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Abstract
Gastrinoma is a tumor that secrets gastrin; hence, it is also known as Gastrin secreting tumor or gastrinoma. Gastrimnomas are the hallmark of Zollinger Ellsion syndrome, which also. It is most commonly found in the duodenum, and less commonly in the pancreas and the stomach . Tumors found in the duodenal wall are commonly small and multiple. They are shown in about 40-50% of patients. Other tumors occurring in the pancreas are known to be more solid and have high rate of malignancy. In addition, more than 80% of gastrinomas are found within the cystic triangle of the gastrointestinal tract that is bound by the junction of cystic common bile ducts superiorly, second and third part of the duodenum towards the inferior area. Lastly, junction of neck and body of the pancreas towards the medial part.

Over 50% of gastrinomas are malignant and can metastasize to regional lymph nodes and liver. One fourth of gastrinomas are related to Multiple endocrine neoplasia type 1, Zollinger- Ellision Syndrom, Peptic Ulcer disease.

Signs and symptoms
Gastrinoma in the early stages will have signs and symptoms of indigestion or similar to Irritable Bowl disease (IBD) such as:
 * Hypergastrinemia
 * Ulcers of the duodenum, stomach, and small intestine.
 * Severe diarrhea.
 * Generalized cancer symptoms.
 * Pain and Bleeding in stool.
 * Obstruction of intestine.
 * Weight loss/ poor appetite
 * Anemia (Due to Vitamin B12 malabsorption, and bleeding)
 * Hematemeisis
 * Acid Reflux
 * Esphageal complications (Barrett esophagus, esophagitis, stricture formation)
 * Vomiting
 * Steatorrhea
 * Depression

Pathophysiology
Gastrin is secreted by the "G" cells located in the antrum of the stomach. Gastrin's primary function is to induce the release of hydrochloric (HCl) acid from the parietal cells located in the fundus of the stomach. Parietal cells are responsible for hydrochloric (HCl) secretion along with intrinsic factor that binds to vitamin B12 and helps with its’ uptake in the terminal ileum. Other functions of Gastrin include stimulation the growth of gastric mucosa and gastric motility, promoting gastric emptying. These mechanisms of the gastrointestinal tract (GIT) are up-regulated by the vagus nerve of the parasympathetic nervous system (PNS), that carries out majority of its’ functions by the release of neurotransmitter Acetylcholine (Ach), and to a lesser extent Gastrin releasing peptide (GRP) protein. On the contrary, the functions of GIT are down-regulated by the activation sympathetic nervous system (SNS), which carries out its’ functions mostly via neurotransmitter epinepherine.

Meal consumption causes distention of the stomach, leading to stimulation of the parasympathetic vagus nerve in the gastric mucosa, which causes the release of GRP protein. In gastrinoma, GRP protein causes larger than normal amounts of gastrin secretion, which leads to hyperplasia of the parietal cells. Hyperplasia of parietal cells causes an abnormal release of HCl into the duodenum, which causes the ulcers of the duodenum. Excessive HCl production also causes hyperperistalsis, a condition marked by excessive rapidity of the passage of food through the stomach and intestine and inhibits the activity of lipase, causing severe fatty diarrhea known as streatohorrea. Evently the long standing hyper-secretion of gastrin stimulate proliferation of the entrochromaffin like cells (ECL). These cells are found along the side the gastric lumen of the digestive tract. They play a main role in regulation of gastric secretion and motility when stimulated by nervous system. These cells in return will undergo progressive dysplastic changes starting with hyperplasia to neoplasia though out the gastrointestinal tract.

Diagnosis
In many cases gastrinoma is diagnosed by the recurring history the patient presents with. In particular, when an individual has the same persistent symptoms of abdominal pain, fatty diarrhea after failed treatment of acid reflex medications. To confirm the diagnosis of grastinoma a series of blood tests must be made. One of those tests is the serum gastrin level, which is the most reliable test for patients suffering from gastrinoma. The normal levels of gastrin are 150 pg/mL ( > 72.15 pmol/L); therefore elevated levels of > 1000 pg/mL (> 480 pmol/L) would establish the diagnosis of gastrinmoa. Another test that can be conducted is the secretin stimulated test, which is useful in patents who have the sign and symptoms of gastrinoma but the gastrin levels are below < 1000 pg/mL. Usually, an Intravenous bolus consisting of secretin 2mcg/kg and is measured in 10 minute intervals up tp 30 minutes total. Secretin, which is a hormone released from the duodenal S cells that induce the release of pancreatic bicarbonate (HCO3) that would neutralize the acidic environment due to high gastrin levels. Therefore, if the patient's level of gastrin remains consistently high indicating gastrin release due to tumor such as gastrinoma.

Other commonly used tests to further confirm the diagnosis are
 * CT scan of the abdominal area
 * Somatostatin receptor scintigraphy which is used to identify the location of the tumor
 * PET scan
 * Endoscopic ultrasound if there are no signs of tumor metastases.

Treatment
Patients who are diagnosed with gastrinoma have few options for treatment that include:


 * Proton Pump Inhibitors such as Omperaziole . This group of medication would suppress the acid secretion.
 * H2- receptor antagonist would similarly decrease acid secretion.
 * Octreotide injections would directly release somatostatin hormone that would inhibit gastrin release.
 * Surgical removal of tumor
 * Chemotherapy

Prognosis
Patients with gastrinomas that are also known to be part of neuroendocrine neoplasms must have to deal with two factors released to this tumor. First, controlling the high amounts by using medications that inhibit gastrin levels. The second part is stabilizing the tumor progression. Gastrinomas have a rate of 60%-90% that will become malignant. Patients who do not seek medical treatment such anti-ulcer medication have high rate of reoccurrence and death secondary to ulcer disease.The prognosis of gastrinoma depends on the level of metastases of the tumor. If patients present with hepatic metastases they might have remaining life span of 1 year with a 5 year survival rate of 20-30%. In patients with localized tumor or localized lymph spread the survival rate of 5 years id 90%. Lastly, surgical resection of local tumor could lead to complete cure without recurrence in 20-25% of patients.

Epidemiology
In the United states it has been reported that gastric carcinoids or neuroendocrine tumors report to account for an estimated 0.6-2% of gastric related polyps. The incidence rate of these tumors has greatly increased in comparison the past decades. However about 20% of gastrin releasing tumors are associated with Neuroendocrine tumors

Research
Recently, research studies have been conducted to seek new medical advances in relation to gastrinoma and Zollinger-Ellison syndrome. The recent studies have shown improved understanding of pathogenesis of pancreatic neuroendrocrine tumors, classifications of those tumors, and new treatments/ preventions to control the gastrin levels in the gastrointestinal tract. In addition, what is the best and safest approach for patients and effectiveness of surgery. The study concluded that the wide used of proton pump inhibitors itself might further induce hypergastrinemia (increased gastrin levels in circulatory system) due to feedback inhibition mechanism. The body will try to induce further release when gastrin levels are depleted. Some of the new treatments might include medication that are directed towards the liver such as embolization, chemoembolization, and radioembolization. In addition to the current offered treatments such as chemotherapy, somatostatin analogs. Other treatments that are still in phase three of clinical trails include liver transplantation and peptide-radioreceptor therapy.

= See Also =


 * Multiple Endocrine Neoplasia-1
 * Zollinger- Ellision Syndrom
 * Peptic Ulcer disease
 * Pancreatic Endocrine Tumors