Pancreatic Cancer

WHAT IS PANCREATIC CANCER?

Pancreatic cancer is a disease in which malignant (cancer) cells form in the tissues of the pancreas.

The pancreas is a gland about 6 inches long that is shaped like a thin pear lying on its side. The wider end of the pancreas is called the head, the middle section is called the body, and the narrow end is called the tail. The pancreas lies behind the stomach and in front of the spine.

The pancreas has two main jobs in the body:

To produce juices that help digest (break down) food.
To produce hormones, such as insulin and glucagon, that help control blood sugar levels. Both of these hormones help the body use and store the energy it gets from food.
The digestive juices are produced by exocrine pancreas cells and the hormones are produced by endocrine pancreas cells. About 95% of pancreatic cancers begin in exocrine cells.


Pancreatic adenocarcinoma. Neoplastic glands of variable size and shape are surrounded by desmoplastic stroma





Pancreatic adenocarcinoma. Perineural invasion is present Gastrinoma. Cells with uniformly small, round nuclei are arranged in nests

WHAT ARE RISK FACTORS OF PANCREATIC CANCER?

Smoking and health history can affect the risk of developing pancreatic cancer.

The following are possible risk factors for pancreatic cancer:

Smoking.
Long-standing diabetes.
Chronic pancreatitis.
Certain hereditary conditions, such as hereditary pancreatitis, multiple endocrine neoplasia type 1 syndrome, hereditary nonpolyposis colon cancer (HNPCC; Lynch syndrome), von Hippel-Lindau syndrome, ataxia-telangiectasia, and the familial atypical multiple mole melanoma syndrome (FAMMM).
HOW TO DETECT PANCREATIC CANCER?

Possible signs of pancreatic cancer include jaundice, pain, and weight loss.

These symptoms can be caused by pancreatic cancer or other conditions. A doctor should be consulted if any of the following problems occur:

Jaundice (yellowing of the skin and whites of the eyes).
Pain in the upper or middle abdomen and back.
Unexplained weight loss.
Loss of appetite.
Fatigue.
Pancreatic cancer is difficult to detect (find) and diagnose early.

Pancreatic cancer is difficult to detect and diagnose for the following reasons:

There aren’t any noticeable signs or symptoms in the early stages of pancreatic cancer.
The signs of pancreatic cancer, when present, are like the signs of many other illnesses.
The pancreas is hidden behind other organs such as the stomach, small intestine, liver, gallbladder, spleen, and bile ducts.
Tests that examine the pancreas are used to detect (find), diagnose, and stage pancreatic cancer.

Pancreatic cancer is usually diagnosed with tests and procedures that produce pictures of the pancreas and the area around it. The process used to find out if cancer cells have spread within and around the pancreas is called staging. Tests and procedures to detect, diagnose, and stage pancreatic cancer are usually done at the same time. In order to plan treatment, it is important to know the stage of the disease and whether or not the pancreatic cancer can be removed by surgery. The following tests and procedures may be used:

Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.


Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. A spiral or helical CT scan makes a series of very detailed pictures of areas inside the body using an x-ray machine that scans the body in a spiral path.


MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radionuclide glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells.
Endoscopic ultrasound (EUS): A procedure in which an endoscope (a thin, lighted tube) is inserted into the body. The endoscope is used to bounce high-energy sound waves (ultrasound) off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. This procedure is also called endosonography.
Laparoscopy: A surgical procedure to look at the organs inside the abdomen to check for signs of disease. Small incisions (cuts) are made in the wall of the abdomen and a laparoscope (a thin, lighted tube) is inserted into one of the incisions. Other instruments may be inserted through the same or other incisions to perform procedures such as removing organs or taking tissue samples for biopsy.
Endoscopic retrograde cholangiopancreatography (ERCP): A procedure used to x-ray the ducts (tubes) that carry bile from the liver to the gallbladder and from the gallbladder to the small intestine. Sometimes pancreatic cancer causes these ducts to narrow and block or slow the flow of bile, causing jaundice. An endoscope (a thin, lighted tube) is passed through the mouth, esophagus, and stomach into the first part of the small intestine. A catheter (a smaller tube) is then inserted through the endoscope into the pancreatic ducts. A dye is injected through the catheter into the ducts and an x-ray is taken. If the ducts are blocked by a tumor, a fine tube may be inserted into the duct to unblock it. This tube (or stent) may be left in place to keep the duct open. Tissue samples may also be taken.
Percutaneous transhepatic cholangiography (PTC): A procedure used to x-ray the liver and bile ducts. A thin needle is inserted through the skin below the ribs and into the liver. Dye is injected into the liver or bile ducts and an x-ray is taken. If a blockage is found, a thin, flexible tube called a stent is sometimes left in the liver to drain bile into the small intestine or a collection bag outside the body. This test is done only if ERCP cannot be done.
Biopsy: The removal of cells or tissues so they can be viewed under a microscope to check for signs of cancer. There are several ways to do a biopsy for pancreatic cancer. A fine needle may be inserted into the pancreas during an x-ray or ultrasound to remove cells. Tissue may also be removed during a laparoscopy (a surgical incision made in the wall of the abdomen).

Gastrinoma. A transabdominal fine needle aspirate (FNA) shows similar features. The FNA sample was centrifuged, and the cell pellet was embedded in paraffin. Sections were stained with hematoxylin and eosin Gastrinoma. Immunohistochemistry of the cell pellet sections using anti-gastrin antibody demonstrates intracytoplasmic gastrin. Brown chromogen marks cells that contain gastrin Gastrinoma. Negative control (no antibody) for

immunohistochemical assay

HOW TO DETECT STAGE OF PANCREATIC CANCER?

Tests and procedures to stage pancreatic cancer are usually done at the same time as diagnosis.

The following stages are used for pancreatic cancer:

Stage I

In stage I, cancer is found in the pancreas only. Stage I is divided into stage IA and stage IB, based on the size of the tumor.

Stage IA: The tumor is 2 centimeters or smaller.
Stage IB: The tumor is larger than 2 centimeters.
Stage II

In stage II, cancer may have spread to nearby tissue and organs, and may have spread to lymph nodes near the pancreas. Stage II is divided into stage IIA and stage IIB, based on where the cancer has spread.

Stage IIA: Cancer has spread to nearby tissue and organs but has not spread to nearby lymph nodes.
Stage IIB: Cancer has spread to nearby lymph nodes and may have spread to nearby tissue and organs.
Stage III

In stage III, cancer has spread to the major blood vessels near the pancreas and may have spread to nearby lymph nodes.

Stage IV

In stage IV, cancer may be of any size and has spread to distant organs, such as the liver, lung, and peritoneal cavity. It may have also spread to organs and tissues near the pancreas or to lymph nodes.



Recurrent Pancreatic Cancer

Recurrent pancreatic cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the pancreas or in other parts of the body.

HOW TO TREAT PANCREATIC CANCER?

There are different types of treatment for patients with pancreatic cancer.

Different types of treatment are available for patients with pancreatic cancer. Some treatments are standard (the currently used treatment), and some are being tested.

Three types of standard treatment are used:

Surgery

One of the following types of surgery may be used to take out the tumor:

Whipple procedure: A surgical procedure in which the head of the pancreas, the gallbladder, part of the stomach, part of the small intestine, and the bile duct are removed. Enough of the pancreas is left to produce digestive juices and insulin.
Ampullary carcinoma. The darker tissue at the top of the photograph is an opened segment of duodenum. The tumor is light tan and the orange-tan tissue is the pancreatic head



Total pancreatectomy: This operation removes the whole pancreas, part of the stomach, part of the small intestine, the common bile duct, the gallbladder, the spleen, and nearby lymph nodes.
Distal pancreatectomy: The body and the tail of the pancreas and usually the spleen are removed.
If the cancer has spread and cannot be removed, the following types of palliative surgery may be done to relieve symptoms:

Surgical biliary bypass
Endoscopic stent placement
Gastric bypass
Radiation therapy

There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

Chemotherapy

Even after surgical resection, there are at least 70% risk of locoregional recurrence. Therefore, adjuvant chemotherapy and radiation therapy should be given. The followingregimen showed a significantly prolonged median survival of 20 months versus 11 months for controls with 43% 2-year actual survival(versus 18% for controls).are recommended.

5-FU,500mg/m2/dayby i.v. bolus for the first 3 days of each 200-cGy segment of radiotherapy(total dose/3 day course of 5-FU,1 500mg/m2),followed by
5-FU, 500mg/m2/week by i.v. bolus injection,weekly for up to 2 years.
Commonly recommended regimens are as below as well:

4 500 to 5 400 cGy in divided doses with 5-FU,500mg/m2 /day daily on the first and last 3 days of radiation. Median survival is about 10 months with this treatment.
Gemcitabine,1 000 mg/m2/week i.v. weekly for 3 weeks(day 1,8 and 15) followed by 1 week without gemcitabine(total dose/cycle,
3 000mg/m2).Treatment cycles are repeated every 28 days.

Other types of treatment are being tested in clinical trials. These include the following:

Biologic therapy

Biologic therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy. Dendritic cell vaccine may be choice.

There are treatments for pain caused by pancreatic cancer.

Pain can occur when the tumor presses on nerves or other organs near the pancreas. When pain medicine is not enough, there are treatments that act on nerves in the abdomen to relieve the pain. The doctor may inject medicine into the area around affected nerves or may cut the nerves to block the feeling of pain. Radiation therapy with or without chemotherapy can also help relieve pain by shrinking the tumor.

Patients with pancreatic cancer have special nutritional needs.

Surgery to remove the pancreas may interfere with the production of pancreatic enzymes that help to digest food. As a result, patients may have problems digesting food and absorbing nutrients into the body. To prevent malnutrition, the doctor may prescribe medicines that replace these enzymes.

Treatment Options by Stage

Stage I Pancreatic Cancer

Treatment of stage I pancreatic cancer may include the following:

Surgery alone.
Surgery with chemotherapy and radiation therapy.
A clinical trial of surgery followed by radiation therapy with chemotherapy. Chemotherapy is given before, during, and after the radiation therapy.
A clinical trial of surgery followed by chemotherapy.
Stage IIA Pancreatic Cancer

Treatment of stage IIA pancreatic cancer may include the following:

Surgery with or without chemotherapy and radiation therapy.
Radiation therapy with chemotherapy.
Palliative surgery to bypass blocked areas in ducts or the small intestine.
A clinical trial of surgery followed by radiation therapy with chemotherapy. Chemotherapy is given before, during, and after the radiation therapy.
A clinical trial of surgery followed by chemotherapy.
A clinical trial of biologic therapy with radiation therapy and/or chemotherapy.
A clinical trial of radiation therapy combined with chemotherapy and/or radiosensitizers (drugs that make cancer cells more sensitive to radiation so more tumor cells are killed), followed by surgery.
A clinical trial of radiation therapy given during surgery or internal radiation therapy.
Stage IIB Pancreatic Cancer

Treatment of stage IIB pancreatic cancer may include the following:

Surgery with or without chemotherapy and radiation therapy.
Radiation therapy with chemotherapy.
Palliative surgery to bypass blocked areas in ducts or the small intestine.
A clinical trial of surgery followed by radiation therapy with chemotherapy. Chemotherapy is given before, during, and after the radiation therapy.
A clinical trial of surgery followed by chemotherapy.
A clinical trial of biologic therapy with radiation therapy and/or chemotherapy.
A clinical trial of radiation therapy combined with chemotherapy and/or radiosensitizers, followed by surgery.
A clinical trial of radiation therapy given during surgery or internal radiation therapy.
Stage III Pancreatic Cancer

Treatment of stage III pancreatic cancer may include the following:

Surgery with or without chemotherapy and radiation therapy.
Radiation therapy with chemotherapy.
Palliative surgery or stent placement to bypass blocked areas in ducts or the small intestine.
A clinical trial of surgery followed by radiation therapy with chemotherapy. Chemotherapy is given before, during, and after the radiation therapy.
A clinical trial of surgery followed by chemotherapy.
A clinical trial of biologic therapy with radiation therapy and/or chemotherapy.
A clinical trial of radiation therapy combined with chemotherapy and/or radiosensitizers, which may be followed by surgery.
A clinical trial of radiation therapy given during surgery or internal radiation therapy.
Stage IV Pancreatic Cancer

Treatment of stage IV pancreatic cancer may include the following:

Chemotherapy.
Palliative treatments for pain, such as nerve blocks, and other supportive care.
Palliative surgery or stent placement to bypass blocked areas in ducts or the small intestine.
Clinical trials of chemotherapy or biologic therapy.
Treatment Options for Recurrent Pancreatic Cancer

Treatment of recurrent pancreatic cancer may include the following:

Chemotherapy.
Palliative surgery or stent placement to bypass blocked areas in ducts or the small intestine.
Palliative radiation therapy.
Other palliative medical care to reduce symptoms, such as nerve blocks to relieve pain.
Clinical trials of chemotherapy or biologic therapy.
NOVAL THERAPIES

Cryosurgery: Experimental cryodestruction of the pancreas performed in 40 dogs served as a basis for selecting the temperature regimen, exposure time and extent of treatment to be subsequently used in man. Cryodestruction and combined cryoradiotherapy were employed in 30 patients with locally advanced pancreatic cancer. The procedure proved effective as it assured alleviation of pain, improvement in performance status and an increase in survival. CA-19-9 level and T-lymphocyte count, which may be used to predict progression of pancreatic cancer. were followed.
125Iodine seeds implantation: Radioactive Iodine-125 seeds were implanted intraoperatively into the tumor to deliver a minimum peripheral dose of 12,000 cGy over one year. This was followed by external beam radiation (50-55 Gy) and systemic chemotherapy (5-FU, Mitomycin-C +/- CCNU). Incidence of peri-operative mortality was 5% (4/81). Early morbidity was observed in 34% of patients and late complications in 32%. A median survival of 12 months and 2- and 5-year survival rates of 21% and 7% were observed. The determinate 2- and 5-year survival rates were 28% and 13%, respectively. The overall 2- and 5-year survival rates with Stage II disease were 27% and 8% and for Stage III disease, 13% and 3%, respectively (p less than 0.05). The determinate 2- and 5-year survival rates were 34% and 19% for Stage II and 19% and 5% for Stage III disease, respectively (p = 0.08). Local control of disease was achieved in 71% of patients. This combined modality approach appears to have achieved satisfactory local control of primary cancer and long term survival of selected patients.
Ultrasonically guided percutaneous implantation of 125I seeds were performed in 19 patients with cancer of the pancreas in our hospital. Satisfactory seed placement and delivery of the planned radiation dose and clinical improvement was seen in most cases. No difference in survival or palliation was observed between patients treated with seeds alone compared with patients treated with seeds and external radiation. Survival after seed implantation was median 140 days, range 7-401 days. It is considered that ultrasonically guided percutaneous implantation of 125I seeds can be recommended in the treatment of unresectable carcinoma of the pancreas.

Photodynamic therapy:Photodynamic therapy produces local necrosis of tissue with light after prior administration of a photosensitising agent, and in experimental studies can be tolerated by the pancreas and surrounding normal tissue. Patients were photosensitised with 0.15 mg/kg meso-tetrahydroxyphenyl chlorin intravenously. Three days later, light was delivered to the cancer percutaneously using fibres positioned under computerised tomographic guidance. Sixteen patients with inoperable adenocarcinomas (2.5-6 cm in diameter) localised to the region of the head of the pancreas were studied. All presented with obstructive jaundice which was relieved by biliary stenting prior to further treatment. All patients had substantial tumour necrosis on scans after treatment. Eleven had a Karnofsky performance status of 100 prior to treatment. In 10 it returned to 100 at one month. There was no treatment related mortality. The median survival time after photodynamic therapy was 9.5 months (range 4-30). Seven of 16 patients (44%) were alive one year after photodynamic therapy. Therefore, photodynamic therapy can produce necrosis in pancreatic cancers, is a available therapy for pancreatic carcinoma.


HOW TO ESTIMATE PROGNOSIS?

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on the following:

Whether or not the tumor can be removed by surgery.
The stage of the cancer (the size of the tumor and whether the cancer has spread outside the pancreas to nearby tissues or lymph nodes or to other places in the body).
The patient’s general health.
Whether the cancer has just been diagnosed or has recurred (come back).
Pancreatic cancer can be controlled only if it is found before it has spread, when it can be removed by surgery. If the cancer has spread, palliative treatment can improve the patient's quality of life by controlling the symptoms and complications of this disease.