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Pancreatic Cancer

 
 

Overview

Pancreatic cancer is a disease in which normal cells in the pancreas malfunction and begin to grow uncontrollably. These cancerous cells can eventually interfere with proper functioning of the pancreas and metastasize (spread) to other parts of the body.

The pancreas is a pear-shaped gland located in the abdomen between the stomach and the spine. It is about 6 inches in length and is composed of two major components: exocrine and endocrine. The exocrine component, made up of ducts and acini (small sacs on the end of the ducts), produce enzymes, which are specialized proteins released into the small intestine that help the body digest and break down food, particularly fats. It is the cells lining these pancreatic ducts that most frequently turn cancerous. These are called ductal adenocarcinomas of the pancreas and represent the most common subtype of pancreatic cancer.

The endocrine component of the pancreas is made up of specialized cells clustered together in islands within the organ, called islets of Langerhans. These cells produce hormones, the most critical one being insulin, an important substance that helps control the amount of sugar in the blood. Rarely, cancer will begin in these islet cells and is appropriately referred to as islet cell tumors or pancreatic endocrine tumors. These neuroendocrine tumors may produce chemicals such as insulin or may grow without producing such hormones. If the tumor produces a hormone(s), the hormone(s) may cause imbalances such as very low (insulinoma) or very high (glucagonoma) blood sugars or such things as severe diarrhea (VIPoma, which produces vasoactive intestinal peptide). It is important to distinguish neuroendocrine tumors from adenocarcinomas of the pancreas because the tumors act very differently.

Because pancreatic cancer often does not cause specific symptoms early on in its development, pancreatic cancers may not be detected until the cancer has metastasized beyond the pancreas to other areas of the body, such as the liver, lungs, or the peritoneum (the tissue lining the abdomen).

Risk Factors

A risk factor is anything that increases a person's chance of developing a disease, including cancer. There are risk factors that can be controlled, such as smoking, and risk factors that cannot be controlled, such as age and family history. Although risk factors can influence disease, for many risk factors it is not known whether they actually cause the disease directly. Some people with several risk factors never develop the disease, while others with no known risk factors do. Knowing your risk factors and communicating them to your doctor may help you make more informed lifestyle and health-care choices.

Although the cause of pancreatic cancer is not known, the following factors can raise a person's risk of developing pancreatic cancer:

Age. The risk of developing pancreatic cancer increases with age. Most cases occur in people older than 60.

Gender. More men are diagnosed with pancreatic cancer than women.

Race. Black people are more likely than Asians, Hispanics, or white people to develop pancreatic cancer.

Smoking. Smokers are two to three times more likely to develop pancreatic cancer than nonsmokers.

Obesity and diet. Eating a high-fat diet is a risk factor for pancreatic cancer. Research has shown that obese and even overweight men and women have a higher risk of dying from pancreatic cancer.

Diabetes. The sudden onset of Type II diabetes can be an early symptom of pancreatic cancer, but studies have shown conflicting results regarding whether diabetes represents a clear risk factor for the development of pancreatic cancer. It appears that long-term diabetes increases an individual's risk of developing pancreatic cancer.

Family history. A person's chance of developing this cancer increases three-fold if a first-degree relative (mother, father, sister, or brother) had pancreatic cancer. That risk increases even further the greater the number of first-degree relatives who are affected. Melanoma that runs in families and certain hereditary forms of colon, breast (BRCA2), and ovarian cancers are also associated with an increased risk of developing pancreatic cancer.

Chronic pancreatitis. Pancreatitis is the inflammation of the pancreas, a painful disease of the pancreas. Some research suggests that having chronic pancreatitis may increase the risk of developing pancreatic cancer.

Chemicals. Exposure to certain chemicals (such as pesticides, benzene, certain dyes, and petrochemicals) may increase the risk of developing pancreatic cancer.

Symptoms

People with pancreatic cancer may experience the following symptoms. Sometimes, people with pancreatic cancer do not show any of these symptoms. Or, these symptoms may be similar to symptoms of other medical conditions. If you are concerned about a symptom on this list, please talk with your doctor.

Doctors often refer to pancreatic cancer as a silent disease because it usually does not cause any symptoms in the beginning. Also, there are currently no blood tests that can reliably detect the cancer while it is in its early stage. As the cancer grows, symptoms may include:

  • Yellow skin and eyes, darkening of the urine, itching, and clay-colored stool, which are signs of obstructive jaundice that may occur during the early stage of the disease
  • Pain in upper abdomen or upper back
  • Burning feeling in stomach or other gastrointestinal discomforts
  • Floating stools with a particularly bad odor, due to malabsorption of fats
  • Weakness
  • Loss of appetite
  • Nausea and vomiting
  • Weight loss with no known explanation

Diagnosis

Doctors use many tests to diagnose cancer and determine if it has metastasized. Some tests may also determine which treatments may be the most effective. A biopsy is necessary to make a definite diagnosis of pancreatic cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the cancer has metastasized and where the tumor(s) are located. Your doctor may consider these factors when choosing a diagnostic test:

  • Age and medical condition
  • The type of cancer
  • Severity of symptoms
  • Previous test results

If a doctor suspects that a person has pancreatic cancer, he or she will first ask about the person's medical history and examine the person to look for signs of the disease.

Common procedures used to diagnose pancreatic cancer include:

Physical examination. The doctor will examine the skin and eyes to see if they are yellow, which is a sign of a condition called jaundice. Jaundice can result from pancreatic cancer. The doctor will also feel the abdomen for changes caused by the cancer, however because the pancreas is in the back of the upper abdomen, often it is not palpable, which means the doctor cannot feel it. The doctor also may check for ascites (an abnormal buildup of fluid in the abdomen), which can signal the presence of cancer.

Laboratory tests. The doctor may take samples of blood to check for abnormal levels of bilirubin and other substances. Bilirubin is a chemical that may reach high levels in patients with pancreatic cancer due to blockage of the common bile duct by a tumor. CA 19-9 is a tumor marker (substances in the body that may be found at higher levels if cancer is present) that can be measured in the blood and is frequently elevated in individuals with pancreatic cancer. An elevated CA 19-9 test by itself should not be used to make the diagnosis of pancreatic cancer, as CA 19-9 can be elevated in other conditions as well (such as pancreatitis, cirrhosis of the liver, and blockage of the common bile duct).

Imaging procedures allow doctors to determine where the cancer is located and whether it has spread from the pancreas to other areas of the body. However, pancreatic cancer tumors often do not develop as a single large tumor mass, and therefore can be difficult to see on imaging.

Computed tomography (CT or CAT) scan. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. It is a scan that shows your body anatomically and provides the doctor with a series of pictures. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. Sometimes, a contrast medium (a special dye) is injected into a vein to provide better detail. A CT scan helps doctors determine the location and extent of the cancer. In this test, a scanner moves around the body and takes hundreds of x-ray images. Then a computer combines them to make a three-dimensional image of the inside of the body. CT scans can typically show tumors that are at least 1 to 2 centimeters (cm) in size.

Positron-emission tomography (PET) scan. In a PET scan, sugar molecules tagged with a marker visible on the scanner are injected into the body. It is a scan that shows your body's metabolic activity. Cancer cells absorb sugar more quickly than normal cells, so they light up on the PET scan. PET scans are often used to complement information gathered from CT scan, magnetic resonance imaging (MRI, uses magnetic fields, not x-rays, to produce detailed images of the body), and physical examination. Sometimes, CT and PET scans can be performed after each other and the images are fused together (called fusion PET/CT).

Ultrasound. Ultrasonography or ultrasound uses sound waves to create a picture of the pancreas and other organs. Tumors generate different echoes of the sound waves than normal tissue does, so when the waves are bounced back to a computer and changed into images, the doctor can locate masses inside the body. There are two types of ultrasound devices: transabdominal and endoscopic.

  • A transabdominal ultrasound device is placed on the abdomen and is slowly moved around by the doctor to produce an image of the pancreas and surrounding structures. This technique is commonly used to look at babies during development, but can also be used to look at many organs.
  • The endoscopic ultrasound (EUS) device consists of a thin, lighted tube that is passed through the patient's mouth and stomach and down into the small intestine in order to take a picture of the pancreas. This procedure is very specialized and requires a gastroenterologist (a doctor who specializes in the function and disorders of the gastrointestinal tract, including stomach, intestines, and associated organs) who has special training in this area and is generally done under sedation, so the patient sleeps through the procedure.

Endoscopic retrograde cholangiopancreatography (ERCP). In this procedure, an endoscope (a thin, lighted tube) is passed into the small intestine through the mouth and stomach. A catheter (smaller tube) is passed through the endoscope and into the bile ducts and pancreatic ducts. Dye is injected into the ducts, and the doctor then takes x-rays that can show whether a duct is compressed or narrowed. Often, a plastic or metal stent can be placed across the obstructed bile duct during ERCP to help relieve the jaundice. Brushings, which can be obtained during this procedure, sometimes help confirm the diagnosis of cancer. A gastroenterologist should perform this procedure. The patient is lightly sedated during this procedure.

Percutaneous transhepatic cholangiography (PTC). In this procedure, a thin needle is inserted through the skin and into the liver. A dye is injected through the needle, so the bile ducts show up on x-rays. By looking at the x-rays, the doctor can tell whether there is a blockage of the bile ducts.

Biopsy. A biopsy removes a small amount of tissue for examination under a microscope. Other tests can suggest that cancer is present, but only a biopsy can make a definite diagnosis. One technique to obtain pancreas tissue is fine needle aspiration, in which a needle is inserted into the pancreas to aspirate (suction out) cells. An x-ray or CT-guided ultrasound is used to help guide the needle. Other ways to collect a sample of pancreas tissue involve the use of ERCP, EUS, or surgery. If the cancer has spread to other organs, a biopsy may be obtained from one of these other sites (such as the liver). A surgical biopsy can be performed either by opening the abdomen or by using a laparoscopic approach, in which small holes are made in the abdomen through which a camera and surgical instruments can be placed.

Some patients, when having surgery or certain types of biopsies, elect to have some of their excess specimen frozen and sent to independent laboratories to have genetic and molecular profiles performed on their specimens. The purpose is to understand at a molecular level the patient's individual genetic makeup, thus helping to predict which treatments a patient may potentially respond to. The use of biospecimens in this manner has not been fully confirmed scientifically in controlled studies. However, with the increase in new drugs called targeted agents, it is an area of increasing interest and scientific focus. It is important to note that many insurance companies do not reimburse for these types of tests yet.

Treatment

The treatment of pancreatic cancer depends on the size and location of the tumor, whether the cancer has spread, and the person's overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan.

If detected at an early stage, pancreatic cancer has a much higher chance of being successfully treated. However, there are treatments that can help control the disease in patients with advanced pancreatic cancer and allow them to live longer. Many doctors advise people with pancreatic cancer to enroll in clinical trials, where they can participate in studies to test new drugs or therapies that may potentially treat the cancer.

The current treatment options for pancreatic cancer are surgery, radiation therapy, or chemotherapy. All of these treatments may be used at any stage of the disease, whether it is an early cancer or an advanced cancer.

Surgery

Surgery may involve removing all or part of the pancreas, depending on the location and size of the cancer within the pancreas. If the cancer is still confined to the pancreas' head, or widest part of the pancreas, the surgeon may perform a Whipple procedure. This is an extensive operation where the surgeon removes the head of the pancreas and part of the small intestine, bile duct, and stomach, and then reconnects the digestive tract and biliary system. An experienced surgeon should perform this procedure.

Another surgical procedure is a distal pancreatectomy, in which the surgeon removes the tail and body of the pancreas, as well as the spleen. In a total pancreatectomy, the surgeon removes the entire pancreas, part of the small intestine, a portion of the stomach, the common bile duct, the gallbladder, the spleen, and nearby lymph nodes.

Sometimes before one of the above major operations, the surgeon may choose to start with a laparoscopy, in which several small holes are made in the abdomen, while a patient is under anesthesia, through which a camera can be passed. This allows the surgeon to assess whether the cancer has spread to other areas within the abdominal cavity, in which case undertaking the full operation to remove the primary tumor would not be warranted.

Surgery may be combined with radiation therapy and/or chemotherapy, both of which may be given either before (neoadjuvant) or after surgery (adjuvant therapy); most often this is done given postoperatively. The purpose of giving radiation therapy and chemotherapy is to try to decrease the likelihood of the cancer returning or increase the chance of resection. Gemcitabine-based chemotherapy is commonly given after surgery, based on evidence that it improves disease-free survival. The role of radiation therapy after surgery remains somewhat controversial, although it is frequently used for individuals who have a high risk of their cancer coming back in the surgical bed (if it is a large tumor, or close or positive surgical margins).

If the tumor is blocking the common bile duct or small intestine, placement of a stent (a tiny tube that helps keep the blocked area open and can be either metal or plastic) can be performed to relieve the blockage using nonsurgical approaches, such as endoscopic cholangiopancreatography (ERCP) or endoscopy (see the Diagnosis section for more information). In some instances, the patient may need surgery to create a bypass, even if the tumor itself cannot be completely removed.

Side effects of surgery include weakness, tiredness, and pain after the first few days following the procedure. The doctor can prescribe medicine to provide relief. The patient will need to stay in the hospital for several days and will probably need to rest at home for about one month. It may be difficult to digest food due to the removal of all or part of the pancreas. A special diet and medications may help. Also, the doctor can prescribe hormones and enzymes to replace those lost by the removal of the pancreas. Another side effect is the development of diabetes due to the loss of insulin, which is produced by the pancreas. The doctor may need to prescribe insulin.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. For this approach, patients are required to go to the hospital or doctor's office five days a week (Monday through Friday) for up to six weeks, although each individual treatment session only lasts a few minutes. Radiation therapy may be used before surgery, during surgery (called intraoperative radiation therapy), or, most commonly, after surgery. Radiation is also used for palliative purposes (relieving pain associated with the cancer) even if the cancer is inoperable (cannot be operated on).

Newer radiation therapy techniques, such as stereotactic radiosurgery (for example, Cyberknife), are starting to play more of a role in the treatment of pancreatic cancer, with the advantage that they can provide more localized treatment and require only single treatment sessions. However, these approaches have not been compared with the more conventional approach of delivering external-beam radiation therapy and should not be considered a replacement for it.

Often, chemotherapy will be administered simultaneously (at the same time) with radiation therapy because it can enhance the effects of the radiation therapy (called radiosensitization).

Fatigue is a major side effect of radiation therapy, and the patient generally becomes more tired as treatment goes on. Although resting is important, patients are advised to stay active, if possible. The therapy also may cause nausea, vomiting, diarrhea, and other digestive problems. Medication or diet changes may help with some of these problems. Another side effect is the skin of the treated area may become red, dry, and tender. Most of these side effects eventually go away after treatment is finished.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. Systemic chemotherapy uses drugs to target cancer cells throughout the body. Chemotherapy can be given orally or by injection, and this can be done as an outpatient treatment at the hospital, doctor's office, or at home.

The most common first-line chemotherapy used for the treatment of pancreatic cancer is gemcitabine (Gemzar). Gemcitabine has been shown not only to improve survival outcomes in patients with advanced pancreatic cancer, but it also helps improve cancer-related symptoms (for example, weight loss, pain, and weakness) in some of patients. A number of large studies have been conducted to evaluate whether combining gemcitabine with other chemotherapy agents (such as fluorouracil [5-FU] or platinum compounds, such as cisplatin, carboplatin [Paraplatin], and oxaliplatin [Eloxatin]) is more effective than gemcitabine alone. Some studies suggest modest improvements in outcomes using combination therapy; however, these combination treatments also tend to be associated with greater side effects. Recently, one large study demonstrated a survival benefit for patients with advanced pancreatic cancer receiving gemcitabine in combination with an oral medication called erlotinib (Tarceva) compared with gemcitabine alone. On this basis, erlotinib was approved by the U.S. Food and Drug Administration (FDA) in November 2005 for use in advanced pancreatic cancer in combination with gemcitabine. Another large study conducted in Europe demonstrated a survival benefit using another gemcitabine-containing drug combination, gemcitabine plus capecitabine. Therefore, while gemcitabine alone has represented the standard of care for patients with advanced pancreatic cancer since its approval in 1997, this standard may be evolving as certain combination regimens demonstrate small but real advantages for patients without excessive side effects.

For patients who are interested, participation in a clinical trial represents a good option. In order to make the progress needed to improve outcomes for pancreatic cancer, research must identify better approaches. Newer targeted therapies that attack cancer cells and spare normal cells are being actively investigated and show promise in individuals with pancreatic cancer (see Current Research).

Side effects of chemotherapy depend on which drugs the patient receives. These include poor appetite, nausea, vomiting, diarrhea, mouth sores, hair loss, and a lack of energy. People undergoing chemotherapy also are more likely to get infections and bruise and bleed easily because chemotherapy decreases bone marrow production of white blood cells, red blood cells, and platelets. These side effects go away between treatments and after the treatments have ended. The doctor can suggest ways to relieve these side effects.

The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications you've been prescribed, their purpose, and their potential side effects or interactions with other medications.

Advanced pancreatic cancer

In advanced disease, the cancer has metastasized outside of the pancreas to nearby lymph nodes and to distant organs. The treatment options for this stage are the same as for earlier stages and include palliative surgery, radiation therapy, and chemotherapy.

In rare instances, chemotherapy and radiation therapy may shrink the tumor enough in patients with locally advanced disease, so it can be removed by surgery. However, in patients where the cancer has spread to other organs away from the pancreas, generally chemotherapy alone is the treatment of choice. Surgery and radiation therapy are usually ineffective and have limited roles. The patient may also consider enrolling in clinical trials of new treatments that may help stop the cancer.

If pancreatic cancer returns after treatment, this is known as recurrent cancer. The treatment options are generally the same as metastatic cancer and may include surgery to relieve symptoms, radiation therapy, and chemotherapy. Additionally, medication or a nerve block to reduce pain may be given. Clinical trials that test new therapies may also be available.

Side Effects of Cancer and Cancer Treatment

Cancer and cancer treatment can cause a variety of side effects; some are easily controlled and others require specialized care. Below are some of the side effects that are more common to pancreatic cancer and its treatments.

Appetite loss. Appetite changes are common with cancer and cancer treatment, including chemotherapy. Individuals with a poor appetite or appetite loss may eat less than usual, not feel hungry at all, or feel satiated (full) after eating only a small amount. Ongoing appetite loss can lead to weight loss, malnutrition, and loss of muscle mass and strength. The combination of weight loss and loss of muscle mass, also called wasting, is referred to as cachexia.

Diarrhea. Diarrhea is frequent, loose, or watery bowel movements. It is a common side effect of certain chemotherapeutic drugs or radiation therapy to the pelvis, such as in women with uterine, cervical, or ovarian cancers. It can also be caused by certain tumors, such as pancreatic cancer.

Fatigue (tiredness). Fatigue is extreme exhaustion or tiredness and is the most common problem patients with cancer experience. More than half of patients experience fatigue during chemotherapy or radiation therapy, and up to 70% of patients with advanced cancer experience fatigue. Patients who feel fatigue often say that even a small effort, such as walking across a room, can seem like too much. Fatigue can seriously affect family and other daily activities, can make patients avoid or skip cancer treatments, and may even affect the will to live.

Fluid in the abdomen (ascites). Ascites is the buildup of fluid in the abdomen, in the area around the organs known as the peritoneal cavity. Ten percent (10%) of all ascites is caused by cancer and is called malignant ascites. Most cancer-related ascites appears in patients with cancers of the ovary, endometrium (lining of the uterus), breast, colon, gastrointestinal (GI) system, or pancreas. These cancers can cause fluid to build up in the body. People with ascites may experience weight gain, abdominal swelling, a sense of fullness or bloating, a sense of heaviness, indigestion, nausea and/or vomiting, changes to the navel, hemorrhoids (a condition that causes painful swelling near the anus), or ankle swelling. In some situations, a procedure known as paracentesis is performed by the doctor to temporarily drain some of the excess fluid to relieve the swelling. Diuretics, such as aldactone, may also help control excessive fluid buildup.

Hair loss (alopecia). A potential side effect of radiation therapy and chemotherapy is hair loss. Radiation therapy and chemotherapy cause hair loss by damaging the hair follicles responsible for hair growth. Hair loss may occur throughout the body, including the head, face, arms, legs, underarms, and pubic area. The hair may fall out entirely, gradually, or in sections. In some cases, the hair will simply thin-sometimes unnoticeably-and may become duller and dryer. Losing one's hair can be a psychologically and emotionally challenging experience and can affect a patient's self-image and quality of life. However, the hair loss is usually temporary, and the hair often grows back.

Mouth sores (mucositis). Mucositis is an inflammation of the inside of the mouth and throat, leading to painful ulcers and mouth sores. It occurs in up to 40% of patients receiving chemotherapy treatments. Mucositis can be caused by a chemotherapeutic drug directly, the reduced immunity brought on by chemotherapy, or radiation treatment to the head and neck area.

Nausea and vomiting. Vomiting, also called emesis or throwing up, is the act of expelling the contents of the stomach through the mouth. It is a natural way for the body to rid itself of harmful substances. Nausea is the urge to vomit. Nausea and vomiting are common in patients receiving chemotherapy for cancer and in some patients receiving radiation therapy. Many patients with cancer say they fear nausea and vomiting more than any other side effects of treatment. When it is minor and treated quickly, nausea and vomiting can be quite uncomfortable but cause no serious problems. Persistent vomiting can cause dehydration, electrolyte imbalance, weight loss, depression, and avoidance of chemotherapy.

Pain. Depending on the stage of disease, 30% to 75% of all patients experience pain from cancer. About 85% to 95% of cancer pain can be treated successfully. Pain can make other aspects of cancer seem worse, such as fatigue (tiredness), weakness, sleep disturbance, and confusion. Pain can come from the tumor itself or may be a result of cancer treatment. Pain from a tumor can be a result of the tumor growing and spreading to the bones or other organs and putting pressure on and damaging nerves. In pancreatic cancer, a common source of pain is tumor involvement with the celiac plexus, a nerve center located in the center of the abdomen behind the pancreas. Sometimes, the doctor can perform a celiac plexus nerve block to lessen the pain either by inserting a needle through the skin or by using an endoscope with ultrasound to identify the nerve center. Pain from surgery is normal and may persist for months or years. Common procedures that cause pain afterward include mastectomy (removal of the breast and, occasionally, the surrounding tissue), chest surgery, neck surgery, and amputation of a limb (stump pain). Phantom pain is perceived pain in an organ or limb that has been removed. Pain may develop after radiation therapy and go away on its own. It can also develop months or years after treatment, especially after radiation therapy to the chest, breast, or spinal cord. Certain chemotherapeutic drugs can cause pain along with numbness in the fingers and toes. Usually this pain goes away when treatment is finished, but sometimes the damage can be permanent.

Skin problems. The skin is an organ system that contains many nerves. Because of this, skin problems can be very painful. Many patients find skin problems especially difficult to cope with because the skin is on the outside of the body and visible to others. Because the skin protects the inside of the body from infection, skin problems can often lead to other serious problems. As with other side effects, prevention or early treatment is best. In other cases, treatment and wound care can often improve pain and quality of life. Skin problems can have many different causes, including chemotherapeutic drugs leaking out of the intravenous (IV) tube, which can cause pain or burning; peeling or burned skin caused by radiation therapy; pressure ulcers (bed sores) caused by constant pressure on one area of the body; and pruritus (itching) in patients with cancer, most often caused by leukemia, lymphoma, myeloma, other cancers, or side effects of treatment. One of the common side effects of erlotinib, the oral drug approved for use in pancreatic cancer (see Treatment section), is the development of a red, acne-like rash that occurs over the face and upper trunk (torso), that can range from mild to quite severe.

After Treatment

For patients who have had surgery, follow-up visits every three to six months with the oncologist are typically recommended. Blood tests, including monitoring of liver function tests and the tumor marker CA 19-9, can be checked during these visits. Routinely, CT scans do not need to be performed, but they may be appropriate depending on an individual's symptoms and any abnormalities detected during the physical examination or with the blood work. Some doctors prefer to use PET scans.

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