Prof. ÖZCAN GÖKÇE, MD Director of the Department of General Surgery Yeditepe University Hospital PERIAMPULLARY TUMORS

Neoplasms of the Endocrine Pancreas INSULINOMA GASTRINOMA VIPoma GLUCAGONOMA SOMATOSTATINOMA NONFUNCTIONING ISLET CELL TUMORS

Passaro's triangle ( The typical location of a gastrinoma)

Radiolabeled octreotide scan

Insulinoma Whipple’s triad 1)Hypoglisemic symptoms by fasting 2)Episodic low blood sugar(below 50 mg/dl) 3)Relief of symptoms by glucose

Treatment Surgery Diazoxide Streptozotocin

GASTRINOMA (Zollinger-Ellison Syndrome) Symptoms Ulcers and diarrhea Treatment Surgery Acid blocking agents Streptozotocin-5FU

VIPoma Verner-Morrison Syndrome…WDHA Watery diarrhea Hypokalemia Achlorhydria Pancreatic Cholera

Treatment Surgery Streptozotocin 5FU Steroids Trifluoperazine Somatostatin

MULTIPL ENDOCRINE NEOPLASIA MEN I….3-P(Pituiatary,parathyroid,pancreas) Autosomal dominant(11q13 coded gene) MEN IIA...(Pheo-Medullary tc-parathyroid tm) MEN IIB..(Pheo-Medullary tc-ganglioneuromas) Mutation in ret proto-oncogene

Neoplasms of the Exocrine Pancreas

PERIAMPULLARY EPITHELIAL TUMORS 1)PANCREATIC CANCER 2)CANCER OF COMMON BILE DUCT 3)CANCER OF DUODENUM 4)TUMOR OF AMPULLA OF WATER 5)BENIGN TUMORS OF THE REGION(EXTREMELY RARE)…cystadenomas

Pancreatic cancer is one of the most serious types of cancer occurring. It is a disease which forms malignant or cancerous cells in the tissues of the pancreas.

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 Cancer has been called a "silent" disease because early Pancreatic Cancer usually does not cause symptoms.

If the tumor blocks the common bile duct and bile cannot pass into the digestive system, the skin and the sclera may become yellow (jaundiced), and the urine darker as a result of accumulated bile pigment called bilirubin.

Pancreatic Cancer Causes The exact as to what damages DNA in the vast majority of cases of pancreatic cancer is not clear. In other words the exact pancreatic cancer causes are not clear. But it is known that a small percentage of people develop the disease as a result of a genetic predisposition. These people who have a close relative, such as a parent or sibling, with pancreatic cancer have a higher risk of developing pancreatic cancer themselves.

A number of genetic diseases have been associated with an increased risk of pancreatic cancer, including familial adenomatous polyposis, nonpolyposis colon cancer, familial breast cancer associated with the BRCA2 gene, hereditary pancreatitis, and familial atypical multiple mole-melanoma syndrome which is a serious type of skin cancer. This means that people who have a hereditary predisposition to develop these cancers are also more likely to develop pancreatic cancer.

Although the above causes are evident only 10 percent of pancreatic cancers result from an inherited tendency. A greater number are caused by environmental or lifestyle factors, such as smoking, diet and chemical exposure.

Age: is also a factor to be considered which increases the incidence of the disease. As age increases the probability of pancreatic cancer also increases. The incidence of Pancreatic Cancer is relatively low in individuals up to age 50, after which it increases significantly. The age group has the highest incidence of Pancreatic Cancer.

Smoking increases the chances of developing Pancreatic Cancer. Study reveals that smokers develop Pancreatic Cancer more than twice as often as nonsmokers.

Non vegetarians have a high risk of getting Pancreatic Cancer, if the intakes of meat & fat are high.

Medical factors such as cirrhosis (a chronic liver disease), chronic pancreatitis, diabetes and a history of surgery to the upper digestive tract also contribute to the risk

Environmental factors such as long-term exposure to certain chemicals, like gasoline and related compounds, as well as certain insecticides, may increase the risk of developing Pancreatic Cancer.

Genetic predisposition should also be considered as the possible reason to increase the risk. Possibly 10% of cases of Pancreatic Cancer are related to genetic disorders.

Pancreatic Cancer Stage To apt for any treatment option the doctor has to know the exact stage of the pancreatic cancer in the patient. Tests and procedures to stage pancreatic cancer are usually done at the same time as diagnosis. The following are pancreatic cancer stage descriptions:

Stage 0: In this stage the cancer is found only in the lining of the pancreas. Stage 0 is also called carcinoma in situ.

Stage I: Cancer is found only in the pancreas in this stage. This stage further 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: Cancer may have spread to nearby tissue and organs, and may have spread to lymph nodes near the pancreas in this stage. This stage is further 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: Cancer has spread to the major blood vessels near the pancreas and may have spread to nearby lymph nodes in this stage. (Beyond this point the patient is surgically incurable)

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.

Pancreatic Cancer Symptoms Discomfort in abdomen or Upper abdominal pain that may radiate to the middle or upper back Yellowing of the skin and the sclera (jaundice) Itching Nausea and vomiting Digestive problems Weight loss Fatigue Loss of appetite Glucose intolerance Malnutrition.

In addition, the pancreas may produce too much insulin, causing such symptoms as dizziness, weakness, diarrhea, chills, or muscle spasms.

The patient may not even notice the gradual onset of these relatively nonspecific symptoms. The doctor may interpret them as being caused by something else. Therefore one should be very careful if any of the above symptoms are experienced.

Pancreatic Cancer Treatment The choice of Pancreatic Cancer treatment depends largely on the stage the pancreatic cancer in the patient. Possible treatments include surgery, chemotherapy, radiation, and biological therapy. Biological therapy is also known as immunotherapy.

Surgery During diagnosis, only about 20% of pancreatic tumors can be removed by surgery. This option is usually reserved for Stage 1 patients whose cancer is resectable. The surgeon may perform a resection, which is the removal of a small part of the pancreas. The standard procedure is called a pancreaticoduodenectomy (Whipple procedure).This surgery for Pancreatic Cancer should be done at centers that perform the procedure frequently. It is the more extensive surgery which is the removal of the pancreas head and nearby structures such as the duodenum. It might be necessary to remove the entire pancreas as well as the spleen, gallbladder, and bile duct.

When the tumor is confined to the pancreas but cannot be removed, a combination of radiation therapy and chemotherapy may be recommended.

Radiation therapy Certain substances emit invisible, high-energy rays, or radiation. These substances are called radioactive. The energy of the rays can kill cells. Special machines aim the rays at the parts of the body with cancerous tumors, so as to kill the cancer cells while minimizing damage to healthy tissue. Unlike chemotherapy, radiation is not necessarily carried throughout the body. As such, it is known as a local therapy, rather than as a systemic therapy. However, there are still potential side effects of radiation including fatigue, localized hair loss, changes to appearance of skin, and digestive problems. Medicines and other treatments can reduce the intensity of the side effects. As with other cancer treatments, the incidence of side effects varies with patient health and the exact nature of the treatment.

Chemotherapy When the tumor has spread to other organs (metastasized) such as the liver, chemotherapy alone is usually used. The standard chemotherapy agent is gemcitabine, but other drugs may be used. Gemcitabine provides clinical improvement in approximately 25% of patients. For patients who have biliary obstruction (blockage of the vessels that transport bile) and the tumor cannot be totally removed, the obstruction must be relieved. There are generally two approaches to this, surgery and placement of a biliary stent (similar to stents placed in the arteries of the heart to relieve blockages) during ERCP.

Immunotherapy This form of therapy involves using drugs to boost the body's natural immune response (its ability to fight disease). Examples of these drugs are interferon and monoclonal antibodies. They work with the body's immune system to block the growth of cancer cells. Biological therapy can be used on its own or in conjunction with other therapies. Immunotherapy can result in side effects that are reminiscent of the flu: fever, aches, weakness, fatigue, and chills. Patients may also experience skin problems such as easy bruising or rashes, as well as diarrhea and nausea.

Pancreatic Cancer Survival Rate Pancreatic Cancer is rarely curable. The overall pancreatic cancer survival rate is less than 4%. The cure rates are highest (although still usually under 25%) if the tumor is small (less than 2 cm in diameter) and is truly localized to the pancreas but, unfortunately, such cases account for fewer than 20% of all cases of Pancreatic Cancer. For patients with advanced cancers, the overall survival rate of all stages is less than 1% at 5 years with most patients dying within 1 year.

Prognosis of periampullary tumors 5-year survival rate Pancreas………… %10 Ampulla of Vater…………...% 35 Duodenum………………….% 30 Bile duct…………………….% 15 After Whipple operation(without lymph node metastases)…………..% 35

CYSTIC NEOPLASMS OF THE PANCREAS MUCINOUS CYSTADENOMA AND CYSTADENOCARCINOMA

CYSTADENOMA