Getting rid of "H. pylori" in those who are infected decreases the risk of stomach cancer, at least in those who are Asian. A 2014 meta-analysis of observational studies found that a diet high in fruits, mushrooms, garlic, soybeans, and green onions was associated with a lower risk of stomach cancer in the Korean population. Low doses of vitamins, especially from a healthy diet, decrease the risk of stomach cancer. A previous review of antioxidant supplementation did not find supporting evidence and possibly worse outcomes.

Little research is conducted on these cancers due to their relative rarity when compared to the more common colorectal cancers. APC-min mice which carry a gene deficiency corresponding to that of humans with FAP also go on to develop small intestinal tumors, though humans do not.

People with Barrett's esophagus (a change in the cells lining the lower esophagus) are at much higher risk, and may receive regular endoscopic screening for the early signs of cancer. Because the benefit of screening for adenocarcinoma in people without symptoms is unclear, it is not recommended in the United States. Some areas of the world with high rates of squamous-carcinoma have screening programs.

Prevention includes stopping smoking or chewing tobacco. Overcoming addiction to areca chewing in Asia is another promising strategy for the prevention of esophageal squamous-cell carcinoma. The risk can also be reduced by maintaining a normal body weight.

According to the National Cancer Institute, "diets high in cruciferous (cabbage, broccoli/broccolini, cauliflower, Brussels sprouts) and green and yellow vegetables and fruits are associated with a decreased risk of esophageal cancer." Dietary fiber is thought to be protective, especially against esophageal adenocarcinoma. There is no evidence that vitamin supplements change the risk.

Resection is sometimes a part of a treatment plan, but duodenal cancer is difficult to remove surgically because of the area that it resides in—there are many blood vessels supplying the lower body. Chemotherapy is sometimes used to try to shrink the cancerous mass. Other times intestinal bypass surgery is tried to reroute the stomach to intestine connection around the blockage.

A 'Whipple' procedure is a type of surgery that is sometimes possible with this cancer. In this procedure, the duodenum, a portion of the Pancreas (the head), and the gall bladder are usually removed, the small intestine is brought up to the Pylorus (the valve at the bottom of the stomach) and the Liver and Pancreas digestive enzymes and bile are connected to the small intestine below the Pylorus.

The removal of part of the Pancreas often requires taking Pancreatic Enzyme supplements to aid digestion. These are available in the form of capsules by prescription.

It is not unusual for a patient having received a Whipple procedure to feel perfectly well, and to lead his/her normal life without difficulty.

It is important for the procedure to be performed by a surgeon with extensive experience having done and observed the procedure, as specific competence makes a big difference.

Some patients need to be fitted with tubes to either add nutrients (feeding tubes) or drainage tubes to remove excess processed food that can not pass the blockage.

The stomach is a muscular organ of the gastrointestinal tract that holds food and begins the digestive process by secreting gastric juice. The most common cancers of the stomach are adenocarcinomas but other histological types have been reported. Signs vary but may include vomiting (especially if blood is present), weight loss, anemia, and lack of appetite. Bowel movements may be dark and tarry in nature. In order to determine whether cancer is present in the stomach, special X-rays and/or abdominal ultrasound may be performed. Gastroscopy, a test using an instrument called endoscope to examine the stomach, is a useful diagnostic tool that can also take samples of the suspected mass for histopathological analysis to confirm or rule out cancer. The most definitive method of cancer diagnosis is through open surgical biopsy. Most stomach tumors are malignant with evidence of spread to lymph nodes or liver, making treatment difficult. Except for lymphoma, surgery is the most frequent treatment option for stomach cancers but it is associated with significant risks.

Barrett's esophagus is a premalignant condition. Its malignant sequela, oesophagogastric junctional adenocarcinoma, has a mortality rate of over 85%. The risk of developing esophageal adenocarcinoma in people who have Barrett's esophagus has been estimated to be 6–7 per 1000 person-years, however a cohort study of 11,028 patients from Denmark published in 2011 showed an incidence of only 1.2 per 1000 person-years (5.1 per 1000 person-years in patients with dysplasia, 1.0 per 1000 person-years in patients without dysplasia). The relative risk of esophageal adenocarcinoma is approximately 10 in those with Barret's esophagus, compared to the general population. Most patients with esophageal carcinoma survive less than one year.

The cancerous mass tends to block food from getting to the small intestine. If food cannot get to the intestines, it will cause pain, acid reflux, and weight loss because the food cannot get to where it is supposed to be processed and absorbed by the body.

Patients with duodenal cancer may experience abdominal pain, weight loss, nausea, vomiting, and chronic GI bleeding.

Many people with Barrett's esophagus do not have dysplasia. Medical societies recommend that if a patient has Barrett's esophagus, and if the past two endoscopy and biopsy examinations have confirmed the absence of dysplasia, then the patient should not have another endoscopy within three years.

Endoscopic surveillance of people with Barrett's esophagus is often recommended, although little direct evidence supports this practice. Treatment options for high-grade dysplasia include surgical removal of the esophagus (esophagectomy) or endoscopic treatments such as endoscopic mucosal resection or ablation (destruction).

The risk of malignancy is highest in the U.S. in Caucasian men over fifty years of age with more than five years of symptoms. Current recommendations include routine endoscopy and biopsy (looking for dysplastic changes). Although in the past physicians have taken a watchful waiting approach, newly published research supports consideration of intervention for Barrett's esophagus. Balloon-based radiofrequency ablation, invented by Ganz, Stern, and Zelickson in 1999, is a new treatment modality for the treatment of Barrett's esophagus and dysplasia, and has been the subject of numerous published clinical trials. The findings demonstrate radiofrequency ablation has an efficacy of 90% or greater with respect to complete clearance of Barrett's esophagus and dysplasia with durability up to five years and a favorable safety profile.

Proton pump inhibitor drugs have not been proven to prevent esophageal cancer. Laser treatment is used in severe dysplasia, while overt malignancy may require surgery, radiation therapy, or systemic chemotherapy. Additionally, a recent five-year random-controlled trial has shown that photodynamic therapy using photofrin is statistically more effective in eliminating dysplastic growth areas than sole use of a proton pump inhibitor. There is presently no reliable way to determine which patients with Barrett esophagus will go on to develop esophageal cancer, although a recent study found the detection of three different genetic abnormalities was associated with as much as a 79% chance of developing cancer in six years.

Endoscopic mucosal resection has also been evaluated as a management technique. Additionally an operation known as a Nissen fundoplication can reduce the reflux of acid from the stomach into the esophagus.

In a variety of studies, nonsteroidal anti-inflammatory drugs (NSAIDS), like aspirin, have shown evidence of preventing esophageal cancer in people with Barrett's esophagus. However, none of these studies have been randomized, placebo-controlled trials, which are considered the gold standard for evaluating a medical intervention. In addition, the best dose of NSAIDs for cancer prevention is not yet known.

Risk factors for small intestine cancer include:

- Crohn's disease

- Celiac disease

- Radiation exposure

- Hereditary gastrointestinal cancer syndromes: familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, Peutz-Jeghers syndrome

- Males are 25% more likely to develop the disease

Benign tumours and conditions that may be mistaken for cancer of the small bowel:

- Hamartoma

- Tuberculosis

Cancer of the stomach, also called gastric cancer, is the fourth-most-common type of cancer and the second-highest cause of cancer death globally. Eastern Asia (China, Japan, Korea, Mongolia) is a high-risk area for gastric cancer, and North America, Australia, New Zealand and western and northern Africa are areas with low risk. The most common type of gastric cancer is adenocarcinoma, which causes about 750,000 deaths each year. Important factors that may contribute to the development of gastric cancer include diet, smoking and alcohol consumption, genetic aspects (including a number of heritable syndromes) and infections (for example, "Helicobacter pylori" or Epstein-Barr virus) and pernicious anemia. Chemotherapy improves survival compared to best supportive care, however the optimal regimen is unclear.

Digestive system neoplasms are tumors which affect the digestive system. Types include:

- esophageal cancer

- gastric cancer

- small intestinal cancer

- colorectal cancer

- anal cancer

Gastrointestinal cancer refers to malignant conditions of the gastrointestinal tract (GI tract) and accessory organs of digestion, including the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The symptoms relate to the organ affected and can include obstruction (leading to difficulty swallowing or defecating), abnormal bleeding or other associated problems. The diagnosis often requires endoscopy, followed by biopsy of suspicious tissue. The treatment depends on the location of the tumor, as well as the type of cancer cell and whether it has invaded other tissues or spread elsewhere. These factors also determine the prognosis.

Overall, the GI tract and the accessory organs of digestion (pancreas, liver, gall bladder) are responsible for more cancers and more deaths from cancer than any other system in the body. There is significant geographic variation in the rates of different gastrointestinal cancers.

Oesophagogastric junctional adenocarcinoma is a cancer of the lower part of the oesophagus, often linked to a Barrett's oesophagus.

The incidence of oesophagogastric junctional adenocarcinoma is rising rapidly in western countries, in contrast to the declining frequency of distal gastric adenocarcinoma. Treatment options for adenocarcinomas involving the oesophagogastric junction are limited and the overall prognosis is extremely poor.

Surgical treatment remains the treatment of choice for cats and dogs diagnosed with intestinal tumors who are in otherwise good health.

Surgery remains the front-line therapy for HNPCC. There is an ongoing controversy over the benefit of 5-fluorouracil-based adjuvant therapies for HNPCC-related colorectal tumours, particularly those in stages I and II.

Apart from not smoking, the American Cancer Society recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains, while decreasing consumption of red and processed meat, although there is no consistent evidence this will prevent or reduce pancreatic cancer specifically. A 2014 review of research concluded that there was evidence that consumption of citrus fruits and curcumin reduced risk of pancreatic cancer, while there was possibly a beneficial effect from whole grains, folate, selenium, and non-fried fish.

In the general population, screening of large groups is not currently considered effective, although newer techniques, and the screening of tightly targeted groups, are being evaluated. Nevertheless, regular screening with endoscopic ultrasound and MRI/CT imaging is recommended for those at high risk from inherited genetics.

Treatment for FAP depends on the genotype. Most individuals with the APC mutation will develop colon cancer by the age of 40, although the less-common attenuated version typically manifests later in life (40–70). Accordingly, in many cases, prophylactic surgery may be recommended before the age of 25, or upon detection if actively monitored. There are several surgical options that involve the removal of either the colon or both the colon and rectum.

- Rectum involved: the rectum and part or all of the colon are removed. The patient may require an ileostomy (permanent stoma where stool goes into a bag on the abdomen) or have an ileo-anal pouch reconstruction. The decision to remove the rectum depends on the number of polyps in the rectum as well as the family history. If the rectum has few polyps, the colon is partly or fully removed and the small bowel (ileum) can be directly connected to the rectum instead (ileorectal anastomosis).

- Rectum not involved: the portion of the colon manifesting polyps can be removed and the ends 'rejoined' (partial colectomy), a surgery that has a substantial healing time, but leaves quality of life largely intact.

Prophylactic colectomy is indicated if more than a hundred polyps are present, if there are severely dysplastic polyps, or if multiple polyps larger than 1 cm are present.

Treatment for the two milder forms of FAP may be substantially different from the more usual variant, as the number of polyps are far fewer, allowing more options.

Various medications are being investigated for slowing malignant degeneration of polyps, most prominently the non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDS have been shown to significantly decrease the number of polyps but do not usually alter management since there are still too many polyps to be followed and treated endoscopically.

OGJ adenocarcinoma is a highly mutated and heterogeneous disease. Microsatellite instability (MSI) can be observed and coincides with an elevated number of somatic mutations. Potentially actionable coding mutations have been identified in 67 genes, including those in CR2, HGF, FGFR4 and ESRRB. Numerous genes harbouring somatic coding mutations and copy number changes in the microsatellite stable (MSS) OGJA are also known to be altered with similar predicted functional consequence in other tumour types. TP53, SYNE1, and ARID1A are among the most frequently mutated genes.

Risk factors for pancreatic adenocarcinoma include:

- Age, gender, and ethnicity; the risk of developing pancreatic cancer increases with age. Most cases occur after age 65, while cases before age 40 are uncommon. The disease is slightly more common in men than women, and in the United States is over 1.5 times more common in African Americans, though incidence in Africa is low.

- Cigarette smoking is the best-established avoidable risk factor for pancreatic cancer, approximately doubling risk among long-term smokers, the risk increasing with the number of cigarettes smoked and the years of smoking. The risk declines slowly after smoking cessation, taking some 20 years to return to almost that of non-smokers.

- Obesity; a BMI greater than 35 increases relative risk by about half.

- Family history; 5–10% of pancreatic cancer cases have an inherited component, where people have a family history of pancreatic cancer. The risk escalates greatly if more than one first-degree relative had the disease, and more modestly if they developed it before the age of 50. Most of the genes involved have not been identified. Hereditary pancreatitis gives a greatly increased lifetime risk of pancreatic cancer of 30–40% to the age of 70. Screening for early pancreatic cancer may be offered to individuals with hereditary pancreatitis on a research basis. Some people may choose to have their pancreas surgically removed to prevent cancer developing in the future.

- Chronic pancreatitis appears to almost triple risk, and as with diabetes, new-onset pancreatitis may be a symptom of a tumor. The risk of pancreatic cancer in individuals with familial pancreatitis is particularly high.

- Diabetes mellitus is a risk factor for pancreatic cancer and (as noted in the Signs and symptoms section) new-onset diabetes may also be an early sign of the disease. People who have been diagnosed with Type 2 diabetes for longer than ten years may have a 50% increased risk, as compared with non-diabetics.

- Specific types of food (as distinct from obesity) have not been clearly shown to increase the risk of pancreatic cancer. Dietary factors for which there is some evidence of slightly increased risk include processed meat, red meat, and meat cooked at very high temperatures (e.g. by frying, broiling or barbecuing).

Prior to reaching the advanced stages of colorectal cancer, the polyps are confined to the inner wall and thickness of the intestinal tract and do not metastasize or 'spread'. So provided FAP is detected and controlled either at the pre-cancerous stage or when any cancerous polyps are still internal to the intestinal tract, surgery has a very high success rate of preventing or removing cancer, without recurrence, since the locations giving rise to cancer are physically removed "in toto" by the surgery.

Following surgery, if a partial colectomy has been performed, colonoscopic surveillance of the remaining colon is necessary as the individual still has a risk of developing colon cancer. However, if this happened, it would be a fresh incident from polyps developing anew in the unremoved part of the colon subsequent to surgery, rather than a return or metastasis of any cancer removed by the original surgery.

In the United States, about 160,000 new cases of colorectal cancer are diagnosed each year. Hereditary nonpolyposis colorectal cancer is responsible for approximately 2 percent to 7 percent of all diagnosed cases of colorectal cancer. The average age of diagnosis of cancer in patients with this syndrome is 44 years old, as compared to 64 years old in people without the syndrome.

Resection of the polyps is required only if serious bleeding or intussusception occurs. Enterotomy is performed for removing large, single nodules. Short lengths of heavily involved intestinal segments can be resected. Colonoscopy can be used to snare the polyps if they are within reach.

Conditions such as ulcerative colitis or certain types of relapsing infectious diarrhea can vary in severity over time, and FOBT may assist in assessing the severity of the disease. Medications associated with gastrointestinal bleeding such as Bortezomib are sometimes monitored by FOBT.

There is a risk of development of cancer with fundic gland polyposis, but it varies based on the underlying cause of the polyposis. The risk is highest with congenital polyposis syndromes, and is lowest in acquired causes. As a result, it is recommended that patients with multiple fundic polyps have a colonoscopy to evaluate the colon. If there are polyps seen on colonoscopy, genetic testing and testing of family members is recommended.

In the gastric adenocarcinoma associated with proximal polyposis of the stomach (GAPPS), there is a high risk of early development of proximal gastric adenocarcinoma.

It is still unclear which patients would benefit with surveillance gastroscopy, but most physicians recommend endoscopy every one to three years to survey polyps for dysplasia or cancer. In the event of high grade dysplasia, polypectomy, which is done through the endoscopy, or partial gastrectomy may be recommended. One study showed the benefit of NSAID therapy in regression of gastric polyps, but the efficacy of this strategy (given the side effects of NSAIDs) is still dubious.