does a colon cleanse cost ?

This varies depending on where you live and who you see. You can find therapists in your area by using our online find a therapist function.

Are there any after effects ?

Most people feel great after a colonic, with renewed energy and vitality. However, occasionally some clients may feel a little under the weather for around 24 hours. If you have any concerns, or you feel unwell, speak to your therapist who will be able to explain your body’s reactions to you.

Are there circumstances in which I shouldn’t have a colon cleanse ?

Yes, certain medical conditions would prevent you from having the treatment. If you are in any doubt, please feel free to call ARCH for professional advice.

Can I have a colonic during my period ?

Yes. There is no reason why the procedure would not be successful.

I’m pregnant. Can I still have a colon cleanse ?

No. ARCH therapists do not treat pregnant women during any term of their pregnancy.

Summary

In summary, the regular use of colon cleaning techniques could, in individuals with serious intestinal motility problems (e.g. people with spinal cord injury & neurogenic bowel, children with constipation/fecal incontinence, functional bowel disorders like irritable bowel syndrome), be an effective part of the stability of intestinal microbiota. Recent observations definitely support this idea that water use does not create imbalances, but rather improves dysbiosis ²⁵. However, more rigorous studies must be performed on colon cleanse short- and long-term effectiveness in view of a recent systematic review ¹², where the investigators concluded that there are no methodologically rigorous controlled trials of colonic cleansing to support the practice for general health promotion. Conversely, there are multiple case reports and case series that describe the adverse effects of colonic cleansing. The practice of colonic cleansing to improve or promote general health is not supported in the published literature and cannot be recommended at this time ¹².

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15. MACE or caecostomy button for idiopathic constipation in children: a comparison of complications and outcomes. Cascio S, Flett ME, De la Hunt M, Barrett AM, Jaffray B. Pediatr Surg Int. 2004 Jul; 20(7):484-7. https://www.ncbi.nlm.nih.gov/pubmed/15221360
16. Sigmoid irrigation tube for the management of chronic evacuation disorders. Gauderer MW, Decou JM, Boyle JT. J Pediatr Surg. 2002 Mar; 37(3):348-51. https://www.ncbi.nlm.nih.gov/pubmed/11877646/
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19. O’Bichere A, Sibbons P, Dore C et al (2002) Experimental study of faecal continence and colostomy irrigation. Br J Surg 87:902–908. https://www.ncbi.nlm.nih.gov/pubmed/10931026
20. Cascio S, Flett ME, De la Hunt M et al (2004) MACE or caecostomy button for idiopathic constipation in children: a comparison of complications and outcomes. Pediatr Surg Int 20:484–487. https://www.ncbi.nlm.nih.gov/pubmed/15221360
21. Use of Peristeen® transanal colonic irrigation for bowel management in children: A single-center experience. Pacilli, Maurizio et al. Journal of Pediatric Surgery, Volume 49, Issue 2, 269-272. http://www.jpedsurg.org/article/S0022-3468(13)00896-8/fulltext
22. Christensen P, Bazzocchi G, Coggrave M et al (2006) Treatment of fecal incontinence and constipation in patients with spinal cord injury: a prospective, randomized, controlled, multicenter trial of transanal irrigation vs conservative bowel management. Gastroenterology 131:738–747. https://www.ncbi.nlm.nih.gov/pubmed/16952543
23. http://www.colonic-association.org/about-colon-hydrotherapy/who-are-colonics-for/
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What is a Rectum

Extending from the sigmoid colon is the rectum. The rectum forms the last 15 cm (6 in.) of the large intestine. The rectum is an expandable organ for the temporary storage of feces. The rectum lies next to the sacrum and generally follows its curvature. The peritoneum firmly attaches the rectum to the sacrum. The rectum ends about 5 centimeters below the tip of the coccyx, where it becomes the anal canal.

The Anus and Anal Canal

The anal canal is the continuation of the large intestine inferior to the rectum. The anal canal is about 3 cm long, it begins where the rectum passes through the levator ani, the muscle that forms the pelvic floor. At its distal end, the anal canal opens to the outside as the anus. Two sphincter muscles guard the anus—an internal anal sphincter muscle, composed of smooth muscle under involuntary control, and an external anal sphincter muscle, composed of skeletal muscle under voluntary control. A portion of the levator ani is responsible for maintaining the anorectal angle, an acute angle between the anus and the rectum that contributes to fecal continence. The anal canal lies entirely external to the abdominopelvic cavity in the perineum.

Internally, the superior half of the anal canal contains longitudinal folds of mucosa, the anal columns. These columns contain the terminal portions of the superior rectal artery and vein (the hemorrhoidal vessels). Neighboring anal columns join each other inferiorly at crescent-shaped transverse folds called anal valves. The pockets just superior to these valves are anal sinuses, which release mucus when they are compressed by feces, providing lubrication that eases fecal passage during defecation. The horizontal line along which the anal valves lie is called the pectinate (“comb-shaped”) line. Because the mucosa superior to this line is innervated by visceral sensory fibers, it is relatively insensitive to pain. Inferior to the pectinate line, however, the mucosa is sensitive to pain because it is innervated by somatic nerves.

The wall of the anal canal contains two sphincter muscles: an internal anal sphincter of smooth muscle and an external anal sphincter of skeletal muscle. The former is a thickening of the circular layer of the muscularis, whereas the latter is a distinct muscle. The external sphincter contracts voluntarily to inhibit defecation, whereas the internal sphincter contracts involuntarily, both to prevent feces from leaking from the anus between defecations and to inhibit defecation during emotional stress. During toilet training, children learn to control the external anal sphincter.

Figure 1. Rectum

Figure 2. Rectum anatomy and Anus (anal canal)

Rectum function

The rectum is usually empty and the anal sphincters contracted. When feces are squeezed into the rectum by mass peristaltic movements, the stretching of the rectal wall initiates the defecation reflex, which account for the urge to defecate that is often felt soon after a meal (Figure 3).

Figure 3. Rectum function and neural control of defecation

The defecation reflexes involve two reflexes:

1.  The intrinsic defecation reflex. This reflex is mediated entirely by the myenteric plexus. Stretch signals travel through the plexus to the muscularis of the descending and sigmoid colon and the rectum. This activates a peristaltic wave that drives feces downward, and it relaxes the internal anal sphincter. This reflex is relatively weak, however, and usually requires the cooperative action of the following reflex.
2. The parasympathetic defecation reflex. This is a spinal reflex. Its principal events are that stretch signals are transmitted to the spinal cord; motor signals return by way of the pelvic nerves; and these signals intensify peristalsis in the descending and sigmoid colon and rectum while they relax the internal anal sphincter. These reflexes are involuntary and are the sole means of controlling defecation in infants and some people with transecting spinal cord injuries. However, the external anal sphincter is under voluntary control, enabling one to limit defecation to appropriate circumstances.

Voluntary retention of feces is also aided by the puborectalis muscle, which loops around the rectum like a sling and creates a sharp anorectal angle that blocks the passage of feces. Defecation normally occurs only when the external anal sphincter and puborectalis muscle are voluntarily relaxed. The kink in the rectum then straightens out and the sphincter opens to allow the feces to fall away. Defecation is also aided by the voluntary Valsalva maneuver, in which a breath hold and contraction of the abdominal muscles increase abdominal pressure, compress the rectum, and squeeze the feces from it. This maneuver can also initiate the defecation reflex by forcing feces from the descending colon into the rectum. The external anal sphincter and external urethral sphincter are controlled together by inhibitory signals from the brainstem, so as this inhibition is released, defecation is usually accompanied by urination.

Some spinal cord injuries and diseases abolish the voluntary control of the external anal sphincter. The resulting inability to voluntarily retain the feces is called fecal incontinence. If the defecation urge is suppressed, contractions cease in a few minutes and the rectum relaxes. The defecation reflexes reoccur a few hours later or when another mass movement propels more feces into the rectum.

Human appendix

The human appendix is a blind tube 2 to 7 cm long, that opens into the posteromedial wall of the cecum. Although almost always illustrated as hanging inferiorly, it more often lies “tucked up” behind to the cecum in the right iliac fossa (right groin region). The appendix has large masses of lymphoid tissue ( lymphocytes) in its wall. Commonly considered a vestigial (rudimentary) organ, current research proposes that the appendix functions as a safe haven for the beneficial bacteria that inhabit the large intestine. According to this theory, beneficial bacteria from the appendix can repopulate the gut following an infectious disease that causes diarrhea and flushes out the intestinal flora.

Figure 1. Appendix

Figure 2. Appendix location

Figure 3. Appendix in relation to large intestine and small intestine

Acute inflammation of the appendix, called appendicitis, results from a blockage that traps infectious bacteria within its lumen. The blockage often is caused by a lump of feces or by a virus-induced swelling of the lymphoid tissue of the appendix wall. Unable to empty its contents, the blocked appendix swells with the mucus it secretes, squeezing off its venous drainage and leading to ischemic necrosis and infection. If the appendix ruptures, bacteria and feces are released into the peritoneum, causing peritonitis. Because the symptoms of appendicitis vary greatly, this condition is notoriously difficult to diagnose. Often, however, the first symptom is pain in the umbilical region, followed by loss of appetite, fever, nausea, vomiting, and relocalization of pain to the lower right quadrant of the abdominal surface. Palpation of this region that causes strong pain after the pressure is removed (so-called rebound tenderness) can indicate appendicitis. Immediate surgical removal of the appendix, called appendectomy, is the usual treatment.

Large intestine

The large intestine also known as the colon, extends from the distal end of the ileum to the anus, a distance of approximately 1.5 m in adults (5 ft) long, making up one-fifth of the length of the gastrointestinal (GI) tract and 6.5 cm (2.5 in.) in diameter. The large intestine is named for its relatively large diameter, not its length. The large intestine consists of the cecum, appendix, ascending colon, transverse colon, descending colon, rectum, and anal canal.

The large intestine is responsible for processing indigestible food material (chyme) after most nutrients are absorbed in the small intestine. The large intestine performs an essential role by absorbing water, vitamins, salts and electrolytes from the gut contents, thus forming feces.

Beginning in the right groin as the cecum, with its associated appendix, the large intestine continues upward as the ascending colon through the right flank and into the right hypochondrium. The ascending colon begins at the ileocecal valve and passes up the right side of the abdominal cavity. It makes a 90° turn at the right colic (hepatic) flexure, near the right lobe of the liver, and crosses the abdomen as the transverse colon to the left hypochondrium. At this position, just below the spleen, the large intestine bends downward, forming the left colic flexure (splenic flexure) and continues as the descending colon through the left flank and into the left groin. Ascending, transverse, and descending colons thus form a squarish, three-sided frame around the small intestine.

The cecum is a blind pouch in the lower right abdominal quadrant inferior to the ileocecal valve. Attached to its lower end is the appendix, a blind tube 2 to 7 cm long. The appendix is densely populated with lymphocytes and is a significant source of immune cells.

Figure 1. Large intestine

The pelvic cavity is narrower than the abdominal cavity, so at the hip bone, the colon turns medially and travels along the iliac fossa before turning downward at the pelvic inlet into the pelvic cavity. The resulting S-shaped portion of the tract is called the sigmoid colon. Visual examination of this region is performed with an instrument called a sigmoidoscope. In the pelvic cavity, the large intestine continues as the rectum, about 15 cm long. Despite its name, the rectum is not quite straight but has three lateral curves as well as an anteroposterior curve. It has three infoldings called transverse rectal folds (rectal valves), which enable it to retain feces while passing gas.

The final 3 cm of the large intestine is the anal canal, which passes through the levator ani muscle of the pelvic floor and terminates at the anus. Here, the mucosa forms longitudinal ridges called anal columns with depressions between them called anal sinuses. As feces pass through the canal, they press the sinuses and cause them to exude extra mucus and lubricate the canal during defecation. Prominent hemorrhoidal veins form superficial plexuses in the anal columns and around the orifice. Unlike veins in the limbs, they lack valves and are particularly subject to distension and venous pooling. Hemorrhoids are permanently distended veins that protrude into the anal canal or form bulges external to the anus. They can result from the impaired venous return that occurs in obesity and pregnancy.

The muscularis externa of the colon is unusual. Although it completely encircles the colon just as it does the small intestine, its longitudinal fibers are especially concentrated in three thickened, ribbonlike strips. Each strip is called a taenia coli. The muscle tone of the taeniae coli contracts the colon lengthwise and causes its wall to bulge, forming pouches called haustra (singular, haustrum). Haustra are conspicuous in colonic X-rays of living patients, because they disappear when muscle tone is lost at death. In the rectum and anal canal, the longitudinal muscle forms a continuous sheet and haustra are absent. The anus is regulated by two sphincters: an internal anal sphincter composed of smooth muscle of the muscularis externa and an external anal sphincter composed of skeletal muscle of the pelvic diaphragm.

The ascending and descending colon are retroperitoneal and have a serosa only on the anterior surface, whereas the transverse and sigmoid colon are entirely enclosed in serosa and anchored to the posterior abdominal wall by the mesocolon. The serosa of the transverse through sigmoid colon often has omental appendages, also called epiploic appendages, are fat-filled pouches of visceral peritoneum that hang from the intestine. Their significance is unknown.

Figure 2. Large intestine location

Figure 3. Large intestine and small intestine

Figure 4. Anal canal

Blood supply to the large intestine

The large intestine is served by mesenteric arteries and veins much like the small intestine. Branches of the superior mesenteric artery fan out to supply the ascending colon and most of the transverse colon; the inferior mesenteric artery supplies the rest of the transverse colon as well as the descending and sigmoid colon and the rectum. The superior and inferior mesenteric veins drain the same parts of the large intestine as the correspondingly named arteries and drain into the hepatic portal system.

Function of large intestine

The large intestine has 3 primary functions: absorbing water and electrolytes, producing and absorbing vitamins, and forming and propelling feces toward the rectum for elimination. By the time indigestible materials have reached the colon, most nutrients and up to 90% of the water has been absorbed by the small intestine. The role of the ascending colon is to absorb the remaining water and other key nutrients from the indigestible material, solidifying it to form stool. The descending colon stores feces that will eventually be emptied into the rectum. The sigmoid colon contracts to increase the pressure inside the colon, causing the stool to move into the rectum. The rectum holds the feces awaiting elimination by defecation.

Functions of the large intestine:

1. Haustral churning, peristalsis, and mass peristalsis drive contents of colon into rectum.
2. Bacteria in large intestine convert proteins to amino acids, break down amino acids, and produce some B vitamins and vitamin K.
3. Absorption of some water, ions, and vitamins.
4. Formation of feces.
5. Defecation (emptying rectum).

Motility

The intestinal wall is made up of multiple layers. The 4 layers of the large intestine from the lumen outward are the mucosa, submucosa, muscular layer, and serosa. The muscular layer is made up of 2 layers of smooth muscle, the inner, circular layer, and the outer, longitudinal layer. These layers contribute to the motility of the large intestine. There are 2 types of motility present in the colon, haustral contraction and mass movement. Haustra are saccules in the colon that give it its segmented appearance. Haustral contraction is activated by the presence of chyme and serves to move food slowly to the next haustra, along with mixing the chyme to help with water absorption. Mass movements are stronger and serve to move the chyme to the rectum quickly.

Absorption of Water and Electrolytes

Absorption of water occurs by osmosis. Water diffuses in response to an osmotic gradient established by the absorption of electrolytes. Sodium is actively absorbed in the colon by sodium channels. Potassium is either absorbed or secreted depending on the concentration in the lumen. The electrochemical gradient created by the active absorption of sodium allows for this. Chloride ions are exchanged for bicarbonate ions across an electrochemical gradient.

Production/Absorption of Vitamins

The colon also plays a role in providing required vitamins through an environment that is conducive for bacterial cultivation. The colon houses trillions of bacteria that protect our gut and produce vitamins. The bacteria in the colon produce substantial amounts of vitamins by fermentation. Vitamin K and B vitamins, including biotin, are produced by the colonic bacteria. These vitamins are then absorbed into the blood. When dietary intake of these vitamins is low in an individual, the colon plays a significant role in minimizing vitamin disparity.

Mechanism

The wall of the large intestine contains the typical four layers found in the rest of the gastrointestinal tract: mucosa, submucosa, muscularis, and serosa. The mucosa consists of simple columnar epithelium, lamina propria (areolar connective tissue), and muscularis mucosae (smooth muscle). The epithelium contains mostly absorptive and goblet cells. The absorptive cells function primarily in water absorption; the goblet cells secrete mucus that lubricates the passage of the colonic contents. Both absorptive and goblet cells are located in long, straight, tubular intestinal glands (crypts of Lieberkühn) that extend the full thickness of the mucosa. Solitary lymphatic nodules are also found in the lamina propria of the mucosa and may extend through the muscularis mucosae into the submucosa.

Compared to the small intestine, the mucosa of the large intestine does not have as many structural adaptations that increase surface area. There are no circular folds or villi; however, microvilli are present on the absorptive cells. Consequently, much more absorption occurs in the small intestine than in the large intestine.

The mucosa of the large intestine has a simple columnar epithelium in all regions except the lower half of the anal canal, where it has a nonkeratinized stratified squamous epithelium. The latter provides more resistance to the abrasion caused by the passage of feces. There are no circular folds or villi in the large intestine, but there are intestinal crypts. They are deeper than in the small intestine and have a greater density of goblet cells; mucus is their only significant secretion. The lamina propria and submucosa have an abundance of lymphatic tissue, providing protection from the bacteria that densely populate the large intestine.

The submucosa of the large intestine consists of areolar connective tissue. The muscularis consists of an external layer of longitudinal smooth muscle and an internal layer of circular smooth muscle. Unlike other parts of the gastrointestinal tract, portions of the longitudinal muscles are thickened, forming three conspicuous bands called the teniae coli that run most of the length of the large intestine. The teniae coli are separated by portions of the wall with less or no longitudinal muscle. Tonic contractions of the bands gather the colon into a series of pouches called haustra (shaped like pouches), which give the colon a puckered appearance. A single layer of circular smooth muscle lies between teniae coli. The serosa of the large intestine is part of the visceral peritoneum. Small pouches of visceral peritoneum filled with fat are attached to teniae coli and are called omental (fatty) appendices.

Figure 5. Large intestine anatomy

Mechanical Digestion in the Large Intestine

The passage of chyme from the ileum into the cecum is regulated by the action of the ileocecal sphincter. Normally, the valve remains partially closed so that the passage of chyme into the cecum usually occurs slowly. Immediately after a meal, a gastroileal reflex intensifies peristalsis in the ileum and forces any chyme into the cecum. The hormone gastrin also relaxes the sphincter. Whenever the cecum is distended, the degree of contraction of the ileocecal sphincter intensifies.

Movements of the colon begin when substances pass the ileocecal sphincter. Because chyme moves through the small intestine at a fairly constant rate, the time required for a meal to pass into the colon is determined by gastric emptying time. As food passes through the ileocecal sphincter, it fills the cecum and accumulates in the ascending colon.

The most common type of colonic motility is a type of segmentation called haustral contractions, which occur about every 30 minutes. Distension of a haustrum with feces stimulates it to contract. This churns and mixes the residue, promotes water and salt absorption, and passes the residue distally to another haustrum. Peristalsis also occurs, although at a slower rate (3–12 contractions per minute) than in more proximal portions of the tract. A final type of movement is mass peristalsis, a strong peristaltic wave that begins at about the middle of the transverse colon and quickly drives the contents of the colon into the rectum. Because food in the stomach initiates this gastrocolic reflex in the colon, mass peristalsis usually takes place three or four times a day, during or immediately aft er a meal. They last about 15 minutes and move residue several centimeters at a time. Mass peristalsis occur especially in the transverse to sigmoid colon, often within an hour after breakfast, moving the feces that accumulated and stretched the colon overnight.

The large intestine takes 36 to 48 hours to reduce the residue of a meal to feces, with the residue spending the greatest time (about 24 h) in the transverse colon. The colon doesn’t chemically change the residue, but reabsorbs water and electrolytes (especially NaCl) from it. Feces usually consist of about 75% water and 25% solids. The solids are about 30% bacteria, 30% undigested dietary fiber, 10% to 20% fat, and smaller amounts of protein, sloughed epithelial cells, salts, mucus, and other digestive secretions. The fat is not from the diet but from bacteria and broken-down epithelial cells.

Chemical Digestion in the Large Intestine

The final stage of digestion occurs in the colon through the activity of bacteria that inhabit the lumen. Mucus is secreted by the glands of the large intestine, but no enzymes are secreted. Chyme is prepared for elimination by the action of bacteria, which ferment any remaining carbohydrates and release hydrogen, carbon dioxide, and methane gases. These gases contribute to flatus (gas) in the colon, termed flatulence when it is excessive. Bacteria also convert any remaining proteins to amino acids and break down the amino acids into simpler substances: indole, skatole, hydrogen sulfide, and fatty acids. Some of the indole and skatole is eliminated in the feces and contributes to their odor; the rest is absorbed and transported to the liver, where these compounds are converted to less toxic compounds and excreted in the urine.

Bacteria also decompose bilirubin to simpler pigments, including stercobilin, which gives feces their brown color. Bacterial products that are absorbed in the colon include several vitamins needed for normal metabolism, among them some B vitamins and vitamin K.

Large Intestine Microbes and Gas

The large intestine harbors about 800 species of bacteria collectively called the gut microbiome. You have a mutually beneficial relationship with many of these. You provide them with room and board while they provide you with nutrients from your food that you are not equipped to extract on your own. For example, they digest cellulose, pectin, and other plant polysaccharides for which you have no digestive enzymes, and you absorb the resulting sugars. Thus, you get more nutrition from your food because of these bacteria than you would get without them. Indeed, one person may get more calories than another from the same amount of food because of differences in their bacterial populations. Some bacteria also synthesize B vitamins and vitamin K, which are absorbed by the colon. This vitamin K is especially important because the diet alone usually does not provide enough to ensure adequate blood clotting.

One of the less desirable and sometimes embarrassing products of these bacteria is intestinal gas. The large intestine contains about 7 to 10 L of gas, expelling about 500 mL/day as flatus and reabsorbing the rest. Much of this is swallowed air that has worked its way through the digestive tract, but the gut microbes add to it. Painful cramping can result when undigested nutrients pass into the colon and furnish an abnormal substrate for bacterial action, so the bacteria produce excess gas—for example, in lactose intolerance. Flatus is composed mostly of nitrogen (N2), carbon dioxide (CO2), hydrogen (H2), methane (CH4), hydrogen sulfide (H2S), and two amines: indole and skatole. Indole, skatole, and H2S produce most of the odor of flatus and feces, whereas the others are odorless. The hydrogen gas is combustible and has been known to explode during the use of electrical cauterization in surgery.

Absorption and Feces Formation in the Large Intestine

By the time chyme has remained in the large intestine 3–10 hours, it has become solid or semisolid because of water absorption and is now called feces. Chemically, feces consist of water, inorganic salts, sloughed-off epithelial cells from the mucosa of the gastrointestinal tract, bacteria, products of bacterial decomposition, unabsorbed digested materials, and indigestible parts of food. Although 90% of all water absorption occurs in the small intestine, the large intestine absorbs enough to make it an important organ in maintaining the body’s water balance. Of the 0.5–1.0 liter of water that enters the large intestine, all but about 100–200 mL is normally absorbed via osmosis. The large intestine also absorbs ions, including sodium and chloride, and some vitamins.

The Defecation Reflex

Mass peristaltic movements push fecal material from the sigmoid colon into the rectum. The resulting distension of the rectal wall stimulates stretch receptors, which initiates a defecation reflex that results in defecation, the elimination of feces from the rectum through the anus. The defecation reflex occurs as follows: In response to distension of the rectal wall, the receptors send sensory nerve impulses to the sacral spinal cord.

Motor impulses from the cord travel along parasympathetic nerves back to the descending colon, sigmoid colon, rectum, and anus. The resulting contraction of the longitudinal rectal muscles shortens the rectum, thereby increasing the pressure within it. This pressure, along with voluntary contractions of the diaphragm and abdominal muscles, plus parasympathetic stimulation, opens the internal anal sphincter.

The external anal sphincter is voluntarily controlled. If it is voluntarily relaxed, defecation occurs and the feces are expelled through the anus; if it is voluntarily constricted, defecation can be postponed. Voluntary contractions of the diaphragm and abdominal muscles aid defecation by increasing the pressure within the abdomen, which pushes the walls of the sigmoid colon and rectum inward. If defecation does not occur, the feces back up into the sigmoid colon until the next wave of mass peristalsis stimulates the stretch receptors, again creating the urge to defecate. In infants, the defecation reflex causes automatic emptying of the rectum because voluntary control of the external anal sphincter has not yet developed.

Figure 6. Defecation neural control

The amount of bowel movements that a person has over a given period of time depends on various factors such as diet, health, and stress. The normal range of bowel activity varies from two or three bowel movements per day to three or four bowel movements per week. Diarrhea is an increase in the frequency, volume, and fluid content of the feces caused by increased motility of and decreased absorption by the intestines. When chyme passes too quickly through the small intestine and feces pass too quickly through the large intestine, there is not enough time for absorption. Frequent diarrhea can result in dehydration and electrolyte imbalances. Excessive motility may be caused by lactose intolerance, stress, and microbes that irritate the gastrointestinal mucosa.

Constipation refers to infrequent or difficult defecation caused by decreased motility of the intestines. Because the feces remain in the colon for prolonged periods, excessive water absorption occurs, and the feces become dry and hard. Constipation may be caused by poor habits (delaying defecation), spasms of the colon, insufficient fiber in the diet, inadequate fluid intake, lack of exercise, emotional stress, and certain drugs. A common treatment is a mild laxative, such as milk of magnesia, which induces defecation. However, many physicians maintain that laxatives are habit-forming, and that adding fiber to the diet, increasing the amount of exercise, and increasing fluid intake are safer ways of controlling this common problem.

Large intestine problems

Pathology of the large intestine is common. One out of every 10 Americans over the age of 40 have diverticular disease, and around 3 million people in the United States have inflammatory bowel disease ¹. It is important to incorporate a healthy diet and lifestyle to maintain a properly functioning colon. Eating a diet high in fiber and drinking plenty of water allows food to easily move through the colon, keeping the colon relatively clean, which can decrease the risk of diverticular disease. It is also important to maintain healthy colonic flora. Maintaining healthy colonic flora will decrease the risk of abdominal bloating, gas, diarrhea, constipation, and infectious colitis.

Disorders of Large Intestinal Motility

Irritable Bowel Syndrome

Irritable bowel syndrome is thought to be due to psychological factors influencing the motility of the large intestine via the extrinsic autonomic nervous system. During times of stress, segmentation contractions may be increased or decreased, resulting in constipation or diarrhea.

Hirschsprung Disease: Megacolon

Hirschsprung disease is a disorder at birth that occurs when nerve cells are absent (Auerbach’s Plexus) in the muscles of the colon. This affects motility in the colon, making it difficult to pass stool.

Diverticulosis/Diverticulitis

Diverticulosis is a disorder in which pockets develop in the colonic mucosa due to the weakness of the muscle layers in the colon wall. This usually occurs over time from chronic attrition of the aging process. Diverticulitis can develop if these pockets get infected or inflamed, causing abdominal pain and change in bowel movements. Diverticular disease is very common, especially in older adults.

Large Intestine Inflammation

Inflammatory Bowel Disease

Inflammatory bowel disease includes either Crohn’s disease or ulcerative colitis. Both cause inflammation and scarring within the digestive tract, disrupting the normal function. The cause of inflammatory bowel disease is not known but is likely due to an abnormal response of the immune system. Ulcerative colitis is confined to the large intestine, whereas Crohn’s disease can occur anywhere in the GI (gastrointestinal) tract, from mouth to anus.

Ischemic colitis

Ischemic colitis is more common in the elderly and occurs when there is decreased blood flow to the colon. Decreased blood flow can cause inflammation or injury to the colon. Some causes of ischemic colitis are atherosclerosis of arteries, low blood pressure, blood clots, and bowel obstruction.

Infectious colitis

Infectious colitis can occur from many different viruses, bacteria, or parasites. Infectious colitis most commonly occurs due to ingestion of contaminated food or water, introducing the infectious organism into the colon. The most common causes are Escherichia coli, Campylobacter, Shigella, and Salmonella. These infectious organisms invade the colon, cause inflammation, and affect the normal function, causing abdominal pain and diarrhea. Clostridium difficile is another organism that can cause colitis in association with antibiotic use. Clostridium difficile is part of healthy, normal flora in the colon but can cause problems if it overgrows. Antibiotic use can destroy other susceptible normal flora in the colon, allowing overgrowth and invasion of Clostridium difficile.

1. Azzouz LL, Sharma S. Physiology, Large Intestine. [Updated 2018 Jun 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507857

Small intestine

The small intestine is the longest part of the alimentary canal and it begins at the pyloric sphincter of the stomach, coils through the central and inferior part of the abdominal cavity, and eventually opens into the large intestine.

The term small intestine refers not to its length but to its diameter—about 2.5 cm (1 in.).

The small intestine is approximately 6 to 7 m long (range 3–7 m) with a narrowing diameter from beginning to end.

The small intestine consists of the duodenum, the jejunum, and the ileum.

The small intestine receives chyme from the stomach and secretions from the pancreas, liver, and gallbladder. It completes digestion of the nutrients in chyme, absorbs the products of digestion, and transports the residue to the large intestine.

The small intestine the site of most enzymatic digestion and about 90 percent of all nutrients absorption and most of the rest occurs in the proximal portion of the large intestine. Its length alone provides a large surface area for digestion and absorption, and that area is further increased by circular folds, villi, and microvilli. Most digestive enzymes that operate within the small intestine are secreted not by the intestine, but by the pancreas. During digestion, the small intestine undergoes active segmentation movements, shuffling the chyme back and forth and thereby maximizing its contact with the nutrient-absorbing mucosa.

Peristalsis propels chyme through the small intestine in about 3–6 hours.

Figure 1. Small intestine

Function of the Small Intestine

The anatomy of the small intestine is specialized to increase its surface area for absorption and secretion. The intestinal lining has a series of ring-shaped projections called circular folds or plicae circulares.

These folds do not disappear as the small intestine fills. Roughly 800 circular folds (about 2 per centimeter) are found along the length of the duodenum, jejunum, and proximal half of the ileum. The mucosa possesses intestinal villi, and each cell of the surface epithelium has small microvilli on its apical surface.

1. Segmentations mix chyme with digestive juices and bring food into contact with mucosa for absorption; peristalsis propels chyme through small intestine.
2. Completes digestion of carbohydrates, proteins, and lipids; begins and completes digestion of nucleic acids.
3. Absorbs about 90% of nutrients and water that pass through digestive system.

Figure 2. Circular folds, villi and microvilli increase the surface area of the small intestine for digestion and absorption

The tissue layers of the small intestine are reminiscent of those in the esophagus and stomach with modifications appropriate for nutrient digestion and absorption. The lumen is lined with simple columnar epithelium. The muscularis externa is notable for a thick inner circular layer and a thinner outer longitudinal layer.

The jejunum and ileum are intraperitoneal and thus covered on all sides with a serosa, which is continuous with the complex, folded mesentery that suspends the small intestine from the posterior abdominal wall. Most of the duodenum is retroperitoneal and has a serosa only on its anterior surface; its other surfaces are covered by adventitia.

Effective digestion and absorption require the small intestine to have a large internal surface area. This is provided by its relatively great length and by three kinds of internal folds or projections: the circular folds, villi, and microvilli. If the mucosa were smooth, like the inside of a hose, it would have a surface area of about 0.3 to 0.5 m2, but with these surface elaborations, its actual surface area is about 200 m2—clearly a great advantage for nutrient absorption.

The circular folds increase the surface area by a factor of 2 to 3, the villi by a factor of 10, and the microvilli by a factor of 20.

Circular folds, the largest of these elaborations, are transverse to spiral ridges up to 1 cm high. These involve only the mucosa and submucosa; they are not visible on the external surface, which is smooth. They slow the progress of the chyme and make it flow on a somewhat spiral path, which increases its contact with the mucosa and promotes more thorough mixing and nutrient absorption. Circular folds begin in the duodenum. In the jejunum, they are especially large, tall, and closely spaced. They become smaller and more sparse in the ileum. These changes are correlated with the relative amount of nutrient absorption occurring in each region. Circular folds are absent from the distal half of the ileum, but most nutrient absorption is completed by that point.

Villi (singular, villus) are tiny projections that give the inner lining of the intestine a fuzzy texture, like a terry cloth towel. They are about 0.5 to 1.0 mm high, with tongue- to finger like shapes. Villi are largest in the duodenum and become progressively smaller in more distal regions of the intestine. Villi are covered with two kinds of epithelial cells: columnar enterocytes (absorptive cells) and mucus-secreting goblet cells. Like epithelial cells of the stomach, those of the small intestine are joined by tight junctions that prevent digestive enzymes from seeping between them and eroding the underlying tissue.

The core of a villus is filled with areolar tissue of the lamina propria and contains an arteriole, blood capillaries, a venule, and a lymphatic capillary called a lacteal. The blood capillaries absorb most nutrients, but the lacteal absorbs most lipids. Lipids give its contents a milky appearance for which the lacteal is named. The core of the villus also has a few smooth muscle cells that contract periodically. This enhances mixing of the chyme in the intestinal lumen and milks lymph down the lacteal to larger lymphatics in the submucosa.

Microvilli are much smaller plasma membrane extensions, about 1 μm high, that form a fuzzy brush border on the surface of each enterocyte. In addition to increasing surface area, they contain brush border enzymes in the plasma membrane. These enzymes carry out some of the final stages of chemical digestion. They are not secreted into the lumen; instead, the chyme must contact the brush border for digestion to occur. This process, called contact digestion, is one reason why it is so important that intestinal contractions churn the chyme and ensure that it all contacts the mucosa.

On the floor of the small intestine, between the bases of the villi, there are numerous pores that open into tubular glands called intestinal crypts. These crypts, similar to the gastric glands, extend as far as the muscularis mucosae. In the upper half, they consist of enterocytes and goblet cells like those of the villi. The lower half is dominated by dividing stem cells. In its life span of 3 to 6 days, an epithelial cell migrates up the crypt to the tip of the villus, where it is sloughed off and digested. A few Paneth cells are clustered at the base of each crypt. They secrete lysozyme, phospholipase, and defensins—defensive proteins that resist bacterial invasion of the mucosa.

The duodenum has prominent duodenal glands in the submucosa. They secrete an abundance of bicarbonate-rich mucus, which neutralizes stomach acid and shields the mucosa from its erosive effects. Throughout the small intestine, the lamina propria and submucosa have a large population of lymphocytes that intercept pathogens before they can invade the bloodstream. In some places, these are aggregated into conspicuous lymphatic nodules such as the Peyer patches of the ileum.

Digestion and Absorption of the Major Organic Nutrients in the Small Intestine

Chemical digestion and nutrient absorption are essentially finished by the time food residue leaves the small intestine and enters the cecum.

Absorption of Water

The digestive system is one of several systems involved in fluid balance. The digestive tract receives about 9 L of water per day—0.7 L in food, 1.6 L in drink, and 6.7 L in the gastrointestinal secretions: saliva, gastric juice, bile, pancreatic juice, and intestinal juice. About 8 L of this is absorbed by the small intestine and 0.8 L by the large intestine, leaving 0.2 L voided in the daily fecal output.

Water is absorbed by osmosis, following the absorption of salts and organic nutrients that create an osmotic gradient from the intestinal lumen to the extracellular fluid (ECF). Diarrhea occurs when the large intestine absorbs too little water. This occurs when the intestine is irritated by bacteria and feces pass through too quickly for adequate reabsorption, or when the feces contain abnormally high concentrations of a solute such as lactose that opposes osmotic  absorption of water. Constipation occurs when fecal movement is slow, too much water is reabsorbed, and the feces become hardened. This can result from lack of dietary fiber, lack of exercise, emotional upset, or long-term laxative abuse.

Absorption of Carbohydrates

Most digestible dietary carbohydrate is starch. Starch is digested first to oligosaccharides up to eight glucose residues long, then into the disaccharide maltose, and finally to glucose, which is absorbed by the small intestine.

The process begins in the mouth, where salivary amylase breaks starch down into shorter segments (oligosaccharides). Salivary amylase functions best at pH 6.8 to 7.0, typical of the oral cavity. It is quickly denatured upon contact with stomach acid, but it can digest starch for as long as 1 to 2 hours in the stomach as long as it is in the middle of a food mass and escapes contact with the acid. Amylase therefore works longer when the meal is larger, especially in the fundus, where gastric motility is weakest and a food bolus takes longer to break up. As acid, pepsin, and the churning contractions of the stomach break up the bolus, amylase is denatured; it cannot function at a pH any lower than 4.5. Being a protein, amylase is then digested by pepsin along with the dietary proteins.

About 50% of the dietary starch is digested before it reaches the small intestine. Its digestion resumes in the small intestine when the chyme mixes with pancreatic amylase. Starch is entirely converted to oligosaccharides and maltose within 10 minutes. Its digestion is completed as the chyme contacts the brush border of the enterocytes. Two brush border enzymes, dextrinase and glucoamylase, hydrolyze oligosaccharides that are three or more residues long, while maltase hydrolyzes maltose. The end product of all of these is glucose, which is then absorbed.

Maltose is also present in some foods, but the major dietary disaccharides are sucrose (cane sugar) and lactose (milk sugar). They are digested by the brush border enzymes sucrase and lactase, respectively, and the resulting monosaccharides are immediately absorbed (glucose and fructose from the former; glucose and galactose from the latter). In most of the world population, however, lactase production ceases or declines to a low level after age 4 and lactose becomes indigestible.

The plasma membrane of the enterocytes has transport proteins that absorb monosaccharides as fast as they are produced by the foregoing enzymes. About 80% of the absorbed sugar is glucose, which is taken up by a sodium–glucose transporter like that of the kidney tubules. The glucose is subsequently transported out the base of the cell into the extracellular fluid (ECF). Sugar entering the extracellular fluid (ECF) increases its osmolarity, and this draws water osmotically from the lumen of the intestine, through the now-leaky tight junctions between the epithelial cells. Water carries more glucose and other nutrients with it by solvent drag, much as it does in the kidney. After a high-carbohydrate meal, solvent drag absorbs two to three times as much glucose as the sodium–glucose transporter.

The sodium–glucose transporter also absorbs galactose, whereas fructose is absorbed by facilitated diffusion using a separate carrier that doesn’t depend on Na+. Inside the enterocyte, most fructose is converted to glucose. Glucose, galactose, and the small amount of remaining fructose are then transported out the base of the cell by facilitated diffusion and absorbed by the blood capillaries of the villus. The hepatic portal system delivers them to the liver.

Absorption of Vitamins

Vitamins are not digested, but absorbed unchanged. The fat-soluble vitamins A, D, E, and K are absorbed with other lipids. Therefore, if they are ingested without fat-containing food, such as by simply popping vitamin tablets with a glass of water, they’re not absorbed at all but passed in the feces and wasted. Water-soluble vitamins (the B complex and vitamin C) are absorbed by simple diffusion. An exception is vitamin B12, an unusually large molecule that is absorbed poorly unless bound to the intrinsic factor (IF) secreted by the stomach’s parietal cells. Then as it passes down the small intestine, the B12–IF complex binds to receptors on absorptive cells of the distal ileum, where it is taken up by receptor-mediated endocytosis.

Absorption of Proteins

The amino acids absorbed by the small intestine come from three sources: (1) dietary proteins, (2) digestive enzymes digested by each other, and (3) sloughed epithelial cells digested by these enzymes. Amino acids from the last two sources total about 30 g/day, compared with about 44 to 60 g/day from the diet.

Enzymes that digest proteins are called proteases (peptidases). They are absent from the saliva but first encountered in the stomach. Here, pepsin hydrolyzes any peptide bond between tyrosine and phenylalanine, thereby digesting 10% to 15% of the dietary protein into shorter polypeptides and a small amount of free amino acids. Pepsin has an optimal pH of 1.5 to 3.5, so it is inactivated when it passes into the duodenum and mixes with the alkaline pancreatic juice (pH 8).

In the small intestine, the pancreatic enzymes trypsin and chymotrypsin take over protein digestion by hydrolyzing polypeptides into even shorter oligopeptides. Finally, these are taken apart one amino acid at a time by three more enzymes: (1) Carboxypeptidase removes amino acids from the —COOH end of the chain; (2) aminopeptidase removes them from the —NH2 end; and (3) dipeptidase splits dipeptides in the middle and releases the last two free amino acids. The last two of these are brush border enzymes, whereas carboxypeptidase is a pancreatic secretion.

Amino acid absorption is similar to that of monosaccharides. Enterocytes have several sodium-dependent amino acid cotransporters for different classes of amino acids. Dipeptides and tripeptides can also be absorbed, but they are hydrolyzed within the enterocytes before their amino acids are released to the bloodstream. At the basal surfaces of the cells, amino acids behave like the monosaccharides discussed previously—they leave the cell by facilitated diffusion, enter the capillaries of the villus, and are carried away in the hepatic portal circulation.

The absorptive cells of infants can take up intact proteins by pinocytosis and release them to the blood by exocytosis. This allows IgA from breast milk to pass into an infant’s bloodstream and confer passive immunity from mother to infant. It has the disadvantage, however, that intact proteins entering the infant’s blood are detected as foreign antigens and sometimes trigger food allergies. As the intestine matures, its ability to pinocytose protein declines but never completely ceases.

Figure 3. Digestion and Absorption of the Major Organic Nutrients in the Small Intestine

Absorption of Lipids

The hydrophobic quality of lipids makes their digestion and absorption more complicated than that of carbohydrates and proteins. Fats are digested by enzymes called lipases. Lingual lipase, secreted by the intrinsic salivary glands of the tongue, digests a small amount of fat while food is still in the mouth, but becomes more active at the acidic pH of the stomach. Here it is joined by gastric lipase, which makes a much larger contribution to preduodenal fat digestion. About 10% to 15% of dietary fat is digested before the chyme passes on to the duodenum.

Being hydrophobic, ingested fat takes the form of large globules that, without further physical processing, could be attacked by these lipases only at their surface. This would result in rather slow, inefficient digestion. The stomach’s vigorous antral pumping, however, breaks the fat up into small droplets dispersed through the watery chyme—that is, it emulsifies the fat, exposing much more of its surface to enzymatic action. The resulting emulsification droplets are promptly passed on to the duodenum and coated by certain components of the bile—lecithin and bile acids. These agents have hydrophobic regions attracted to the surface of a fat droplet and hydrophilic regions attracted to the surrounding water. The agitation produced by intestinal segmentation breaks the fat up further into droplets as small as 1 μm, and the coating of lecithin and bile acids keeps it broken up, preventing the droplets from coalescing into larger globules.

There is enough pancreatic lipase in the small intestine after a meal to digest the average daily fat intake in as little as 1 or 2 minutes. When lipase acts on a triglyceride, it removes the first and third fatty acids from the glycerol backbone and usually leaves the middle one. The products of lipase action are therefore two free fatty acids (FFAs) and a monoglyceride. Being smaller than triglycerides, these are more soluble in the enterocyte plasma membrane and thus easier to absorb.

The absorption of lipids depends on minute droplets in the bile called micelles. Micelles, made in the liver, consist of 20 to 40 bile acid molecules aggregated with their hydrophilic side groups facing outward and their hydrophobic steroid rings facing inward. Bile phospholipids and cholesterol diffuse into the center of the micelle to form its core. The micelles pass down the bile duct into the duodenum, where they absorb fat-soluble vitamins, more cholesterol, and the fatty acids and monoglycerides produced by fat digestion. Because of their charged, hydrophilic surfaces, micelles remain suspended in water more easily than free lipids do. They travel to the surfaces of the enterocytes, where they release their lipid cargo. Some of the lipids simply diffuse through the plasma membrane into the enterocytes, but these cells also have specific carrier proteins that facilitate their uptake. The micelles are reused, picking up another cargo of lipids and ferrying them to the enterocytes. Without micelles, the small intestine absorbs only about 40% to 50% of the dietary fat and almost no cholesterol.

Within the enterocytes, fatty acids and monoglycerides are transported into the smooth endoplasmic reticulum and resynthesized into triglycerides. The Golgi complex combines these with a small amount of cholesterol and coats the complex with a film of phospholipid and protein, forming droplets 75 to 1,200 nm in diameter called chylomicrons. It packages chylomicrons into secretory vesicles that migrate to the basal surface of the cell and release their contents into the core of the villus. Although some free fatty acids enter the blood capillaries, chylomicrons are too large to penetrate the endothelium. They are taken up instead by the more porous lacteals into the lymph. This fatty, milk-white intestinal lymph, called chyle, flows through larger and larger lymphatic vessels of the mesenteries, eventually passing through the cisterna chyli to the thoracic duct, then entering the bloodstream at the left subclavian vein.

Absorption of Minerals

Minerals (electrolytes) are absorbed along the entire length of the small intestine. Sodium ions are cotransported with sugars and amino acids. Chloride ions are actively transported in the distal ileum by a pump that exchanges them for bicarbonate ions, reversing the chloride–bicarbonate exchange that occurs in the stomach. Potassium ions are absorbed by simple diffusion. The K+ concentration of chyme rises as water is absorbed, creating a gradient favorable to K+ absorption. In diarrhea, when water absorption is hindered, potassium ions remain in the intestine and pass with the feces; therefore, chronic diarrhea can lead to hypokalemia.

Most minerals are absorbed at fairly constant rates regardless of need, leaving it to the kidneys to excrete any excess. Iron is one exception; its absorption is hormonally regulated. Intestinal enterocytes bind ferrous ions (Fe2+) and take them in by active transport; they cannot absorb ferric ions (Fe3+), but stomach acid (HCl) reduces most Fe3+ to absorbable Fe2+. Fe2+ is transported to the basal surface of the cell and there taken up by the extracellular protein transferrin. The transferrin–iron complex diffuses into the blood and is carried to such places as the bone marrow for hemoglobin synthesis, muscular tissue for myoglobin synthesis, and the liver for storage.

Excess dietary iron, if absorbed, binds irreversibly to ferritin in the enterocyte and is held there until that cell sloughs off and passes in the feces. Iron absorption and mobilization are regulated by the liver hormone hepcidin. An iron overload is dangerously toxic (indeed, a leading cause of death in young children who get into a parent’s iron supplement pills), but hepcidin normally prevents overload. It inhibits intestinal iron absorption and the mobilization of iron from the liver, thus preventing the blood iron level from rising too high. Anemia and hypoxia reduce hepcidin synthesis, removing its inhibitory effect and thus allowing increased absorption of dietary iron and mobilization of stored iron so it becomes available for hemoglobin synthesis.

The small intestine absorbs nearly all dietary phosphate, predominantly by active transport. By contrast, it absorbs only about 40% of the dietary calcium, leaving the rest to pass in the feces. In the duodenum, calcium is absorbed by the transcellular route. It enters the enterocytes through calcium channels in the apical plasma membrane and binds to a cytoplasmic protein called calbindin. This keeps the intracellular concentration of free calcium low, maintaining a gradient that favors uptake. What free calcium exists in the cytoplasm is then pumped out the basal side of the cell by active transport, using a protein called calcium–ATPase as well as a sodium–calcium antiport. From there, it enters the blood capillaries of the villus.

Transcellular calcium uptake is under hormonal influence. Parathyroid hormone is secreted in response to a drop in blood calcium level. It stimulates the kidneys to synthesize vitamin D from the precursors made by the epidermis and liver. Vitamin D then affects the absorptive cells of the duodenum in three ways: It increases the number of calcium channels in the apical membrane, the amount of calbindin in the cytoplasm, and the number of calcium–ATPase pumps in the basal membrane. Thus, it increases absorption of dietary calcium and raises the level of calcium in the blood.

Because of their much greater length, the jejunum and ileum absorb much more calcium than the duodenum does, but here it is by the paracellular route (passing between cells) and is independent of hormones. Most absorbed calcium is from meat and dairy products. Although green leafy vegetables are high in calcium, little of this is absorbed because they also contain an agent, oxalate, that binds calcium and makes it unavailable for absorption. Dietary fat retards calcium absorption by reacting with it to form poorly absorbed calcium soaps.

Absorption of Nucleic Acids

The nucleic acids, DNA and RNA, are present in much smaller quantities than the polymers discussed previously. The nucleases (ribonuclease and deoxyribonuclease) of pancreatic juice hydrolyze these to their constituent nucleotides. Nucleosidases and phosphatases of the brush border then decompose the nucleotides into phosphate ions, nitrogenous bases, and simple sugars (ribose from RNA and deoxyribose from DNA). These products are transported across the intestinal epithelium by membrane carriers and enter the capillary blood of the villus.

Intestinal Secretion

The intestinal crypts secrete 1 to 2 L of intestinal juice per day, especially in response to acid, hypertonic chyme, and distension of the intestine. This fluid has a pH of 7.4 to 7.8. It contains water and mucus but relatively little enzyme. Most enzymes that function in the small intestine are found in the brush border and pancreatic juice.

Regulation of Small Intestinal Secretions

Goblet cells and intestinal glands secrete their products when chyme provides both mechanical and chemical stimulation. Distension of the intestinal wall activates the nerve plexuses within the wall and stimulates parasympathetic reflexes that also trigger release of small intestinal secretions.

Intestinal Motility

Contractions of the small intestine serve three functions: (1) to mix chyme with intestinal juice, bile, and pancreatic juice, allowing these fluids to neutralize acid and digest nutrients more effectively; (2) to churn chyme and bring it into contact with the mucosa for contact digestion and nutrient absorption; and (3) to move residue toward the large intestine.

Segmentation is a movement in which stationary ringlike constrictions appear at several places along the intestine and then relax as new constrictions form elsewhere. This is the most common type of intestinal contraction. Its effect is to knead or churn the contents. Pacemaker cells of the muscularis externa set the rhythm of segmentation, with contractions about 12 times per minute in the duodenum and 8 to 9 times per minute in the ileum. Since the contractions are less frequent distally, segmentation causes slow progression of the chyme toward the colon. The intensity (but not frequency) of contractions is modified by nervous and hormonal influences.

When most nutrients have been absorbed and little remains but undigested residue, segmentation declines and peristalsis begins. The duodenum secretes a hormone called motilin that triggers a peristaltic wave beginning in the duodenum. The wave travels 10 to 70 cm and dies out, only to be followed by another wave that begins a little farther down the tract than the first one. These successive, overlapping waves of contraction are called a migrating motor complex. They milk the chyme toward the colon over a period of about 2 hours. A second complex then expels residue and bacteria from the small intestine, thereby helping to limit bacterial colonization. Refilling of the stomach at the next meal suppresses peristalsis and reactivates segmentation as new chyme enters the small intestine.

The ileocecal valve is usually closed. Food in the stomach, however, triggers both the release of gastrin and the gastroileal reflex, both of which enhance segmentation in the ileum and relax the valve. As the cecum fills with residue, the pressure pinches the valve shut and prevents the reflux of cecal contents into the ileum.

Chemical digestion and nutrient absorption are essentially finished by the time food residue leaves the small intestine and enters the cecum. But before going on to the functions of the large intestine, we trace each major class of nutrients—especially carbohydrates, proteins, and fats—from the mouth through the small intestine to see how it is chemically degraded and absorbed.

Parts of the small intestine

The small intestine consists of three parts: the duodenum, the jejunum, and the ileum.

The small intestine is a coiled mass of hollow tube filling most of the abdominal cavity inferior to the stomach and liver. A double-layered fold of peritoneal membrane called mesentery suspends the jejunum and ileum from the posterior abdominal wall. The mesentery supports the blood vessels, nerves, and lymphatic vessels that supply the intestinal wall. A filmy, double fold of peritoneal membrane called the greater omentum drapes like an apron from the stomach over the transverse colon and the folds of the small intestine. If the wall of the alimentary canal becomes infected, cells from the omentum may adhere to the inflamed region, helping to wall off the area. This action prevents spread of the infection to the peritoneal cavity.

Duodenum

The first part of the small intestine is the duodenum. This C-shaped structure, adjacent to the head of the pancreas, is 20 to 25 cm long and 5 centimeters in diameter. The duodenum is a “mixing bowl” that receives chyme from the stomach and digestive secretions from the pancreas and liver. Almost all essential digestive enzymes enter the small intestine from the pancreas.

The duodenum begins at the pyloric valve, arcs around the head of the pancreas and passes to the left, and ends at a sharp bend called the duodenojejunal flexure. Slightly distal to the pyloric valve, it exhibits wrinkles called the major and minor duodenal papillae, where it receives the pancreatic duct and accessory pancreatic duct, respectively. Along with the pancreas, most of the duodenum is retroperitoneal. It receives the stomach contents, pancreatic juice, and bile. Stomach acid is neutralized here, fats are physically broken up (emulsified) by the bile acids, pepsin is inactivated by the elevated pH, and pancreatic enzymes take over the job of chemical digestion.

The duodenum is above the level of the umbilicus; its lumen is the widest of the small intestine. It is retroperitoneal except for its beginning, which is connected to the liver by the hepatoduodenal ligament, a part of the lesser omentum.

Figure 4. Duodenum

The duodenum is divided into four parts.

1. The superior part (first part) extends from the pyloric orifice of the stomach to the neck of the gallbladder, is just to the right of the body of vertebra LI, and passes anteriorly to the bile duct, gastroduodenal artery, portal vein, and inferior vena cava. Clinically, the beginning of this part of the duodenum is referred to as the ampulla or duodenal cap, and most duodenal ulcers occur in this part of the duodenum.
2. The descending part (second part) of the duodenum is just to the right of midline and extends from the neck of the gallbladder to the lower border of vertebra LIII. Its anterior surface is crossed by the transverse colon, posterior to it is the right kidney, and medial to it is the head of the pancreas. This part of the duodenum contains the major duodenal papilla, which is the common entrance for the bile and pancreatic ducts, and the minor duodenal papilla, which is the entrance for the accessory pancreatic duct, and the junction of the foregut and the midgut just below the major duodenal papilla.
3. The inferior part (third part) of the duodenum is the longest section, crossing the inferior vena cava, the aorta, and the vertebral column. It is crossed anteriorly by the superior mesenteric artery and vein.
4. The ascending part (fourth part) of the duodenum passes upward on, or to the left of, the aorta to approximately the upper border of vertebra LII and terminates at the duodenojejunal flexure. This duodenoj ejunal flexure is surrounded by a fold of peritoneum containing muscle fibers called the  suspensory muscle (ligament) of duodenum (ligament of Treitz).

Jejunum

The jejunum, by definition, is the first 40% of the small intestine beyond the duodenum—about 1.0 to 1.7 m in a living person. The jejunum begins in the upper left quadrant of the abdomen but lies mostly within the umbilical region. Its wall is thick and muscular, and it has an especially rich blood supply, which gives it a relatively red color. Most digestion and nutrient absorption occur here.

The arterial supply to the jejunum includes jejunal arteries from the superior mesenteric artery.

Ileum

The ileum forms the last 60% of the post-duodenal small intestine (about 1.6 to 2.7 m). It occupies mainly the hypogastric region and part of the pelvic cavity. Compared with the jejunum, its wall is thinner, less muscular, less vascular, and has a paler pink color. On the side opposite from its mesenteric attachment, the ileum contains 20–30 masses of lymphoid tissue called submucous aggregated lymphoid nodules or Peyer’s patches, which are readily visible to the naked eye and become progressively larger approaching the large intestine. These lymphoid tissues are most abundant in the terminal portion of the ileum, near the entrance to the large intestine. The lymphocytes in the aggregated lymphoid nodules protect the small intestine from bacteria that normally inhabit the large intestine.

The end of the small intestine is the ileocecal junction, where the ileum joins the cecum of the large intestine. The muscularis of the ileum is thickened at this point to form a sphincter, the ileocecal valve, which protrudes into the cecum. The ileocecal valve surrounds the opening into the large intestine and it regulates the passage of food residue into the large intestine and prevents feces from backing up into the ileum.

The ileocecal valve is usually closed. Food in the stomach, however, triggers both the release of gastrin and the gastroileal reflex, both of which enhance segmentation in the ileum and relax the valve. As the cecum fills with residue, the pressure pinches the valve shut and prevents the reflux of cecal contents into the ileum.

Blood supply of the small intestine

The small intestine receives nearly all of its blood supply from the superior mesenteric artery, which fans out through the mesentery to give rise to 12 to 15 jejunal and ileal arteries leading to the intestinal wall. Branches of these arteries travel through the submucosa and give rise to capillary beds in the villi (see Figure 2), where the blood picks up all absorbed nutrients except lipids. Blood from here converges on another fanlike array of mesenteric veins, which leave by way of the superior mesenteric vein. This joins the splenic vein and then flows into the hepatic portal system, headed for the liver with its load of nutrients.

What is the Pancreas

The pancreas is a large gland that sits behind the greater curvature of the stomach and close to the first part of the small intestine (the duodenum). The pancreas is shaped a bit like a fish with a wide head, a tapering body, and a narrow, pointed tail. In adults it’s about 12–15 cm (5–6 inches) long and 2.5 cm (1 in.) thick but less than 2 inches (5 centimeters) wide. The pancreas is both an endocrine and exocrine gland (see Figures 1 and 2).

The pancreas has 3 parts, the head, body, and tail.

• the wide end is called the head. The head of the pancreas is on the right side of the abdomen (belly), behind where the stomach meets the duodenum (the first part of the small intestine).
• the bit in the middle is called the body. The body of the pancreas is behind the stomach.
• the thin end is called the tail. The tail of the pancreas is on the left side of the abdomen next to the spleen.

About 99% of the pancreas is exocrine tissue made up of small clusters of glandular epithelial cells called acinar cells (acini), which secretes 1,200 to 1,500 mL of pancreatic juice per day – that are released into the small intestines to help you digest foods (especially fats). The digestive enzymes are first released into tiny tubes called central ducts. These merge to form larger ducts, which empty into the pancreatic duct (duct of Wirsung). The pancreatic duct merges with the common bile duct (the duct that carries bile from the liver), and empties into the duodenum (the first part of the small intestine) at the ampulla of Vater (also known as the hepatopancreatic ampulla). The ampulla of Vater (hepatopancreatic ampulla) is where the pancreatic duct and bile duct join together to drain into the duodenum, which is the first part of the small intestine. The passage of pancreatic juice and bile through the hepatopancreatic ampulla (ampulla of Vater) into the duodenum of the small intestine is regulated by a mass of smooth muscle surrounding the ampulla known as the sphincter of the hepatopancreatic ampulla, or sphincter of Oddi. The other major duct of the pancreas, the accessory duct (duct of Santorini), that branches from the main pancreatic duct and opens independently into the duodenum about 2.5 cm (1 in.) superior to the hepatopancreatic ampulla (ampulla of Vater) at the minor duodenal papilla. The accessory duct (duct of Santorini) bypasses the sphincter and allows pancreatic juice to be released into the duodenum even when bile is held back.

The endocrine part of the pancreas consists of groups of cells that are closely associated with blood vessels. These remaining 1% of the cell clusters form “islands” of cells called pancreatic islets (Islets of Langerhans). The Islets of Langerhans cells secrete the hormones glucagon, insulin, somatostatin, and pancreatic polypeptide. The pancreatic islets include two distinct types of cells—alpha cells, which secrete the hormone glucagon, and beta cells, which secrete the hormone insulin (Figure 2). Both insulin and glucagon are important hormones which help control blood sugar levels and are released directly into the bloodstream.

Pancreatic islets (Islets of Langerhans) are relatively concentrated in the tail of the pancreas, whereas the head is more exocrine. Over 90% of pancreatic cancers arise from the ducts of the exocrine portion (ductal carcinomas), so cancer is most common in the head of the pancreas.

Figure 1. The pancreas

Figure 2. Pancreas cell types

Footnotes: Exocrine pancreatic acinar cells constitute most of the pancreatic tissue, these cells produce digestive enzymes which are transported via the pancreatic ducts. The endocrine pancreas is illustrated with all cell types; alpha, beta, delta, pancreatic polypeptide (PP) and epsilon. The endocrine pancreas cells are arranged in compact Islets of Langerhans and secrete a number of classical and ‘nonclassical’ peptides, as depicted.

Figure 3. Pancreas location

Figure 4. Relationship of the pancreas to the liver, gallbladder, and duodenum

What does the pancreas do?

About 99% of the pancreas is exocrine tissue made up of small clusters of glandular epithelial cells called acinar cells (acini), which secretes 1,200 to 1,500 mL of pancreatic juice per day – that are released into the small intestines to help you digest foods (especially fats). The cells of the secretory acini exhibit a high density of rough ER (endoplasmic reticulum) and secretory vesicles (zymogen granules). The acini open into a system of branched ducts that eventually converge on the main pancreatic duct. This duct runs lengthwise through the middle of the gland and joins the bile duct at the hepatopancreatic ampulla (ampulla of Vater). The hepatopancreatic sphincter (sphincter of Oddi) thus controls the release of both bile and pancreatic juice into the duodenum. Usually, however, there is a smaller accessory pancreatic duct (duct of Santorini) that branches from the main pancreatic duct and opens independently into the duodenum at the minor duodenal papilla, proximal to the major papilla. The accessory duct (duct of Santorini) bypasses the hepatopancreatic sphincter (sphincter of Oddi) and allows pancreatic juice to be released into the duodenum even when bile is held back.

Pancreatic juice is an alkaline mixture of water, enzymes, zymogens, sodium bicarbonate, and other electrolytes. The acini secrete the enzymes and zymogens, whereas the ducts secrete the sodium bicarbonate. The bicarbonate buffers HCl (hydrochloric acid) arriving from the stomach.

Sodium bicarbonate buffers the hydrochloric acid arriving from the stomach, with the reaction:

• HCl + NaHCO3 ⟶ NaCl + H2CO3 (carbonic acid).

The carbonic acid then breaks down to carbon dioxide (CO2) and water. CO2 is absorbed into the blood and ultimately exhaled. What is left in the small intestine, therefore, is salt water—sodium chloride (NaCl) and H2O. Sodium bicarbonate is therefore important in protecting the intestinal mucosa from hydrochloric acid (HCl) as well as raising the intestinal pH to the level needed for activity of the pancreatic and intestinal digestive enzymes.

The pancreatic zymogens are trypsinogen, chymotrypsinogen and procarboxypeptidase. When trypsinogen is secreted into the intestinal lumen, it is converted to trypsin by enteropeptidase, an enzyme on the brush border of the duodenum. Trypsin is autocatalytic—it converts trypsinogen into still more trypsin. Trypsin also converts the other two zymogens into chymotrypsin and carboxypeptidase, in addition to its primary role of digesting dietary protein.

Pancreatic acinar cells also secrete a protein called trypsin inhibitor that combines with any trypsin formed accidentally in the pancreas or in pancreatic juice and blocks its enzymatic activity.

Other pancreatic enzymes include pancreatic amylase, which digests starch; pancreatic lipase, which digests fat; and ribonuclease and deoxyribonuclease, which digest RNA and DNA, respectively. Unlike the zymogens, these enzymes are not altered after secretion. They become fully active, however, only upon exposure to bile or ions in the intestinal lumen.

Regulation of Pancreatic Secretion

Three stimuli are chiefly responsible for the release of pancreatic juice and bile.

• Acetylcholine (ACh), coming from the vagus nerves and enteric neurons. ACh stimulates the pancreatic acini to secrete their enzymes even during the cephalic phase of gastric control, before food is swallowed. The enzymes remain stored in the pancreatic acini and ducts, however, in preparation for release later when chyme enters the duodenum.
• Cholecystokinin (CCK), secreted by the mucosa of the duodenum and proximal jejunum (the next segment of the small intestine), primarily in response to fats in the small intestine. CCK also stimulates the pancreatic acini to secrete enzymes, but it is named for its strongly stimulatory effect on the gallbladder. It induces contractions of the gallbladder and relaxation of the hepatopancreatic sphincter, discharging bile into the duodenum.
• Secretin, produced by the same regions of the small intestine, mainly in response to the acidity of chyme from the stomach. Secretin stimulates the ducts of both the liver and pancreas to secrete an abundant sodium bicarbonate solution. In the pancreas, this flushes the enzymes into the duodenum.

Hormones of the Pancreatic Islets

The pancreas is primarily an exocrine digestive gland. Scattered throughout the exocrine tissue, are 1 to 2 million endocrine groups of cells that are closely associated with blood vessels called pancreatic islets (islets of Langerhans). Although they are less than 2% of the pancreatic tissue, the islets of Langerhans secrete the hormone glucagon and the hormone insulin of vital importance, especially in the regulation of glycemia, the blood glucose concentration. The pancreatic islets of Langerhans include two distinct types of cells—alpha cells, which secrete the hormone glucagon, and beta cells, which secrete insulin hormone. A typical islet measures about 75 × 175 μm and contains from a few to 3,000 cells. Islets of Langerhans main cell types are alpha cells (20%), beta cells (70%), and delta cells (5%). Islets of Langerhans respond directly to blood nutrient levels associated with the cycle of eating and fasting. Their functions are as follows:

• Alpha (α) cells, or A cells, secrete glucagon between meals when the blood glucose concentration falls below 100 mg/dL (5.6 mmol/L). Glucagon exerts two primary actions on the liver: (1) glycogenolysis, the breakdown of glycogen into glucose; and (2) gluconeogenesis, the synthesis of glucose from fats and proteins. These effects lead to the release of glucose into circulation, thus raising the blood glucose level. In adipose tissue, glucagon stimulates fat catabolism and the release of free fatty acids. Glucagon is also secreted in response to rising amino acid levels in the blood after a high-protein meal. It promotes amino acid absorption and thereby provides cells with the raw material for gluconeogenesis.
• Beta (β) cells, or B cells, secrete two hormones, insulin and amylin. Insulin, “the hormone of nutrient abundance,” is secreted during and immediately following a meal when blood nutrient levels are rising. Osteocalcin, a hormone from the osteoblasts of bone, also stimulates multiplication of beta cells, insulin secretion, and insulin sensitivity of other body tissues. The principal targets of insulin are the liver, skeletal muscles, and adipose tissue. In times of plenty, insulin stimulates cells to absorb glucose, fatty acids, and amino acids and to store or metabolize them; therefore, it lowers the level of blood glucose and other nutrients. It promotes the synthesis of glycogen, fat, and protein, thereby promoting the storage of excess nutrients for later use and enhancing cellular growth and differentiation. It also antagonizes glucagon, thus suppressing the use of already-stored fuels. The brain, liver, kidneys, and red blood cells absorb and use glucose without need of insulin, but insulin does promote glycogen synthesis in the liver. Insulin insufficiency or inaction is well known as the cause of diabetes. The beta cells also secrete another hormone, amylin, simultaneously with insulin. Amylin helps to reduce spikes in blood glucose by slowing the emptying of the stomach; modulating the secretion of gastric enzymes, acid, and bile; inhibiting glucagon secretion; and stimulating the sense of satiety (having had enough to eat).
• Delta (δ) cells, or D cells, secrete somatostatin (growth hormone–inhibiting hormone) concurrently with the release of insulin by the beta cells. Somatostatin a peptide hormone that inhibits the secretion of glucagon and insulin by the nearby alpha and beta cells. Somatostatin also work with amylin to limit the secretion of stomach acid.
• Other, minor types of pancreatic cells, about 5% of the total, are called pancreatic polypeptide (PP) and G cells. Pancreatic polypeptide (PP) cells secrete pancreatic polypeptide, a hormone that may inhibit the exocrine activity of the pancreas.

Any hormone that raises blood glucose concentration is called a hyperglycemic hormone. You may have noticed that glucagon is not the only hormone that does so; so do growth hormone, epinephrine, norepinephrine, cortisol, and corticosterone. Insulin is called a hypoglycemic hormone because it lowers blood glucose levels.

Glucagon raises the blood sugar concentration by stimulating the liver to break down glycogen and convert certain noncarbohydrates, such as amino acids, into  glucose. These actions raise the blood glucose concentration. Glucagon much more effectively elevates blood glucose than does epinephrine (adrenaline).

A negative feedback system regulates glucagon secretion. A low blood glucose concentration stimulates alpha cells to release glucagon. When the blood glucose concentration rises, glucagon secretion falls. This control prevents hypoglycemia when the blood glucose concentration is relatively low, such as between meals, or when glucose is used rapidly, such as during exercise.

The main effect of insulin is to lower the blood glucose level, exactly opposite that of glucagon. Insulin does this in part by promoting facilitated diffusion of glucose into cells that have insulin receptors, for use in cellular respiration. Such cells include those of adipose tissue, liver, and skeletal muscle. (Glucose uptake by active skeletal muscle does not require insulin.) Insulin also stimulates the liver to form glycogen from glucose and inhibits conversion of noncarbohydrates into glucose. In addition, insulin promotes transport of amino acids into cells, increases the rate of protein synthesis, and stimulates adipose cells to synthesize and store fat.

A negative feedback system sensitive to the blood glucose concentration regulates insulin secretion. When the blood glucose concentration is high, such as after a meal, beta cells release insulin. Insulin helps prevent too high a blood glucose concentration by promoting glycogen formation in the liver and entrance of glucose into adipose and muscle cells.

When glucose concentration falls, such as between meals or during the night, insulin secretion decreases. As insulin secretion decreases, less glucose enters adipose and resting muscle cells. Cells that lack insulin receptors and are therefore not dependent on insulin, such as nerve cells, can still take up glucose from the blood. At the same time that insulin is decreasing, glucagon secretion is increasing. Nerve cells, including those of the brain, obtain glucose by a facilitated diffusion mechanism that does not require insulin, but rather depends only on the blood glucose concentration. For this reason, nerve cells are particularly sensitive to changes in blood glucose concentration. Conditions that cause such changes—for example, oversecretion of insulin leading to decreased blood glucose—are likely to affect brain functions.

Insulin and glucagon are coordinated to maintain a relatively stable blood glucose concentration, despite great variation in the amount of carbohydrates a person eats. About 85% to 90% of people with diabetes mellitus have type 2 diabetes, in which the beta cells produce insulin but body cells lose the ability to recognize it. On the other hand, type 1 diabetes mellitus usually appears before age twenty and it is an autoimmune disease: the immune system destroys the beta cells of the pancreas.

The Gallbladder

The gallbladder is a pear-shaped sac in a depression on the liver’s under surface. The gallbladder is lined with epithelial cells and has a strong layer of smooth muscle in its wall. The gallbladder stores bile between meals, reabsorbs water to concentrate bile, and contracts to release bile into the small intestine. It connects to the cystic duct, which in turn joins the common hepatic duct (Figure 2).

The common hepatic duct and cystic duct join to form the bile duct (common bile duct). It leads to the duodenum where the hepatopancreatic sphincter guards its exit (Figure 3). Because this sphincter normally remains contracted, bile collects in the bile duct. It backs up into the cystic duct and flows into the gallbladder, where it is stored.

Cholesterol in bile may precipitate under certain conditions and form crystals called gallstones. Gallstones in the bile duct may block bile flow into the small intestine and cause considerable pain. A surgical procedure called a cholecystectomy can remove the gallbladder when gallstones are obstructive. The surgery can often be done with a laparoscope (small, lit probe) on an outpatient basis.

Figure 1. Gallbladder location

Figure 2. Gallbladder anatomy

Figure 3. The common bile duct is closely associated with the pancreatic duct and the duodenum

Gallbladder function

Following a meal, the mixing movements of the stomach wall aid in producing a semifluid paste of food particles and gastric juice called chyme.

As chyme enters the duodenum (the proximal portion of the small intestine), accessory organs—the pancreas, liver, and gallbladder—add their secretions.

Bile is a yellowish-green liquid continuously secreted from hepatic (liver) cells. In addition to water, bile contains bile salts, bile pigments (bilirubin and biliverdin), cholesterol, and electrolytes. Of these, bile salts are the most abundant and are the only bile components that have a digestive function.

Bile pigments are breakdown products of hemoglobin from red blood cells and are normally secreted in the bile.

Normally bile does not enter the duodenum until cholecystokinin stimulates the gallbladder to contract. Proteins and fats in chyme in the duodenum stimulate
the intestinal wall to release cholecystokinin. Cholecystokinin travels via the bloodstream to the pancreas also, where it stimulate the pancreas to release its pancreatic juice that has a high concentration of digestive enzymes.

The hepatopancreatic sphincter usually remains contracted until a peristaltic wave in the duodenal wall approaches it. Then the sphincter relaxes, and bile is squirted into the duodenum (see Figure 4).

Note: Cholecystokinin produced by the intestinal wall cells, in response to proteins and fats in the small intestine, decreases secretory activity of gastric glands and inhibits gastric motility; stimulates pancreas to secrete fluid with a high digestive enzyme concentration and stimulates gallbladder to contract and release bile.

Figure 4. Fatty chyme entering the duodenum stimulates the gallbladder to release bile

The Liver

Your liver is the largest organ inside your body, weighing about 1.4 kg (3 pounds) in an average adult. The liver is in the right upper quadrant of the abdominal cavity, just inferior to the diaphragm in the right superior part of the abdominal cavity and under your right ribs just beneath your right lung – filling much of the right hypochondriac and epigastric regions and extending into the left hypochondriac region. The liver is partially surrounded by the ribs, and extends from the level of the fifth intercostal space to the lower margin of the right rib cage, which protects this highly vascular organ from blows that could rupture it. The liver is shaped like a wedge, the wide base of which faces right and the narrow apex of which lies just inferior to the level of the left nipple. The reddish-brown liver is well supplied with blood vessels.

Liver anatomy

A fibrous capsule encloses the liver, and ligaments divide the organ into a large right lobe and a smaller left lobe (Figure 2).

The liver also has two minor lobes, the quadrate lobe and the caudate lobe. Each lobe is separated into many tiny hepatic lobules, the liver’s functional units (Figure 3). A lobule consists of many hepatic cells radiating outward from a central vein. Blood-filled channels called hepatic sinusoids separate platelike groups of these cells from each other. Blood from the digestive tract, carried in the hepatic portal vein, brings newly absorbed nutrients into the sinusoids and nourishes the hepatic cells.

Large phagocytic macrophages called Kupffer cells are fixed to the inner linings of the hepatic sinusoids. They remove bacteria or other foreign particles that enter the blood through the intestinal wall, and are brought to the liver via the hepatic portal vein. Blood passes from these sinusoids into the central veins of the hepatic lobules and exits the liver via the hepatic veins.

Within the hepatic lobules are many fine bile canaliculi, which carry secretions from hepatic cells to bile ductules. The ductules of neighboring lobules converge to ultimately form the hepatic ducts. These ducts merge, in turn, to form the common hepatic duct.

Figure 1. Location of the human liver

Figure 2. Liver anatomy

Figure 3. Liver lobule

Footnote: (a) Cross section of a hepatic lobule. (b) Enlarged longitudinal section of a hepatic lobule. (c) Light micrograph of hepatic lobules in cross section.

Figure 4. Human liver microscopic anatomy

Liver functions

Amazingly versatile, your liver performs over 500 functions. Its digestive function is to produce bile, a green alkaline liquid that is stored in the gallbladder and secreted into the duodenum. Bile salts emulsify fats in the small intestine; that is, they break up fatty nutrients into tiny particles, just as dish detergent breaks up a pool of fat drippings in a roasting pan. These smaller particles are more accessible to digestive enzymes from the pancreas. The liver also performs many metabolic functions and you cannot live without your liver:

• Picks up glucose from nutrient-rich blood returning from the alimentary canal and stores this carbohydrate as glycogen for subsequent use by the body.
• Processes fats and amino acids and stores certain vitamins.
• Detoxifies many poisons and drugs in the blood.
• Makes the blood proteins.
• It breaks down and stores many of the nutrients absorbed from the intestine that your body needs to function. Some nutrients must be changed (metabolized) in the liver before they can be used for energy or to build and repair body tissues.
• It makes most of the clotting factors that keep you from bleeding too much when you are cut or injured.
• It secretes bile into the intestines to help absorb nutrients (especially fats).
• It breaks down alcohol, drugs, and toxic wastes in the blood, which then pass from the body through urine and stool.

Almost all of these functions are carried out by a type of cell called a hepatocyte or simply a liver cell.

The liver carries on many important metabolic activities. The liver plays a key role in carbohydrate metabolism by helping maintain concentration of blood glucose within the normal range. Liver cells responding to the hormone insulin lower the blood glucose level by polymerizing glucose to glycogen. Liver cells responding to the hormone glucagon raise the blood glucose level by breaking down glycogen to glucose or by converting noncarbohydrates into glucose.

The liver’s effects on lipid metabolism include oxidizing (breaking down) fatty acids at an especially high rate; synthesizing lipoproteins, phospholipids, and cholesterol; and converting excess portions of carbohydrate molecules into fat molecules. The blood transports fats synthesized in the liver to adipose tissue for storage.

Other liver functions concern protein metabolism. They include deaminating amino acids; forming urea; synthesizing plasma proteins such as clotting factors; and converting certain amino acids into other amino acids.

The liver also stores many substances, including glycogen, iron, and vitamins A, D, and B12. In addition, macrophages in the liver help destroy damaged red blood cells and phagocytize foreign antigens. The liver also removes toxic substances such as alcohol and certain drugs from blood (detoxification). Table 1 summarizes the major functions of the liver.

Table 1. Major Functions of the Liver

The Bile

Bile is a yellowish-green liquid continuously secreted from hepatic cells. In addition to water, bile contains bile salts, bile pigments (bilirubin and biliverdin), cholesterol, and electrolytes. Of these, bile salts are the most abundant and are the only bile components that have a digestive function.

Bile pigments are breakdown products of hemoglobin from red blood cells and are normally secreted in the bile.

Jaundice, a yellowing of the skin and mucous membranes due to accumulation of bile pigment, has several causes. In obstructive jaundice bile ducts are blocked, perhaps by gallstones or tumors. In hepatocellular jaundice the liver is diseased, as in cirrhosis or hepatitis. In hemolytic jaundice red blood cells are destroyed too rapidly, as happens with an incompatible blood transfusion or a blood infection.

Regulation of Bile Release

Normally bile does not enter the duodenum until cholecystokinin stimulates the gallbladder to contract. The intestinal mucosa releases this hormone in response to proteins and fats in the small intestine. The hepatopancreatic sphincter usually remains contracted until a peristaltic wave in the duodenal wall approaches it. Then the sphincter relaxes, and bile is squirted into the duodenum.

Functions of Bile Salts

Bile salts aid digestive enzymes. Bile salts affect fat globules (clumped molecules of fats) much like a soap or detergent would affect them. That is, bile salts break fat globules into smaller droplets that are more soluble in water. This action, called emulsification, greatly increases the total surface area of the fatty substance. The resulting fat droplets disperse in water. Fat-splitting enzymes (lipases) can then digest the fat molecules more effectively. Bile salts also enhance absorption of fatty acids, cholesterol, and the fat-soluble vitamins A, D, E, and K.

Low levels of bile salts result in poor lipid absorption and vitamin deficiencies.

The Gallbladder

The gallbladder is a pear-shaped sac in a depression on the liver’s inferior surface. The gallbladder is lined with epithelial cells and has a strong layer of smooth muscle in its wall. The gallbladder stores bile between meals, reabsorbs water to concentrate bile, and contracts to release bile into the small intestine. It connects to the cystic duct, which in turn joins the common hepatic duct.

The common hepatic duct and cystic duct join to form the bile duct (common bile duct). It leads to the duodenum where the hepatopancreatic sphincter guards its exit. Because this sphincter normally remains contracted, bile collects in the bile duct. It backs up into the cystic duct and flows into the gallbladder, where it is stored.

A liver function important to digestion is bile secretion.