The production of pancreatic enzymes is suppressed by restricting the patient's oral intake of food patient in conjunction with the use of long-acting somatostatin analogues. The patient's nutrition is maintained by total parenteral nutrition.

This treatment is continued for 2–3 weeks, and the patient is observed for improvement. If no improvement is seen, the patient may receive endoscopic or surgical treatment. If surgical treatment is followed, an ERCP is needed to identify the site of the leak.

Fistulectomy is done in which the involved part of the pancreas is also removed.

Pancreatic pseudocyst treatment should be aimed at avoiding any complication (1 in 10 cases become infected). They also tend to rupture, and have shown that larger cysts have a higher likelihood to become more symptomatic, even needing surgery. If no signs of infection are present, initial treatment can include conservative measures such as bowel rest (NPO), parenteral nutrition (TPN), and observation. Serum amylase levels can be trended. If symptoms do not improve by 6 weeks, surgical intervention may be appropriate.

In the event of surgery:

- Cystogastrostomy: In this surgical procedure a connection is created between the back wall of the stomach and the cyst such that the cyst drains into the stomach.

- Cystjejunostomy: In this procedure a connection is created between the cyst and the small intestine so that the cyst fluid directly into the small intestine.

- Cystduodenostomy: In this procedure a connection is created between the duodenum (the first part of the intestine) and the cyst to allow drainage of the cyst content into duodenum. The type of surgical procedure depends on the location of the cyst. For pseudocysts that occur in the head of the pancreas a cystduodenostomy is usually performed.

A pancreatic fistula is an abnormal communication between the pancreas and other organs due to leakage of pancreatic secretions from damaged pancreatic ducts. An "external" pancreatic fistula is one that communicates with the skin, and is also known as a pancreaticocutaneous fistula, whereas an internal pancreatic fistula communicates with other internal organs or spaces. Pancreatic fistulas can be caused by pancreatic disease, trauma, or surgery.

Treatment of hemosuccus pancreaticus depends on the source of the hemorrhage. If the bleeding is identified on angiography to be coming from a vessel that is small enough to occlude, embolization through angiography may stop the bleeding. Both coils in the end-artery and stents across the area of bleeding have been used to control the hemorrhage. However, the bleeding may be refractory to the embolization, which would necessitate surgery to remove the pancreas at the source of hemorrhage. Also, the cause of bleeding may be too diffuse to be treated with embolization (such as with pancreatitis or with pancreatic cancer). This may also require surgical therapy, and usually a distal pancreatectomy, or removal of the part of the pancreas from the area of bleeding to the tail, is required.

Simple cholecystectomy is suitable for type I patients. For types II–IV, subtotal cholecystectomy can be performed to avoid damage to the main bile ducts. Cholecystectomy and bilioenteric anastomosis may be required. Roux-en-Y hepaticojejunostomy has shown good outcome in some studies.

The cause of pancreatic pseudocyst can occur due to a variety of reasons, among them pancreatitis (chronic), pancreatic neoplasm and/or pancreatic trauma.

Treatment usually is bypassing the obstructed segment of duodenum by duodeno-jejunostomy. Another approach is laparoscopic gastrojejunostomy or duodenojejunostomy.

Treatment of accessory pancreas depends on the location and extent of the injured tissue. Surgery may be an option, or some physicians order prophylactic antibiotics.

There are no approved treatments for canine pancreatitis. Treatment for this disease is supportive, and may require hospitialization to attend to the dog's nutritional and fluid needs, pain management, and addressing any other disease processes (infection, diabetes, etc.) while letting the pancreas heal on its own. Treatment often involves "resting" the pancreas for a short period of time by nil per os/nothing per os (NPO)/nil by mouth (NBM), in which the patient receives no food or fluids by mouth, but is fed and hydrated by intravenous fluids and a feeding tube. Dehydration is also managed by the use of fluid therapy. However, a specialist from Texas A&M University has stated "There is no evidence whatsoever that withholding food has any beneficial effect." Other specialists have agreed with his opinion.

Canine pancreatitis is complex, often limiting the ability to approach the disease.

A low fat diet is indicated. The use of drugs which are known to have an association with pancreatitis should be avoided. Some patients benefit from the use of pancreatic enzymes on a supplemental basis. One study indicated that 57 percent of dogs, who were followed for six months after an acute pancreatitis attack, either continued to exhibit inflammation of the organ or had decreased acinar cell function, even though they had no pancreatitis symptoms.

Mirizzi's syndrome is a rare complication in which a gallstone becomes impacted in the cystic duct or neck of the gallbladder causing compression of the common bile duct (CBD) or common hepatic duct, resulting in obstruction and jaundice. The obstructive jaundice can be caused by direct extrinsic compression by the stone or from fibrosis caused by chronic cholecystitis (inflammation). A cholecystocholedochal fistula can occur.

Hemosuccus pancreaticus, also known as pseudohematobilia or Wirsungorrhage, is a rare cause of hemorrhage in the gastrointestinal tract. It is caused by a bleeding source in the pancreas, pancreatic duct, or structures adjacent to the pancreas, such as the splenic artery, that bleed into the pancreatic duct. Patients with hemosuccus may develop symptoms of gastrointestinal hemorrhage, such as blood in the stools, maroon stools, or melena. They may also develop abdominal pain. Hemosuccus pancreaticus is associated with pancreatitis, pancreatic cancer and aneurysms of the splenic artery. Angiography may be used to diagnose hemosuccus pancreaticus, where the celiac axis is injected to determine the blood vessel that is bleeding. Concomitant embolization of the end vessel may terminate the hemorrhage. Alternatively, a distal pancreatectomy may be required to stop the hemorrhage.

It can occur as a complication following biliary trauma (such as cholelithiasis), as an iatrogenic effect or as a result of a penetrating injury.

A biliary fistula is a type of fistula in which bile flows along an abnormal connection from the bile ducts into nearby hollow structure. Types of biliary fistula include:

- bilioenteric fistula: abnormal connection to small bowel, usually duodenum.

- thoracobiliary fistula: abnormal connection to pleural space or bronchus (rare).

These may be contrasted to a bile leak, in which bile escapes the bile ducts through a perforation or faulty surgical anastomosis into the abdominal cavity. Damage to a bile duct may result in a leak, which may eventually become a biliary fistula.

Annular pancreas is a rare condition in which the second part of the duodenum is surrounded by a ring of pancreatic tissue continuous with the head of the pancreas. This portion of the pancreas can constrict the duodenum and block or impair the flow of food to the rest of the intestines. It is estimated to occur in 1 out of 12,000 to 15,000 newborns. The ambiguity arises from the fact that not all cases are symptomatic.

Pancreas divisum in individuals with no symptoms does not require treatment. Treatment of those with symptoms varies and has not been well established. A surgeon may attempt a sphincterotomy by cutting the minor papilla to enlarge the opening and allow pancreatic enzymes to flow normally. During surgery, a stent may be inserted into the duct to ensure that the duct will not close causing a blockage. This surgery can cause pancreatitis in patients, or in rare cases, kidney failure and death.

An association with adenoma of the minor papilla has been reported.

Medication (to prevent spasms) or Sphincterotomy (surgical procedure to cut the muscle) are the standard treatments for sphincter of Oddi dysfunction. One or the other may be better based on the classification of the condition.

Patients with enteric content exiting a wound on their abdomen are motivated to undergo operation. The majority will close spontaneously within approximately 6 weeks. If it has not closed by 12 weeks, it is unlikely to do so and definitive surgery should be planned. The median time to definitive repair from fistula onset was 6 months (range 1 day to 28 months). The 6-month time course is commonly utilized by groups with significant experience treating fistulas, owing to the trend in encountering a less hostile abdomen than in the early phases. Some evidence also suggests that somatostatin can be an effective treatment with respect to reducing closure time and improving the spontaneous closure rate of enterocutaneous fistulas.

Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack of digestive enzymes made by the pancreas. EPI is found in humans afflicted with cystic fibrosis and Shwachman–Diamond syndrome. It is caused by a progressive loss of the pancreatic cells that make digestive enzymes. Chronic pancreatitis is the most common cause of EPI in humans. Loss of digestive enzymes leads to maldigestion and malabsorption of nutrients.

Hemosuccus pancreaticus, also known as pseudohematobilia or Wirsungorrhage is a rare cause of hemorrhage in the gastrointestinal tract. It is caused by a bleeding source in the pancreas, pancreatic duct, or structures adjacent to the pancreas, such as the splenic artery, that bleed into the pancreatic duct, which is connected with the bowel at the duodenum, the first part of the small intestine. Patients with hemosuccus may develop symptoms of gastrointestinal hemorrhage, such as blood in the stools, maroon stools, or melena, which is a dark, tarry stool caused by digestion of red blood cells. They may also develop abdominal pain. It is associated with pancreatitis, pancreatic cancer and aneurysms of the splenic artery. Hemosuccus may be identified with endoscopy (esophagogastroduodenoscopy), where fresh blood may be seen from the pancreatic duct. Alternatively, angiography may be used to inject the celiac axis to determine the blood vessel that is bleeding. This may also be used to treat hemosuccus, as embolization of the end vessel may terminate the hemorrhage. However, a distal pancreatectomy—surgery to removal of the tail of the pancreas—may be required to stop the hemorrhage.

Antibiotics are commonly used as a curing method for pancreatic abscesses although their role remains controversial. Prophylactic antibiotics are normally chosen based on the type of flora and the degree of antibiotic penetration into the abscess. Pancreatic abscesses are more likely to host enteric organisms and pathogens such as "E. coli", "Klebsiella pneumonia", "Enterococcus faecalis", "Staphylococcus aureus", "Pseudomonas aeruginosa", "Proteus mirabilis", and "Streptococcus" species. Medical therapy is usually given to people whose general health status does not allow surgery. On the other hand, antibiotics are not recommended in patients with pancreatitis, unless the presence of an infected abscess has been proved.

Although there have been reported cases of patients who were given medical treatment and survived, primary drainage of the abscess is the main treatment used to cure this condition. Drainage usually involves a surgical procedure. It has been shown that CT-guided drainage brought inferior results than open drainage. Hence, open surgical procedure is preferred to successfully remove the abscess. However, CT-guided drainage is the option treatment for patients who may not tolerate an open procedure. Endoscopic treatment is at the same time a treatment option that increased in popularity over the last years.

In people with renal failure, requiring dialysis, a cimino fistula is often deliberately created in the arm by means of a short day surgery in order to permit easier withdrawal of blood for hemodialysis.

As a radical treatment for portal hypertension, surgical creation of a portacaval fistula produces an anastomosis between the hepatic portal vein and the inferior vena cava across the omental foramen (of Winslow). This spares the portal venous system from high pressure which can cause esophageal varices, caput medusae, and hemorrhoids.

When there is no pancreatic duct injury, typically hemostasis and surgical drainage are the main form of treatment. Surgical repair is undertaken when there is evidence or suspicion of ductal injury. The type of surgery depends on the degree of the injury and its proximity to the mesenteric blood vessels that serve the pancreas. When injuries are not close to the mesenteric vessels, a distal pancreatectomy may be done; this procedure preserves much of the pancreas and usually avoids loss of its endocrine and exocrine functions. In severe cases of pancreaticoduodenal injury, a pancreaticoduodenectomy can be used. Common complications after surgery include pancreatitis, pancreatic fistula, abscess, and pseudocyst formation. Initial management of hemorrhage includes controlling it by packing the wound.

Pancreaticobiliary maljunction is a congenital malformation, in which the pancreatic and bile ducts join anatomically outside the duodenal wall, forming a markedly long common channel. This anomaly prevents normal control by the sphincter of Oddi located in the duodenal wall, allowing regurgitation of pancreatic juices into the biliary tract and possibly leading to a higher probability of pancreaticobiliary cancers.

Low-output fistula: < 200 mL/day

Moderate-output fistula: 200-500 mL/day

High-output fistula: > 500 mL/day