Initial treatment of bleeding from gastric varices focuses on resuscitation, much as with esophageal varices. This includes administration of fluids, blood products, and antibiotics.

The results from the only two randomized trials comparing band ligation vs cyanoacrylate suggests that endoscopic injection of cyanoacrylate, known as gastric variceal obliteration or GVO is superior to band ligation in preventing rebleeding rates. Cyanoacrylate, a common component in 'super glue' is often mixed 1:1 with lipiodol to prevent polymerization in the endoscopy delivery optics, and to show on radiographic imaging. GVO is usually performed in specialized therapeutic endoscopy centers. Complications include sepsis, embolization of glue, and obstruction from polymerization in the lumen of the stomach.

Other techniques for refractory bleeding include:

- Transjugular intrahepatic portosystemic shunts (TIPS)

- Balloon occluded retrograde transvenous obliteration techniques (BORTO)

- Gastric variceal ligation, although this modality is falling out of favour

- Intra-gastric balloon tamponade as a bridge to further therapy

- a caveat is that a larger balloon is required to occupy the fundus of the stomach where gastric varices commonly occur

- Liver transplantation

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.

The usual treatment is splenopexy, fixation of the spleen, but if there is no blood flow after unwinding the spleen through detorsion then splenectomy must be performed. Although there have been few reported cases of treatment through laparoscopic surgery due to the rarity of the disease, it has been proven to be an effective surgical technique.

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 is no real treatment for Felty's syndrome, rather the best method in management of the disease is to control the underlying rheumatoid arthritis. Immunosuppressive therapy for RA often improves granulocytopenia and splenomegaly; this finding reflects the fact that Felty's syndrome is an immune-mediated disease. A major challenge in treating FS is recurring infection caused by neutropenia. Therefore, in order to decide upon and begin treatment, the cause and relationship of neutropenia with the overall condition must be well understood. Most of the traditional medications used to treat RA have been used in the treatment of Felty's syndrome. No well-conducted, randomized, controlled trials support the use of any single agent. Most reports on treatment regimens involve small numbers of patients.

Splenectomy may improve neutropenia in severe disease.

Use of rituximab and leflunomide have been proposed.

Use of gold therapy has also been described.

Prognosis is dependent on the severity of symptoms and the patient's overall health.

In ideal circumstances, patients with known varices should receive treatment to reduce their risk of bleeding. The non-selective β-blockers (e.g., propranolol, timolol or nadolol) and nitrates (e.g., isosorbide mononitrate (IMN) have been evaluated for secondary prophylaxis. Non-selective β-blockers (but not cardioselective β-blockers like atenolol) are preferred because they decrease both cardiac output by β blockade and splanchnic blood flow by blocking vasodilating β receptors at splanchnic vasculature. The effectiveness of this treatment has been shown by a number of different studies.

However, non-selective β-blockers do not prevent the "formation" of esophageal varices.

When medical contraindications to beta-blockers exist, such as significant reactive airway disease, then treatment with prophylactic endoscopic variceal ligation is often performed.

In emergency situations, care is directed at stopping blood loss, maintaining plasma volume, correcting disorders in coagulation induced by cirrhosis, and appropriate use of antibiotics such as quinolones or ceftriaxone. Blood volume resuscitation should be done promptly and with caution. The goal should be hemodynamic stability and hemoglobin of over 8 g/dl. Resuscitation of all lost blood leads to increase in portal pressure leading to more bleeding. Volume resuscitation can also worsen ascites and increase portal pressure. (AASLD guidelines)

Therapeutic endoscopy is considered the mainstay of urgent treatment. The two main therapeutic approaches are variceal ligation or banding and sclerotherapy.

In cases of refractory bleeding, balloon tamponade with a Sengstaken-Blakemore tube may be necessary, usually as a bridge to further endoscopy or treatment of the underlying cause of bleeding (usually portal hypertension). Esophageal devascularization operations such as the Sugiura procedure can also be used to stop complicated variceal bleeding. Methods of treating the portal hypertension include: transjugular intrahepatic portosystemic shunt, or a distal splenorenal shunt procedure or a liver transplantation.

Nutritional supplementation is not necessary if the patient is not eating for four days or less.

Terlipressin and octreotide for 1 to 5 days have also been used.

There no standardized effective treatment strategies for the condition. Severe fatal respiratory failure can develop; long-term treatment with macrolides such as clarithromycin, erythromycin and azithromycin has been empirically applied for the treatment of primary ciliary dyskinesia in Japan, though controversial due to the effects of the medications.

Because of the increased risk of infection, physicians administer oral antibiotics as a prophylaxis after a surgical splenectomy (or starting at birth, for congenital asplenia or functional asplenia).

Those with asplenia are also cautioned to start a full-dose course of antibiotics at the first onset of an upper or lower respiratory tract infection (for example, sore throat or cough), or at the onset of any fever.

Except in the most severe cases, ischemic colitis is treated with supportive care. IV fluids are given to treat dehydration, and the patient is placed on bowel rest (meaning nothing to eat or drink) until the symptoms resolve. If possible, cardiac function and oxygenation should be optimized to improve oxygen delivery to the ischemic bowel. A nasogastric tube may be inserted if an ileus is present.

Antibiotics are sometimes given in moderate to severe cases; the data supporting this practice date to the 1950s, although there is more recent animal data suggesting that antibiotics may increase survival and prevent bacteria from crossing the damaged lining of the colon into the bloodstream. The use of prophylactic antibiotics in ischemic colitis has not been prospectively evaluated in humans, but many authorities recommend their use based on the animal data.

Patients being treated supportively are carefully monitored. If they develop worsening symptoms and signs such as high white blood cell count, fever, worsened abdominal pain, or increased bleeding, then they may require surgical intervention; this usually consists of laparotomy and bowel resection.

Abdominal pain is often the predominant symptom in patients with acute pancreatitis and should be treated with analgesics.

Opioids are safe and effective at providing pain control in patients with acute pancreatitis. Adequate pain control requires the use of intravenous opiates, usually in the form of a patient-controlled analgesia pump. Hydromorphone or fentanyl (intravenous) may be used for pain relief in acute pancreatitis. Fentanyl is being increasingly used due to its better safety profile, especially in renal impairment. As with other opiates, fentanyl can depress respiratory function. It can be given both as a bolus as well as constant infusion.

Meperidine has been historically favored over morphine because of the belief that morphine caused an increase in sphincter of Oddi pressure. However, no clinical studies suggest that morphine can aggravate or cause pancreatitis or cholecystitis. In addition, meperidine has a short half-life and repeated doses can lead to accumulation of the metabolite normeperidine, which causes neuromuscular side effects and, rarely, seizures.

Ulcerative colitis can be treated with a number of medications, including 5-ASA drugs such as sulfasalazine and mesalazine. Corticosteroids such as prednisone can also be used due to their immunosuppressive and short-term healing properties, but because their risks outweigh their benefits, they are not used long-term in treatment. Immunosuppressive medications such as azathioprine and biological agents such as infliximab and adalimumab are given only if people cannot achieve remission with 5-ASA and corticosteroids. Such treatments are used less commonly due to their possible risk factors, including but not limited to increased risk of cancers in teenagers and adults, tuberculosis, and new or worsening heart failure (these side effects are rare). A formulation of budesonide was approved by the FDA for treatment of active ulcerative colitis in January 2013. The evidence on methotrexate does not show a benefit in producing remission in people with ulcerative colitis. Off-label use of drugs such as ciclosporin and tacrolimus has shown some benefits. Fexofenadine, an antihistamine drug used in treatment of allergies, has shown promise in a combination therapy in some studies. Opportunely, low gastrointestinal absorption (or high absorbed drug gastrointestinal secretion) of fexofenadine results in higher concentration at the site of inflammation. Thus, the drug may locally decrease histamine secretion by involved gastrointestinal mast cells and alleviate the inflammation.

Sulfasalazine has been a major agent in the therapy of mild to moderate ulcerative colitis for over 50 years. In 1977, Mastan S. Kalsi "et al." determined that 5-aminosalicylic acid (5-ASA and mesalazine) was the therapeutically active component in sulfasalazine. Since then, many 5-ASA compounds have been developed with the aim of maintaining efficacy but reducing the common side effects associated with the sulfapyridine moiety in sulfasalazine.

Splenic flexure syndrome is a term sometimes used to describe bloating, muscle spasms of the colon, and upper abdominal discomfort thought to be caused by trapped gas at the splenic (as opposed to hepatic) flexure in the colon; the pain caused can be excruciating and debilitating, and may mimic that of a heart attack (because of the proximity of the splenic flexure to the diaphragm and referred pain from irritation to the diaphragmatic sensory nerves).

Some physicians classify splenic flexure syndrome as a type of IBS; others consider it a separate condition.

Treatment is possible and these are the steps taken:

Resuscitate the patient with fluids to stabilize them before surgically

- correcting the malrotation (counterclockwise rotation of the bowel),

- cutting the fibrous bands over the duodenum,

- widening the mesenteric pedicle by separation of the duodenum and cecum.

With this condition the appendix is often on the wrong side of the body and therefore removed as a precautionary measure during the surgical procedure.

One surgical technique is known as "Ladd's procedure", after Dr. William Ladd. Long term research on the Ladd procedure shows that even after the procedure, patients are susceptible to have complaints and might need further surgery.

In the management of acute pancreatitis, the treatment is to stop feeding the patient, giving them nothing by mouth, giving intravenous fluids to prevent dehydration, and sufficient pain control. As the pancreas is stimulated to secrete enzymes by the presence of food in the stomach, having no food pass through the system allows the pancreas to rest. Approximately 20% of patients have a relapse of pain during acute pancreatitis. Approximately 75% of relapses occur within 48 hours of oral refeeding.

The incidence of relapse after oral refeeding may be reduced by post-pyloric enteral rather than parenteral feeding prior to oral refeeding. IMRIE scoring is also useful.

Splenic infarction can be induced for the treatment of such conditions as portal hypertension or splenic injury. It can also be used prior to splenectomy for the prevention of blood loss.

Initial treatment usually consists of the administration of corticosteroids, a group of medications that suppress the immune system. The dose and mode of administration is determined by platelet count and whether there is active bleeding: in urgent situations, infusions of dexamethasone or methylprednisolone may be used, while oral prednisone or prednisolone may suffice in less severe cases. Once the platelet count has improved, the dose of steroid is gradually reduced while the possibility of relapse is monitored. 60–90 percent will experience a relapse during dose reduction or cessation. Long-term steroids are avoided if possible because of potential side-effects that include osteoporosis, diabetes and cataracts.

There is increasing use of immunosuppressants such as mycophenolate mofetil and azathioprine because of their effectiveness. In chronic refractory cases, where immune pathogenesis has been confirmed, the off-label use of the "vinca" alkaloid and chemotherapy agent vincristine may be attempted. However, vincristine has significant side effects and its use in treating ITP must be approached with caution, especially in children.

It is suggested that splenectomized persons receive the following vaccinations, and ideally prior to planned splenectomy surgery:

- Pneumococcal polysaccharide vaccine (not before 2 years of age). Children may first need one or more boosters of pneumococcal conjugate vaccine if they did not complete the full childhood series.

- Haemophilus influenzae type b vaccine, especially if not received in childhood. For adults who have not been previously vaccinated, two doses given two months apart was advised in the new 2006 UK vaccination guidelines (in the UK may be given as a combined Hib/MenC vaccine).

- Meningococcal conjugate vaccine, especially if not received in adolescence. Previously vaccinated adults require a single booster and non-immunised adults advised, in UK since 2006, to have two doses given two months apart. Children too young for the conjugate vaccine should receive meningococcal polysaccharide vaccine in the interim.

- Influenza vaccine, every winter, to help prevent getting secondary bacterial infection.

If the splenomegaly underlies hypersplenism, a splenectomy is indicated and will correct the hypersplenism. However, the underlying cause of the hypersplenism will most likely remain; consequently, a thorough diagnostic workup is still indicated, as, leukemia, lymphoma and other serious disorders can cause hypersplenism and splenomegaly. After splenectomy, however, patients have an increased risk for infectious diseases.

Patients undergoing splenectomy should be vaccinated against "Haemophilus influenzae", "Streptococcus pneumoniae", and "Meningococcus". They should also receive annual influenza vaccinations. Long-term prophylactic antibiotics may be given in certain cases.

In cases of infectious mononucleosis splenomegaly is a common symptom and health care providers may consider using abdominal ultrasonography to get insight into a person's condition. However, because spleen size varies greatly, ultrasonography is not a valid technique for assessing spleen enlargement and should not be used in typical circumstances or to make routine decisions about fitness for playing sports.

Most (>95%) infants with biliary atresia will undergo an operation designed to retain and salvage the native liver, restore bile flow and reduce the level of jaundice. This is known as the Kasai procedure (after Morio Kasai, the Japanese surgeon who first developed the technique) or hepatoportoenterostomy. Although the procedure is not thought of as curative, it may relieve jaundice, and stop liver fibrosis allowing normal growth and development. Published series from Japan, North America and the UK show that bilirubin levels will fall to normal values in about 50-55% of infants allowing 40-50% to retain their own liver to reach the age of 5 and 10 years (and beyond). Liver transplantation is an option for those children whose liver function and symptoms fail to respond to a Kasai operation.

Recent large-scale studies by Davenport et al. ("Annals of Surgery", 2008) show that the age of the patient is not an absolute clinical factor affecting prognosis. The influence of age differs according to the disease etiology—i.e., whether biliary atresia is isolated, cystic (CBA), or accompanied by splenic malformation (BASM).

It is widely accepted that corticosteroid treatment after a Kasai operation, with or without choleretics and antibiotics, has a beneficial effect on postoperative bile flow and can clear jaundice, but the dosing and duration of the ideal steroid protocol are controversial. Furthermore, it has been observed in many retrospective longitudinal studies that corticosteroid treatment does not prolong survival of the native liver or transplant-free survival. Davenport et al. also showed ("Hepatology" 2007) that short-term, low-dose steroid therapy following a Kasai operation had no effect on the mid- or long-term prognosis of biliary atresia patients.

In addition to fluid support, impactions are often treated with intestinal lubricants and laxatives to help move the obstruction along. Mineral oil is the most commonly used lubricant for large colon impactions, and is administered via nasogastric tube, up to 4 liters once or twice daily. It helps coat the intestine, but is not very effective for severe impactions or sand colic since it may simply bypass the obstruction. Mineral oil has the added benefit of crudely measuring GI transit time, a process which normally takes around 18 hours, since it is obvious when it is passed. The detergent dioctyl sodium sulfosuccinate (DDS) is also commonly given in oral fluids. It is more effective in softening an impaction than mineral oil, and helps stimulate intestinal motility, but can inhibit fluid absorption from the intestine and is potentially toxic so is only given in small amounts, two separate times 48 hours apart. Epsom salts are also useful for impactions, since they act both as an osmotic agent, to increase fluid in the GI tract, and as a laxative, but do run the risk of dehydration and diarrhea. Strong laxatives are not recommended for treating impactions.

Endotoxemia is a serious complication of colic and warrants aggressive treatment. Endotoxin (lipopolysaccharide) is released from the cell wall of gram-negative bacteria when they die. Normally, endotoxin is prevented from entering systemic circulation by the barrier function of the intestinal mucosa, antibodies and enzymes which bind and neutralize it and, for the small amount that manages to enter the blood stream, removal by Kupffer cells in the liver. Endotoxemia occurs when there is an overgrowth and secondary die-off of gram negative bacteria, releasing mass quantities of endotoxin. This is especially common when the mucosal barrier is damaged, as with ischemia of the GI tract secondary to a strangulating lesion or displacement. Endotoxemia produces systemic effects such as cardiovascular shock, insulin resistance, and coagulation abnormalities.

Fluid support is essential to maintain blood pressure, often with the help of colloids or hypertonic saline. NSAIDs are commonly given to reduce systemic inflammation. However, they decrease the levels of certain prostaglandins that normally promote healing of the intestinal mucosa, which subsequently increases the amount of endotoxin absorbed. To counteract this, NSAIDs are sometimes administered with a lidocaine drip, which appears to reduce this particular negative effect. Flunixin may be used for this purpose at a dose lower than that used for analgesia, so can be safely given to a colicky horse without risking masking signs that the horse requires surgery. Other drugs that bind endotoxin, such as polymyxin B and Bio-Sponge, are also often used. Polymixin B prevents endotoxin from binding to inflammatory cells, but is potentially nephrotoxic, so should be used with caution in horses with azotemia, especially neonatal foals. Plasma may also be given with the intent of neutralizing endotoxin.

Laminitis is a major concern in horses suffering from endotoxemia. Ideally, prophylactic treatment should be provided to endotoxic horses, which includes the use of NSAIDs, DMSO, icing of the feet, and frog support. Horses are also sometimes administered heparin, which is thought to reduce the risk of laminitis by decreasing blood coagulability and thus blood clot formation in the capillaries of the foot.

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.